Each recommendation is identified as falling into one of three
categories of endorsement, indicated by a bracketed Roman numeral
following the statement. The three categories represent varying
levels of clinical confidence:
[I] Recommended with substantial clinical
confidence
[II] Recommended with moderate clinical
confidence
[III] May be recommended on the basis of
individual circumstances
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B. Psychiatric Management
Panic disorder is a common and often disabling mental disorder.
Treatment is indicated when symptoms of the disorder interfere with
functioning or cause significant distress [I]. Effective
treatment for panic disorder should lead not only to reduction in
frequency and intensity of panic attacks, but also reductions in
anticipatory anxiety and agoraphobic avoidance, optimally with full
remission of symptoms and return to a premorbid level of functioning [I].
Psychiatric management consists of a comprehensive array of activities and
interventions that should be instituted for all patients with panic
disorder, in combination with specific modalities that have demonstrated
efficacy [I].
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1. Establishing a
therapeutic alliance
Psychiatrists should work to establish and maintain a therapeutic
alliance so that the patient's care is a collaborative
endeavor [I]. Careful attention to the patient's
preferences and concerns with regard to treatment is essential to
fostering a strong alliance [I]. In addition,
education about panic disorder and its treatment should be provided
in language that is readily understandable to the patient [I].
Many patients with panic disorder are fearful of certain aspects
of treatment (e.g., medication side effects, confronting agoraphobic
situations). A strong therapeutic alliance is important in supporting
the patient through phases of treatment that may be anxiety provoking [I].
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2. Performing the
psychiatric assessment
Patients should receive a thorough diagnostic evaluation both
to establish the diagnosis of panic disorder and to identify other
psychiatric or general medical conditions [I].
This evaluation generally includes a history of the present illness and
current symptoms; past psychiatric history; general medical history;
history of substance use; personal history (e.g., major life events);
social, occupational, and family history; review of the patient's
medications; previous treatments; review of systems; mental status
examination; physical examination; and appropriate diagnostic tests
(to rule out possible medical causes of panic symptoms) as indicated [I].
Assessment of substance use should include illicit drugs, prescribed and
over-the-counter medications, and other substances (e.g., caffeine)
that may produce physiological effects that can trigger or exacerbate
panic symptoms [I].
Delineating the specific features of panic disorder that characterize
a given patient is an essential element of assessment and treatment
planning [I]. It is crucial to determine if agoraphobia
is present and to establish the extent of situational fear and avoidance [I].
The psychiatrist also should evaluate other psychiatric disorders,
as co-occurring conditions may affect the course, treatment, and
prognosis of panic disorder [I]. It must be determined
that panic attacks do not occur solely as a result of a general
medical condition or substance use and that they are not better
conceptualized as a feature of another diagnosis [I].
The presence of medical disorders, substance use, and other psychiatric
disorders does not preclude a concomitant diagnosis of panic disorder.
If the symptoms of panic disorder are not deemed solely attributable
to these factors, then diagnosing (and treating) both panic disorder
and another condition may be warranted [I].
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3. Tailoring the
treatment plan for the individual patient
Tailoring the treatment plan to match the needs of the particular
patient requires a careful assessment of the frequency and nature
of the patient's symptoms [I]. It may
be helpful, in some circumstances, for patients to monitor their
panic symptoms using techniques such as keeping a daily diary [I]. Such
monitoring can aid in identification of triggers for panic symptoms,
which may become a focus of subsequent intervention.
Continuing evaluation and management of co-occurring psychiatric
and/or medical conditions is also essential to developing
a treatment plan for an individual patient [I].
Co-occurring conditions may influence both selection and implementation
of pharmacological and psychosocial treatments for panic disorder [I].
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4. Evaluating the
safety of the patient
A careful assessment of suicide risk is necessary for all
patients with panic disorder [I]. Panic disorder
has been shown to be associated with an elevated risk of suicidal
ideation and behavior, even in the absence of co-occurring conditions such
as major depression. An assessment of suicidality includes identification
of specific psychiatric symptoms known to be associated with suicide
attempts or suicide; assessment of past suicidal behavior, family
history of suicide and mental illness, current stressors, and potential
protective factors such as positive reasons for living; and specific
inquiry about suicidal thoughts, intent, plans, means, and behaviors [I].
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5. Evaluating types
and severity of functional impairment
Panic disorder can impact numerous spheres of life including work,
school, family, social relationships, and leisure activities. The
psychiatrist should develop an understanding of how panic disorder
affects the patient's functioning in these domains [I] with
the aim of developing a treatment plan intended to minimize impairment [I].
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6. Establishing goals
for treatment
All treatments for panic disorder aim to reduce the frequency and
intensity of panic attacks, anticipatory anxiety, and agoraphobic
avoidance, optimally with full remission of symptoms and return
to a premorbid level of functioning [I]. Treatment
of co-occurring psychiatric disorders when they are present is an
additional goal [I]. The intermediate objectives
that will help achieve these goals will depend on the chosen modality
or modalities [I].
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7. Monitoring the
patient's psychiatric status
The different elements of panic disorder may resolve at different
points during the course of treatment (e.g., panic attacks may remit
before agoraphobic avoidance is eliminated). The psychiatrist should
continue to monitor the status of all symptoms originally presented
by the patient [I]. Psychiatrists may consider
using rating scales to help monitor the patient's status
at each session [I]. Patients also can be asked
to keep a daily diary of panic symptoms to aid in ongoing assessment [I].
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8. Providing education
to the patient and, when appropriate, to the family
Education alone may relieve some of the symptoms of panic disorder
by helping the patient realize that his or her symptoms are neither
life-threatening nor uncommon. Thus, once a diagnosis of panic disorder
is made, the patient should be informed of the diagnosis and educated
about panic disorder and treatment options [I].
Regardless of the treatment modality selected, it is important to
inform the patient that in almost all cases the physical sensations
that characterize panic attacks are not acutely dangerous and will
abate [I]. Educational tools such as books, pamphlets,
and trusted web sites can augment the face-to-face education provided
by the psychiatrist [I].
Providing the family with accurate information about panic
disorder and its treatment is also important for many patients [I].
Education sometimes includes discussion of how changes in the patient's
status affect the family system and of how responses of family members
can help or hinder treatment of the patient's panic disorder [II].
Patient education also includes general promotion of healthy
behaviors such as exercise, good sleep hygiene, and decreased use
of caffeine, tobacco, alcohol, and other potentially deleterious
substances [I].
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9. Coordinating the
patient's care with other clinicians
Many patients with panic disorder will be evaluated by or
receive treatment from other health care professionals in addition
to the psychiatrist. Under such circumstances, the clinicians should
communicate periodically to ensure that care is coordinated and
that treatments are working in synchrony [I].
It is important to ensure that a general medical evaluation has
been done (either by the psychiatrist or by another health care
professional) to rule out medical causes of panic symptoms [I].
Extensive or specialized testing for medical causes of panic symptoms
is usually not indicated but may be conducted based on individual
characteristics of the patient [III].
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10. Enhancing treatment
adherence
Problems with treatment adherence can result from a variety
of factors (e.g., avoidance that is a manifestation of panic disorder, logistical
barriers, cultural or language barriers, problems in the therapeutic
relationship). Whenever possible, the psychiatrist should assess
and acknowledge potential barriers to treatment adherence and should
work collaboratively with the patient to minimize their influence [I].
Many standard pharmacological and psychosocial treatments for
panic disorder can be associated with short-term intensification
of anxiety (e.g., because of medication side effects or exposure
to fear cues during therapy). These temporary increases in anxiety
may contribute to decreased treatment adherence. The psychiatrist
should adopt a stance that encourages patients to articulate their
fears about treatment and should provide patients with a realistic
notion of what they can expect at different points in treatment [I].
In particular, patients should be informed about when a positive
response to treatment can be expected so that they do not prematurely
abandon treatment due to misconceptions about the time frame for
response [I]. Patients should also be encouraged
to contact the psychiatrist (e.g., by telephone if between visits)
if they have concerns or questions, as these can often be readily
addressed and lead to enhanced treatment adherence [I].
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11. Working with
the patient to address early signs of relapse
Although standard treatments effectively reduce the burden of
panic disorder for the majority of patients, even some patients
with a good treatment response may continue to have lingering symptoms
(e.g., occasional panic attacks) or have a recurrence of symptoms
after remission. Patients should be reassured that fluctuations
in symptoms can occur during the course of treatment before an acceptable
level of remission is reached [I]. Patients should
also be informed that symptoms of panic disorder may recur even
after remission and be provided with a plan for how to respond [I].
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C. Formulation and Implementation
of a Treatment Plan
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1. Choosing a treatment
setting
The treatment of panic disorder is generally conducted entirely
on an outpatient basis, as the condition by itself rarely warrants
hospitalization [I]. However, it may be necessary
to hospitalize a patient with panic disorder because of symptoms of
co-occurring disorders (e.g., when acute suicidality associated
with a mood disorder is present or when inpatient detoxification
is required for a substance use disorder) [I].
Under such circumstances, the treatment of panic disorder can be initiated
in the hospital along with treatment of the disorder that prompted
hospitalization [I]. Rarely, hospitalization or partial
hospitalization is required in very severe cases of panic disorder
with agoraphobia when administration of outpatient treatment has
been ineffective or is impractical [I]. Home visits
are another treatment option for patients with severe agoraphobia
who are limited in their ability to travel or leave the house [II].
When accessibility to mental health care is limited (e.g., in remote
or underserved areas), telephone- or Internet-based treatments may
be considered [II].
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2. Choosing an initial
treatment modality
A range of specific psychosocial and pharmacological interventions
have proven benefits in treating panic disorder. The use of a selective
serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake
inhibitor (SNRI), tricyclic antidepressant (TCA), benzodiazepine
(appropriate as monotherapy only in the absence of a co-occurring
mood disorder), or cognitive-behavioral therapy (CBT) as the initial treatment
for panic disorder is strongly supported by demonstrated efficacy
in numerous randomized controlled trials [I]. A
particular form of psychodynamic psychotherapy, panic-focused psychodynamic
psychotherapy (PFPP), was effective in one randomized controlled
trial and could be offered as an initial treatment under certain
circumstances [II].
There is insufficient evidence to recommend any of these pharmacological
or psychosocial interventions as superior to the others, or to routinely
recommend a combination of treatments over monotherapy [II].
Although combination treatment does not appear to be significantly
superior to standard monotherapy as initial treatment for most individuals
with panic disorder, psychiatrists and patients may choose this
option based on individual circumstances (e.g., patient preference) [II].
Considerations that guide the choice of an initial treatment modality
include patient preference, the risks and benefits for the particular
patient, the patient's past treatment history, the presence
of co-occurring general medical and other psychiatric conditions,
cost, and treatment availability [I]. Psychosocial
treatment (with the strongest evidence available for CBT) is recommended
for patients who prefer nonmedication treatment and can invest the
time and effort required to attend weekly sessions and complete
between-session practices [I]. One caveat is that
CBT and other specialized psychosocial treatments are not readily
available in some geographic areas. Pharmacotherapy (usually with
an SSRI or SNRI) is recommended for patients who prefer this modality
or who do not have sufficient time or other resources to engage
in psychosocial treatment [I]. Combined treatment
should be considered for patients who have failed to respond to
standard monotherapies and may also be used under certain clinical circumstances
(e.g., using pharmacotherapy for temporary control of severe symptoms
that are impeding the patient's ability to engage in psychosocial
treatment) [II]. Adding psychosocial treatment
to pharmacotherapy either from the start, or at some later point
in treatment, may enhance long-term outcomes by reducing the likelihood
of relapse when pharmacological treatment is stopped [II].
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3. Evaluating whether
the treatment is working
After treatment is initiated, it is important to monitor change in
key symptoms such as frequency and intensity of panic attacks, level
of anticipatory anxiety, degree of agoraphobic avoidance, and severity
of interference and distress related to panic disorder [I].
Effective treatment should produce a decrease in each of these domains,
although some may change more quickly than others. The severity
of co-occurring conditions also should be assessed at regular intervals,
as treatment of panic disorder can influence co-occurring conditions (e.g.,
major depression; other anxiety disorders) [I].
Rating scales are a useful adjunct to ongoing clinical assessment
for the purpose of evaluating treatment outcome [I].
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4. Determining if
and when to change treatment
Some individuals do not respond, or respond incompletely,
to first-line treatments for panic disorder. Whenever treatment response
is unsatisfactory, the psychiatrist should first consider the possible
contribution of fundamental clinical factors such as an underlying
untreated medical illness that accounts for the symptoms, interference
by co-occurring general medical or psychiatric conditions (including
depression and substance use), inadequate treatment adherence, problems
in the therapeutic alliance, the presence of psychosocial stressors, motivational
factors, and inability to tolerate a particular treatment [I].
These potential impediments to successful treatment should be addressed
as early as possible in treatment [I]. In addition,
if panic-related concerns are leading the patient to minimize the
impact of avoidance or accept functional limitations, the patient
should be encouraged to think through the costs and benefits of
accepting versus treating functional limitations [I]. Clinicians
should be reluctant to accept partial improvement as a satisfactory
outcome and should aim for remission whenever feasible [I].
If response to treatment remains unsatisfactory, and if an adequate
trial has been attempted, it is appropriate for the psychiatrist
and the patient to consider a change [I]. Decisions
about whether and how to make changes will depend on the level of
response to the initial treatment (i.e., none versus partial), the
palatability and feasibility of other treatment options for a given
patient, and the level of symptoms and impairment that remain [I].
Persistent significant symptoms of panic disorder despite a lengthy
course of a particular treatment should trigger a reassessment of
the treatment plan, including possible consultation with another
qualified professional [I].
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5. Approaches to
try when a first-line treatment is unsuccessful
If fundamental clinical issues have been addressed and it
is determined that a change is desirable, the psychiatrist and patient
can either augment the current
treatment by adding another agent (in the case of pharmacotherapy)
or another modality (i.e., add CBT if the patient is already receiving pharmacotherapy,
or add pharmacotherapy if the patient is already receiving CBT) [I],
or they can decide to switch to
a different medication or therapeutic modality [I].
Decisions about how to address treatment resistance are usually
highly individualized and based on clinical judgment, since few
studies have tested the effects of specific switching or augmentation strategies.
However, augmentation is generally a reasonable approach if some
significant benefits were observed with the original treatment [II].
On the other hand, if the original treatment failed to provide any
significant alleviation of the patient's symptoms, a switch
in treatment may be more useful [II].
If one first-line treatment (e.g., CBT, an SSRI, an SNRI) has
failed, adding or switching to another first-line treatment is recommended [I].
Adding a benzodiazepine to an antidepressant is a common augmentation
strategy to target residual symptoms [II]. If
the treatment options with the most robust evidence have been unsuccessful,
other options with some empirical support can be considered (e.g.,
a monoamine oxidase inhibitor [MAOI], PFPP) [II].
After first- and second-line treatments and augmentation strategies
have been exhausted (either due to lack of efficacy or intolerance
of the treatment by the patient), less well-supported treatment
strategies may be considered [III]. These include
monotherapy or augmentation with gabapentin or a second-generation
antipsychotic or with a psychotherapeutic intervention other than CBT
or PFPP [III]. Psychiatrists are encouraged to
seek consultation from experienced colleagues when developing treatment
plans for patients whose symptoms have been resistant to standard
treatments for panic disorder [I].
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6. Specific psychosocial
interventions
Psychosocial treatments for panic disorder should be conducted
by professionals with an appropriate level of training and experience
in the relevant approach [I]. Based on the current
available evidence, CBT is the psychosocial treatment that would
be indicated most often for patients presenting with panic disorder [I].
Cognitive-behavioral therapy is a time-limited treatment (generally
10–15 weekly sessions) with durable effects. It can be
successfully administered individually or in a group format [I].
Self-directed forms of CBT may be useful for patients who do not
have ready access to a trained CBT therapist [II].
Cognitive-behavioral therapy for panic disorder generally includes
psychoeducation, self-monitoring, countering anxious beliefs, exposure
to fear cues, modification of anxiety-maintaining behaviors, and
relapse prevention [I]. Exposure therapy, which
focuses almost exclusively on systematic exposure to fear cues,
is also effective [I].
Panic-focused psychodynamic psychotherapy also has demonstrated
efficacy for panic disorder, although its evidence base is more
limited. Panic-focused psychodynamic psychotherapy may be indicated
as an initial psychosocial treatment in some cases (e.g., patient
preference) [II]. Panic-focused psychodynamic
psychotherapy is a time-limited treatment (twice weekly for 12 weeks)
that is administered on an individual basis. Panic-focused psychodynamic
psychotherapy utilizes the general principles of psychodynamic psychotherapy,
with special focus on the transference as the therapeutic agent
promoting change, and encourages patients to confront the emotional
significance of their panic symptoms with the aim of promoting greater
autonomy, symptom relief, and improved functioning. Although psychodynamic psychotherapies
(other than PFPP) that focus more broadly on emotional and interpersonal
issues have not been formally tested for panic disorder, some case
report data and clinical experience suggest this approach may be
useful for some patients [III].
Other psychosocial treatments have not been formally tested
for panic disorder or have proven ineffective (e.g., eye movement
desensitization and reprocessing [EMDR]) or inferior
to standard treatments such as CBT (e.g., supportive psychotherapy).
Group CBT is effective and can be recommended for treatment
of panic disorder [I]. Other group therapies (including
patient support groups) are not recommended as monotherapies for
panic disorder, although they may be useful adjuncts to other effective
treatments for some patients [III].
Couples or family therapy alone is not recommended as a treatment
for panic disorder, although it may be helpful in addressing co-occurring
relationship dysfunction [III]. It can be beneficial
to include significant others in CBT (e.g., partner-assisted exposure
therapy for agoraphobia), especially if they are educated in the
cognitive-behavioral model of panic disorder and enlisted to help
with between-session practices [II]. When pursuing
other treatments for panic disorder (e.g., pharmacotherapy), education
of significant others about the nature of the disorder and enlisting
significant others to improve treatment adherence may also be helpful [III].
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7. Specific pharmacological
interventions
Selective serotonin reuptake inhibitors, SNRIs, TCAs, and benzodiazepines
have demonstrated efficacy in numerous controlled trials and are
recommended for treatment of panic disorder [I].
Monoamine oxidase inhibitors appear effective for panic disorder
but, because of their safety profile, they are generally reserved
for patients who have failed to respond to several first-line treatments [II].
Other medications with less empirical support (e.g., mirtazapine,
anticonvulsants such as gabapentin) may be considered as monotherapies
or adjunctive treatments for panic disorder when patients have failed to
respond to several standard treatments or based on other individual
circumstances [III].
Because SSRIs, SNRIs, TCAs, and benzodiazepines appear roughly
comparable in their efficacy for panic disorder, selecting a medication
for a particular patient mainly involves considerations of side
effects (including any applicable warnings from the U.S. Food and
Drug Administration [FDA]), cost, pharmacological
properties, potential drug interactions, prior treatment history,
co-occurring general medical and psychiatric conditions, and the
strength of the evidence base for the particular medication in treatment
of panic disorder [I]. The relatively favorable
safety and side effect profile of SSRIs and SNRIs makes them the
best initial choice for many patients with panic disorder [I].
Although TCAs are effective, the side effects and greater toxicity
in overdose associated with them often limit their acceptability
to patients and their clinical utility. Selective serotonin reuptake
inhibitors, SNRIs, and TCAs are all preferable to benzodiazepines
as monotherapies for patients with co-occurring depression or substance
use disorders [I]. Benzodiazepines may be especially
useful adjunctively with antidepressants to treat residual anxiety
symptoms [II]. Benzodiazepines may be preferred (as
monotherapies or in combination with antidepressants) for patients
with very distressing or impairing symptoms in whom rapid symptom
control is critical [II]. The benefit of more
rapid response to benzodiazepines must be balanced against the possibilities
of troublesome side effects (e.g., sedation) and physiological dependence
that may lead to difficulty discontinuing the medication [I].
Patients should be educated about the likely time course of
treatment effects associated with a particular medication [I].
Because patients with panic disorder can be sensitive to medication
side effects, low starting doses of SSRIs, SNRIs, and TCAs (approximately
half of the starting doses given to depressed patients) are recommended [I].
The low dose is maintained for several days then gradually increased
to a full therapeutic dose over subsequent days and as tolerated
by the patient [I]. Underdosing of antidepressants
(i.e., starting low and then not increasing gradually to full therapeutic
dosages as needed) is common in treatment of panic disorder and
is a frequent source of partial response or nonresponse [II].
A regular dosing schedule rather than a p.r.n. ("as needed") schedule
is preferred for patients with panic disorder who are taking benzodiazepines [II],
where the goal is to prevent panic attacks rather than reduce symptoms
once an attack has already occurred.
Once an initial pharmacotherapy has been selected, patients
are typically seen every 1–2 weeks when first starting
a new medication, then every 2–4 weeks until the dose is
stabilized [I]. After the dose is stabilized and
symptoms have decreased, patients will most likely require less
frequent visits [I].
When considering any specific medication, the psychiatrist
must balance the risks associated with the medication against the
clinical need for pharmacotherapy [I]. The FDA has
warned of the possibility that antidepressants may increase the
risk of suicidal ideation and behavior in patients age 25 years
and younger; this is an important factor to consider before using
an SSRI, an SNRI, or a TCA for panic disorder. Other important safety
considerations for SSRIs include possible increased likelihood of
upper gastrointestinal bleeding (particularly when taken in combination
with nonsteroidal anti-inflammatory drugs [NSAIDs] or
with aspirin) and increased risk of falls and osteoporotic fractures
in patients age 50 years and older. With venlafaxine extended release
(ER), a small proportion of patients may develop sustained hypertension.
It is recommended that psychiatrists assess blood pressure during
treatment, particularly when venlafaxine ER is titrated to higher
doses [I].
Tricyclic antidepressants should not be prescribed for patients
with panic disorder who also have acute narrow-angle glaucoma or
clinically significant prostatic hypertrophy. Tricyclic antidepressants
may increase the likelihood of falls, particularly among elderly
patients. A baseline electrocardiogram should be considered before
initiating a TCA, because patients with preexisting cardiac conduction abnormalities
may experience significant or fatal arrhythmia with TCA treatment.
Overdoses with TCAs can lead to significant cardiac toxicity and
fatality, and therefore TCAs should be used judiciously in suicidal
patients.
Benzodiazepines may produce sedation, fatigue, ataxia, slurred
speech, memory impairment, and weakness. Geriatric patients taking
benzodiazepines may be at higher risk for falls and fractures. Because
of an increased risk of motor vehicle accidents with benzodiazepine
use, patients should be warned about driving or operating heavy
machinery while taking benzodiazepines [I]. Patients
should also be advised about the additive effects of benzodiazepines
and alcohol [I]. Caution and careful monitoring
is indicated when prescribing benzodiazepines to elderly patients,
those with preexisting cognitive impairment, or those with a history
of substance use disorder [I].
For women with panic disorder who are pregnant, nursing, or
planning to become pregnant, psychosocial interventions should be
considered in lieu of pharmacotherapy [II]. Pharmacotherapy
may also be indicated [III] but requires weighing
and discussion of the potential benefits and risks with the patient,
her obstetrician, and, whenever possible, her partner [I].
Such discussions should also consider the potential risks to the
patient and the child of untreated psychiatric illness, including
panic disorder and any co-occurring psychiatric conditions [I].
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D. Maintaining or Discontinuing
Treatment After Response
Pharmacotherapy should generally be continued for 1 year or more
after acute response to promote further symptom reduction and decrease
risk of recurrence [I]. Incorporating maintenance
treatment (e.g., monthly "booster" sessions focused on
relapse prevention) into psychosocial treatments for panic disorder
also may help maintain positive response [II],
although more systematic investigation of this issue is needed.
Before advising a taper of effective pharmacotherapy, the psychiatrist
should consider several factors, including the duration of the patient's
symptom stability, the presence of current or impending psychosocial
stressors in the patient's life, and the extent to which
the patient is motivated to discontinue the medication [II].
Discussion of medication taper should also include the possible
outcomes of taper, which could include discontinuation symptoms
and recurrence of panic symptoms [I]. If medication
is tapered, it should be done in a collaborative manner with continual
assessment of the effects of the taper and the patient's
responses to any changes that emerge [I].
If a decision is made to discontinue successful treatment with
an SSRI, an SNRI, or a TCA, the medication should be gradually tapered
(e.g., one dosage step down every month or two), thereby providing
the opportunity to watch for recurrence and, if desired, to reinitiate
treatment at a previously effective dose [II].
However, under more urgent conditions (e.g., the patient is pregnant
and the decision is made to discontinue medications immediately),
these medications can be discontinued much more quickly [I].
The approach to benzodiazepine discontinuation also involves
a slow and gradual tapering of dose [I]. Withdrawal symptoms
and symptomatic rebound are commonly seen with benzodiazepine discontinuation,
can occur throughout the taper, and may be especially severe toward
the end of the taper. This argues for tapering benzodiazepines very
slowly for patients with panic disorder, probably over 2–4
months and at rates no higher than 10% of the dose per
week [I]. Cognitive-behavioral therapy may be
added to facilitate withdrawal from benzodiazepines [I].
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II. Formulation and
Implementation of a Treatment Plan
The formulation of a treatment
plan considers the full range of predispositions, precipitants,
and symptoms exhibited by patients with panic disorder. Effective
treatment involves not only resolution of panic attacks but also
satisfactory reductions in anticipatory anxiety and agoraphobic
avoidance, optimally with full remission of symptoms and return
to a premorbid level of functioning.
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A. Psychiatric Management
Psychiatric management consists of a comprehensive array of
activities and interventions that should be instituted by psychiatrists
for all patients with panic disorder, in combination with specific
treatment modalities.
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1. Establishing a
therapeutic alliance
As in all of medical practice, the physician first works to
establish and then to maintain a therapeutic alliance so that the patient's
care is a collaborative endeavor. By the very nature of the illness,
many patients with panic disorder are anxious about treatment. Therefore,
education and support are important components of the psychiatric
management of panic disorder. As is true for most individuals who
are first initiating treatment for psychiatric or general medical
disorders, patients with panic disorder may require additional support
and access to their health care professionals in the early phase
of treatment, before symptoms resolve. Patients should be informed
about courses of action they can pursue if they need help urgently,
such as having the psychiatrist paged, going to the emergency department,
or calling 911. This information should be provided in the context
of education that panic symptoms themselves are rarely dangerous
and that occurrence of panic symptoms does not usually require immediate medical
attention.
Panic disorder can be a chronic condition for which adherence
to a treatment plan is important. Hence, a strong treatment alliance
is crucial. It is often the case that the treatment of panic disorder
involves asking the patient to do things that may be frightening
and uncomfortable, such as confronting agoraphobic situations. Here
again, a strong treatment alliance is necessary to support the patient
in doing these things.
Therapeutic communications explaining panic disorder should
be made in language that is culturally sensitive and worded in a
way that the patient can understand. Careful attention to the patient's
fears and wishes with regard to his or her treatment is essential
in establishing and maintaining the therapeutic alliance. Management
of the therapeutic alliance may involve an awareness of the patient's
beliefs about medication and psychotherapy, cultural differences,
transference, countertransference, and other factors that may influence
the psychiatrist-patient relationship.
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2. Performing the
psychiatric assessment
Patients with panic symptoms should receive a thorough diagnostic
evaluation both to determine whether a diagnosis of panic disorder
is warranted and to identify the presence of other psychiatric or
general medical conditions. This evaluation will generally include
a history of the present illness and current symptoms; past psychiatric
history; general medical history and history of substance use; personal
history (e.g., major life events); social, occupational (including
military), and family history; review of the patient's
medications; review of previous treatments; review of systems; mental
status examination; physical examination; and diagnostic tests (to
rule out possible general medical causes of panic symptoms) as indicated.
Family history of anxiety disorders and childhood traumatic events
are reported more often by patients with panic disorder than by
many comparison groups (3–5),
and longitudinal data suggest that childhood physical and sexual
abuse are risk factors for panic disorder (6). Patients
with panic disorder also report more stressful events in the month
preceding panic onset, compared with control participants (7).
Therefore, the psychiatric assessment should include careful inquiry
about the patient's developmental history, life events,
family history, and the events that preceded onset of the panic
symptoms. Additional details about the general principles and components
of a complete psychiatric evaluation have been outlined in APA's Practice
Guideline for the Psychiatric Evaluation of Adults, Second Edition (8).
Delineating the features of panic disorder that are present in
a given patient is also important in establishing a diagnosis of
panic disorder and developing a plan of treatment. The essential
features of panic disorder are recurrent panic attacks and persistent
concern about these attacks (or change in behavior as a result of
the attacks). Panic attacks are discrete periods of intense fear
or discomfort that have abrupt onset and usually reach a peak within
10 minutes. These attacks are characterized by distressing physical
and psychological symptoms and often by a sense of imminent danger
and an urge to escape. Persistent concern about panic attacks can manifest
in several ways: worry about having additional attacks, worry about
the implications or consequences of the attacks, or changes in behavior
that are intended to prevent attacks or cope with an attack should
one occur. Fear and avoidance of situations and places such as driving,
restaurants, shopping malls, and elevators commonly occur in individuals
with panic disorder; this avoidance is referred to as agoraphobia.
Patients with concurrent agoraphobia fear and/or avoid
situations in which escaping or obtaining help may be difficult
or embarrassing if they have panic symptoms. In any evaluation of
panic disorder, it is crucial to determine if agoraphobia is present
and to establish the extent of situational fear and avoidance. Tables
1, 2, 3, and 4 provide the DSM-IV-TR criteria for the diagnoses of
panic attack, agoraphobia, panic disorder without agoraphobia, and
panic disorder with agoraphobia. More detailed discussion of the diagnostic
features of panic disorder can be found in DSM-IV-TR and in Section
IV.A of this guideline.
In addition to a full assessment of the features of panic
disorder and agoraphobia, a comprehensive psychiatric assessment
is essential to identify other anxiety disorders, mood disorders,
substance use disorders, personality disorders, and other disorders
that often co-occur with panic disorder (9–33). Co-occurring
psychiatric disorders require particular attention as some of them
affect the course, treatment response, and prognosis of panic disorder
(34).
Establishing the context in which panic attacks occur is important
for accurate diagnosis. Panic attacks frequently occur in other
disorders, and in only a subset of individuals is panic disorder
an appropriate diagnosis. First, it must be determined that panic
attacks do not occur solely as a result of a general medical condition.
Some examples of medical conditions that can be associated with
panic symptoms include hyperthyroidism, hypothyroidism, hypercalcemia,
hypoglycemia, pheochromocytoma, vestibular dysfunction (e.g., Ménière's
disease), seizure disorders, and cardiac conditions such as arrhythmias
and supraventricular tachycardia (35). With most of
these conditions, definitive causal relationships between the general
medical condition and panic disorder have not been established.
Although there appears to be an increased co-occurrence of mitral
valve prolapse and panic disorder (36–39),
mitral valve prolapse is typically an incidental finding in a patient
with panic disorder and does not usually change the treatment plan
(i.e., the panic disorder remains the primary target of treatment).
Section III.B provides further discussion of the impact of co-occurring
medical conditions on treatment planning for panic disorder.
Panic attacks are often associated with intoxication with (e.g.,
cannabis, stimulant) or withdrawal from (e.g., sedative-hypnotic,
alcohol, benzodiazepine) drugs of abuse. Prescription or over-the-counter
medications, including decongestants (pseudoephedrine, phenylpropanolamine),
stimulants, dopaminergic agents, and agents to treat asthma (beta-adrenergic
agonist inhalers, theophylline, steroids) may also induce or worsen
panic attacks. Finally, caffeine and related compounds in beverages
(e.g., coffee, colas, tea, "energy drinks") and
other ingested products (e.g., "energy bars")
can induce panic attacks in anyone at excessive doses (typically
more than 800–1,000 mg/day), but can do so even
at lower doses in individuals susceptible to panic disorder. Reduction
or elimination of intake of such medications and substances may
lead to a marked decrease or cessation of panic episodes.
Psychiatrists also should consider other psychiatric disorders
for which panic attacks can be an associated feature. A diagnosis
of panic disorder requires the presence of at least some unexpected
attacks during the course of illness that are not triggered by a
specific stimulus. Psychiatrists should consider other disorders
when panic attacks appear to be exclusively associated with the
following:
- Exposure to a specific feared
situation or stimulus (specific phobia)
- Exposure to situations in which the patient fears negative evaluation
(social phobia)
- Exposure to the focus of an obsession or a situation
in which the patient was prevented from performing a compulsive
behavior (obsessive-compulsive disorder)
- Exposure to a reminder of a traumatic experience or
to a situation in which the patient feels that safety is threatened
(posttraumatic stress disorder)
- Intense bouts of worrying (generalized anxiety disorder)
- Exposure to separation from home or an attachment figure
in children or adolescents (separation anxiety disorder)
- Hallucinations or delusional thinking (psychotic disorders)
- Use or withdrawal from use of a substance (substance
use disorders; especially, intoxication with central nervous system
stimulants or cannabis and withdrawal from central nervous system
depressants)
In addition to establishing that panic attacks are not exclusively
associated with the circumstances listed above, it must be determined
that the patient has experienced 1 month or more of worry about
having more attacks, worry about the implications of the attacks,
or panic-related behavioral changes. If a patient reports panic
attacks without associated worry or behavioral change, the psychiatrist
should consider whether panic attacks are an associated feature
of another disorder or represent a subthreshold panic disorder (i.e.,
the patient demonstrates many features of panic disorder but does
not meet full criteria). Although subthreshold panic disorder is
associated with a lesser degree of symptoms, comorbidity, and functional
impairment than full panic disorder (40), subthreshold
panic disorder is often distressing for the patient, can interfere
with functioning, and may progress to full panic disorder in some
individuals (41). Standard treatments for panic disorder
are generally indicated for patients presenting with subthreshold
symptoms, although education or a briefer course of treatment may
be sufficient as a first treatment step if symptoms are mild.
Panic attacks that occur in the absence of worry about the attacks
or behavior change in response to the attacks also may be conceptualized
as associated features of other disorders. For instance, it is fairly
common for patients with mood disorders to report occasional unexpected
panic attacks; however, if persistent concerns about the attacks
and behavioral changes in response to the attacks are both absent,
then the panic attacks should be conceptualized as an associated feature
of the mood disorder. In other cases, patients may present with
panic attacks that are part of a reaction to a specific stressful
situation; in this circumstance, a diagnosis of adjustment disorder
may be indicated. Finally, patients may report panic symptoms that,
upon further examination, appear to be normal reactions to truly
threatening situations (e.g., deployment to a war zone, diagnosis
of a serious illness).
Some patients endorse worry about panic-like symptoms and/or
avoidance of situations because of fears of developing panic-like
symptoms; however, the episodes of fearfulness they describe do
not meet DSM-IV-TR criteria for a panic attack. In these cases,
a diagnosis of agoraphobia without history of panic disorder should
be considered. Patients with this diagnosis often fear and avoid
situations that are commonly avoided by patients with panic disorder
(e.g., crowded places, driving long distances). In contrast to patients
with panic disorder, such patients report only limited symptom attacks
(i.e., subthreshold panic attacks) or perhaps one discrete symptom
(e.g., stomach distress). Standard treatments for panic disorder
(especially cognitive-behavioral approaches) are indicated for most
patients with agoraphobia without history of panic disorder, although
they should be tailored to address the patient's particular
concerns and symptoms.
Some atypical presentations of panic disorder may be misinterpreted
as other disorders. For instance, some patients experience choking
sensations as a prominent symptom of panic and avoid eating many
foods due to fears of choking. Their restricted eating may cause
them to initially appear to have a primary eating disorder. However,
upon further questioning these patients reveal that they avoid eating
certain foods because they fear choking and that the symptoms they
experience while eating are consistent with the definition of a
panic attack. If the patient also reports some unexpected panic
attacks, the diagnosis of panic disorder may be appropriate. If unexpected
attacks are absent, then a specific phobia of choking may be a more
accurate diagnosis. Regardless, determining the concern (fear of
gaining weight versus fear of panicking and choking) that motivates
the problematic behavior (restricted eating) is essential to differential
diagnosis.
Finally, it is important to note that the presence of general medical
conditions, substance use, and other psychiatric disorders does
not preclude a concomitant diagnosis of panic disorder. If the symptoms
of panic disorder are not deemed to be solely attributable to these
factors, then diagnosing both panic disorder and another condition
(medical, psychiatric, or substance related) may be warranted.
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3. Tailoring the
treatment plan for the individual patient
Although patients with panic disorder share common features of
the illness, there may be important individual differences. The
frequency of panic attacks varies widely among patients, and the
symptoms associated with panic attacks can be highly individualized.
For example, some patients report attacks that primarily involve
somatic symptoms (e.g., palpitations, chest pain), whereas others
are more focused on psychological symptoms (e.g., depersonalization,
fear of "going crazy"). The amount of anticipatory
anxiety and the degree of agoraphobic avoidance also vary from patient
to patient. Many patients with panic disorder exhibit only mild
levels of avoidance; at the opposite extreme are patients who will
not leave the house without a trusted companion. Patients also present
with significant variation in their profiles of panic-related apprehension,
which seem to fall into one or more of several major foci of concern (i.e.,
physical, social, or mental catastrophe) (42). Sensitivity
to these individual differences in the elements of panic disorder
is essential for two reasons. First, it is important for the patient
to feel that the psychiatrist understands his or her individual
experience of panic symptoms. Second, treatment selection, delivery,
and response may be influenced by the particular constellation of
symptoms of a given patient.
Tailoring the treatment to match the needs of the particular
patient requires a careful assessment of the frequency and nature
of the patient's symptoms. It may be helpful for patients
to monitor their panic symptoms using techniques such as keeping
a daily diary, in order to gather information regarding the relationship
of panic symptoms to internal stimuli (e.g., emotions) and external
stimuli (e.g., substances, particular situations or settings). Such
monitoring can reveal triggers of panic symptoms that may be the
focus of subsequent intervention.
In addition, it is extremely
important when formulating the treatment plan to address the presence
of any of the many psychiatric and medical conditions that frequently
co-occur with panic disorder. Continuing evaluation and management
of co-occurring conditions are a crucial part of the treatment plan.
In some individuals, treatment of co-occurring conditions may be required
before interventions for panic disorder can become successful. For
example, patients with serious substance use disorders may need
detoxification before it is possible to institute treatment for
panic disorder. However, total abstinence should not usually be
a condition of initiating panic disorder treatment, especially if
the substance use appears to be triggered by panic disorder symptoms.
Symptoms of co-occurring personality disorders (e.g., borderline
personality disorder) may also be so prominent that they interfere
with symptom-based treatment of panic disorder. In these circumstances,
the personality disorder may require appropriate intervention before
or concomitant with the panic treatment (see APA's Practice
Guideline for the Treatment of Patients With Borderline Personality
Disorder [43]).
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4. Evaluating the
safety of the patient
A careful assessment of suicide risk is an essential element
of the evaluation of all patients with panic disorder. Panic disorder
has been shown to be associated with an elevated risk of suicidal
ideation and behavior, even after controlling for the effects of
co-occurring conditions (44). The assessment should
include 1) identification of specific psychiatric symptoms known
to be associated with suicide attempts or suicide, which include
aggression, violence toward others, impulsiveness, hopelessness,
agitation, psychosis, mood disorders, and substance use disorders;
2) assessment of past suicidal behavior, including the intent and
lethality of self-injurious acts; 3) family history of suicide and
mental illness; 4) current stressors such as recent losses, poor
social support, family dysfunction, physical illnesses, chronic
pain, or financial, legal, occupational, or relationship problems;
5) potential protective factors such as positive reasons for living
(e.g., children, other family members, pets, positive therapeutic
relationships, sense of responsibility to others), spirituality/religious beliefs,
or good reality testing, frustration tolerance, or coping skills;
and 6) specific inquiry about suicidal thoughts, intent, plans,
means, and behaviors. For more information about assessing and managing
suicidality, readers may consult APA's Practice
Guideline for the Assessment and Treatment of Patients With Suicidal
Behaviors (45). Issues relating to
the potential for emergence of suicidality with antidepressant treatment
are reviewed in Section II.H.
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5. Evaluating types
and severity of functional impairment
The degree of functional impairment varies considerably among
patients with panic disorder. While panic attack frequency and severity
contribute to functional impairment, so do the extent of anticipatory
anxiety and agoraphobic avoidance. In particular, agoraphobic avoidance
can lead to considerable dysfunction in both work and social domains. Levels
of agoraphobic avoidance and apprehension have been shown to be
stronger predictors of functional impairment and quality of life
than frequency of panic attacks (46). Even after panic
attacks have subsided, the patient may continue to have significant
functional limitations that should be addressed in treatment.
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6. Establishing goals
for treatment
The ultimate goals of first-line
treatments for panic disorder are reducing the frequency and intensity
of panic attacks, anticipatory anxiety, and agoraphobic avoidance, optimally with
full remission of symptoms and attainment of a premorbid level of
functioning. Treatment of co-occurring psychiatric disorders when
they are present is an additional goal. The intermediate objectives
that will help achieve these goals will depend on the chosen modality
or modalities (see Section II.C). For example, in the case of pharmacotherapy
the initial objectives include educating the patient about panic
disorder and medication treatment (including medication side effects), selecting
an appropriate starting dose of medication, titrating up to a therapeutic
dose, promoting adherence to the medication regimen, and recommending
and reinforcing positive behavioral changes. When any psychosocial
treatment is pursued, a coherent explanation of how that treatment
is thought to influence panic disorder should be provided to the patient.
The conceptual model of panic pertinent to the type of therapy or
therapies being deployed, principles of treatment, and expected
outcomes should be made explicit to the patient.
Treatment of panic disorder should also include substantial
effort to alleviate or minimize functional impairment that may be
associated with panic attacks, associated anxiety, and agoraphobic
avoidance. In addressing such functional impairment, it is critical
to determine how patients define satisfactory outcomes and desirable
levels of functioning for themselves, but also to assist patients
who may not believe certain goals are attainable to become aware
of the possibility of functional gains.
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7. Monitoring the
patient's psychiatric status
The different elements of panic disorder often resolve at
different points during the course of treatment. Usually, panic attacks
are controlled first, but subthreshold panic attacks, anticipatory
anxiety, and agoraphobic avoidance often continue and require further
treatment (47). The psychiatrist should continue to
monitor the status of all of the symptoms with which the patient
originally presented and should monitor the effectiveness of the
treatment plan on an ongoing basis. Many illnesses, including depression
and substance use disorders, co-occur with panic disorder at higher
rates than are seen in the general population (33).
Therefore, the psychiatrist should monitor the patient's
mood (and symptoms of any other co-occurring disorder) on an ongoing
basis.
Psychiatrists may consider
using rating scales to help monitor the patient's status
at each session. Other resources provide detailed information about
rating scales that may help with ongoing measurement of the severity
of panic disorder symptoms and symptoms of co-occurring conditions (48, 49).
Rating scales such as the Panic Disorder Severity Scale (PDSS) (50)
may complement the psychiatrist's interview by offering
a quantitative measure of severity that can be tracked over time.
The PDSS can be administered and rated by the psychiatrist (50, 51),
or a self-report version can be used (52). Rating scales
that measure symptoms of anxiety more broadly also may aid in monitoring
the patient's status. The Overall Anxiety Severity and
Impairment Scale (OASIS) (53) is an example of a rating
scale that measures symptoms of anxiety more broadly (i.e., includes
both panic and other anxiety disorder symptoms), which may also
be a useful way to measure outcome for some patients. Many other
rating scales for anxiety, panic symptoms, and agoraphobia are available.
Psychiatrists may refer to clinical handbooks to find other appropriate
measures of panic symptoms as well as measures of common co-occurring
illnesses (e.g., depression). These handbooks offer descriptions
of various rating scales along with information about reliability
and validity, administration and scoring, and instructions about
how to obtain each scale (48, 49).
Psychiatrists also can evaluate the frequency and severity of
a patient's panic symptoms by asking the patient to keep
a daily diary that includes information such as the time, location,
nature, and intensity of panic symptoms. Before instructing patients
to monitor panic symptoms, the psychiatrist should discuss the potential
costs (e.g., temporary increase in anxiety because of increased
focus on symptoms) and benefits (e.g., more accurate assessment
of symptoms than by using retrospective report) of this assessment
strategy (54).
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8. Providing education
to the patient and, when appropriate, to the family
Once the diagnosis of panic disorder is made, the patient
should be informed of the diagnosis and educated about panic disorder, its
clinical course, and its complications. The psychiatrist should
convey hope and reasonable expectations for how treatment will influence
the course of the disorder. Regardless of the treatment modality
selected, it is important to inform the patient that in almost all
cases the physical sensations that characterize panic attacks are
not acutely dangerous and will abate. In a few rare circumstances
(e.g., possible elevated risk of hypoperfusion or placental abruption
in pregnant women with panic attacks), panic attacks may in fact
be associated with harmful effects; this information should be disseminated
as needed for individual patients who present with co-occurring
conditions that put them at risk for possible complications of panic
attacks.
Many patients with panic disorder believe they are suffering
from a disorder of an organ system other than the central nervous
system. They may fervently believe, for example, that they have
heart or lung disease. Partners and involved family members of patients
with panic disorder may share these beliefs, may be frustrated by
the patient's disability, or may insist that absolutely
nothing is wrong with the patient. Educating both the family and
the patient and emphasizing that panic disorder is a real illness
requiring support and treatment can be crucial. Regardless of the
method of treatment selected, successful therapies of panic disorder
usually begin by explaining to the patient that the attacks themselves
are not life-threatening. By helping the patient realize that these
symptoms are neither life-threatening nor uncommon, education alone
may relieve some of the symptoms of panic disorder. This information
also may enhance motivation for treatment. The family may be helped
to understand that panic attacks are terrifying to the patient,
that avoidant behavior can perpetuate panic symptoms, and that the
disorder, unless treated, can interfere significantly with the patient's
life. In addition to receiving education provided by the treating
psychiatrist, patients and their families may benefit from access
to organizations and to materials that promote understanding of
anxiety disorders and other mental health problems (see Appendix).
As with other therapeutic communication, cultural and language differences may
need to be considered and accommodated in imparting information
about panic disorder to patients and their families.
There are rare situations in which agoraphobic avoidance becomes
such a routine part of the patient's life that the family
is actually reluctant to see it remit. A patient who is homebound
because of panic disorder, for example, may have assumed all of
the household chores for the family. Remission of this kind of agoraphobic
avoidance might lead the patient to engage in more activities outside
of the home and create a potential for conflict in the family system.
Without recognizing this, family members might tacitly undermine
a potentially successful treatment to avoid disrupting their ingrained
patterns. It is also possible (although not necessarily common)
that successful resolution of agoraphobia may place strain on significant
relationships as others adjust to the changes in the patient's
ability to pursue independent activities (55). Therefore,
education sometimes includes discussion of how changes in the patient's
status might affect the family system and how responses of family
members can help or hinder treatment of the patient's panic
disorder.
Patient education also includes general promotion of healthy
behaviors such as exercise, good sleep hygiene, and decreased use
of caffeine, tobacco, alcohol, and other potentially deleterious
substances. Preliminary evidence suggests that aerobic exercise
may benefit individuals with panic symptoms (56–59).
Given the myriad health benefits of exercise, even if benefits for
panic disorder are largely unproven, psychiatrists should consider
recommending aerobic exercise (e.g., walking for 60 minutes or running
for 20–30 minutes at least 4 days per week) to patients
who are physically able. However, in doing so the psychiatrist should
consider that fears of physical exertion are common in patients
with panic disorder and that exercise may actually trigger panic
attacks in some patients (although most patients can tolerate exercise without
difficulty) (60). In these individuals, the psychiatrist may
wish to incorporate exercise into the treatment regimen more gradually,
as the patient experiences symptom relief and develops coping skills
for panic symptoms. For patients receiving CBT, aerobic exercise
can be incorporated into the interoceptive exposure component of
treatment.
When co-occurring tobacco use is present, smoking cessation
interventions may be useful adjuncts to standard treatments for
panic disorder. Epidemiologic data suggest that daily smoking increases
risk for panic attacks and panic disorder. Thus, smoking may be
a causal or exacerbating factor in some individuals with panic disorder.
The effects of other substance use disorders on panic disorder symptoms
and treatment are reviewed in Section III.A.2.
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9. Coordinating the
patient's care with other clinicians
Many patients with panic disorder will be evaluated by or
will receive treatment from other health care professionals in addition
to the psychiatrist. Under such circumstances, the clinicians should
communicate periodically to ensure that care is coordinated and
that any treatments are working in synchrony. Psychiatric management
may also involve educating nonpsychiatric health care professionals
about panic disorder, including the ability of panic attacks to
masquerade as other general medical conditions and strategies for
assisting patients who are convinced that panic attacks represent
serious abnormalities of other organ systems.
It is important to ensure that a general medical evaluation has
been done (either by the psychiatrist or by another physician) to
rule out medical causes of panic symptoms. By the time a psychiatrist
is consulted, many patients with panic disorder may already have
undergone medical testing, which the psychiatrist should review.
Generally, physicians should test thyroid-stimulating hormone levels
to rule out thyroid disease and obtain a substance use history (including
caffeine, nicotine, alcohol, and other potentially deleterious substances)
to rule out overuse, abuse, or dependence that could be causing
or exacerbating symptoms of panic disorder. If cardiac symptoms
are prominent, an electrocardiogram may be warranted, and if seizures
are suspected the physician should refer the patient to a neurologist
for evaluation. Extensive or specialized testing for medical causes
is usually not indicated during the initial assessment but may be conducted
based on the patient's specific presentation (e.g., frequent
palpitations may be cause to conduct a Holter monitoring examination
or other specific cardiac tests). In fact, attempting to diagnose
and treat a variety of nonspecific somatic symptoms may delay initiation
of treatment for the panic disorder itself. However, with some patients
it may be therapeutic and enhance the therapeutic alliance to undertake assessment
that will disconfirm other causative sources for the panic attacks.
Therefore, the extent of assessment for medical causes of panic
attacks will vary according to the individual patient.
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10. Enhancing treatment
adherence
The treatment of panic disorder involves confronting many things
that the patient fears. Patients are often afraid of medically adverse
events; hence, they fear taking medications and can be very sensitive
to somatic sensations induced by them (e.g., initial tremulousness
or nervousness caused by antidepressants). As described in Section
II.G.1, patients receiving CBT may be required to confront both
interoceptive fear cues (i.e., feared bodily sensations) and external
fear cues (i.e., agoraphobic situations) and to keep careful records
of anxiety symptoms. These activities may temporarily increase the
patient's anxiety level.
The short-term intensification of anxiety in association with
standard treatments for panic disorder may decrease adherence. For
example, some patients may miss or arrive late for treatment sessions,
may abruptly stop medication, or may not complete required assignments
during CBT. Recognition of these possibilities guides the psychiatrist
to adopt a stance that encourages the patient to articulate his
or her fears. It is also helpful to inform the patient that response
is not likely to be immediate and that there may even be an initial
increase in anxiety as treatment begins. Patients should be educated
that relapses may occur during the course of recovery but that these
events do not typically indicate that treatment will be ineffective
over time. The psychiatrist should indicate how the patient could
obtain help in the event of a severe relapse.
Problems with treatment adherence can result from a variety
of factors. An empathic and nonjudgmental stance can facilitate
discussion of adherence issues such as missed sessions, lapses in
medication use, or failure to complete CBT homework assignments.
In addition, incomplete adherence may simply be a manifestation
of the disorder. For example, the patient might be afraid of somatic
sensations that accompany medication use or be afraid to complete
an exposure to a feared situation. Agoraphobic avoidance might also
cause patients to miss sessions because of fears of leaving the house
or traveling. Psychiatrists should acknowledge the possibility that
anxiety might sometimes interfere with adherence to treatment and
should help patients plan ahead to minimize this possibility. For
example, for a patient who fears driving, initially arrangements
could be made for a family member to drive the patient to sessions.
Family members or other trusted individuals also may play other
helpful roles in improving treatment adherence, such as reminding
the patient to take medication at scheduled times or giving the
patient positive reinforcement for confronting situations previously
avoided.
Adherence may be limited not only by the disorder but also
by practical issues such as scheduling conflicts, lack of transportation
or child care, or insufficient financial resources. With regard
to scheduling, transportation, and child care issues, it is useful
to identify these potential obstacles at an early juncture and help
the patient generate possible solutions. Pharmaceutical companies
may provide free medications for patients with severe financial
limitations, with the exact criteria differing from company to company.
Information on patient assistance programs is available from the
web site of the Partnership for Prescription Assistance (http://www.helpingpatients.org)
and from Rx Assist (http://www.rxassist.org).
Finally, incomplete adherence may reflect issues in the psychiatrist-patient
relationship. If adherence is not improved by measures such as discussing
fears, providing reassurance and nonpunitive acceptance, providing
education, and mobilizing family support, it may indicate more complex
resistance that is not within the patient's awareness and
that may need to become the main focus of treatment.
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11. Working with
the patient to address early signs of relapse
Studies have shown that panic disorder is often a chronic
illness, especially for patients with agoraphobia (61, 62). Symptom
exacerbation can occur even while the patient is undergoing treatment
and may indicate the need for reevaluation of the treatment plan.
Because such exacerbations can be disconcerting, the patient and,
when appropriate, the family should be reassured that fluctuations
in symptom levels can occur during treatment before an acceptable
level of remission is reached. Although treatment works for most
patients to reduce the burden of panic disorder, patients may continue
to have lingering symptoms, including occasional panic attacks and
residual avoidance. Other problems, such as a depressive episode,
could also develop and require specific attention.
Relapse following treatment cessation is also possible. Patients
should be instructed that panic disorder may recur and that, if
it does, it is important to initiate treatment quickly to reduce
the likelihood of complications such as agoraphobic avoidance (63).
The patient should be assured that he or she is welcome to contact
the psychiatrist and that resuming treatment almost always results
in improvement.
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B. Choosing a Treatment Setting
The treatment of panic disorder
is generally conducted entirely on an outpatient basis, and the
condition by itself rarely warrants hospitalization. Occasionally,
the first contact between patient and psychiatrist occurs in the
emergency department or the hospital when the patient has been admitted in
the midst of an acute panic episode. The patient may even be admitted
by emergency department staff to rule out myocardial infarction
or other serious general medical events. In such individuals, the
psychiatrist may be able to make the diagnosis of panic disorder
and initiate treatment once other general medical conditions have
been ruled out. Because panic disorder frequently co-occurs with
mood disorders and may elevate the risk of suicide attempts, it
may also be necessary to hospitalize the patient with panic disorder
when suicidal ideation is of clinical concern. Similarly, patients with
panic disorder frequently have co-occurring substance use disorders,
which can occasionally require inpatient detoxification. Under such
circumstances, the treatment of panic disorder can be initiated
in the hospital along with treatment of the disorder that prompted
hospitalization. Rarely, hospitalization or partial hospitalization
is required in very severe cases of panic disorder with agoraphobia
when administration of outpatient treatment has been ineffective
or is impractical. For example, a housebound patient may require
more intensive and closely supervised treatment in the initial phase
of therapy than that provided by outpatient care (64, 65).
Home visits are another option for severely agoraphobic patients
who are limited in their ability to travel or leave the house.
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C. Choosing an Initial Treatment
Modality
A range of specific psychosocial and pharmacological interventions
have proven benefits in treating panic disorder. The use of an SSRI
(66–87), SNRI (88, 89),
TCA (70, 72, 79, 90–112),
benzodiazepine (appropriate as a monotherapy only in the absence
of a co-occurring mood disorder) (104, 113–132), or
CBT (67, 111, 133–144)
as the initial treatment for panic disorder is strongly supported
by demonstrated efficacy in numerous controlled trials. A particular
form of psychodynamic psychotherapy called panic-focused psychodynamic
psychotherapy (145) has also been shown to be effective
in a randomized controlled trial (146), suggesting
that under certain circumstances (e.g., patient preference for a
dynamically oriented therapy), PFPP could be offered as an initial
treatment. Other psychosocial treatments for patients with panic
disorder have either been found equivalent to placebo conditions (e.g.,
EMDR), have proven inferior to standard treatments (e.g., supportive
psychotherapy [147]), or have not
been formally tested in controlled studies (e.g., certain forms
of psychodynamic psychotherapy).
There is insufficient evidence to recommend any proven efficacious
psychosocial or pharmacological intervention over another or to
recommend a combination of treatments over monotherapy. Considerations
that guide the choice of an initial treatment modality include patient
preference, the risks and benefits of the two modalities for the
particular patient, the patient's past treatment history,
the presence of co-occurring general medical and other psychiatric
conditions, cost, and treatment availability. Advantages of pharmacotherapy include
ready availability and the need for less effort by the patient for
treatment to take effect. Disadvantages include risks of adverse
effects, with roughly 10%–20% of patients
in clinical trials of common medications for panic disorder specifically
citing medication side effects as a reason for dropping out of the
trial. Discontinuation symptoms can be an additional disadvantage,
necessitating that patients taper medication slowly if a decision
is made to stop medication. Costs of medications vary and are affected
by the choice and dose of the agent, the availability of generic
preparations, the duration of treatment, requirements for additional
pharmacotherapy or psychosocial treatment, and the cost of treating
medication-related side effects. From the standpoint of patient preference, many
patients do not wish to take medications (148), and they
may perceive a psychosocial treatment as a more favorable option.
For example, studies of CBT have shown that patients may prefer
it to pharmacotherapy (111, 149). On the other
hand, psychotherapy requires considerable time and discipline on
the part of the patient to confront feared situations or perform
the "homework" associated with treatment. With
CBT, approximately 10%–30% of patients
have been found unwilling or unable to do this (133–135, 137).
Patients who are reluctant to invest time, effort, and short-term
increases in anxiety in exchange for possible longer-term resolution
of symptoms may not desire, and are less likely to benefit from,
psychosocial treatment. In terms of psychosocial treatment costs,
contributory factors include the duration and frequency of treatment,
its administration in an individual or group setting, and any requirements
for additional psychosocial or pharmacological treatment. An additional
disadvantage of specialized psychotherapies is that they may not
be readily available to patients in some areas.
Combining psychotherapy and pharmacotherapy is intuitively
attractive and common in clinical practice. Several specific combination
treatments have been studied and shown to be effective for panic
disorder, including CBT (or exposure therapy) plus imipramine (91, 111, 150–155),
CBT plus paroxetine (69), exposure therapy plus fluvoxamine
(68), psychodynamic psychotherapy plus clomipramine
(156), and algorithm-based pharmacotherapy plus a collaborative
care intervention that included CBT (157–159).
With regard to the comparative efficacy of combined treatment
versus monotherapy, the most recent meta-analysis of randomized
controlled trials of treatments for panic disorder suggested a small
but significant advantage for the combination of antidepressants
plus psychotherapy over monotherapies in the acute phase of treatment
(160). However, combined treatment was no better than
psychotherapy alone in longer-term follow-up, although it was superior
to pharmacotherapy alone (160). In addition, some studies
have raised concerns about the possibility that simultaneously initiating benzodiazepines
(149, 161) or antidepressant medications (111)
with CBT may diminish the durability of response to CBT after all
treatments are withdrawn. These results, which are by no means definitive,
should be considered in treatment of patients who plan to pursue
CBT and are also contemplating starting medication.
Although combination treatment does not appear to be significantly
superior to standard monotherapies for most individuals with panic
disorder, psychiatrists and patients may choose this option for
a variety of individual circumstances. For example, many clinicians
combine pharmacotherapy to provide more immediate control of distressing
symptoms with psychosocial treatments intended to address symptoms over
the long term and reduce future need for medications.
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D. Evaluating Whether
the Treatment Is Working
After treatment is initiated, it is important to monitor change in
the patient's key symptom domains, such as frequency and
intensity of panic attacks, level of anticipatory anxiety, degree
of agoraphobic avoidance, and severity of interference and distress
related to panic disorder. Effective treatment should produce a
decrease in each of these domains, although some may change more
quickly than others (e.g., the frequency of panic attacks may decrease
before agoraphobic avoidance decreases). The pattern of symptom
resolution varies depending on the individual patient; for example,
some experience "sudden gains" in which they manifest
a significant decrement in symptoms in a brief period of time, whereas
others experience steady and gradual improvement over a period of
many weeks. As described earlier in Section II.A.7, rating scales
can be a useful adjunct to ongoing clinical assessment in evaluating
treatment outcome. The severity of co-occurring conditions also
should be assessed at regular intervals, as effective treatment
of panic disorder can influence co-occurring conditions.
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E. Determining If
and When to Change Treatment
Clinical trials suggest that many individuals do not respond, or
respond incompletely, to first-line treatments for panic disorder.
Whenever treatment response is unsatisfactory (e.g., inadequate
reduction of panic attacks, continued agoraphobic avoidance), the
psychiatrist should first consider the possible contribution of
the following factors: an underlying untreated medical illness,
interference by co-occurring general medical or psychiatric conditions
(including substance use), inadequate adherence to treatment recommendations,
problems in the therapeutic alliance, the presence of psychosocial stressors,
motivational factors (e.g., secondary gain that results from the
patient's panic disorder symptoms), and inability to tolerate
a particular treatment. These potential impediments to successful
treatment should be addressed as early as possible. With pharmacotherapy,
the dose of medication may also be an important consideration. Clinical
experience suggests that patients who do not respond after several
weeks at the lower therapeutic dose range may do better with a further
dose increase (i.e., to the highest tolerable level within accepted
dosage ranges), although this strategy has not been systematically
studied.
It is important for the psychiatrist to remember that patients
with panic disorder may have become accustomed to avoiding anxiety-
and panic-provoking situations and may resist treatments that focus
on eliminating this avoidance (e.g., CBT, exposure instructions
assigned as an adjunct to pharmacotherapy). Thus, the psychiatrist
should explore whether fearfulness is leading the patient to minimize
reporting the impact of avoidance or to accept functional limitations
resulting from avoidance. If such fears are an issue, the patient
can be encouraged to think through the costs and benefits of accepting
versus treating functional limitations.
Another important consideration is that many patients with
panic disorder have co-occurring depression. If the patient is in
a dysphoric state he or she may be hopeless about the possibility
of change. It is important to mitigate the effects of depression
on the patient's level of optimism about treatment options
(e.g., point out that depression may be affecting the patient's
perceptions and recommend trying something new even if the patient
is doubtful that it will work).
If response to treatment remains unsatisfactory, and if an adequate
trial has been attempted, it is appropriate for the psychiatrist
and the patient to consider a change. Although there is a lack of
evidence for what constitutes an adequate trial, it is important
to consider the usual time course of response to specific therapies.
For example, with CBT, the literature shows that improvement may
not plateau until 12 sessions of treatment have been completed.
With benzodiazepines, psychiatrists and patients often note some
reduction in panic within the first week of treatment, although
full blockade of panic attacks can take several weeks, particularly
as the dose is being titrated for the individual. With SSRIs, SNRIs,
and TCAs, reduction in panic attack frequency, anticipatory anxiety,
and avoidance may start within the first 3–4 weeks of treatment.
However, there is evidence that therapeutic response continues to
accrue with continued pharmacotherapy. For some patients and particularly
for those with a significant level of agoraphobic avoidance, full
remission of symptoms, including the complete cessation of panic
attacks, full resolution of anticipatory anxiety and agoraphobia,
and full return to functioning, may take up to 6 months or longer (72)
(including 4–6 weeks at the highest comfortably tolerated
dose). Thus, many experts recommend waiting at least 6 weeks from
initiation of antidepressant treatment, with at least 2 of those
weeks at full dose, before deciding whether more intensive, additional,
or alternative treatments are warranted. When a patient's
symptoms are severe, however, it is often not feasible to wait that
long. Consequently, the approach and timing of treatment changes
must be individualized to the patient's symptoms and circumstances.
Decisions about whether to
make changes will also depend on the following factors: level of
partial response (e.g., if virtually no benefits are apparent, a
change should almost certainly be undertaken; if slow but steady
progress is apparent, the psychiatrist and patient may decide to
continue the current trial for a brief period then reassess); the
palatability and feasibility of other treatment options (e.g., a
patient who does not respond to psychosocial treatment might benefit from
pharmacotherapy, but some patients are unwilling to take medication;
a patient who does not respond to medication might benefit from
psychosocial treatment, but psychosocial treatment may not be feasible
because the patient cannot commit the time for weekly sessions and
homework with CBT); and the level of symptoms and impairment the patient
is willing to accept (e.g., the patient may still avoid some situations
but may not be motivated to overcome those fears at present; the
patient may still experience occasional panic attacks but may view
this as tolerable and not wish to pursue further treatment to eliminate
remaining symptoms). However, persistent significant symptoms of
panic disorder despite a lengthy course of a particular treatment
should trigger a reassessment of the treatment plan, including possible consultation.
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F. Approaches to
Try When a First-Line Treatment Is Unsuccessful
If the fundamental clinical issues described in the previous section
have been addressed and it is determined that a change in treatment
approach is desirable, the psychiatrist and patient have two basic
options. The first option is to augment the
current treatment by adding another agent (in the case of pharmacotherapy)
or another modality. Alternatively, the psychiatrist and patient
may decide to switch to a different
medication or therapeutic modality.
Decisions about how to address treatment resistance are likely
to be highly individualized and based on clinical judgment, since
few studies have tested the effects of specific augmentation and
switching strategies. Decisions, however, can be informed by the
extent of the patient's response and by the evidence that
supports specific treatments as initial monotherapies. In general,
if one first-line treatment has failed, adding or switching to another
first-line treatment is recommended. Augmentation is also a reasonable
approach if some significant benefits were observed with the original treatment.
For instance, for a patient who had partial response to an SSRI
or SNRI, the psychiatrist may consider adding a benzodiazepine or
a course of CBT. On the other hand, if the original treatment did
not provide any alleviation of
the patient's symptoms, a switch in treatment may be more useful.
For example, patients who do not respond to standard pharmacotherapies
may respond to CBT (162–164),
whereas those who do not respond to CBT or exposure therapy may benefit
from pharmacotherapy (165, 166). If a
patient's first unsuccessful treatment is with an SSRI
or an SNRI, a recommended approach is to switch to a different SSRI
or SNRI. If the patient's symptoms do not respond to two
different SSRIs or SNRIs, switching to or adding other classes of
medication that have demonstrated efficacy for panic disorder (e.g., TCAs,
benzodiazepines) may be considered. When switching between antidepressants,
psychiatrists will often cross-titrate (e.g., decreasing the dose
of the original medication over 1–2 weeks while gradually
increasing the dose of the new medication). Adding or switching
to CBT may also be considered at any point when a patient shows
incomplete or nonresponse to standard pharmacotherapy.
If the above treatment options, which have the highest levels
of empirical support, have been unsuccessful, other options with
some empirical support can be considered. Monoamine oxidase inhibitors
are widely regarded as effective for panic disorder. Although the
safety profile of MAOIs limits their use, they have demonstrated
efficacy in older studies that included patients with probable panic
disorder. Thus, MAOIs may be considered if the psychiatrist is experienced
in managing these agents and if the patient is willing to adhere
to a low-tyramine diet and to restrictions on the use of certain
other medications. In addition, before switching to an MAOI, the
psychiatrist should discontinue other antidepressant medications
and allow a sufficient washout period (usually at least 2 weeks
for most antidepressants and longer for those with very long half-lives
such as fluoxetine) before treatment with the MAOI is initiated.
The effectiveness of PFPP is supported by positive findings of a
randomized controlled trial (146), making it another
reasonable choice to consider for patients who prefer nonmedication
treatments or for those who have not responded to other treatments.
Other forms of psychodynamic psychotherapy have not been formally
tested but are supported by case report evidence and clinical experience;
these forms of treatment also may be considered as options for patients
who have not responded to other treatments for panic disorder.
Other treatments with even more limited evidence also may
be considered as monotherapies or augmentation agents under some
circumstances (e.g., several other treatments have been unsuccessful;
the patient cannot tolerate other treatments). Mirtazapine and gabapentin
have modest evidence bases that support their use in some individuals
with panic disorder. Although beta-blockers have generally been found
ineffective as monotherapy for panic disorder, there is some preliminary
support for the use of pindolol as an augmentation agent to enhance
antidepressant response. Antipsychotics are not recommended because
of limited evidence for their efficacy and concerns about side effects.
However, there is very preliminary evidence for the efficacy of
second-generation antipsychotics such as olanzapine and adjunctive risperidone,
so these agents could be considered for patients with very severe,
treatment-resistant panic disorder. Some clinical experience suggests
that patient support groups may be helpful, adjunctive to other
treatment. With the exception of group CBT, which has demonstrated
efficacy in controlled trials, other forms of group therapy are
unstudied and have unclear efficacy. Eye movement desensitization
and reprocessing and couples and family therapy have been shown
to be ineffective in the treatment of panic disorder.
Sections II.G and II.H provide
additional information on the second- and third-line psychotherapeutic
and pharmacological treatments described above, as well as for other
unproven treatments. Psychiatrists are encouraged to seek consultation
from experienced colleagues when developing treatment plans for
patients whose symptoms have been resistant to first-line treatments
for panic disorder.
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G. Specific Psychosocial Interventions
The following sections review psychosocial interventions that
have been formally evaluated for treatment of panic disorder, as
well as some treatments that have not been tested but are occasionally
utilized by patients with panic disorder. Psychosocial treatments
for panic disorder should be conducted by professionals with an
appropriate level of training and experience in the relevant approach.
Based on the current available evidence, CBT is the psychosocial
treatment that would be indicated most often for patients presenting
with panic disorder. The efficacy of CBT (including exposure therapy
alone) for panic disorder has been documented in numerous controlled
trials. CBT is effective when delivered individually or in a group
format. Individually administered PFPP also has demonstrated efficacy
for panic disorder, although research on this treatment is in earlier
stages and its evidence base is more limited. Panic-focused psychodynamic
psychotherapy may be indicated as an initial psychosocial treatment
for panic disorder in some circumstances (e.g., with a patient who
is motivated for and able to engage in this approach). Other psychosocial treatments
either have not been formally tested for panic disorder (e.g., certain
forms of psychodynamic psychotherapy) or have proven ineffective
or inferior to standard treatments (e.g., EMDR, emotion-focused
therapy).
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1. Cognitive-behavioral
therapy
The use of CBT for panic disorder is based on the assumption that
maladaptive patterns of cognition and behavior maintain panic disorder.
Cognitive-behavioral therapy generally targets these maintaining
factors and places less emphasis on determining the origins of panic
disorder for a particular patient. Cognitions hypothesized to maintain
panic disorder include catastrophic misinterpretations of physical
symptoms (e.g., the belief that palpitations signal an impending
heart attack) (for example, see references 167 and 168).
Therefore, many versions of CBT seek to identify and change mistaken beliefs
about physical symptoms and their consequences. The symptoms of
panic disorder and agoraphobia also have been conceptualized as
resulting from conditioning processes (for example, see references 169–171).
Consequently, many versions of CBT include techniques aimed at 1) weakening
or extinguishing learned associations between stimuli (both internal
and external) and panic and 2) creating opportunities for learning
and strengthening nonanxious responses. All forms of CBT conceptualize
avoidance behavior as a maintaining factor in panic disorder, either
because it prevents patients from disconfirming their anxious beliefs
or because it prevents habituation of fear responses. Thus, confronting feared
stimuli and situations is an essential part of CBT for panic disorder.
Most forms of panic-focused
CBT employ the following treatment components: psychoeducation,
self-monitoring, cognitive restructuring, exposure to fear cues,
modification of anxiety-maintaining behaviors, and relapse prevention.
In providing CBT, the clinician may opt to focus more on certain
treatment components than on others, depending on the patient's
symptom profile and response to different CBT techniques.
Panic-focused CBT is generally administered in 10–15 weekly
sessions (172). Therapy usually begins with one or more
psychoeducation sessions that serve to identify the patient's
symptoms and areas of impairment, provide accurate information about
the nature and purpose of anxiety and fear, conceptualize the patient's
experiences in terms of the CBT model, and outline a rationale and
plan for treatment. Information gathering and education are done
in an interactive manner, with a continual focus on applying the
CBT model to a patient's particular symptoms and situations.
The CBT therapist adopts a collaborative stance, and the educational material
sets the stage for the therapist and patient to develop a shared
understanding of the patient's problems. A major goal of
psychoeducation for panic disorder is conveying that panic symptoms
result from the body's natural fear response and are not
dangerous. Reading material that reinforces the concepts introduced
in the psychoeducation sessions is usually assigned for homework
(see the Appendix for titles of patient workbooks that include these
materials).
Self-monitoring is another core component of CBT. Patients
monitor their panic attacks using techniques such as keeping a daily
diary. They are asked to record the date, time, location, and any
perceived triggers of the panic attack. They also may be asked to
record the physical symptoms, anxious thoughts, and behavioral responses
that occurred during the attack. Patients are informed that this
will help to assess the frequency and nature of their panic attacks
and to provide data regarding the relationship of panic symptoms
to potential triggers.
Another component of CBT is exposure to fear cues. Patients
with panic disorder can experience panic attacks in response to
internal and external cues (169). The most common internal
fear cues are bodily sensations (e.g., heart racing, dizziness,
shortness of breath). Common external fear cues include situations
in which having a panic attack would be embarrassing or in which
escape would be difficult (e.g., public places, enclosed spaces).
For most patients, exposure to both internal and external fear
cues is necessary for remission of panic symptoms to occur. Exposure
proves to be the most challenging and often the most potent component
of CBT. Additional effort on the part of the clinician is often
required to motivate the patient to initiate and persevere with
increasingly difficult exposure practices. Internal fear cues are
addressed through interoceptive exposure. Interoceptive exposure
involves exposing the patient to feared bodily sensations in a systematic
way, until he or she no longer responds fearfully to those sensations.
Feared bodily sensations are provoked using a series of exercises
such as running in place (to induce heart pounding), spinning in
a chair or while standing up (to induce dizziness), and hyperventilation
or breathing through a straw (to induce light-headedness or shortness
of breath). The CBT therapist first assesses which of these exercises
produce symptoms that are anxiety provoking for the patient, and
then instructs the patient to perform those exercises repeatedly
until the patient is no longer afraid of the exercises or the symptoms
that result. External fear cues are targeted through situational
exposure, which involves confronting situations or activities that
commonly provoke fear. Situational exposure can include a wide variety
of exercises such as driving on a highway, riding in an elevator,
or visiting a grocery store or shopping mall.
The process of conducting exposures to internal and external
fear cues is systematic. The therapist first works with the patient
to identify a hierarchy of fear-evoking situations. The degree of
anxiety elicited in each of these situations is graded on a 0–10
scale, and several situations that evoke anxiety at each level are
documented. The patient is then asked to confront the symptom or
situation, usually beginning at the low end of the hierarchy on
a regular (usually daily) basis until the fear has attenuated. The
symptom or situation that arouses the next level of anxiety is then
targeted. Interoceptive exposures are usually conducted in the therapist's
office and at home in naturalistic situations. Situational exposures
are best carried out in the actual situation(s). Patients typically
conduct situational exposures on their own for homework; however,
some CBT therapists will accompany patients to locations for situational
exposures. Whereas the usual practice is to start with the least
anxiety-provoking exercises and move up in intensity, patients who
are motivated to treat their panic disorder more aggressively can
begin exposure treatment with exercises that are more challenging
(i.e., those near the top of their hierarchy) with the notion that
this approach may help them achieve their treatment goals more quickly
(54). Patients also are encouraged to combine interoceptive
and situational exposure as they progress through treatment (e.g.,
deliberately hyperventilating while driving) in order to learn that
they can enter feared situations and cope with them even while experiencing
intense physical sensations.
Most CBT practitioners include cognitive restructuring techniques
as one element of treatment, although some CBT therapists and some
studies (for example, see reference 140) have questioned
whether cognitive restructuring provides benefits beyond those obtained
with exposure. When used as a CBT component, cognitive restructuring
focuses on identifying and countering erroneous beliefs that contribute
to panic disorder. Patients with panic disorder commonly interpret
panic symptoms in a catastrophic manner (e.g., as signs of an impending
heart attack or fainting spell). They also typically underestimate
their ability to cope with panic attacks (42). In CBT,
the therapist encourages the patient to recognize the thoughts that
occur during panic attacks and to consider the evidence for and
against these thoughts. When erroneous or exaggerated beliefs are
identified, the CBT therapist and patient work together to review
the evidence and generate a more realistic appraisal of the situation.
The skill of countering anxious thoughts and generating more evidence-based thoughts
is reinforced throughout treatment with in-session practice and
homework assignments. Many CBT therapists integrate cognitive and
exposure procedures. This integration focuses on using the exposure
to fear cues as a vehicle for helping the patient acquire corrective
threat-disconfirming information (e.g., "even though I
felt anxious and dizzy while at the grocery store, I did not faint").
Modification of anxiety-maintaining "safety behaviors" is
another common goal of CBT. Common safety behaviors include carrying
medication bottles, establishing exit routes, and checking the locations
of hospitals (173). Safety behaviors often provide
the patient with an immediate feeling of security; however, within
CBT they are conceptualized as maintaining anxiety in the longer
term. Safety behaviors may reinforce the notion that everyday situations
are inherently dangerous, prevent patients from disconfirming their
threat-laden beliefs, and interfere with deriving maximum benefit from
exposure practices (174). Fading and eventual elimination
of safety behaviors is therefore a goal of most CBT protocols.
Some CBT protocols also teach slow, diaphragmatic breathing
as a skill that patients can use to decrease anxiety and interrupt
the cycle of panic (for example, see reference 111). Although
the evidence suggests that breathing retraining is likely not a
necessary component of treatment (175), it is still often
included in CBT for panic disorder and may be a useful anxiety-reduction
tool for some patients.
Cognitive-behavioral therapy for panic disorder is often provided
individually, but there is evidence that group treatments may be
equally effective (137, 142, 176–179).
Exposure treatments for patients with agoraphobia also are efficacious
when conducted in a group format (178). The inclusion
of the spouse or significant other in treatment can be helpful,
especially if the significant other is educated about the CBT model
of panic disorder and can provide support and encouragement when
the patient confronts feared situations (180, 181).
Because CBT is not widely available in some communities, some
patients may have to travel a great distance to see a clinician
who is proficient in CBT, or they may not have access to CBT at
all. Some evidence suggests that high-density therapy (i.e., several
hours of therapy within a few days) can be effective (182, 183),
and this approach may be useful for patients who cannot attend a
standard course of weekly sessions. One small waiting-list-controlled
study showed that telephone-based CBT was effective for patients
with severe agoraphobia who lived in rural areas (184).
Self-directed forms of CBT and exposure therapy that are guided
by a computer (often with minimal therapist contact via email or phone)
also have been shown to be effective in several controlled studies
(185, 186). Studies that directly compare
live CBT to largely computer-guided formats have generally shown
both to be effective, but in some studies live CBT produced larger
effects and was associated with lower dropout rates (139, 186–189).
When available, computer-guided CBT may be a useful option for patients
with panic disorder who do not have ready access to a specialist.
The available data suggest that the benefits of a short-term course
of CBT are long-lasting (for example, see reference 160).
However, once patients have achieved a satisfactory reduction in
symptoms and impairment, the focus of CBT shifts, and development
of a specific relapse prevention plan becomes an integral part of
treatment. The therapist normalizes fluctuations in anxiety and
anticipates that the patient may experience periods of increased
anxiety (including occasional panic attacks) in the future. The
therapist and patient collaborate to anticipate potential triggers
for these periods of increased anxiety (e.g., work stress, moving
to an unfamiliar place) and to develop an individualized relapse
prevention plan that the patient can follow if symptoms recur. This plan
typically involves a return to more intensive practice of CBT skills
that were previously helpful such as exposure and cognitive restructuring.
If symptoms do not improve with the implementation of the practice
plan, the therapist and patient can consider the option of "booster
sessions" (i.e., a short course of CBT to help the patient
reinstitute skills that were previously helpful). If efforts to
boost response are unsuccessful, the psychiatrist should consider
trying a different treatment modality or referring the patient to
another qualified professional.
There is little evidence to suggest that CBT and commonly
prescribed medications for panic disorder either enhance or counteract
one another in the acute term. One randomized controlled trial found
that fluvoxamine plus exposure therapy was superior to either alone
in treatment of panic disorder with moderate to severe agoraphobia
(68); however, this result has not been replicated.
In contrast, another study found that, 6 months after treatments
were withdrawn, patients who responded to a combination of imipramine
and CBT for panic disorder displayed poorer maintenance of response
than those who received CBT alone or CBT plus placebo (111).
This finding raises some concern that simultaneously initiating
medication and CBT may negatively affect the durability of the effects
of CBT after treatments are withdrawn. This topic requires further
study before firm conclusions can be drawn. Concern also exists
about possible decreases in the efficacy of CBT if combined with benzodiazepines,
although there is a dearth of systematic empirical data on this
topic (190). One large randomized controlled trial
showed that although adding alprazolam to exposure therapy marginally
enhanced gains during acute treatment, patients who received the
combination relapsed more after treatment withdrawal compared to
those who received exposure plus placebo (149). Another
small study showed that patients taking benzodiazepines had poorer memory
for the educational material presented in CBT than patients who
were taking no medications (161). Clinical experience
suggests that p.r.n. ("as needed") use of benzodiazepines
to block anxiety symptoms can be difficult to reconcile with certain
components of CBT, and many CBT therapists discourage p.r.n. benzodiazepine
use as soon as the patient has developed other anxiety management
skills.
Cognitive-behavioral therapy for panic disorder has been shown
to be effective in treating not only the targeted panic disorder
but also in reducing the rates and severity of some co-occurring
conditions (191–194).
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2. Psychodynamic
psychotherapy
The goal of psychodynamic psychotherapy is to achieve remission
of panic disorder symptoms through a therapeutic process that encourages
exploration of feelings and past and present traumatic experiences.
The core principles of psychodynamic psychotherapy are 1) the appreciation
that much of mental life is unconscious, 2) childhood experiences
in concert with genetic and constitutional factors shape adult personality,
and 3) individual symptoms and behaviors may serve multiple functions
(195).
Many studies suggest that acute stressors, or "life
events," occur just prior to panic disorder onset (196–198).
According to psychodynamic theory, the psychological meaning of
these events as well as symptoms, behaviors, and coping styles are determined
by complex forces that may be unavailable to the patient's
conscious awareness (199–201).
In patients with panic disorder, one of the goals of psychodynamic
psychotherapy is to uncover and understand the thoughts and feelings
associated with panic symptoms as well as the unconscious psychological
meanings of these panic symptoms, issues that are theorized to be
related to separation, autonomy, self-esteem, anger, or aggression.
Understanding of transference and interpretation are used to elucidate
these issues as well as related interpersonal conflicts. In addition,
the therapist attempts to identify and alter core conflicts in order to
reduce vulnerability to future panic symptoms (145).
Given the highly individualized nature of these thoughts, feelings, and
conflicts, the length and intensity of most psychodynamic psychotherapy
also tends to be individualized.
In psychodynamic psychotherapy, symptom relief or resolution
is theorized to result from emotional growth and understanding of
the various developmental and psychological issues that relate to
the patient's symptoms. Examples include both conscious
and unconscious problems of self-esteem and self-cohesion, unresolved
developmental trauma, and psychic conflict (e.g., unacceptable impulses,
unrealistic or harsh issues of self-esteem and conscience, unadaptive
psychological defenses). The therapist places the current symptoms
in the context of the patient's life history and current
realities. The therapist-patient relationship is often used as a
vehicle to achieve insightful awareness by bringing the unconscious
into consciousness, as well as to facilitate intrapsychic growth.
Because psychodynamic therapies are rooted in various psychoanalytic
and/or psychodynamic theoretical models, there are a variety
of methods for conducting psychodynamic psychotherapy.
Panic-focused psychodynamic psychotherapy is a twice weekly,
12-week manualized treatment program developed by Milrod and associates
(145) that has been tested in a randomized controlled
trial (146). It focuses on the underlying psychological
meaning of panic symptoms and on current social and emotional functioning.
Panic-focused psychodynamic psychotherapy is based on the postulate
that panic symptoms carry a specific emotional significance that
the patient must confront before remission of the panic symptoms
can occur. According to this theoretical model, patients with panic
disorder are conceptualized as having difficulty separating from
important attachment figures and perceiving themselves as autonomous,
which is thought to motivate agoraphobic avoidance. The combination
of perceiving their environment and relationships as overly dangerous
and themselves as inadequate and lacking autonomy triggers high
levels of anxiety that perpetuate panic and agoraphobic avoidance.
Panic symptoms in turn are thought to reinforce conflicted interpersonal
relationships in which the patient feels excessively dependent on
significant others and frightened of losing them. Panic-focused psychodynamic
psychotherapy focuses on the transference as a mutative therapeutic
agent and does not require behavioral exposure to agoraphobic situations.
It helps patients to confront the emotional significance of their
physical symptoms and recognize that their fears of upcoming catastrophe
reflect an internal emotional state rather than reality. Through
these techniques, PFPP encourages patients to function more autonomously
and may help patients with panic disorder to achieve a greater sense
of personal efficacy, yielding improved function and symptomatic
relief.
Compared to PFPP, other approaches to psychodynamic psychotherapy
often have a wider focus on other psychological and interpersonal
issues in the patient's life. These alternative approaches
have not been the subject of rigorous research studies. Consequently,
evidence for the use of other psychodynamic psychotherapy approaches
in panic disorder is limited to case reports and opinions of psychodynamic psychotherapy
experts. No studies have compared the efficacy of the different
psychodynamic psychotherapy approaches or have compared psychodynamic
psychotherapy with other psychosocial treatments in patients with
panic disorder.
As with all psychiatric treatments, psychodynamic psychotherapy
(including PFPP) should be conducted by appropriately trained therapists,
and patients need to understand the rationale, goals, and potential
risks and benefits of the treatment. The exploration of memories
and important conflicted relationships and the surfacing of unconscious
material may sometimes be associated with powerful affects and transient
upsets in the therapeutic and other relationships. These occurrences
tend to decline in both frequency and intensity as the patient experiences
how they relate to and help resolve the symptoms and problems that
brought the patient to treatment.
Many patients with panic disorder have complicating co-occurring
Axis I and/or Axis II conditions. The broad focus of some
forms of psychodynamic psychotherapy may be useful in reducing symptoms
or maladaptive behaviors in these associated conditions. For example,
some preliminary data showed that PFPP demonstrated superiority
to applied relaxation therapy for patients with Cluster C personality
disorders, compared to patients without Cluster C personality disorders
(202).
Although evidence is limited, psychodynamic techniques have
been used in combination with pharmacotherapies or with elements
of CBT (145, 203, 204). For
example, patients with agoraphobic avoidance may be encouraged to
expose themselves to frightening situations and explore the feelings that
the exposure aroused to gain a deeper understanding of the conflicts
surrounding feared situations. In practice, psychodynamic therapies
are often used adjunctively with medication to assist in the resolution
of the panic symptoms (204, 205).
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3. Supportive psychotherapy
The available evidence suggests that supportive psychotherapy
is inferior to standard treatments for panic disorder. One controlled
study compared the efficacy of emotion-focused therapy, CBT, imipramine,
and pill placebo in patients with panic disorder (147).
Emotion-focused therapy was described as a short-term psychotherapy
that involved empathic listening and supportive strategies. Emotion-focused
psychotherapy was based on the theory that unrecognized emotions
(typically triggered by interpersonal situations) trigger panic
attacks; therefore, patients were encouraged to explore and process
their emotional reactions with the aim of resolving panic symptoms.
Results suggested that emotion-focused psychotherapy was less effective
than CBT and imipramine in treatment of panic disorder and that its
effect was approximately equivalent to that of placebo. Therefore,
emotion-focused therapy and other supportive psychotherapies that
resemble it cannot be recommended as treatments for panic disorder.
+
4. Eye movement desensitization
and reprocessing
Eye movement desensitization and reprocessing was originally
developed as a treatment for posttraumatic stress disorder (206),
but it has been studied as a possible treatment for panic disorder.
Eye movement desensitization and reprocessing involves reprocessing
distressing memories while engaging in guided eye movement. When
applied to panic disorder, EMDR targets distressing memories such
as the memory of the first panic attack and life events that the
patient associates with panic disorder (207).
Empirical data on the use of EMDR in treating panic disorder
are limited. In one trial, six sessions of EMDR were superior to
a waiting-list control at posttreatment; however, the investigators
questioned the clinical significance of the treatment's
effect because very few patients who received EMDR showed substantial
functional recovery at 3-month follow-up (207). Another
study found EMDR to be equivalent in its effects to a credible attention-placebo
control (208). Eye movement desensitization and reprocessing
therefore cannot be recommended as a treatment for panic disorder
at this time.
Clinical experience suggests that possible benefits of a group format
for treating panic disorder include 1) decreasing shame and stigma
by providing experiences with others who have similar symptoms and
difficulties; 2) providing opportunities for modeling, inspiration,
and reinforcement by other group members; and 3) providing a naturally
occurring exposure environment for patients who fear having panic
symptoms in social situations. Most approaches to group therapy
have not been empirically tested for panic disorder. However, group CBT
for panic disorder has been shown to be effective in controlled
studies and therefore can be recommended with confidence as a treatment
for panic disorder (137, 176–179).
When considering a patient for inclusion in a CBT group, the therapist
should consider the severity of the patient's panic disorder, co-occurring
disorders, level of insight, interpersonal skills, and the patient's
preference for a group versus individual format.
There is limited evidence from a small uncontrolled trial for
the effectiveness of group mindfulness-based stress reduction for
patients with panic disorder (209, 210).
This modality includes training in meditation and relaxation strategies.
Other types of groups, such as medication support groups, may provide
useful adjunctive experiences for patients with panic disorder but
have not been tested empirically.
+
6. Couples and family
therapy
Patients with panic disorder have symptoms that can disrupt day-to-day
patterns of relationships and may place a family member in a caretaker
or rescuer role. Increased dependency needs of patients with panic
disorder may lead to frustration in family members, and relationships
may be jeopardized. Results are mixed with regard to whether panic
disorder is associated with increased incidence of relationship
dysfunction or whether relationship dysfunction affects outcome
of standard treatments for panic disorder (180).
The scant available literature
suggests that marital therapy alone is less effective than established
treatments in relieving panic symptoms (211). Based
on the available data, couples or family therapy alone cannot be
recommended as a treatment for panic disorder. In contrast, partner-assisted
exposure therapy for panic disorder has been shown to reduce symptoms
of panic disorder in several studies (180). Other studies have
documented benefits of including patients' significant others
in group-based CBT (177, 212, 213)
and of adding couples-based communication training to exposure treatment (214).
Therefore, including a significant other in CBT or exposure-based
treatment may be a useful approach for some patients.
When pursuing other treatments for panic disorder (e.g., pharmacotherapy),
educating significant others about the nature of the disorder and
enlisting them to improve treatment adherence may also be helpful.
However, no empirical studies of involving partners or family members
in other types of treatment have been published.
+
7. Patient support
groups
Patient support groups may be helpful for some patients with panic
disorder. Patients who participate in support groups have the opportunity
to learn that they are not unique in experiencing panic attacks
and to share ways of coping with the illness. Family members of
patients with panic disorder also may benefit from the educational
aspects of patient support groups. In deciding to refer a patient
or family member to a support group, it is important that the psychiatrist
obtain information about the nature of the group and the credentials
of its leader(s). Support groups are not a substitute for effective treatment;
rather, they are complementary.
+
8. Complementary
and alternative treatments
A review of research on a variety of self-help and alternative treatments
for anxiety disorders concluded that there was no evidence for efficacy
of most of these treatments for panic disorder (215).
Treatments evaluated included natural products (e.g., kava, St.
John's wort, inositol), other physical treatments (e.g.,
acupuncture, massage), and lifestyle treatments (e.g., yoga, relaxation).
Most of the treatments had never been formally tested in patients
with panic disorder. Very preliminary support is available for the
efficacy of the glucose isomer inositol in treatment of panic disorder;
however, inositol is rarely used clinically, and more extensive clinical
research is necessary to establish its efficacy (216, 217).
Evidence of efficacy has also been found for relaxation training
(215). Although one controlled study found applied relaxation
to be as effective as CBT and exposure therapy (218),
a recent meta-analysis suggested that relaxation training is less
effective than CBT for patients with panic disorder (219).
+
H. Specific Pharmacological Interventions
Because medications from four
classesSSRIs, SNRIs, TCAs, and benzodiazepinesare
roughly comparable in efficacy, the decision regarding which medication
to choose for panic disorder mainly involves considerations of side
effects, cost, prior treatment history, the presence of co-occurring
general medical and other psychiatric conditions, and the strength
of the evidence base for the particular medication in treatment
of panic disorder. Medication choice can also be influenced by pharmacological
properties such as medication half-life, drug metabolism (e.g.,
effects of cytochrome P450 isoenzymes), and the potential for drug
interactions. These latter factors are particularly important when treating
older adults and individuals taking multiple medications.
Selective serotonin reuptake inhibitors or SNRIs are likely to
be the best choice of pharmacotherapy for many patients with panic
disorder, though SSRIs have a larger evidence base and are more
likely to be chosen as a first-line treatment. Although SSRIs and
SNRIs do carry a risk of sexual side effects, they lack the significant
cardiovascular and anticholinergic side effects associated with
TCAs, which are particularly troublesome for older patients and
for patients with general medical conditions. Although cost was
previously a concern, most SSRIs are now available in less expensive
generic forms. For patients with co-occurring depression, SSRIs,
SNRIs, and TCAs are preferable to benzodiazepines as monotherapies
because, in contrast to benzodiazepines, these agents will likely
alleviate the depressive symptoms. Because they have no liability
for abuse, SSRIs, SNRIs, and TCAs are also preferable to benzodiazepines
in individuals with current or prior substance use disorders.
Benzodiazepines are often used for treatment of panic disorder,
and some studies suggest that these medications are still used with
greater frequency than the SSRIs (220). Although consideration
must be given to potential side effects of benzodiazepines (e.g.,
sedation, memory difficulties, increased rates of falls or motor
vehicle accidents), one advantage of benzodiazepines is their earlier
onset of action as compared to antidepressants (101, 221).
Because demonstration of some improvement often takes 4–6
weeks with SSRIs, SNRIs, and TCAs, benzodiazepines may be useful
for patients with very distressing or impairing symptoms in whom
rapid symptom control is critical. Furthermore, several studies
suggest that the short-term (4–6 week) addition of benzodiazepines
(alprazolam and clonazepam) to antidepressants produces a more rapid
therapeutic response (100, 222, 223).
Consequently, benzodiazepines may be used along with antidepressants
to help control symptoms until the antidepressant takes effect,
followed by slow tapering of the benzodiazepine. With benzodiazepines,
the benefit of more rapid response to treatment must be balanced
against the possibility that the patient may have difficulty tolerating
the tapering and discontinuation of benzodiazepine; with ongoing
use, all benzodiazepines will produce physiological dependence in
most patients. To reduce the possibility of physiological dependence,
psychiatrists sometimes prescribe benzodiazepines on an as-needed
(p.r.n.) basis. Unfortunately, this practice has a number of adverse
effects. Irregular use promotes fluctuating blood levels that may aggravate
anxiety. One study also showed worse CBT outcomes in participants
using benzodiazepines on a p.r.n. basis compared to those taking
benzodiazepines on a regular schedule and those not taking benzodiazepines
(224). Because many individuals may end up taking as-needed
medication on an almost daily basis, it may be preferable to encourage
regular use rather than use linked to or associated with surges
of anxiety.
Once an initial pharmacotherapy has been selected, patients are
typically seen every 1–2 weeks when first starting a medication,
then every 2–4 weeks until the dose is stabilized. After the
dose is stabilized and symptoms have decreased, patients will most
likely require less frequent visits.
When implementing treatment with SSRIs, SNRIs, and TCAs, it
is helpful to educate patients about the likely time course of treatment
effects. In addition, some patients with panic disorder may be hypersensitive
to medication side effects at treatment initiation. Thus, it is
recommended that starting doses of SSRIs, SNRIs, and TCAs be approximately half
of those given to depressed patients (225). The low dose is maintained
for several days then gradually increased to a full therapeutic
dose over subsequent days and as tolerated by the patient.
Table 5 summarizes usual dosing for antidepressant and benzodiazepine
pharmacotherapy for panic disorder.
With antidepressant medications, concerns have been raised about
the potential for treatment-related increases in self-harming or
suicidal behaviors. Based primarily on data in children and adolescents
(226), the FDA has issued warnings that apply to all
antidepressants, which indicate that the risk of increased suicidal thinking
and behavior in patients under the age of 25 must be balanced with
the clinical need for pharmacotherapy (227). No deaths
from suicide occurred in any of the pediatric clinical trials, but
pooled analyses of 24 placebo-controlled trials of nine antidepressants
in pediatric patients with a variety of psychiatric disorders showed
a risk of suicidal thinking and behavior during the first few months
of antidepressant treatment that was approximately twice that of
patients receiving placebo (4% in the active treatment
groups vs. 2% in the placebo groups) (226, 228, 229).
A more recent meta-analysis suggested that benefits of antidepressant
treatment were greater than the risks of increased suicidal ideation
or behaviors across indications, including anxiety disorders (230).
In adults, antidepressant treatment does not appear to be associated
with an increase in suicide risk per se (227, 231, 232).
Although some evidence from meta-analyses of randomized controlled
trials (primarily in patients with depression) suggests an increased
likelihood of self-harming behaviors (231) or suicide
attempts (233), these results may be confounded by
the difficulty in calculating precise suicide risks from meta-analytic
data (234). In a pooled analysis of placebo-controlled
trials involving adults with major depressive disorder or other
psychiatric disorders that included a total of 295 short-term trials
(median duration of 2 months) of 11 antidepressant drugs in more
than 77,000 patients, a reduction of suicidal thinking and behavior
was seen in adults older than age 65 years who received antidepressants,
compared to placebo, and adults between ages 25 and 65 years showed
no change in risk with antidepressant treatment (227).
Furthermore, studies using other methods showed no increases in
the likelihood of suicide or suicide attempts with antidepressant
treatment (235–237), and an additional
study noted a small increase in the likelihood of self-harm but
no increase in the risk of suicide (238). In addition,
most, but not all (239, 240) studies of
the relationship between antidepressant prescription rates and rates of
suicide and suicide attempts suggest that increases in SSRI prescriptions
are associated with decreases in suicide and suicide attempt rates
in a variety of patient populations (241–248) and
that decreases in SSRI prescriptions are associated with increases
in suicide rates (249). Nevertheless, it is conceivable that
side effects (e.g., anxiety, agitation, insomnia, irritability) may
increase the chance of self-harming behaviors in some individuals
(234, 250). Thus, careful monitoring for
such side effects as well as for evidence of self-harming or suicidal thoughts
or behaviors is important in adults as well, particularly in the
early phases of treatment and after increases in antidepressant
dose. Against these small risks, the benefits of antidepressant
treatment must always be considered (230, 251–253)
and weighed against the corresponding risks and benefits of other
options for the treatment of panic disorder. Additional information
may be found at the web sites of the FDA (http://www.fda.gov/cder/drug/antidepressants/default.htm),
the APA (http://www.psych.org), and the American Academy
of Child and Adolescent Psychiatry (http://www.aacap.org).
+
1. Selective serotonin
reuptake inhibitors
Six SSRIs are now available in the United States: fluoxetine, sertraline,
paroxetine (immediate release [IR] and controlled release [CR] formulations),
fluvoxamine, citalopram, and escitalopram. Numerous clinical trials
have shown that each of them is effective for panic disorder, and
threefluoxetine, sertraline, and paroxetine (both IR and
CR)carry FDA approval for this indication. There is no
evidence of differential efficacy between agents in this class,
although differences in side-effect profile (e.g., potential for
weight gain, discontinuation-related symptoms), drug half-life,
propensity for drug interactions, and availability of generic formulations
may be clinically relevant (254, 255).
Recommended starting and therapeutic doses are summarized
in Table 5. As is the case with TCAs, some patients with panic disorder
experience an initial feeling of increased anxiety, jitteriness,
shakiness, and agitation when beginning treatment with an SSRI.
For that reason, the initial dose should be lower than that usually
prescribed to patients with depression. The recommended starting
doses for SSRIs are as follows: 10 mg/day or less of fluoxetine,
25 mg/day of sertraline, 10 mg/day of paroxetine
IR, 12.5 mg/day of paroxetine CR, 50 mg/day of
fluvoxamine, 10 mg/day of citalopram, and 5–10
mg/day of escitalopram. Although some patients may respond
to lower doses and some may require higher doses for response, clinical
trials suggest that the following are therapeutic doses for the
SSRIs: 10–20 mg/day of fluoxetine (74),
20–40 mg/day of paroxetine (73),
50–200 mg/day of sertraline (76),
100–150 mg/day of fluvoxamine (256), 20–30
mg/day of citalopram (71), and 10 mg/day
of escitalopram (86). It is recommended that the initial
low dose of the SSRI be maintained for approximately 3–7
days, then gradually increased (e.g., in weekly increments) to a
more standard daily dose, adjusting the timing of titration to the individual
patient's tolerability (257). Because elimination of
SSRIs involves hepatic metabolism, doses may need to be adjusted
for patients with liver disease.
Abrupt discontinuation of
SSRIs (or SNRIs) can lead to a discontinuation syndrome with neurosensory
(e.g., paresthesias, shock-like reactions, myalgias), neuromotor
(e.g., tremor, unstable gait, visual disturbances), gastrointestinal
(e.g., nausea, diarrhea), neuropsychiatric (e.g., anxiety, irritability),
vasomotor (e.g., diaphoresis, flushing), and other manifestations (e.g.,
insomnia, fatigue, dizziness, headache) (85, 258).
Selective serotonin reuptake inhibitors with very long half-lives (e.g.,
fluoxetine) are less likely to be associated with this discontinuation
syndrome. Symptoms of SSRI discontinuation syndrome typically begin
within 24 hours, peak about 5 days after withdrawal, and generally
resolve within 2 weeks (67, 259). Tapering
SSRIs over at least 7–10 days, or a longer period if clinical
circumstances permit, can minimize the risk of SSRI discontinuation
syndrome. If discontinuation symptoms do occur, reinstatement of
the medication at the previous dosage level for a few days, followed
by a return to an even slower taper schedule, is the preferred course
of action.
In terms of significant side effects, SSRIs are safer than TCAs
and MAOIs. They are rarely lethal in overdose and have few serious
effects on cardiovascular function. Because they lack clinically
significant anticholinergic effects, they can be prescribed to patients
with prostatic hypertrophy or narrow-angle glaucoma. The most common
side effects of SSRIs are headaches, irritability, nausea and other gastrointestinal
issues, insomnia, sexual dysfunction, weight gain, increased anxiety,
drowsiness, and tremor. Some of these effects (e.g., nausea) are
usually transient, lasting 1–2 weeks. Others (e.g., sexual
dysfunction) commonly last for the duration of treatment. Side effects
of SSRIs are highly individualized. For example, a particular SSRI
may cause insomnia in one patient but somnolence in another. Thus,
although comparative studies may tend to favor one medication over
another for a particular side effect, a given patient may still
experience that particular side effect. Fortunately, there are several SSRIs
on the market, and it is usually possible to find one that the patient
can tolerate well; this may require a process of engaging in several
therapeutic trials until the optimal medication is found for a given
patient.
There are scattered reports in the literature of extrapyramidal
side effects, but these have not been observed in large multicenter
trials and may be idiosyncratic. Some evidence suggests that SSRIs
may be associated with an increased likelihood of upper gastrointestinal
bleeding, particularly when taken in combination with NSAIDs or
with aspirin (260, 261). Use of SSRIs
also has been found to be associated with low bone mineral density
in male patients age 65 years and older (262), increased
rate of bone loss at the hip in older female patients (263),
and increased risk of falls and of osteoporotic fractures in patients
age 50 years and older (264, 265). In
addition, as described earlier in Section II.H, the FDA has warned
of the possibility that SSRIs and other antidepressants may increase the
risk of suicidal ideation and behavior in patients age 25 years
and younger (227).
+
2. Serotonin-norepinephrine
reuptake inhibitors
Venlafaxine ER has been shown to be effective for panic disorder
and has FDA approval for this indication (88, 89).
Venlafaxine ER has been shown to be effective in the range of 75 to
225 mg/day. As with SSRIs and TCAs, venlafaxine and venlafaxine
ER should be initiated gradually to reduce the likelihood of side
effects: as described in Table 5, dosing is often initiated at 37.5
mg for the first 3–7 days, then increased to a minimum
of 75 mg/day. Although increasing the dose after initial
nonresponse or partial response to 150 mg/day is clinically
recommended, the timing of such increase or the effectiveness of
increasing the dose in those with initial poor or partial response
has not been systematically studied. The level of initial response
and tolerability should be taken into consideration. In clinical
practice, some patients require and tolerate higher doses. Titration
to these higher doses should be done gradually, and potential side
effects, including blood pressure elevations should be monitored
carefully.
Venlafaxine ER is generally well tolerated and has a side
effect profile similar to the SSRIs. The most common side effects of
SNRIs in studies of panic disorder include nausea, dry mouth, constipation,
anorexia, insomnia, sweating, somnolence, tremor, and sexual dysfunction.
Because a small proportion of individuals may develop sustained
hypertension, an effect that may be dose related, it is reasonable
to assess blood pressure prior to and during treatment, particularly
when venlafaxine ER is titrated to higher doses. In addition to
the concerns and debate regarding the relationship between antidepressants
and increased suicidality, described earlier in Section II.H, some
observational studies found that venlafaxine ER was associated with
higher rates of lethal overdose than SSRIs (266–268). However,
later studies suggested that this finding may be attributable to
confounding patient factors (e.g., patients prescribed venlafaxine
displayed more pretreatment suicide risk factors) (269, 270).
No systematic data are currently available supporting the use
of another SNRI, duloxetine, in panic disorder, although its mechanism
of action, which is similar to that of venlafaxine, suggests it
might be an effective agent.
Abrupt discontinuation of SNRIs can produce a discontinuation
syndrome similar to that associated with SSRIs. Symptoms can include
dizziness, headache, and nausea (271). Tapering the
SNRI over at least 7–10 days, or a longer period if clinical
circumstances permit, can minimize the risk of a discontinuation
syndrome.
+
3. Tricyclic antidepressants
Imipramine is effective for panic disorder and is the most well
studied of the TCAs (90–92, 94–102, 104, 105, 107, 108, 111).
Clomipramine also has considerable empirical support (70, 72, 79, 93, 102, 103, 109, 110).
Although few controlled studies have evaluated other TCAs for panic
disorder, those that have are generally supportive of the efficacy of
desipramine (106) and nortriptyline (112).
Given the equivalency of TCAs in treating depression, there is little reason
to expect other TCAs to work less well for panic disorder. However,
TCAs that are more noradrenergic (e.g., desipramine, maprotiline)
may be less effective than agents that are more serotonergic (272).
Psychiatrists have often noticed, and research studies have occasionally
shown, that some patients with panic disorder are hypersensitive
to both the beneficial and adverse effects of TCAs (91, 106).
Patients sometimes experience a stimulating response, including
anxiety, agitation, or insomnia, when treatment with antidepressant
medication of any class is initiated. For this reason, it is recommended
that, similar to the SSRIs and SNRIs, TCAs be started for patients
with panic disorder at doses substantially lower than those for
patients with depression or other psychiatric conditions. One common strategy
is to begin with only 10 mg/day of imipramine or its equivalent
and gradually titrate the dose upward over the ensuing weeks.
Few studies have rigorously addressed the optimum dose of
TCAs for panic disorder. Results of clinical trials suggest that
it is reasonable to titrate the imipramine dose of patients with
panic disorder to approximately 100 mg/day and wait for
at least 4 weeks to see whether there is a response. If tolerated,
the dose can then be increased to as high as 300 mg/day
if initial response is either absent or inadequate (108).
Evidence suggests that clomipramine may be effective in somewhat
lower doses than imipramine; clomipramine can generally be used
effectively in doses ranging from 50 to 150 mg/day (93, 102).
Although there is no evidence of a correlation between blood levels
of TCAs and clinical response in panic disorder, blood level monitoring
may be helpful for patients who display inadequate response despite
seemingly adequate doses or for patients who display signs of toxicity despite
doses that are in the therapeutic range.
The most common side effects of TCAs as reported in clinical
trials for panic disorder are 1) anticholinergic effects, including
dry mouth, constipation, difficulty urinating, increased heart rate,
and blurry vision; 2) increased sweating; 3) sleep disturbance;
4) orthostatic hypotension and dizziness; 5) fatigue and weakness;
6) cognitive disturbance; 7) weight gain, especially for long-term
users; and 8) sexual dysfunction (273). Higher doses
of TCAs are associated with a higher dropout rate in research studies
(108), and one naturalistic follow-up study found that
one-third of patients prescribed TCAs discontinued them because
of side effects (274).
Tricyclic antidepressants should not be prescribed for patients
with panic disorder who also have acute narrow-angle glaucoma or
clinically significant prostatic hypertrophy. The risk of falls
may be increased by TCAs, particularly among elderly patients, because
of orthostasis. Because patients with preexisting cardiac conduction
abnormalities may experience significant or fatal arrhythmia with
TCA treatment (275), a baseline electrocardiogram should
be considered before initiating a TCA. Overdoses with TCAs can lead
to significant cardiac toxicity and fatality (275).
For this reason and because of the concerns and debate regarding
the relationship between antidepressants and increased suicidality (see
discussion earlier in Section II.H), TCAs should be used judiciously
in suicidal patients.
Alprazolam has the largest number of clinical trials supporting
its efficacy for treatment of panic disorder and is FDA approved
for this indication (104, 116, 118, 122, 123, 126, 276, 277).
The data support the efficacy of alprazolam in treating multiple
dimensions of illness (i.e., preventing panic attacks, reducing
anticipatory anxiety and avoidance) in patients with panic disorder.
However, because of its short half-life, frequent (3–4
times daily) dosing is required, which creates practical difficulty
for many patients and results in more rapid and profound withdrawal
symptoms with missed doses. A sustained-release form of alprazolam
is also FDA approved based on two placebo-controlled studies (125, 129).
Although this formulation is approved for once daily dosing, clinical experience
suggests that twice daily dosing of alprazolam, sustained release,
may be required to maximize efficacy.
It is necessary to be flexible in choosing the alprazolam dose
for an individual patient. Most patients require three to four doses
per day to avoid breakthrough or rebound symptoms, although some
may achieve symptom control with two doses of alprazolam per day.
For patients who have not taken alprazolam in the past, the starting
dose should be 0.25 mg three or four times daily. The dose should
be titrated up to 2–3 mg/day over the first week
or two, but an increase to as high as 5–6 mg/day
may in rare instances be necessary to obtain symptom control. Although
the literature on alprazolam, sustained release, is much more sparse,
most studies have tested doses in the range of 2–4 mg/day.
The manufacturer's recommendation for alprazolam treatment
of panic disorder notes that doses above 4 mg/day are usually
necessary and that doses up to 10 mg/day are sometimes
required. However, very few studies have empirically evaluated dose
requirements, and those studies that have been conducted have produced
mixed results regarding the advantages of higher doses (e.g., 6
mg/day) over lower doses (e.g., 2 mg/day) (95, 278).
Clonazepam is also FDA approved for the treatment of panic
disorder, and several clinical trials support its efficacy (122, 131, 132).
Its longer half-life results in less severe withdrawal symptoms
with missed doses and usually allows once or twice a day administration.
These factors lead some psychiatrists to prefer clonazepam over
other benzodiazepines for the long-term maintenance treatment of
panic disorder, largely because of the ease of clonazepam dosing.
For patients without prior clonazepam treatment, starting doses
are usually in the range of 0.5–1 mg/day and may
be titrated to higher doses as needed. Studies of clonazepam suggest
that daily doses of 1–2 mg offer the best balance of therapeutic
benefits and side effects. These doses are the equivalent of 2–4
mg of alprazolam or less. Patients can usually be switched from
alprazolam to clonazepam by taking the total daily alprazolam dose
in milligrams and administering half that daily dose in milligrams of
clonazepam (usually as twice daily or bedtime-only treatment).
Results of several studies suggest a relationship between alprazolam
and clonazepam blood levels and treatment response (279–281).
In patients who do not respond to usual dose titrations, dose adjustment
may be facilitated by monitoring of alprazolam and clonazepam blood
levels, although this is rarely done.
Additional studies suggest that other benzodiazepines (e.g.,
diazepam, lorazepam), when given in equivalent doses, may be as
effective as alprazolam in the treatment of panic disorder (113–116, 119–121, 124, 127, 128, 130, 282).
In general, benzodiazepines seem to be well tolerated by patients
with panic disorder, with very few serious side effects. When side
effects of benzodiazepines do occur in patients with panic disorder,
they appear similar to those reported when benzodiazepines are used
for other indications. Side effects include primarily sedation,
fatigue, ataxia, slurred speech, memory impairment, and weakness.
Geriatric patients taking benzodiazepines may be at higher risk
for falls and fractures because of these side effects (283–287).
Because of an increased risk of motor vehicle accidents in association
with benzodiazepine use (288), patients should be warned
about driving or operating heavy machinery while taking benzodiazepines,
particularly when these medications are started or with dose increases.
Patients should also be advised about the additive effects of benzodiazepines
and alcohol, in particular combined sedative and respiratory effects. Although
patients may be able to safely drink small amounts of alcohol, they
should consume alcohol slowly and exercise extra caution when doing
so (e.g., avoid operating vehicles).
For patients in stable recovery from substance use disorders,
there is not an absolute contraindication to benzodiazepine use,
but the decision to use benzodiazepines should be made cautiously.
In patients in early remission or with active substance use disorders,
concerns regarding potential misuse of the benzodiazepine or relapse
of the substance use disorder are greater; in these circumstances
other treatments for panic disorder that have a lower abuse potential
are recommended for first-line use (289–291).
If benzodiazepines are felt to be necessary after careful consideration
of other treatment options, the psychiatrist should closely monitor
their use (e.g., dispense in limited quantities and on a time-limited basis,
supervise medication administration, track prescription refills
or use pill counts to assess medication adherence, increase office
visit frequency to monitor the ongoing medical necessity for and
the patient's response to the medication). In addition,
selection of an agent that is more slowly absorbed (e.g., oxazepam,
clorazepate) may limit the potential for abuse (291).
Cognitive effects of benzodiazepines have been the subject
of debate and some empirical research (292–294).
It is clear that benzodiazepines at higher doses can cause memory impairment
(101). One meta-analysis concluded that long-term benzodiazepine
users performed worse than control participants on numerous domains
of cognitive functioning (295). However, another review
concluded that the literature as a whole does not provide convincing
evidence of cumulative long-term cognitive effects of benzodiazepines
in anxious patients (296). Nevertheless, patients should
be monitored for the development of cognitive impairment, which
may be more problematic at higher doses and in patients performing
complex information-processing tasks at work. Caution is indicated
when prescribing benzodiazepines to elderly patients or those with
preexisting cognitive impairment.
+
5. Other antidepressants
Monoamine oxidase inhibitors are widely regarded as effective for
panic disorder. However, there have been virtually no studies involving
the use of MAOIs for panic disorder since the introduction of the
panic disorder diagnosis in DSM-III in 1980. One study included
patients with what would now be called panic disorder and found
phenelzine to be effective (297). The commonly held
belief that MAOIs are actually more potent antipanic agents than
TCAs has never been convincingly proven in the scientific literature
and is only supported by clinical anecdote. There has been considerable
clinical interest in medications that are reversible inhibitors
of monoamine oxidase A, because these medications do not generally
require adherence to the low-tyramine diet that is mandatory for
patients treated with phenelzine, tranylcypromine, or isocarboxazid.
However, none of these medications is currently approved for use
in the United States in either oral or patch form, although moclobemide
is available in other countries, including Canada. Four studies
have examined the effectiveness of moclobemide in panic disorder,
and the results are mixed and only modestly encouraging (298–301).
Although the monoamine oxidase B inhibitor selegiline is available
in the United States, there are no data to support its efficacy
for the treatment of panic disorder.
Doses of phenelzine in controlled trials for illnesses that resemble
panic disorder have tended to be low, often no higher than 45 mg/day
(297, 302). Some authors have commented
that higher doses may be more effective. Doses of phenelzine up
to 90 mg/day and of tranylcypromine up to 60 mg/day
are said by experienced psychiatrists to be necessary for some patients
with panic disorder. Patients rarely get significant benefit before
several weeks have elapsed, and periods up to 12 weeks may be necessary
before the full effectiveness of the medication can be judged. No
maintenance studies of MAOIs for panic disorder have been published.
Hence, the optimal length of treatment that provides the least chance
of relapse has not been established.
Adverse effects are a major concern with MAOIs, and these
medications are generally reserved for use when a patient has not
responded to several other treatments. The complexity of these medications
suggests that they should be prescribed by physicians with experience
in monitoring MAOI treatment. A major risk of taking an MAOI is
the induction of a hypertensive crisis with ingestion of tyramine. Hence,
patients taking phenelzine or tranylcypromine must adhere to a special
low-tyramine diet (303). Certain medications, including
but not limited to sympathomimetic amines and decongestants, can
also precipitate a hypertensive crisis and must not be used with
MAOIs. Another serious drug-drug interaction to be avoided is the "serotonin
syndrome," which can be fatal and is characterized by confusion,
agitation, hyperthermia, and other autonomic unstable vital signs
(e.g., shivering, diaphoresis, nausea, diarrhea) and neuromuscular signs
(e.g., tremor, hyperreflexia, clonus, myoclonus, ataxia) (304).
Serotonin syndrome can occur when MAOIs are used with other antidepressants
(particularly SSRIs); the antibiotic linezolid; the analgesics meperidine,
fentanyl, and tramadol; the over-the-counter medication dextromethorphan;
and other medications acting on serotonin such as buspirone, fenfluramine,
sibutramine, and the anti-migraine triptan medications (305, 306).
Even when the risks of hypertensive crises and serotonin syndrome
are obviated by strict adherence to dietary and medication restrictions,
MAOIs have substantial adverse effects. These include hypotension
(sometimes leading to syncope), weight gain, sexual dysfunction,
paresthesia, myoclonic jerks, dry mouth, edema, and a paradoxical
syndrome of excessive daytime sleepiness, nocturnal insomnia, and
shorter sleep length.
There is minimal support for the use of trazodone in panic disorder.
It appears less effective than imipramine and alprazolam and does
not enhance outcome when used to augment CBT (221, 307, 308).
Although there are a few small uncontrolled studies showing benefits
of nefazodone in some patients with panic disorder (309–311),
its use has been limited by concerns about liver toxicity (312).
Thus, neither trazodone nor nefazodone can be recommended as a first-line treatment
for panic disorder.
Bupropion (including extended release formulations) was effective
in one small trial (313) and ineffective in another (314).
Although it might be useful in some cases, given the limited and
mixed systematic data regarding its efficacy, bupropion cannot be
recommended as a first-line treatment for panic disorder.
A few open short-term studies support the potential efficacy
of mirtazapine for panic disorder (315–319),
and a comparison of mirtazapine and paroxetine in a very small randomized
controlled trial involving 27 patients suggested similar efficacy
of the two medications (320). However, mirtazapine
should not be considered a first-line treatment for panic disorder
because tolerability issues have been noted, with common side effects
including somnolence and weight gain. In addition, there are no
available data from large controlled studies supporting its efficacy
in panic disorder.
The concerns and debate regarding the relationship between
antidepressants and increased suicidality have been reviewed earlier
in Section II.H and may apply to the other antidepressants discussed
in this section.
There are limited data concerning the use of anticonvulsant medications
in the treatment of panic disorder. One randomized controlled trial
of gabapentin provided partial support for its efficacy and safety
in panic disorder (321), but no further research has
been conducted. Thus, gabapentin should not be considered a first-line
treatment but may be useful in individual circumstances, either
alone or as an adjunct to antidepressants. Small open-label studies
have suggested that valproic acid may benefit some patients with
panic disorder (322–324), but
this medication has significant side effects (325),
and controlled investigations are needed before it can be recommended.
One small open-label study of levetiracetam (326) and
very preliminary case report data for tiagabine (327)
and vigabatrin (327) suggest that these agents may
be worthy of further study in panic disorder. However, controlled
trials are needed before any of these medications can be recommended
as treatments for panic disorder. A small placebo-controlled trial
suggested that carbamazepine was not effective for panic disorder
(328).
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b. Antipsychotic
agents
First-generation (i.e., typical) antipsychotic medications
are rarely appropriate in the treatment of panic disorder. There
is no evidence that they are effective, and the risk of neurological
side effects outweighs any potential benefit. Among the second-generation
(i.e., atypical) antipsychotics, there is limited positive evidence
for olanzapine (329) and adjunctive risperidone (330),
suggesting the possibility that second-generation antipsychotics
may be useful for patients with severe, treatment-resistant panic
disorder. At present, however, evidence for efficacy is limited,
and there is growing concern about side effects of second-generation
antipsychotics, including weight gain, poor glycemic control, and
metabolic syndrome (331). Consequently, at this time
these agents cannot be broadly recommended for patients with panic
disorder, although they may have a role in individual circumstances.
The available scant literature suggests that beta-adrenergic blocking
agents (e.g., propranolol, atenolol) are ineffective for panic disorder
(115, 332, 333). However,
these agents continue to be used occasionally by psychiatrists who
have observed that they can help reduce somatic sensations (e.g., palpitations)
in some patients. There is limited evidence supporting the potential
efficacy of a particular beta-blocker, pindolol, as augmentation
for patients with SSRI-resistant panic disorder (334).
Given the frequent side effects associated with beta-adrenergic
blocking agents (e.g., fatigue, sleep disturbance, and possibly,
the worsening of depression), these agents should not be considered
in the routine treatment of panic disorder.
Although historically there was interest in treating panic attacks
with calcium channel blockers, they are rarely used clinically,
and efficacy data are very limited (335). Similarly, there
are limited data suggesting clonidine may have mild and/or
transient effects only (336, 337). Thus,
calcium channel blockers and clonidine cannot be recommended as
first-line or adjunctive treatments for panic disorder.
The available data suggest that buspirone monotherapy is not effective
for panic disorder (338, 339) and does
not enhance the efficacy of CBT (340). Although it
is sometimes used clinically in individual circumstances as an augmentation strategy
for patients with panic disorder, there are no published data except
case reports (341) to support this practice.
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I. Maintaining or
Discontinuing Treatment After Response
There are few data on optimum length of treatment following response.
Studies of acute treatment for panic disorder have been conducted
over 6–12 weeks, with some studies including long-term
follow-up periods of 1 to 2 years. Studies of CBT (which include
some of the longer follow-up intervals) suggest that the majority
of patients maintain benefits derived from a short-term course of
CBT. Some clinical trials have included several months of maintenance
CBT (i.e., monthly "booster sessions" focused
on relapse prevention), which may have helped sustain positive response
to CBT. However, the incremental benefit of periodic booster sessions
has yet to be empirically proven. In general, CBT can be discontinued
after 10–15 sessions (or sooner if the patient responds
quickly) with specific instructions for continued independent practice
of CBT skills. Many clinicians and patients also find addition of
several monthly booster sessions useful.
With each of the antidepressant medications, therapeutic effects
are generally maintained for as long as medication is continued.
For responders to an SSRI or a TCA, clinical experience and some
data suggest that continuing treatment for 6 months or more after
acute response can lead to further symptom reduction and decreased
risk of recurrence (70, 85, 99, 104, 342, 343).
Although no empirical data are available addressing this question,
clinical experience suggests patients with treatment-resistant panic
disorder or prior relapse with treatment discontinuation may require
longer term treatment. For venlafaxine ER, there are minimal systematic
data addressing the optimum length of treatment following response,
although discontinuation of venlafaxine ER after only 12 weeks of
treatment has been shown to result in an increased likelihood of
relapse (344).
Before advising a taper of effective medication, the psychiatrist
should consider whether the patient is currently motivated to discontinue
the medication as well as the duration of the patient's
symptom remission. The timing of medication discontinuation is often
influenced by factors such as the presence of psychosocial stressors
or supports, the stability of co-occurring conditions, and the availability
of alternative treatment options. Discussion of medication taper
should also include the possible outcomes of tapering, which include
the potential recurrence of panic symptoms, potential withdrawal
symptoms, or both. If medication is tapered, it should be done in
a collaborative manner with continual assessment of the effects
of the taper and the patient's responses to any changes
that emerge. Similarly, discontinuation of psychosocial treatment
should be planned collaboratively with the patient. Before terminating
treatment, clinicians providing CBT help patients develop personalized
relapse prevention plans. They also frequently offer patients the
option of scheduling "booster sessions" focused
on maintaining and enhancing treatment gains.
If an SSRI, SNRI, or TCA is to be discontinued, most psychiatrists
and patients prefer to taper medications over a period of several
weeks or months. This both allows for an opportunity to monitor
for the possible reemergence of panic symptoms as well as decreases
the likelihood of discontinuation effects, particularly for those
patients who are taking higher doses or after prolonged use. However,
under more urgent conditions (e.g., the patient is pregnant and
wants to discontinue medications immediately), these medications
can be discontinued much more quickly.
There are fewer data examining the issue of benzodiazepine
discontinuation, but existing studies support continuing benzodiazepine
treatment to prevent recurrence (99, 104).
Clinical experience also suggests that many patients can be maintained
with stable doses of benzodiazepines for many years with no recurrence
of symptoms. Although major concerns about benzodiazepine tolerance
and withdrawal have been raised, there is no evidence for significant
dose escalation in patients with panic disorder or with long-term benzodiazepine
use (294, 345–347).
The approach to benzodiazepine discontinuation also involves
a gradual tapering of dose. Withdrawal symptoms and symptomatic
rebound are commonly seen with benzodiazepine discontinuation, can
occur throughout the taper, and may be especially severe toward
the end of the taper. This argues for tapering benzodiazepines very
slowly for patients with panic disorder, probably over 2–4
months and at rates no higher than 10% of the dose per
week (348–350). Although is it
commonly believed that benzodiazepines with shorter half-lives produce
more severe withdrawal symptoms than those with longer half-lives,
most studies suggest that half-life is less of a factor than the
use of a gradual taper schedule (126, 351). In
addition, withdrawal symptoms can occur after relatively short-term
periods of treatment and have been observed after as little as 6–8
weeks of treatment with alprazolam (352). The likelihood
of discontinuation effects may be increased in patients with panic
disorder who have traits such as high anxiety sensitivity and high
levels of avoidance (353); for such patients, close
monitoring should be performed and special care should be taken
during the discontinuation process. Cognitive-behavioral therapy,
which counteracts tendencies to amplify bodily sensations and catastrophize
discontinuation symptoms, has been found to effectively facilitate
withdrawal from benzodiazepines (354–357).
There is also some evidence for the utility of concurrent psychotherapy
to maintain response after discontinuation of antidepressants. One
small controlled study showed that combining brief psychodynamic
psychotherapy and clomipramine reduced the likelihood of relapse
of panic disorder after clomipramine discontinuation (156).
Furthermore, in a meta-analysis of antidepressant pharmacotherapy
and psychotherapy (in which nearly all psychotherapy studies administered
CBT), combination treatment was more effective than antidepressants
alone after treatment had been withdrawn (160).
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III. Specific Clinical
Features Influencing the Treatment Plan
The following sections review data pertinent to the treatment of
individuals with panic disorder who have specific clinical features
that may alter the general treatment considerations that are discussed
in Sections II.B, II.C, II.D, II.E, II.F, II.G, II.H, and II.I. These sections are necessarily brief
and are not intended to stand alone as a set of treatment recommendations.
The recommendations reviewed in Sections II.B, II.C, II.D, II.E, II.F, II.G, II.H, and II.I, including
the use of psychiatric management, generally apply unless otherwise indicated.
The relationship between panic disorder and suicide is a controversial
topic. Determining whether specific suicide risks are associated
with panic disorder has been complicated by the frequency of co-occurring
disorders that are themselves associated with increases in suicide
risk. From a logical perspective, it can be difficult to reconcile
how a patient with panic disorder who manifests a strong fear of
dying could also experience a wish to die. However, panic disorder
can be a severely distressing condition that motivates suicidal thoughts
and behaviors in some patients. Evidence exists that panic disorder
may contribute to an increased risk of suicidality. Because risk
factors for suicide may differ from those for suicidal ideation
and suicide attempts, we will review these areas separately.
Early studies, summarized in a meta-analysis by Harris and
Barraclough (358), demonstrated that panic disorder
was associated with a 10-fold increase in mortality due to suicide. However,
individuals with panic disorder are identified in a relatively small
proportion of suicides. For example, a psychological autopsy study
of 1,397 suicides in Finland found that only 1.22% met
the criteria for DSM-III-R panic disorder (359). These
low rates may relate to an underreporting of panic disorder symptoms
in such studies, because of masking of panic disorder symptoms by
substance use (360) or by affective symptoms. Even
in individuals identified in psychological autopsies as having panic
disorder, co-occurring mood, substance use, and personality disorders
are the norm (359, 361). In individuals
with panic disorder who are studied longitudinally, co-occurring
disorders are almost always present in those who die by suicide
(362, 363). Additional evidence suggests
that the presence of co-occurring panic attacks may be associated
with an increase in suicide risk among individuals with major depression,
particularly early in the course of illness (364).
In summary, the evidence is mixed as to whether panic disorder and
panic attacks are associated with an increased risk of suicide in
and of themselves or whether the apparent increase in associated
risk is related to co-occurring mood and substance use disorders.
It is similarly controversial whether panic disorder is independently
or uniquely associated with suicidal ideation or suicidal attempts
(i.e., after adjusting for co-occurring mental disorders, especially
major depression) (365, 366). Some studies
have noted an association of panic disorder with suicidal behavior
even after adjusting for effects of co-occurring mental disorders
(44), whereas other studies have not found these results
(365, 366). Overall, however, most (44, 367–371)
but not all (372) research with cross-sectional clinical and
community samples has demonstrated that panic disorder and panic
attacks are associated with suicidal ideation and suicide attempts.
Substantial rates of suicidal ideation and attempts as well as high
frequencies of co-occurring disorders have also been observed in
smaller studies of patients with panic disorder in a variety of
settings (369, 373–376).
The association between panic disorder and suicidal behavior
is of considerable clinical significance, even if most or all of
the increased risk is attributable to lifetime comorbidity. The
vast majority of patients with panic disorder have current or past
co-occurring Axis I or Axis II disorders. Thus, uncomplicated panic
disorder is relatively uncommon. Furthermore, co-occurring conditions
may go undetected in busy clinical settings. Thus, it is important
to be aware that patients presenting with panic disorder are at
high risk for lifetime suicidal ideation and attempts. All patients
presenting with panic attacks should be asked about suicidal ideation,
past suicide attempts, about access to firearms and other means
of suicide, and about co-occurring conditions likely to increase
risk and to require specific treatment (e.g., bipolar disorder,
major depressive disorder, or substance use disorders). When significant
mood disorder and/or suicidal ideation exist, treatment
should be initiated that is appropriate for the co-occurring diagnosis
and a decision should be made about whether the patient can safely
be treated as an outpatient. When a substance use disorder is present,
it must also be monitored closely and addressed in treatment.
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2. Co-occurring substance
use disorder
In clinical and epidemiological studies, patients with panic disorder
with or without agoraphobia have higher than average rates of cocaine,
alcohol, and sedative abuse and dependence (377–383).
Approximately 50% of people with panic disorder and substance
use disorder have the onset of the substance use disorder prior
to the onset of panic symptoms (378). Other individuals
develop substance use disorders after the onset of panic disorder.
Although the two problems may or may not be functionally related,
some individuals may attempt to decrease panic and anxiety symptoms
by using alcohol or other substances. In a recent epidemiological
study, for example, 23% of subjects with a diagnosis of
panic disorder reported using alcohol or drugs to reduce their anxiety
symptoms (384).
Despite the anxiolytic effects perceived by some patients, use
of many substances can trigger or worsen panic symptoms. Heavy alcohol
use, acute alcohol withdrawal, and more prolonged subacute withdrawal
may cause or exacerbate panic symptoms (382, 385).
Cocaine, other stimulants, and marijuana have been reported to precipitate
panic attacks in adolescents and adults (386–388).
Panic attacks may also be triggered or worsened through the use
of a number of legal substances, such as caffeine, sympathomimetics
(e.g., nasal decongestants), and nicotine (389–393).
Psychiatrists should be certain to screen for substance use in
patients with panic disorder. Substance use may play a role in causing
or exacerbating panic symptoms, and patients with co-occurring panic
disorder and substance use disorder have a poorer prognosis than
those with either disorder alone (382, 385).
It may be useful to incorporate formal drug screens into the treatment
plan for patients with co-occurring substance use disorder (291).
Psychiatrists also should consider referring the patient to community
resources (e.g., Alcoholics Anonymous) and may need to coordinate
care with addiction specialists who are providing concurrent care
for the patient.
When the patient reports both problematic substance use and
panic symptoms, treatment of the substance use disorder is essential.
It is unclear whether specific antipanic treatment is necessary
for patients with primary substance abuse (i.e., where it is clear
that the panic attacks are a result of the substance use or withdrawal).
The occurrence of several panic attacks in decreasing frequency
during the early weeks of abstinence often warrants no treatment
other than support and reassurance until the attacks abate (394, 395).
However, if the panic attacks and other symptoms of panic disorder
continue after several weeks of abstinence, making a diagnosis of
panic disorder and initiating treatment is warranted. A return to
substance use is common in patients who have ongoing symptoms of
panic disorder in the period following substance use cessation (396–400).
A controlled trial suggested that combined CBT and SSRI treatment
significantly reduced anxiety symptoms in patients with co-occurring
anxiety disorders (including agoraphobia) and alcohol dependence
(401). However, there were no differences in relapse
rates when patients who received anxiety treatment plus relapse
prevention were compared to those who participated in relapse prevention alone.
This study provides preliminary evidence that standard treatments
for panic disorder can be effective for individuals who are in early
stages of remission from substance use disorders, though effective
treatment of anxiety does not necessarily translate into decreased relapse
potential.
When panic symptoms persist after the initial period of detoxification,
the psychiatrist must decide whether to pursue integrated or sequential
treatment. Empirical data that provide guidance on this matter are
lacking, and therefore this decision must be based on clinical judgment.
Although integrated treatment is generally recommended (291),
there are some individuals in whom the substance use disorder should
be the primary target of the first phase of treatment. For example,
most forms of CBT involve deliberately provoking anxiety symptoms
or confronting anxiety-provoking situations. If these temporary
increases in anxiety are likely to trigger compensatory substance
use, a decision could be made to delay CBT until the patient has
the support and skills to maintain sobriety even in the face of
stress or discomfort.
In treating panic symptoms in patients with co-occurring substance
use disorder, benzodiazepines should be avoided whenever possible
in favor of CBT and/or antidepressants. A history of abuse
of other substances, both licit and illicit, is associated with
a higher prevalence of benzodiazepine abuse, a greater euphoric
response to benzodiazepines, and a higher rate of unauthorized use
of alprazolam during treatment for panic disorder (289, 402).
If antidepressant treatment is indicated, SSRIs or SNRIs are preferred
because the side effect and safety profiles of TCAs (e.g., increased
risk of cardiac toxicity and seizures; greater lethality of TCAs
in overdose) are of increased concern in the context of a co-occurring
substance use disorder (403). More information about
treating co-occurring panic disorder and substance use disorders
is available in APA's Practice Guideline
for the Treatment of Patients With Substance Use Disorders, Second
Edition (291).
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3. Co-occurring mood
disorder
Substantial evidence from clinical and epidemiological studies
demonstrates that panic disorder and panic attacks frequently co-occur
with unipolar and bipolar mood disorders (14, 17, 33).
Many studies indicate that patients with panic disorder and co-occurring
mood disorders exhibit greater impairment, more hospitalizations,
and generally more psychopathological symptoms than patients with
panic disorder who do not have a co-occurring mood disorder (404, 405).
As described in Section III.A.1, a co-occurring mood disorder can also
augment the risk of suicidality in individuals with panic disorder.
In treating patients with co-occurring panic disorder and mood disorder,
the psychiatrist should select treatments that can target both disorders
(e.g., psychosocial treatment and/or antidepressants rather
than benzodiazepines alone for a patient with panic disorder and
major depressive disorder).
With regard to CBT, most studies suggest that co-occurring
major depressive disorder does not adversely affect response to
CBT for panic disorder (191, 406). In
some individuals major depressive disorder may occur as a reaction
to the impairment created by the panic disorder (e.g., the patient
feels depressed because panic symptoms limit his or her participation
in activities). When the depression appears to be secondary, focusing
on panic disorder in CBT and monitoring changes in depressive symptoms
is a reasonable strategy. Some evidence suggests that if panic disorder
is targeted using CBT, depressive symptoms may spontaneously improve
(193, 194). For individuals who still
have significant symptoms of depression after a course of CBT for
panic, the therapist can shift focus and target the depression directly.
If depressive symptoms are severe, associated with suicidality, or
interfering with adherence to the treatment for panic disorder,
the emphasis of the CBT should be shifted so that the depression
becomes the primary focus of treatment.
Treatment of mood disorders may also be prioritized during
pharmacological treatment for panic disorder; this is especially
true for patients who present with suicidal ideation. When panic
disorder co-occurs with bipolar illness, the psychiatrist should
consider that antidepressants commonly used for treating panic disorder
might exacerbate the bipolar disorder. Patients with co-occurring
panic disorder and bipolar disorder should generally be treated
with a mood stabilizing medication before the addition of an antidepressant
is considered for treatment of the panic disorder. Careful monitoring
is required whenever an antidepressant is added to the treatment
regimen of an individual with bipolar disorder (407).
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4. Other co-occurring
anxiety disorders
Although spontaneous or unexpected panic attacks are a hallmark
of panic disorder, panic attacks can occur in other anxiety disorders.
Consequently, the psychiatrist must perform a detailed assessment
to ensure that panic disorder is an appropriate diagnosis (see Section
II.A.2). In many individuals presenting for treatment, panic disorder
occurs concomitantly with other anxiety disorders (for example,
see reference 408), and in these circumstances multiple
disorders may need to be targeted in treatment.
Treatment with SSRIs, SNRIs, or CBT is appropriate for most
individuals with co-occurring anxiety disorders. Medications commonly
used to treat panic disorder often have a positive effect on the
symptoms of other anxiety disorders. In addition, psychotherapy
for panic disorder may have a positive effect on other symptoms
even when co-occurring anxiety disorders are not directly targeted
in treatment (191–194, 409).
However, in some cases where panic disorder is part of a more complicated
pattern of co-occurring conditions, a highly tailored and multimodal
therapy may be required for optimal recovery. Although the first-line
treatments may be similar under these conditions, specificity of
treatment (e.g., addition of specific CBT modules, or other psychotherapeutic
modalities, focused on co-occurring disorders) may make the difference
between full response, partial response, and perceived treatment
resistance.
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5. Co-occurring personality
disorders
Studies have shown that 40%–50% of
patients with panic disorder additionally meet the criteria for
one or more Axis II disorders (410–413).
The personality disorders most frequently observed in panic disorder
patients are three from the anxious cluster: avoidant, obsessive-compulsive,
and dependent (414–416). In addition,
patients with panic disorder often show traits from other personality
disorders, such as affective instability and/or impulsivity
(from borderline personality disorder), impulsivity (from antisocial
personality disorder) (417, 418), and
hypersensitivity to people (from paranoid personality disorder)
(411). Longitudinal data suggest that panic attacks
early in life predict the subsequent onset of personality disorders
(419).
Results of studies examining the impact of co-occurring personality
disorders on the course of panic disorder have been mixed. Several
studies have shown that presence of co-occurring personality disorders
predicts worse long-term outcome for patients with panic disorder
(413, 420, 421). However,
a large-scale, prospective, naturalistic study showed that, in contrast
to social phobia and generalized anxiety disorder, the presence
of a personality disorder did not predict longer time to remission
in patients with panic disorder (422).
The majority of studies suggest that co-occurring personality
disorders are associated with poorer response to standard treatments
for panic disorder. A review of studies that examined the impact
of co-occurring personality disorders on CBT outcome suggested that
presence of a personality disorder at baseline was associated with
poorer treatment outcome (423). Patients with co-occurring
personality disorders also show less improvement and seem more likely
to relapse following medication treatment for panic disorder (411, 414–416, 424, 425).
In working with patients who have co-occurring panic disorder
and personality disorder, the therapist may need to devote more
time to strengthening the therapeutic alliance and developing a
hierarchy of specific treatment goals. One recent study provided
preliminary evidence that a psychodynamic approach to treating panic
disorder was effective for patients with co-occurring personality
disorders (146).
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B. Concurrent General Medical
Conditions
Panic attacks are associated with prominent physical symptoms
and may be misinterpreted as general medical conditions by patients
and/or physicians. Moreover, panic symptoms may be an acute
manifestation of a general medical condition (notably thyroid disease)
or may result from the effects of prescribed medications to treat
such conditions. An additional possibility is that a general medical
condition is co-occurring with panic disorder. Studies show that
panic and other anxiety disorders are more prevalent in medically
ill patients than in the population at large, with physical conditions that
have been specifically associated with panic disorder (426)
including thyroid disease (427), cancer (428),
chronic pain (429), cardiac disease (430),
irritable bowel syndrome (431), migraine (432),
mitral valve prolapse (36, 38, 39),
vestibular disorders (433), and allergic and respiratory
disease (434–436). To distinguish
among these possibilities and to identify unrecognized general medical
conditions that contribute to the clinical presentation requires
a general medical evaluation as delineated in APA's Practice
Guideline for the Psychiatric Evaluation of Adults, Second Edition (8).
Even when results are negative, a careful assessment can provide needed
reassurance to patients who fear that their panic attacks represent
serious physical illness. In addition to the initial evaluation,
assessments for general medical conditions may be indicated at other
points in the treatment course. For example, among patients whose
symptoms worsen or do not respond to initial treatments, a contributory
general physical condition is worth considering.
Whenever a general medical condition is identified, the postulated
relationship between that condition and the panic disorder will
determine the approach to the patient. If the medical condition
(e.g., hyperthyroidism) or treatment (e.g., oral corticosteroids)
appears to be the primary cause of the panic symptoms, the specific
treatment of panic disorder may be delayed until the general medical
condition is treated or the precipitating medication discontinued.
In some instances, medications that cause or worsen panic symptoms
may be essential and cannot be discontinued; in these cases, concurrent treatment
of panic disorder should be initiated. In other instances, a general
medical condition or its treatment is not directly causing panic
disorder (e.g., asthma) but may be worsening it. For example, data
from some studies suggest that panic disorder and agoraphobic anxiety
may increase the risk of mortality in patients with cardiovascular
disease (362, 437, 438).
Thus, with co-occurring general medical conditions and panic disorder,
a simultaneous focus on optimizing treatment of the medical condition
and the panic disorder may be indicated.
To date, there are no systematic evaluations of psychological
or pharmacological treatment in patients with co-occurring panic
disorder and general medical disorders. As far as pharmacological
treatment, it is important for psychiatrists to choose medications
that have the fewest drug-drug interactions. Adverse drug interactions
may occur between medications utilized for panic disorder and medications
used for general medical conditions. Furthermore, panic disorder
patients with concurrent medical conditions may have difficulty differentiating
symptoms of the general medical condition (e.g., migraine, asthma
attack, angina) from those related to panic attacks. Thus, they
may not be clear whether to take medication for their general medical
conditions or to take medication for their anxiety. In the specific
example of co-occurring panic disorder and asthma, patients often
encounter difficulties knowing whether to utilize asthma treatment
medications (i.e., beta-agonists) or anxiolytic medications. If
they misinterpret a panic attack as an asthma attack, utilizing
a beta-agonist is likely to worsen the panic attack symptoms. On
the other hand, an asthma attack that is interpreted as being a
panic attack would not resolve with an anxiolytic medication. However,
because the symptoms of panic attacks and asthma may be very difficult
to differentiate, a therapeutic trial of the various strategies
is often required.
Psychosocial treatments for panic disorder may need to be adapted
depending on the presence and severity of a co-occurring general
medical condition. It is often necessary to adapt the psychosocial
treatment to the physical or medical realities in the patient's
life. However, the clinician also must be alert to the possibility
that the patient is viewing the dangers of the medical condition
as more threatening than they truly are or is incorrectly interpreting
panic symptoms as signs of another medical illness. In any form
of psychosocial treatment, learning to differentiate anxiety symptoms
from those related to the general medical condition often becomes an
important goal. This work can be done through careful self-monitoring.
Adaptation of other aspects of treatment may also be required. For
example, physically challenging interoceptive exposure exercises
that are used in CBT may need to be modified for patients with co-occurring
panic disorder and medical conditions (e.g., asthma, heart disease).
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C. Demographic Variables
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1. Children and adolescents
This section contains a brief
overview of formal clinical trial data regarding the treatment of
children and adolescents with panic disorder. Given the limited
data in the child and adolescent literature, many treatment plans
will necessarily include components that are not well studied. Unless
otherwise stated, the general considerations outlined in Sections
II.B through II.I apply to children; this is especially true of
the importance of psychiatric management. In addition, treatment
plans for children and adolescents frequently require attention
to developmental issues (from psychological and physiological perspectives)
and involvement of multiple systems (e.g., schools, family, and
community). Information and recommendations regarding the etiology,
diagnosis, and assessment of pediatric panic disorder are beyond
the scope of this section. The reader is referred to the American
Academy of Child and Adolescent Psychiatry's Practice
Parameter for the Assessment and Treatment of Children and Adolescents
With Anxiety Disorders (439) for a
more detailed discussion.
Although empirical data are
limited, expert opinion generally suggests that treatment of panic
disorder in children and adolescents consists of CBT and, when necessary,
pharmacotherapy (439). Depending upon the age and the
physiological and psychological maturity of the patient, adjustments
in the treatment plan may be needed. For example, a developmental adaptation
of CBT that is appropriate for adolescents with panic disorder has
been described in the literature (440). One randomized
controlled trial of this treatment has been completed, but the results
have not yet been published. Several published randomized controlled
trials have shown CBT to be effective for other pediatric anxiety
disorders (441–443). In addition,
one randomized controlled trial showed that CBT was effective in
a sample of pediatric patients with various anxiety disorders, including
some who were diagnosed with panic disorder (444).
Thus, the early available evidence suggests beneficial effects of
CBT in adolescents.
No randomized controlled trials have been conducted that evaluate
the efficacy of pharmacotherapy for panic disorder in pediatric
samples; therefore, medication recommendations are based on uncontrolled
studies in patients with pediatric panic disorder and some controlled
studies demonstrating efficacy for other pediatric anxiety disorders. In
pediatric patients with panic disorder, one open trial treated 12
patients with various SSRIs (some in combination with a benzodiazepine)
and found significant improvement in 75% of patients (ages
14–17 years, except for one 7-year-old patient) (445).
Another study based on chart review of 18 pediatric patients (ages
7–16 years) showed that paroxetine was well tolerated and
significantly reduced panic disorder symptoms in approximately 80% of
the patients in the study (446). The findings from
these uncontrolled studies, as well as evidence from randomized
controlled trials showing SSRIs to be effective for other pediatric
anxiety disorders (447, 448), suggest
that SSRIs are a reasonable treatment option for children and adolescents
with panic disorder. However, such treatment must be undertaken
with full consideration of potential risks and benefits of antidepressant
use in pediatric patients (see Section II.H).
A few case reports (449, 450) and
case series (451) suggest that imipramine and the high-potency
benzodiazepines alprazolam and clonazepam also may have some use
in treating pediatric panic disorder; however, these medications
would not be considered first-line treatment options.
Although anxiety symptoms and disorders are among the most
common psychiatric ailments experienced by older adults, epidemiological
studies suggest that the prevalence of panic disorder in later life
may be lower than that in midlife (452). When panic
disorder does occur, it is more likely to be preexisting rather
than new in onset (453) and is more likely to be associated
with co-occurring general medical or psychiatric disorders, especially
depression (454) or emerging dementia. Thus, for elderly
patients presenting with new panic symptoms, a vigorous search for
alternative and co-occurring diagnoses should be undertaken, with
particular attention to general medical conditions (e.g., hypercalcemia
due to malignancy) and effects of general medical pharmacological
agents. When panic disorder is present without other co-occurring
psychiatric disorders, elderly patients often have less severe symptoms
and less anxiety sensitivity than younger patients (455).
There have been few systematic
prospective clinical trials to determine the efficacy of standard
medications and/or psychosocial treatments for anxiety
disorders among the elderly. Some evidence suggests that elderly
patients with panic disorder may benefit from cognitive-behavioral
treatments, although there are no randomized controlled trials with samples
comprised exclusively of geriatric patients with panic disorder
(456). Less is known about the efficacy of other psychosocial
treatments or medication for treating panic disorder in elderly
patients. If medication is used, however, general principles of
psychopharmacology would suggest that the starting doses and therapeutic
doses of medication may be lower than those for younger patients
and that dose titration should occur more slowly than in younger adults.
Medications with longer half-lives will eventually reach higher
steady-state blood levels and toxicity may develop more slowly than
anticipated, confounding interpretation of adverse effects and potentiating
interactions with other medications. Given the high rates of co-occurring mood
disorder in elderly patients with panic disorder, an antidepressant
is recommended as first-line pharmacotherapy (457).
Selective serotonin reuptake inhibitors or SNRIs are preferred because
of their lesser side effect burden relative to other antidepressant
medications in geriatric patients. Benzodiazepine use should be
avoided whenever possible, since use of long half-life benzodiazepines
and long-term benzodiazepine use can be problematic in geriatric
patients (295, 458).
Panic disorder is more common in women for reasons that are not
yet fully understood. In epidemiological surveys, the lifetime prevalence
of panic disorder is approximately twice as high in women as in
men (33, 459). This gender difference
appears to decrease in elderly cohorts (460). Despite
numerous studies, few consistently replicable differences have been found
between men and women in panic disorder phenomenology, course of
illness, or treatment responsivity. However, women with panic disorder
are more likely to have severe agoraphobia than are men with panic
disorder. The proportion of female patients increases as the level
of agoraphobia intensifies (461–463),
even though, after controlling for level of agoraphobia, few sex
differences emerge in self-reported panic disorder symptoms (464–466).
Several studies have explored the relationship between panic
disorder and the perinatal period, an important issue in light of
the high rate of panic disorder in younger women. The limited available
data suggest that the course of panic disorder is highly variable
during pregnancy and the postpartum period (467–469).
It is also not clear whether uncontrolled symptoms of panic disorder
affect the course or outcome of pregnancy (470).
The treatment of pregnant and nursing women raises certain
specific concerns regarding the use of antipanic medications (471, 472).
With women of childbearing age, the risks of treatment during pregnancy
and nursing should be discussed actively and preferably before conception
(473). Treatment with SSRIs during pregnancy (reviewed
in references 474 and 475) may be associated
with increased rates of spontaneous abortion (476)
and with a greater risk of low birth weight and respiratory difficulties
in the neonate (477). Older reports generally failed
to find associations between antidepressants and risk of congenital
malformations; however, more recent findings suggest an increase
in the rate of cardiac malformations with paroxetine treatment,
raising increased caution about its use during pregnancy (475, 478).
In addition, SSRI exposure in the third trimester has been associated
with a rare but increased likelihood of persistent pulmonary hypertension
of the newborn (479) and, more commonly, a neonatal
behavioral syndrome suggestive of antidepressant discontinuation
that typically resolves with supportive care (480–483).
A comparable discontinuation syndrome appears to occur with SNRI
treatment and may be more pronounced in preterm neonates (483).
The effects of benzodiazepines on fetal development are unclear;
a meta-analysis of pooled case-control study data showed an increased
relative risk of major malformations and oral clefts with benzodiazepine
treatment whereas meta-analysis of cohort studies showed no such
effect (484). When used near term, however, benzodiazepines
have been associated with neonatal lethargy, sedation, and weight
loss; these findings suggest that their use should be minimized
whenever possible (485). In considering the literature
on prenatal exposure to psychotropic medications for anxiety and
mood disorders, it is also important to note that many studies have
not controlled for potentially confounding factors (e.g., rates
of smoking in women taking psychotropic medications during pregnancy).
The benefits of breast-feeding for women and their infants are
well documented (486). However, antidepressants and benzodiazepines
are secreted into breast milk in measurable quantities, and their
central nervous system effects on the nursing infant are unknown
(471, 487–489).
Despite the dearth of literature on the use of psychosocial interventions
for women with panic disorder who are pregnant, nursing, or planning
to become pregnant, these interventions should be considered in
lieu of pharmacotherapy. Pharmacotherapy may also be indicated but
requires consideration and discussion of the potential benefits
and risks with the patient, her obstetrician, and, whenever possible,
her partner. In making decisions about breast-feeding, discussions
with the infant's pediatrician are also useful. Discussions
should also consider the potential risks to the patient and the
child of untreated psychiatric illness (475), including
panic disorder and any co-occurring psychiatric conditions.
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4. Ethnicity and
cultural issues
Ethnicity and cultural factors are important to consider in
assessing and treating individuals with panic disorder. As part of
the assessment process, the DSM-IV-TR Outline on Cultural Formulation
(490) can provide a systematic approach to determining
the role of cultural factors in the clinical presentation. It also
allows the psychiatrist to view the individual patient and the therapeutic
relationship within the context of the patient's cultural
background and support systems.
Relatively little research has been done pertaining to anxiety
disorders in ethnic or cultural subgroups. In African Americans,
data on the prevalence of anxiety disorders are somewhat conflicting.
The National Institute of Mental Health Epidemiologic Catchment
Area Study indicated that African Americans have a higher lifetime
prevalence of agoraphobia but not panic disorder (491),
the National Comorbidity Survey found no racial differences in the
prevalence of any anxiety disorder (492), and the National
Comorbidity Survey Replication found lower rates for panic disorder,
generalized anxiety disorder, and social phobia (492–495).
In Hispanic whites, the National Comorbidity Survey Replication
showed lower risk of panic disorder relative to non-Hispanic whites
in young (younger than age 43 years) cohorts (495).
There is some evidence that panic disorder may present differently
in individuals of different cultural backgrounds. For example, panic
disorder in African Americans has been specifically associated with
isolated sleep paralysis (496), more intense fears
of dying or "going crazy" (497),
and hypertension (498, 499). Studies show
that African American patients seen in primary care settings report
more severe somatic symptoms and have a higher prevalence of panic
disorder than whites (500). In addition, African Americans
are more likely to seek help in medical than in mental health facilities
(501, 502). The culture-bound syndrome ataque
de nervios resembles panic disorder and may be
relevant to understanding the symptom presentation of individuals
from some Latino groups (e.g., those of Caribbean background). Although
ataque de nervios is similar to a panic attack in that the patient
experiences sudden and intense distress, loss of emotional control
(e.g., crying, uncontrollable shouting) is a more prominent feature
of ataque de nervios. Ataque de nervios also seems to be a more
inclusive concept than panic disorder: only 36% of people
with ataque de nervios met panic attack criteria, and only 17%–33% met
panic disorder criteria (503). Finally, studies have
examined the phenomenon of panic among Cambodian and Vietnamese
refugees and highlighted several cultural syndromes that appear
to be the equivalent of panic disorder. These include "sore
neck," in which Cambodian patients fear that "wind" and
blood pressure may burst the blood vessels in this area, and the
syndrome of orthostatic dizziness, which is a frequent cue and concomitant
of panic attacks in Vietnamese patients, who also report fears of
a "wind overload" (504, 505).
In terms of treatment considerations, research findings indicate
that African American (506), Latino (507),
and Vietnamese (508) patients with panic attacks and
panic disorder respond well to CBT treatments that are culturally
adapted to fit these groups. When medications are a part of the
treatment plan, the individual's cultural context may influence
his or her beliefs about medication (509). Genetic
polymorphisms (e.g., of cytochrome P450 isoenzymes) that vary in
frequency among different ethnic groups may influence the patient's
biological response to medication (e.g., metabolism, sensitivity
to side effects) (510–512); as
our understanding of genetic polymorphisms expand, these variations
may become useful in individualizing treatment selection (509, 513).