• Throughout the formulation of a treatment plan and all subsequent phases of treatment, the following principles of psychiatric management should be kept in mind:

1. Perform a diagnostic evaluation.

• For general principles and components of a psychiatric evaluation, refer to APA's Practice Guideline for the Psychiatric Evaluation of Adults.
• Determine whether the diagnosis is depression.
• Determine whether there is psychiatric and general medical comorbidity.
• Include the following in the evaluation:
  • History of the present illness and current symptoms
  • Psychiatric history, including symptoms of mania
  • Treatment history with current treatments and responses to previous treatments
  • General medical history
  • History of substance use disorders
  • Personal history (e.g., psychological development, response to life transitions, major life events)
  • Social, occupational, and family histories
  • Review of the patient's medications
  • Review of systems
  • Mental status examination
  • Physical examination
  • Diagnostic tests as indicated

2. Evaluate the safety of the patient and others.

• Assessment of suicide risk is essential (see Table 1).
• If the patient demonstrates suicidal or homicidal ideation, intention, or plans, close monitoring is required.
• Hospitalization should be considered if risk is significant.
• Note, however, that the ability to predict attempted or completed suicide is poor.

3. Evaluate and address functional impairments.

• Impairments include deficits in interpersonal relationships, work and living conditions, and other medical- or health-related needs.
• Address identified impairments (e.g., scheduling absences from work).

4. Determine the treatment setting.

• Choose appropriate site, considering the following:
  • Clinical condition (including symptom severity, comorbidity, suicidality, homicidality, and level of functioning)
  • Available support systems
  • Ability of the patient to adequately care for self, provide reliable feedback to the psychiatrist, and cooperate with treatment
• Reevaluate optimal setting on an ongoing basis.
• Consider hospitalization if the patient
  • poses serious threat of harm to self or others (involuntary hospitalization may be necessary if patient refuses),
  • is severely ill and lacks adequate social supports (alternatively, intensive day treatment may be appropriate),
  • has certain comorbid psychiatric or general medical conditions, or
  • has not responded adequately to outpatient treatment.

5. Establish and maintain a therapeutic alliance.

• It is important to pay attention to the concerns of the patient and his or her family.
• Be aware of transference and countertransference issues.

6. Monitor psychiatric status and safety.

• Monitor the patient for changes in destructive impulses to self and others.
• Be vigilant in monitoring changes in psychiatric status, including major depressive symptoms and symptoms of potential comorbid conditions.
• Consider diagnostic reevaluation if symptoms change significantly or if new symptoms emerge.

7. Provide education to the patient and, when appropriate, to his or her family.

• Emphasize that major depressive disorder is a real illness.
• Education about treatments helps patients make informed decisions, be aware of side effects, and adhere to treatment.

8. Enhance medication adherence.

• To improve adherence, emphasize
  • when and how often to take medication,
  • the typical 2- to 4-week lag for beneficial effects to be noticed,
  • need to continue medication even after feeling better,
  • need to consult with the prescribing doctor before medication discontinuation, and
  • what to do if problems arise.
• Improve adherence in elderly patients by simplifying the medication regimen and minimizing cost.
• Consider psychotherapeutic intervention for serious or persistent nonadherence.

9. Address early signs of relapse.

• Inform the patient (and, when appropriate, the family) about the significant risk of relapse.
• Educate the patient (and the family) about how to identify early signs and symptoms of new episodes.
• Emphasize seeking help if signs of relapse appear, to prevent full-blown exacerbation.

1. Choice of Initial Treatment Modality

• See Figure 1.

a. Pharmacotherapy

• Features suggesting that medication may be the preferred treatment include the following:
  • History of prior positive response
  • Severe symptomatology
  • Significant sleep or appetite disturbances or agitation
  • Anticipation of need for maintenance therapy
  • Patient preference
  • Lack of available alternative treatment modalities

b. Psychotherapy Alone

• If the severity of the major depressive episode is mild to moderate, use psychotherapy if preferred by the patient.
• Features suggesting the use of psychotherapeutic interventions include the following:
  • Presence of significant psychosocial stressors
  • Intrapsychic conflict
  • Interpersonal difficulties
  • Comorbid personality disorder
  • Pregnancy, lactation, or wish to become pregnant
  • Patient preference

c. Combined Pharmacotherapy and Psychotherapy

• Consider the use of combined pharmocotherapy and psychotherapy if the severity of the major depressive episode is mild to severe with clinically significant psychosocial issues, interpersonal problems, or a comorbid personality disorder.
• Other features suggesting combination treatment include the following:
  • History of only partial response to single treatment modalities
  • Poor adherence to treatments (combine medication with a psychotherapeutic approach that focuses on treatment adherence)

d. Electroconvulsive Therapy

• Consider ECT if any of the following features are present:
  • Major depressive episode with a high degree of symptom severity and functional impairment
  • Psychotic symptoms or catatonia
  • Urgent need for response (e.g., suicidality or nutritional compromise in a patient refusing food)
• ECT may be the preferred treatment when
  • the presence of comorbid medical conditions precludes the use of antidepressant medications,
  • there is a prior history of positive response to ECT, or
  • the patient expresses a preference for ECT.

2. Choice of Antidepressant

a. Principles of Choosing an Initial Antidepressant

• See Table 2 for a list of antidepressants and dosage ranges.

• Because there is comparable efficacy between and within classes of medications, the initial selection is based largely on the following considerations:
  • Anticipated side effects
  • Safety or tolerability of side effects for individual patients
  • Patient preference
  • Quantity and quality of clinical trial data
  • Cost
  Based on these factors, the following medications are likely to be effective for most patients: selective serotonin reuptake inhibitors (SSRIs), desipramine, nortriptyline, bupropion, venlafaxine, and mirtazapine.
• Consider other features, including the following:
  • History of prior response with a particular antidepressant
  • Presence of comorbid psychiatric or general medical conditions (e.g., tertiary amine tricyclic antidepressants [TCAs] may not be optimal in patients with cardiovascular conditions or acute-angle glaucoma)
• Use monoamine oxidase inhibitors (MAOIs) only for patients who do not respond to other treatments, because of MAOIs' dietary restrictions and potentially serious side effects.
  • MAOIs may be particularly effective for major depressive episodes with atypical features (although in clinical practice, SSRIs are now commonly used for atypical depression because of their more favorable adverse effect profile).

b. Implementation of Antidepressant Therapy

• Start at the dosage levels suggested in Table 2.
• Titrate to full therapeutic dosage, taking the following considerations into account:
  • Side effects
  • Patient's age
  • Comorbid illnesses (e.g., starting and therapeutic doses should be reduced [generally to half] in elderly or medically frail patients)
• Determine the monitoring frequency. Frequency depends on
  • severity of illness,
  • suicide risk,
  • significant side effects or drug interactions,
  • patient's cooperation with treatment,
  • availability of social supports, and
  • presence of comorbid general medical problems.
• Determine the method of monitoring (face-to-face, phone, or e-mail contact, contact with a physician knowledgeable about the patient) according to clinical context.
• Monitor to assess the following:
  • Treatment response
  • Side effects (see Figure 2, below)
  • Clinical condition
  • Safety
• Monitor adults closely for worsening of depression and for increased suicidal thinking or behavior as some evidence suggest that antidepressant treatment may increase suicidality in children and adolescents (see Web sites of the FDA [http://www.fda.gov], the American Academy of Child and Adolescent Psychiatry [http://www.aacap.org], and APA [http://www.psych.org]).
• Specific monitoring may be indicated with particular drugs (e.g., life-threatening hepatic failure has been reported with nefazodone use, duloxetine is not suggested for use in individuals with chronic hepatitis or substantial alcohol use).
• Serotonin syndrome can occur when SSRIs, SNRIs, or MAOIs are used alone, but it is typically seen and is of greater severity when several serotonergenic drugs are given concurrently or when an MAOI is given with a serotonergic agent.

c. Initial Failure to Respond

• If the patient is not at least moderately improved after 4 to 8 weeks, reappraise the treatment regimen (see Figure 3).
• Investigate the patient's adherence to treatment.
• Consider pharmacokinetic/pharmacodynamic factors (may require serum antidepressant medication levels).
• Revise the treatment plan and consider the following options:
  • Maximize the initial therapeutic treatment dose.
    • - For partial responders, extend the trial (e.g., by 2 to 4 weeks).
    • - For nonresponders on moderate doses or those with low serum levels, raise the dose and monitor for increased side effects.
  • Add, change, or increase the frequency of psychotherapy.
  • Switch to another non-MAOI medication (see Table 2 and Table 3) in either the same class or a different class, particularly if there is lack of partial response.
  • Especially if there is partial response, augment with
    • - a non-MAOI antidepressant from a different class (be alert to drug-drug interactions), or
    • - another adjuvant medication (e.g., lithium, thyroid hormone, anticonvulsants, psychostimulants).
  • Switch to an MAOI.
  • Institute ECT.

d. Continued Failure to Respond

• Verify the patient's diagnosis and adherence to treatment.
• If the patient does not show at least moderate improvement after an additional 4 to 8 weeks, explore the presence of other factors that might interfere with improvement:
  • Comorbid general medical conditions
  • Comorbid psychiatric disorders (including substance abuse)
  • Significant psychosocial problems
• If the steps above do not clarify the reason for the nonresponse, consider consultation or possibly ECT.

3. Choice of Psychotherapy

a. Principles of Choosing a Psychotherapy

• Choose the modality of therapy:
  • Cognitive behavior therapy and interpersonal therapy have the best research-documented efficacy.
  • Psychodynamic psychotherapy, supported by broad clinical consensus, is usually oriented toward both symptomatic improvement and broader personality issues.
• Consider other factors:
  • Patient preference
  • Availability of clinicians with appropriate training and expertise in the specific approach

b. Psychotherapy Implementation

• Determine the frequency of psychotherapy.Frequency generally ranges from once to several times per week in the acute phase and depends on
  • specific type and goals of psychotherapy,
  • need to create and maintain a therapeutic relationship,
  • need to ensure treatment adherence, and
  • need to monitor and address suicidality.
• In situations with more than one treating clinician, maintain ongoing contact with the patient and other clinicians.
• If the patient does not show at least moderate improvement after 4 to 8 weeks, conduct a thorough review and reappraisal (see Figure 3).

4. Choice of Medication Plus Psychotherapy

• Consider the same issues that influence the choice of medication (see section B.2) and psychotherapy (see section B.3).
• If the patient does not show at least moderate improvement after 4 to 8 weeks, conduct a thorough review, including of adherence and pharmacokinetic/pharmacodynamic factors.
• If the patient does not show at least moderate improvement after an additional 4 to 8 weeks following a change, conduct another thorough review and consider consultation or possibly ECT.

5. Assessing Adequacy of Treatment Response

• Do not conclude acute phase treatment if the patient shows only partial response. Partial response is associated with poor functional outcome.

• The continuation phase is defined as the 16- to 20-week period after sustained and complete remission from the acute phase.
• To prevent relapse, continue antidepressant medication at the same dose used during the acute phase.
• Consider the use of psychotherapy to help prevent relapse.
• Consider providing ECT if medication or psychotherapy has not been effective.
• Set frequency of visits depending on clinical condition and specific treatments used. Frequency can vary from once every 2 to 3 months to multiple times per week.

• The goal during the maintenance phase is to prevent recurrences of major depressive episodes (see Table 4 for factors to consider).

• Continue using the treatment that was effective in the acute and continuation phases.
• Employ the same full antidepressant medication dosages used in prior phases of treatment.
• Set the frequency of visits according to clinical condition and specific treatments used.Frequency can range from as low as once every 2 to 3 months for stable patients to as high as multiple times per week for those in psychodynamic psychotherapy.
• Consider ECT maintenance for patients who have repeated moderate or severe episodes despite adequate pharmacological treatment (or who are unable to tolerate maintenance medication).

• Consider whether to discontinue treatment based on the same factors considered in the decision to initiate maintenance treatment.For example, consider the probability of recurrence and the frequency and severity of past episodes (see Table 4 and Table 5).
• When discontinuing psychotherapy, the best method depends on the patient's needs and type of psychotherapy, the duration of treatment, and the intensity of treatment.
• To discontinue pharmacotherapy, taper the dose over at least several weeks.
  • Facilitates more rapid return to a full dose if symptoms recur.
  • Minimizes the risk of antidepressant discontinuation syndromes (more likely with shorter–half-life antidepressants).
• Establish a plan to restart treatment in case of relapse.
• If the patient experiences a relapse when medication is discontinued, resume the previously successful treatment.