• Goals of treatment

    • Prevent harm.

    • Control disturbed behavior.

    • Reduce the severity of psychosis and associated symptoms (e.g., agitation, aggression, negative symptoms, affective symptoms).

    • Determine and address the factors that led to the occurrence of the acute episode.

    • Effect a rapid return to the best level of functioning.

    • Develop an alliance with the patient and family.

    • Formulate short- and long-term treatment plans.

    • Connect the patient with appropriate aftercare in the community.


1. Assessment in the Acute Phase

  • Goals of acute phase assessment

    • Evaluate the reason for the recurrence or exacerbation of symptoms (e.g., medication nonadherence).

    • Determine or verify the patient's diagnosis.

    • Identify any comorbid psychiatric or medical conditions, including substance use disorders.

    • Evaluate general medical health.

    • Identify the patient's strengths and limitations.

    • Engage the patient in a therapeutic alliance.

  • Undertake a thorough initial workup, including complete psychiatric and general medical histories and physical and mental status examinations.

  • Routinely interview family members or other individuals knowledgeable about the patient, unless the patient refuses to grant permission.

  • In emergency circumstances (e.g., safety risk), it may be necessary and permissible to speak with others without the patient's consent.

  • Conduct laboratory tests, including a complete blood count (CBC); measurements of blood electrolytes and glucose; tests of liver, renal, and thyroid function; a syphilis test; and, when indicated, a urine or serum toxicology screen, hepatitis C test, and determination of HIV status.

  • Consider use of a computed tomography (CT) or magnetic resonance imaging (MRI) scan (MRI is preferred) for patients with a new onset of psychosis or with an atypical clinical presentation, because findings (e.g., ventricular enlargement, diminished cortical volume) may enhance confidence in the diagnosis and provide information relevant to treatment planning and prognosis.

  • Assess risk factors for suicide (such as prior attempts, depressed mood, suicidal ideation, presence of command hallucinations, hopelessness, anxiety, extrapyramidal side effects, and alcohol or other substance use).

  • Assess likelihood of dangerous or aggressive behavior, including potential for harm to others.


2. Psychiatric Management in the Acute Phase

  • Reduce overstimulating or stressful relationships, environments, and life events.

  • Provide the patient with information (appropriate to his or her ability to assimilate) on the nature and management of the illness.

  • Initiate a relationship with family members. Refer family members to local chapters of the National Alliance for the Mentally Ill (NAMI) and to the NAMI web site (http://www.nami.org).


3. Use of Antipsychotic Medications in the Acute Phase

  • Initiate antipsychotic medication as soon as it is feasible. It may be appropriate to delay pharmacologic treatment for patients who require more extensive diagnostic evaluation or who refuse medications or if psychosis is caused by substance use or acute stress reactions.

  • Discuss risks and benefits of the medication with the patient before initiating treatment, if feasible, and identify target symptoms (e.g., anxiety, poor sleep, hallucinations, and delusions) and acute side effects (e.g., orthostatic hypotension, dizziness, dystonic reactions, insomnia, and sedation).

  • Assess baseline levels of signs, symptoms, and laboratory values relevant to monitoring effects of antipsychotic therapy.

    • Measure vital signs (pulse, blood pressure, temperature).

    • Measure weight, height, and body mass index (BMI), which can be calculated with the formula weight in kilograms/(height in meters)2 or the formula 703 x weight in pounds/(height in inches)2 or with a BMI table: http://win.niddk.nih.gov/statistics/index.htm#table

    • Assess for extrapyramidal signs and abnormal involuntary movements.

    • Screen for diabetes risk factors and measure fasting blood glucose.

    • Screen for symptoms of hyperprolactinemia.

    • Obtain lipid panel.

    • Obtain ECG and serum potassium measurement before treatment with thioridazine, mesoridazine, or pimozide; obtain ECG before treatment with ziprasidone in the presence of cardiac risk factors.

    • Conduct ocular examination, including slit-lamp examination, when beginning antipsychotics associated with increased risk of cataracts.

    • Screen for changes in vision.

    • Consider a pregnancy test for women with childbearing potential.

  • Minimize acute side effects (e.g., dystonia) that can influence willingness to accept and continue pharmacologic treatment.

  • Initiate rapid emergency treatments when an acutely psychotic patient is exhibiting aggressive behaviors toward self or others.

    • Try talking to the patient in an attempt to calm him or her.

    • Restraining the patient should be done only by a team trained in safe restraint procedures.

    • Use short-acting parenteral formulations of first- or second-generation antipsychotic agents with or without parenteral benzodiazepine.

    • Alternatively, use rapidly dissolving oral formulations of second-generation agents (e.g., olanzapine, risperidone) or oral concentrate formulations (e.g., risperidone, haloperidol).

  • See Tables 1 and 2 and Figure 1 for guidance in determining somatic treatment.

  • Select medication depending on the following factors:

    • Prior degree of symptom response

    • Past experience of side effects

    • Side effect profile of prospective medications (see Table 3)

    • Patient's preferences for a particular medication, including route of administration

    • Available formulations of medications (e.g., tablet, rapidly dissolving tablet, oral concentrate, short- and long-acting injection)

  • Consider second-generation antipsychotics as first-line medications because of the decreased risk for extrapyramidal side effects and tardive dyskinesia.

    • For patients who have had prior treatment success or who prefer first-generation agents, these medications are useful and for specific patients may be the first choice.

    • With the possible exception of clozapine for patients with treatment-resistant symptoms, antipsychotics generally have similar efficacy in treating positive symptoms.

    • Second-generation antipsychotics may have superior efficacy in treating global psychopathology and cognitive, negative, and mood symptoms.

  • Consider long-acting injectable antipsychotic medication for patients with recurrent relapses related to partial or full nonadherence. The oral form of the same medication (e.g., fluphenazine, haloperidol, and risperidone) is the logical choice for initial treatment.

  • Titrate as quickly as tolerated to the target therapeutic dose (sedation, orthostatic hypotension, and tachycardia are generally the side effects that limit the rate of increase), and monitor clinical status for at least 2 to 4 weeks.

    • The optimal dose of first-generation antipsychotics is, for most patients, at the "extrapyramidal symptom (EPS) threshold," or the dose at which minimal rigidity is detectable on physical examination.

    • For second-generation antipsychotics, target dose usually falls within the therapeutic dose range specified by the manufacturer and in the package labeling approved by the U.S. Food and Drug Administration.

  • If the patient is not improving, consider whether the lack of response can be explained by medication nonadherence, rapid medication metabolism, or poor medication absorption.

  • Consider measuring plasma concentration for those medications for which plasma concentration relates to clinical response (e.g., haloperidol, clozapine).

  • If the patient is adhering to treatment and has an adequate plasma concentration but is not responding to treatment, consider raising the dose for a finite period (if tolerated) or switching medications.

Table Reference Number
TABLE 1. Commonly Used Antipsychotic Medications
Table Reference Number
TABLE 2. Choice of Medication in the Acute Phase of Schizophrenia
FIGURE 1. Somatic Treatment of Schizophrenia
Table Reference Number
TABLE 3. Selected Side Effects of Commonly Used Antipsychotic Medications

4. Use of Adjunctive Medications in the Acute Phase

  • Use adjunctive medications to treat comorbid conditions (e.g., major depression, obsessive-compulsive disorder) or associated symptoms (e.g., agitation, aggression, affective symptoms), to address sleep disturbances, and to treat antipsychotic drug side effects.

  • Be aware that some antidepressants (those that inhibit catecholamine reuptake) can potentially sustain or exacerbate psychotic symptoms in some individuals.

  • Benzodiazepines may be helpful for managing both anxiety and agitation during the acute phase of treatment.

  • Mood stabilizers and beta-blockers may be effective in reducing the severity of recurrent hostility and aggression.

  • Consider the following factors when deciding on the prophylactic use of medications to treat extrapyramidal side effects:

    • Propensity of the antipsychotic medication to cause extrapyramidal symptoms Table 3)

    • Patient's preferences

    • Patient's prior history of extrapyramidal symptoms

    • Other risk factors for extrapyramidal symptoms (especially risk factors for dystonia)

    • Risk factors for and potential consequences of anticholinergic side effects

  • Other potential strategies for treating extrapyramidal symptoms include lowering the dose of the antipsychotic medication or switching to a different antipsychotic medication.


5. Use of ECT and Other Somatic Therapies in the Acute Phase

  • Consider adding ECT to antipsychotic treatment for individuals with schizophrenia or schizoaffective disorder who have persistent severe psychosis and/or suicidal ideation or behaviors and for whom prior treatments, including clozapine, have failed.

  • Also consider ECT for individuals with prominent catatonic features that have not responded to an acute trial of lorazepam (e.g., 1 to 2 mg i.v. or i.m. or 2 to 4 mg p.o., repeated as needed over 48 to 72 hours).

  • For patients with schizophrenia and comorbid depression, ECT may also be beneficial if depressive symptoms are resistant to treatment or if features such as inanition or suicidal ideation or behavior, which necessitate a rapid response to treatment, are present.


6. Special Issues in Treatment of First-Episode Patients

  • Closely observe and document signs and symptoms over time, because a first episode of psychosis can be polymorphic and evolve into a variety of specific disorders (e.g., schizophreniform disorder, bipolar disorder, schizoaffective disorder).

  • More than 70% of first-episode patients achieve a full remission of psychotic signs and symptoms within 3 to 4 months, and more than 80% achieve stable remission at the end of 1 year. Predictors of poor treatment response include

    • male gender,

    • pre- or perinatal injury,

    • more severe hallucinations and delusions,

    • attentional impairments,

    • poor premorbid function,

    • longer duration of untreated psychosis,

    • development of extrapyramidal side effects, and

    • distressing emotional climate (e.g., hostile and critical attitudes and overprotection by others in one's living situation or high levels of expressed emotion).

  • Strive to minimize risk of relapse in a remitted patient, because of its clinical, social, and vocational costs (i.e., recurrent episodes are associated with increasing risk of chronic residual symptoms and evidence of neuroanatomical changes).

  • Aim to eliminate exposure to cannabinoids and psychostimulants, enhance stress management, and employ maintenance antipsychotic treatment.

  • Discuss candidly the high risk of relapse and factors that may minimize relapse risk. Prudent treatment options include 1) indefinite antipsychotic maintenance medication and 2) medication discontinuation with close follow-up and a plan of antipsychotic reinstitution with symptom recurrence.

Table Reference Number
TABLE 1. Commonly Used Antipsychotic Medications
Table Reference Number
TABLE 2. Choice of Medication in the Acute Phase of Schizophrenia
Table Reference Number
TABLE 3. Selected Side Effects of Commonly Used Antipsychotic Medications


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