Evidence-Based Reviews

First psychotic episode—a window of opportunity: Seize the moment to build a therapeutic alliance

Current Psychiatry. 2003 April;2(4):50-67

References

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A moving target. As treatment moves from acute to consolidation and maintenance, target symptoms may change, side effects can limit the preferred approach, and partial or nonresponse may require drug or dosing adjustments. It is prudent to be prepared to re-evaluate the initial diagnosis as new symptoms emerge, response patterns develop, additional test or historical data become available, or as the illness’ course becomes more clear. To improve outcome, address comorbid or concurrent diseases—such as substance abuse or dependence, mood disorders, anxiety and obsessive-compulsive symptoms, or eating disorders.

Diagnostic work-up

As in Mr. C’s case (Box), a first psychotic episode is characterized by DSM-IV diagnostic criteria for schizophrenia, including hallucinations, delusions, disorganized thoughts or speech, disorganized behavior(s), or negative symptoms (such as anhedonia, amotivation, asociality, alogia, or affective flattening). The work-up is more comprehensive than that for subsequent episodes and includes a thorough history, complete physical examination, and brain imaging (Table 1) to explore other possible medical and psychiatric diagnoses (Table 2).

Table 1

WORK-UP OF PATIENTS PRESENTING WITHA FIRST EPISODE OF PSYCHOSIS

Priority	Mode of evaluation
Routine	History Symptoms, time course, medical conditions, current/previous medications, herbs, drugs Medical and neurologic exam Blood work: CBC with differential, complete metabolic panel, thyroid and liver function tests, syphilis serology, pregnancy test, toxicology Urinalysis, toxicology ECG
Recommended	Fasting glucose and lipid profile (ideally before starting atypical antipsychotic) Head CT (especially if history of recent trauma) or brain MRI
Optional	Erythrocyte sedimentation rate, antinuclear antibodies, lumbar puncture, sleep-deprived EEG

The history—ideally gathered from the patient and others—includes:

medical and psychiatric diagnoses
medications (prescribed and over-the-counter remedies)
presence of stressors/triggers
chronology of symptoms
potential for the episode to endanger the patient or others.

Imaging. Despite a relatively low yield, we recommend that every patient with a first psychotic episode undergo a brain CT or MRI to rule out a potentially treatable organic cause for the psychosis.¹⁴

Other tests. Because of the increased risk of hyperglycemia, dyslipidemia, and possible cardiac conduction abnormalities with atypical antipsychotics, obtain a baseline fasting blood glucose, lipid profile, and ECG. A sleep-deprived EEG is recommended for patients with unclear motor movements or family history of epilepsy.

Choosing medications

Medication choices for the patient with first-episode schizophrenia are influenced by:

target symptoms
whether the symptoms endanger the patient or others
the patient’s personal or family history of medication response or side effects
a generally increased sensitivity to side effects in patients who have never been exposed to antipsychotics
concurrent medical and/or psychiatric disorders
prescriber, patient, and family preferences.

Psychiatrists generally select psychotropic classes by symptom domains (Table 3) and individual agents in each class by side effect profile. Except for clozapine’s superior effectiveness in patients with refractory psychosis, controlled studies have shown no clinically significant differences in efficacy among the drugs in each class—including the antipsychotics. Individual patients, however, may respond differently to different agents.

Principles of prescribing antipsychotics

Antipsychotics are effective in treating most psychotic core symptoms, such as hallucinations, delusions, agitation, aggression, and disorganized thinking and behavior. Other medications can be added to speed up or enhance treatment response or to target other domains.

Dosages. First-episode patients often require lower dosages and slower titration than multi-episode patients. As a rule, antipsychotics are started at about one-half the dosage given to patients with a chronic treatment history, although symptom severity and absence of side effects at lower dosages can help individualize titration.

Side effects. Atypical antipsychotics are preferred because of their reduced risk of extrapyramidal symptoms (EPS), positive effects on depressive and cognitive symptoms, and improved patient satisfaction and adherence, compared with the older antipsychotics.^15-17 Atypicals’ potential side effects include weight gain, hyperglycemia, and dyslipidemia,¹⁸ as well as often-overlooked sexual side effects.¹⁹

Table 2

DIFFERENTIAL DIAGNOSIS OF FIRST-EPISODE PSYCHOSIS

Possible diagnosis	Key points for differentiation
Schizophrenia	6 months of psychosis* (including prodromal symptoms); total duration of mood episodes brief relative to active and residual psychotic phases; not directly caused by medical condition or substance
Schizophreniform disorder	Same as above, except symptoms are present 1 to 6 months
Brief psychotic disorder	Same as above, except symptoms are present 1 day to 1 month
Delusional disorder	Apart from non-bizarre delusions, functioning not markedly impaired; total duration of mood episodes brief relative to active and residual psychotic phases; not caused by direct physiologic effects of medical condition or substance
Psychotic disorder NOS	Psychotic symptoms insufficient to make a specific diagnosis
Schizoaffective disorder	Like schizophrenia for at least 2 weeks, but with mania or major depression present for much of the active and residual psychotic periods
Mood disorder with psychosis	Psychotic symptoms occur exclusively during mood disorder episodes
Psychosis due to general medical condition	Psychotic symptoms caused by direct physiologic effects of a general medical condition
Delirium due to general medical condition	Psychotic symptoms associated with a disturbance in consciousness and other cognitive deficits; characterized by a fluctuating course
Dementia due to general medical condition	Psychotic symptoms associated with memory impairment and other cognitive deficits
Substance-induced psychotic disorder	Psychotic symptoms caused by direct physiologic effects of a substance; reaction exceeds that usually encountered with intoxication or withdrawal
Substance-induced psychotic delirium	Similar to above, but associated with a disturbance in consciousness and other cognitive deficits; characterized by a fluctuating course
Substance intoxication or withdrawal	Caused by direct physiologic effects of a substance; reaction is typically encountered with intoxication or withdrawal
Conversion disorder	Contradictory and inconsistent history and presentation; secondary gain
Malingering	Contradictory and inconsistent history and presentation; primary gain
* Psychotic symptoms must interfere with functioning, and at least two of the following are required: delusions, hallucinations, disorganized thoughts or speech, disorganized behavior, or negative symptoms (avolition, alogia, affective flattening, asociality, or anhedonia), unless delusions are bizarre (impossible), or hallucinations consist of a running commentary or of two or more voices conversing with each other.
Source: Adapted from DSM-IV handbook of differential diagnosis. Washington, DC: American Psychiatric Press, 1995.