Schizophrenia is characterized by psychosis (loss of contact with reality), hallucinations (false perceptions), delusions (false beliefs), disorganized speech and behavior, flattened affect (restricted range of emotions), cognitive deficits (impaired reasoning and problem solving), and occupational and social dysfunction. The cause is unknown, but evidence for a genetic component is strong. Symptoms usually begin in adolescence or early adulthood. One or more episodes of symptoms must last ≥ 6 mo before the diagnosis is made. Treatment consists of drug therapy, psychotherapy, and rehabilitation.

Worldwide, the prevalence of schizophrenia is about 1%. The rate is comparable among men and women and relatively constant cross-culturally. The rate is higher among lower socioeconomic classes in urban areas, perhaps because its disabling effects lead to unemployment and poverty. Similarly, a higher prevalence among single people may reflect the effect of illness or illness precursors on social functioning. The average age at onset is 18 yr in men and 25 yr in women. Onset is rare in childhood, but early-adolescent onset or late-life onset (when it is sometimes called paraphrenia) may occur.


Although its specific cause is unknown, schizophrenia has a biologic basis, as evidenced by alterations in brain structure (eg, enlarged cerebral ventricles, decreased size of the anterior hippocampus and other brain regions) and by changes in neurotransmitters, especially altered activity of dopamine

and glutamate. Some experts suggest that schizophrenia occurs in
people with neurodevelopmental vulnerabilities and that the onset, remission, and recurrence of symptoms are the result of interactions between these enduring vulnerabilities and environmental stressors.

Neurodevelopmental vulnerability: Vulnerability may result from genetic predisposition; intrauterine, birth, or postnatal complications; or viral CNS infections. Maternal exposure to famine and influenza during the 2nd trimester of pregnancy, birth weight 6 mg, dose-dependent prolactin elevation, or metabolic syndrome

Only SGA with a long-acting injectable form

3–12 mg po at bedtime
6 mg po at bedtime
Metabolite of risperidone

Similar to risperidone



10–20 mg po at bedtime
15 mg po at bedtime
Most common adverse effects: Somnolence, metabolic syndrome, and dizziness



150–375 mg po bid
200 mg po bid
Low potency allowing wide dosing

May cause metabolic syndrome

No anticholinergic effect

Dose titration required because of blocking of α2 receptors

Requires bid dosing



40–80 mg po bid
80 mg po bid
Inhibition of serotonin and norepinephrine

possibly with antidepressant effects

Shortest half-life of new drugs

Requires bid dosing with food

IM form available for acute treatment

Low risk of metabolic syndrome



10–30 mg po at bedtime
15 mg po at bedtime

-2 partial agonist

Low risk of metabolic syndrome

SGA = Second-generation antipsychotic.

*Monitoring for metabolic syndrome and type 2 diabetes is recommended for this class of antipsychotics.

†All SGAs have been associated with increased mortality in elderly patients with dementia.

SGA = second-generation antipsychotic.

Newer SGAs are very similar to each other in efficacy but differ in adverse effects, so drug choice is based on individual response and on other drug characteristics. For example, olanzapine

, which has a relatively high rate of sedation, may be prescribed for patients with
prominent agitation or insomnia; less sedating drugs might be preferred for patients with lethargy. A 4- to 8-wk trial is usually required to assess efficacy. After acute symptoms have stabilized, maintenance treatment is initiated; for it, the lowest dose that prevents symptom recurrence is used. Risperidone

is the only SGA available in a long-acting injectable

Weight gain, hyperlipidemia, and elevated risk of type 2 diabetes are the major adverse effects of SGAs. Thus, before treatment with SGAs is begun, all patients should be screened for risk factors, including personal or family history of diabetes, weight, waist circumference, BP, and fasting plasma glucose and lipid profile. Those found to have or be at significant risk of metabolic syndrome may be better treated with ziprasidone

or aripiprazole

than the other
SGAs. Patient and family education regarding symptoms and signs of diabetes, including polyuria, polydipsia, weight loss, and diabetic ketoacidosis (nausea, vomiting, dehydration, rapid respiration, clouding of sensorium), should be provided. In addition, nutritional and physical activity counseling should be provided to all patients when they start taking an SGA. All patients taking an SGA require periodic monitoring of weight, body mass index, and fasting plasma glucose and referral for specialty evaluation if they develop hyperlipidemia or type 2 diabetes.

Rehabilitation and community support services: Psychosocial skill training and vocational rehabilitation programs help many patients work, shop, and care for themselves; manage a household; get along with others; and work with mental health care practitioners. Supported employment, in which patients are placed in a competitive work setting and provided with an on-site job coach to promote adaptation to work, may be particularly valuable. In time, the job coach acts only as a backup for problem solving or for communication with employers.

Support services enable many patients with schizophrenia to reside in the community. Although most can live independently, some require supervised apartments where a staff member is present to ensure drug adherence. Programs provide a graded level of supervision in different residential settings, ranging from 24-h support to periodic home visits. These programs help promote patient autonomy while providing sufficient care to minimize the likelihood of relapse and need for inpatient hospitalization. Assertive community treatment programs provide services in the patient’s home or other residence and are based on high staff-to-patient ratios; treatment teams directly provide all or nearly all required treatment services.

Hospitalization or crisis care in a hospital alternative may be required during severe relapses, and involuntary hospitalization may be necessary if patients pose a danger to themselves or others. Despite the best rehabilitation and community support services, a small percentage of patients, particularly those with severe cognitive deficits and those poorly responsive to drug therapy, require long-term institutional or other supportive care.

Psychotherapy: The goal of psychotherapy is to develop a collaborative relationship between the patients, family members, and physician so that patients can learn to understand and manage their illness, take drugs as prescribed, and handle stress more effectively. Although individual psychotherapy plus drug therapy is a common approach, few empirical guidelines are available. Psychotherapy that begins by addressing the patient’s basic social service needs, provides support and education regarding the nature of the illness, promotes adaptive activities, and is based on empathy and a sound dynamic understanding of schizophrenia is likely to be most effective. Many patients need empathic psychologic support to adapt to what is often a lifelong illness that can substantially limit functioning.

For patients who live with their families, psychoeducational family interventions can reduce the rate of relapse. Support and advocacy groups, such as the National Alliance for the Mentally Ill, are often helpful to families.

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