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Am Fam Physician. 2021;104(4):355-356

Author disclosure: No relevant financial affiliations.

Clinical Question

Does maintenance therapy with antipsychotic drugs prevent symptom relapse in patients with schizophrenia?

Evidence-Based Answer

Compared with placebo, using antipsychotic drugs for maintenance therapy in patients with schizophrenia is associated with relapse prevention at seven to 12 months (number needed to treat [NNT] = 3; 95% CI, 2 to 3). (Strength of Recommendation [SOR]: A, based on consistent, good-quality patient-oriented evidence.) Hospitalizations are less likely among individuals receiving maintenance therapy with antipsychotics (NNT = 8; 95% CI, 6 to 14). (SOR: A, based on consistent, good-quality patient-oriented evidence.) People taking antipsychotic drugs are more likely to experience adverse effects, including movement disorders (number needed to harm [NNH] = 20; 95% CI, 14 to 50) and weight gain (NNH = 25; 95% CI, 20 to 50).1 (SOR: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

Schizophrenia is the most common psychotic disease, with an estimated prevalence of 0.25% to 0.64% in the U.S. population.2 Given the limited access to psychiatrists in many parts of the country, family physicians are often called on to screen, diagnose, and treat a variety of psychiatric conditions, including schizophrenia.3,4 In particular, family physicians may be in a position to counsel patients and families on the benefits and risks of continuing antipsychotic medications for the treatment of schizophrenia. This Cochrane review aimed to answer questions about whether maintaining antipsychotic therapy prevented relapse of schizophrenia symptoms, reduced hospitalizations, improved quality of life and social functioning, or was associated with adverse effects.

The Cochrane review included 75 randomized controlled trials involving 9,145 patients with schizophrenia or schizophrenia-like illness and compared those taking antipsychotic medications with those taking placebo.1 The included trials were published between 1959 and 2017.

The primary outcome was whether antipsychotic drugs were effective at preventing relapse of psychotic symptoms among individuals with schizophrenia or schizophrenia-like illness. The meta-analysis found that these medications were effective at preventing symptom relapse at seven to 12 months (NNT = 3; 95% CI, 2 to 3). Individuals receiving antipsychotic drugs were also less likely to be hospitalized compared with those taking placebo (NNT = 8; 95% CI, 6 to 14).

Quality of life and social functioning may be better for patients receiving antipsychotics, based on low- and moderate-certainty evidence, respectively. No statistically significant differences were identified between groups for likelihood of employment or death from suicide.

Individuals receiving antipsychotic drugs were more likely to experience movement disorders (NNH = 20; 95% CI, 14 to 50) and weight gain (NNH = 25; 95% CI, 20 to 50). In both cases, the rate of adverse effects associated with the antipsychotic medication increased over time, with no statistically significant differences identified during the first three months of treatment. There was a trend toward increased sedation among those treated with antipsychotics vs. placebo, but the difference was not statistically significant.

A practice guideline from the American Psychiatric Association recommends that patients with schizophrenia whose symptoms have improved with antipsychotic use continue treatment. It also states that when antipsychotic drugs are administered on a long-term basis, adverse effects such as movement disorders and weight gain are common. For this reason, the American Psychiatric Association recommends preventive interventions such as early intervention for weight gain and regular screening for lipid and glucose abnormalities. Similarly, patients should be monitoring for movement disorders, with a continual discussion around benefits and adverse effects associated with the medications in the context of shared medical decision-making.4

The practice recommendations in this activity are available at

Editor's Note: Dr. Salisbury-Afshar is a contributing editor for AFP.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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