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Various atypical antipsychotics have FDA indications for schizophrenia, bipolar illness, and depression but are increasingly used off-label for other conditions. These researchers examined the efficacy and safety of off-label uses in meta-analyses of controlled trials and large observational studies.
Strong evidence from 14 placebo-controlled trials indicated small effects of atypical antipsychotics for behavioral disturbances in dementia, with no difference among aripiprazole, olanzapine, and risperidone. Modest evidence from three placebo-controlled trials indicated small effects of quetiapine for generalized anxiety disorder. Modest evidence from three placebo-controlled studies showed large effects of risperidone augmentation of antidepressants in obsessive-compulsive disorder (OCD). Support for antipsychotic use was nonexistent in eating disorders and substance abuse and marginal in personality disorders and post-traumatic stress disorder (see JW Psychiatry Aug 2 2011). Various antipsychotics in older populations were associated with increased risk for death (number needed to harm [NNH], 87), stroke (risperidone: NNH, 53), extrapyramidal symptoms (EPS; olanzapine: NNH, 10), and urinary tract symptoms (NNH, 16–36). Problems in nonelderly populations included weight gain (olanzapine: NNH, 3), fatigue, akathisia, and EPS.
Maher AR et al. Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults. JAMA 2011 Sep 28; 306:1359.
Comment
The benefits and harms of these drugs for off-label indications vary by condition, agent, and whether they are used alone or adjunctively. Their small benefits for dementia or generalized anxiety disorder seem outweighed by serious risks; numerous effective, less risky anti-anxiety drugs are available. Large effects in OCD seem to justify risperidone as a second-line supplement when OCD fails to respond to first-line selective serotonin reuptake inhibitors or clomipramine. Clinicians using these drugs for personality disorders and PTSD should know that evidence of efficacy is marginal at best. In general, antipsychotics should be considered for treatment-resistant conditions only when other medications have failed and only after carefully assessing the specific risks for the individual patient.