Atypical Antipsychotics Appear to Be Effective For Only Few Off-Label Uses

A review of previous studies suggests that even though atypical antipsychotic medications are commonly used for off-label conditions such as behavioral symptoms ofdementia, anxiety, and obsessive-compulsive disorder, these medications are effective for only a few off-label conditions, and that the benefits and harms of these medications for these uses vary, according to an article in the September 28 issue of JAMA.

"Atypical antipsychotic medications are approved for marketing and labeling by the U.S. Food and Drug Administration (FDA) for treating schizophrenia, bipolar disorder, and depression under drug-specific circumstances. The use of atypical antipsychotic medications is rapidly increasing in the United States, with 1 study estimating an increase from 6.2 million to 14.3 million treatment visits between 1995 and 2008. The estimated use of these drugs for off-label indications, meaning those without FDA approval for these indications, doubled during this period," according to background information in the article.

Alicia Ruelaz Maher, M.D., of RAND Health, Santa Monica, Calif., and colleagues conducted a systemic review and meta-analysis to examine the efficacy and adverse events associated with off-label use of atypical antipsychotic medications for behavioral symptoms in dementia, anxiety, obsessive-compulsive disorder (OCD), eating disorders, posttraumatic stress disorder (PTSD), insomnia, personality disorders, depression, and substance abuse. The authors searched the medical literature for controlled trials comparing an atypical antipsychotic medication (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, orpaliperidone) with placebo, another atypical antipsychotic medication, or other pharmacotherapy for adult off-label conditions. Observational studies with sample sizes of greater than 1,000 patients were included to assess adverse events.

For this study, the researchers identified and included 162 trials with efficacy outcomes and 231 trials or large observational studies with adverse events. Among the findings of the authors, aripiprazole, olanzapine, and risperidone were associated with small but statistically significant benefits for the treatment in elderly patients of behavioral symptoms of dementia, such as psychosis, mood alterations, and aggression. For generalized anxiety disorder, a pooled analysis of 3 trials showed that quetiapine was associated with a 26 percent increase in the chance of a favorable response at 8 weeks compared with placebo. For obsessive-compulsive disorder, three pooled studies of risperidone resulted in an approximate 4-fold increase in the chance of responding compared with placebo. Evidence did not support using atypical medications for substance abuse or eating disorders.

"In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH] = 87), stroke (NNH = 53 for risperidone), extrapyramidal symptoms [movement disorders; NNH = 10 for olanzapine; NNH = 20 for risperidone], and urinary tract symptoms (NNH range-16-36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akathisia [inability to remain motionless] (for aripiprazole), and extrapyramidal symptoms," the authors write.

"The benefits and harms vary among atypical antipsychotic medications for off-label use," the authors write. "This evidence should prove useful for clinicians considering off-label prescribing of atypical antipsychotic medications, and should contribute to optimal treatment decision making for individual patients with specific clinical symptoms and unique risk profiles."
(JAMA 2011;306[12]:1359-1369. Available pre-embargo to the media at www.jamamedia.org)