Physicians and psychiatrists got a wake-up call Tuesday when it comes to prescribing atypical antipsychotics for uses not approved by the U.S. Food and Drug Administration (FDA). A new analysis of previous research suggests the widespread prescription of such medications isn’t indicated for many uses.
For instance, the new research — which included 162 trials with efficacy outcomes and 231 trials or large observational studies with adverse events — found no support for the use of atypical antipsychotic medications for eating disorders or substance abuse.
Atypical antipsychotic medications are commonly used for off-label conditions such as behavioral symptoms of dementia, anxiety, and obsessive-compulsive disorder.
Off-label indications, meaning those without FDA approval for these indications, doubled from 1995 to 2008.
“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,” according to the researchers.
Alicia Ruelaz Maher, M.D., of RAND Health, 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, or paliperidone) 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.
The research found that 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 approximately four-fold increase in the chance of responding compared with placebo.
“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),” noted the researchers. Number needed to harm (NNH) refers to the number of patients that need to be treated before one patient is harmed; a lower number suggests a far greater risk of the medication than a larger number.
Adverse events in younger and middle-aged adults included weight gain (particularly with olanzapine), fatigue, sedation, akathisia — the inability to remain motionless — (for aripiprazole), and extrapyramidal symptoms.
“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.”
According to the study, the use of atypical antipsychotic medications is rapidly increasing in the United States, with previous research estimating an increase from 6.2 million to 14.3 million treatment visits between 1995 and 2008.
The new study appears in the September 28 issue of JAMA.