Author Insights: Off-Label Use of Antipsychotics Helpful for Only a Few Conditions

Alicia Ruelaz Maher, MD, a researcher at RAND Health in Santa Monica, Calif, and her colleagues found that patients with eating disorders and substance abuse problems don’t benefit from treatment with atypical antipsychotic medications. (Image: Caara Shayne)

While off-label use of atypical antipsychotics has skyrocketed in recent years, such treatment is beneficial for only a handful of conditions, an analysis published today in JAMA found.

The US Food and Drug Administration has approved the use of atypical antipsychotic medications to treat adult patients with schizophrenia and bipolar disorder. Certain antipsychotics have also been approved for treating a subset of patients with depression. However, US physicians are also allowed to use drugs “off label” to treat other conditions. A doubling of such off-label use of atypical antipsychotics is a driving force behind an increase in medication visits related to these drugs, from 6.2 million visits in 1995 to 14.3 million in 2008.

These trends have raised concerns among some clinicians because this class of drugs is associated with serious adverse events that include substantial weight gain, movement disorders, and even death.

To assess the efficacy and the potential adverse effects of off-label use of atypical antipsychotics, Alicia Ruelaz Maher, MD, a researcher at RAND Health based in Santa Monica, Calif, and her colleagues conducted a meta-analysis. They found that data support the efficacy of such treatment only for patients with generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), and dementia. Maher, who is also a psychiatrist, spoke with news@JAMA about their findings.

news@JAMA: Why are such drugs used off label?

Dr Maher: In psychiatry, we often find that if a drug is effective for symptoms in one condition it might be useful for similar symptoms in another condition. Sometimes drugs will eventually gain approval for these other uses.

news@JAMA: How would you like physicians to use your data?

Dr Maher: Physicians have been using these medications for off-label indications in a vacuum. This is the largest study of its kind on the topic of atypical antipsychotic use. We’d like physicians to know how much information is out there. We hope it will help with their risk-benefit analysis.

news@JAMA: Do your data support the FDA’s warning that physicians should avoid using these medications to treat dementia in older adults because it can increase the risk of death?

Dr Maher: Our findings are consistent with the warning, but there was also some evidence of an improvement of behavioral symptoms in older patients with dementia. With medically ill patients, sometimes their behavioral symptoms can make it hard for them to get the medical treatment they need. So even though there is a very serious risk profile, there still are cases where the benefit outweighs the risk.

news@JAMA: How much did patients with GAD or OCD benefit from treatment with these medications?

Dr Maher: I would classify the effect as moderate. For GAD, 3 large trials showed a 26% greater likelihood of a positive response after 8 weeks of treatment with atypical antipsychotics compared to placebo. For patients with OCD, there was a benefit with risperidone treatment among those who had failed to respond to treatment with selective serotonin reuptake inhibitors.

news@JAMA: You found no evidence to support the use of these drugs in patients with eating disorders, even though weight gain has been an adverse effect for many patients taking these agents. You also found no evidence to support their use in patients with substance abuse problems. Do you think physicians should stop such use?

Dr Maher: Given the lack of evidence, I don’t think it would make sense to expose people to the side effects of these drugs. Surprisingly, atypical antipsychotic use did not lead to weight gain in patients with eating disorders.

Categories: Adverse Effects, Aging/Geriatrics, Dementias, Evidence-Based Medicine, Psychiatry