Off-Label Use of Antipsychotics Common, Concerning

Caroline Cassels

September 10, 2009

September 10, 2009 — New research shows that off-label use of antipsychotics among a population of US veterans is upward of 60% — a finding that raises questions about whether this constitutes optimal care and is an appropriate use of healthcare resources.

A study examining national data from the Department of Veterans Affairs shows that of 279,778 veterans who received an antipsychotic medication in the 2007 fiscal year, 162,442 (60.2%) had no record of a diagnosis for which these drugs were approved.

"We found it quite striking that such a large proportion of patients on these drugs had no diagnosis for an indicated use — that is, schizophrenia and bipolar disorder — and that this rate is significantly higher than off-label use for other classes of drugs," lead investigator Douglas L. Leslie, PhD, from the Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania, told Medscape Psychiatry.

"One of the dangers of this practice from a public health perspective is that it uses resources that could potentially be used in other ways. In addition, we've learned over the last decade that the side effects associated with atypical antipsychotics, such as weight gain, an increased risk of diabetes, and cardiovascular problems, are significant.

"Given that the evidence of the effectiveness of these drugs [for other psychiatric indications] is pretty sketchy, perhaps they should be used with greater caution," Dr. Leslie added.

The study is published in the September issue of Psychiatric Services.

Cost Implications

As one of the investigators involved in the Clinical Antipsychotic Trial of Intervention Effectiveness for Alzheimer's Disease (CATIE-AD), which found no difference between atypical antipsychotics and placebo in treating neuropsychiatric symptoms among patients with Alzheimer's disease, Dr. Leslie said he was intrigued to know more about off-label use of these medications.

"The use of antipsychotics in Alzheimer's disease is pretty prevalent, even though there is little evidence to support their use. The results of the CATIE study showed that atypical antipsychotics were not superior to placebo. So this got us wondering how much other off-label use was going on and how we might look at this issue," said Dr. Leslie.

The authors note that atypical antipsychotics are currently used off-label to treat a wide variety of conditions, most commonly agitation in dementia, depression, obsessive-compulsive disorder, posttraumatic stress disorder, Tourette's syndrome, and autism.

Further, the investigators point out that if their estimate that 60% of antipsychotic use is off-label, then this would mean that approximately "$4 to $5 billion of antipsychotic expenditures in 2007 may have been for off-label uses with little or no documented clinical benefit and a substantial risk of adverse side effects."

Although a few previous studies have looked at the issue of off-label antipsychotic use, they were less than ideal either because they were outdated or because they relied on self report for diagnostic information, said Dr. Leslie.

The current study, he said, is based on current data and offers more precise estimates because it is based on actual prescription records.

Off-Label Doses Low

To determine the prevalence of off-label use of antipsychotic medications and mental illness in the VA healthcare system and explore patient sociodemographic and clinical characteristics associated with off-label use, the researchers used data from the national VA administrative databases.

The researchers identified all veterans who were prescribed an antipsychotic medication during the 2007 fiscal year. They then went back and looked at participants' diagnoses. Those who had a diagnosis of schizophrenia or bipolar disorder were deemed on-label users, and those with any other diagnosis were considered off-label users.

When investigators analyzed characteristics of off-label users, they found that more than 40% of patients given prescriptions for antipsychotic medications off-label were diagnosed with posttraumatic stress disorder. Other common diagnoses among off-label users included minor depression (39.5%), major depression (23.4%), anxiety disorder (20%), alcohol use or dependence (15.1%), and drug abuse or dependence (12.6%).

At 42.9%, quetiapine (Seroquel, AstraZeneca) was the most commonly prescribed antipsychotic among off-label users, followed by risperidone (Risperdal, Janssen Pharmaceuticals) and first-generation antipsychotics at 21.2% and 20.5%, respectively. In addition, the investigators found that doses of antipsychotics prescribed off-label were low.

Logistic regression models reveled that patients diagnosed as having other psychosis or dementia had the highest odds of receiving an antipsychotic medication off-label.

Challenging Illness

Although the study was not designed to determine factors driving off-label use of antipsychotics, Dr. Leslie speculated that the challenge of managing individuals with mental health disorders likely plays a role.

"The fact is, managing mental illness can be very challenging, so when a clinician has tried all of the other tools in their arsenal, it can be very tempting to reach for another agent to see if it works, even if the science isn't quite there to back up that clinical decision," he said.

Further research is needed to replicate these findings in a general population and to determine whether there is any scientific basis for prescribing these medications for conditions other than those approved by the US Food and Drug Administration.

In the meantime, Dr. Leslie said, physicians prescribing these medications off-label need to carefully weigh the risks against the potential benefits.

Dr. Leslie has disclosed no relevant financial relationships. Disclosure information for the other authors can be viewed in the study.

Psychiatr Serv. 2009;60:1175–1181. Abstract


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