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Study Questions ‘Off-Label’ Use of Antipsychotics

They’re being increasingly prescribed for psychiatric disorders such as depression, dementia
FRIDAY, Jan. 19 (HealthDay News) — Newer antipsychotic medications are being used widely for a variety of psychiatric disorders for which they were not initially approved.

This “off label” use comes without strong evidence that the drugs are effective for these conditions and with a risk for serious side effects, said a report issued this week by the Agency for Healthcare Research and Quality (AHRQ).

The medications were approved to treat conditions such as schizophrenia and bipolar disorder, but are now being prescribed to millions of Americans for depression, dementia, and other psychiatric disorders without strong evidence that such off-label uses are effective, the report stated.

“The issue of off-label indications is a problem across medications, but I think it’s particularly of concern with drugs that affect mental-health issues,” said Dr. David Atkins, chief medical officer at AHRQ’s Center for Outcomes and Evidence.

The revelation, contained in an AHRQ report titled Efficacy and Comparative Effectiveness of Off-Label Use of Atypical Antipsychotics, was not startling to clinicians.

“The surprise is that people have not been more adamant about this earlier,” said Dr. Julio Licinio, chairman of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine.

The report comes on the heels of another study that found that antipsychotic drugs, commonly prescribed to treat psychosis, agitation and aggression in Alzheimer’s patients, are essentially no more effective than a sugar pill.

Atypical antipsychotics such as aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal) and ziprasidone (Geodon) are designed to cause fewer neurological complications than older antipsychotics. They are approved to treat schizophrenia and bipolar disorder but are increasingly used to treat dementia, geriatric aggression, depression, obsessive-compulsive disorder, post-traumatic stress disorder and personality disorders.

Using the drugs “off label’ for conditions other than their original approval is perfectly legal but causes concern among some experts. A 2001 report by the AHRQ concluded that about 21 percent of prescribed drug use was for conditions not indicated on the label.

Atypical antipsychotics have also been studied for treating Tourette syndrome and autism in children.

“Off-label use isn’t necessarily bad,” Atkins said. “To say it’s not an approved indication doesn’t mean there’s no evidence.”

But after reviewing 84 published studies on atypical antipsychotics, the authors of the new study concluded there can be problems. Not only is quality evidence lacking to support off-label use of the drugs, there is evidence of severe side effects, including weight gain, tremors and stroke.

“These drugs have a lot of side effects,” Licinio confirmed. “They also tend to be very expensive.”

Although some patients can benefit from the off-label use, many can be treated with a different drug without the side effects, he added.

The drugs are also used widely in children for off-label purposes, said Dr. Cheryl Corcoran, assistant professor of psychiatry at Columbia University and a researcher in schizophrenia at the New York State Psychiatric Institute in New York City.

“There are very few clinical trials in children, but there’s enough information from other sources to show that these medications can be very problematic for children, with side effects such as weight gain, insulin resistance and changes in cholesterol,” she said.

Licinio added there are few studies that looked at the drugs in “real-world” settings, which often means in combination with other drugs. “It’s not only that people are getting anti-psychotics, they are being added to what they are already taking,” he said. “They are being added, and they have not been tested in combinations, and I think it’s a problem.”

The study authors called for more head-to-head trials of the drugs.

“The clearest finding was that the quality of evidence for the most common uses was not very clear-cut, which doesn’t prove the case that these aren’t appropriate to consider in individual patients. But it does say that given the amount of use they’re getting, we need some better research to try to clarify how to identify the right patients to get these drugs,” Atkins said.

But Corcoran and others called for a different approach.

“Our sense is not more head-to-head trials but the need to develop other kinds of treatments for disorders other than psychosis, drugs that are safer, more appropriate, using rationale drug design,” she said.

SOURCES: David Atkins, M.D., chief medical officer, Center for Outcomes and Evidence, Agency for Healthcare Research and Quality, Rockville, Md.; Julio Licinio, M.D., chairman, department of psychiatry and behavioral sciences, University of Miami Miller School of Medicine; Cheryl Corcoran, M.D., assistant professor of psychiatry, Columbia University, and researcher in schizophrenia, New York State Psychiatric Institute, New York City; Jan. 17, 2007, Efficacy and Comparative Effectiveness of Off-Label Use of Atypical Antipsychotics, Agency for Healthcare Research and Quality

By Amanda Gardner
HealthDay Reporter
Last Updated: Jan. 19, 2007

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