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Antipsychotics May Be Overprescribed To Treat Bipolar Disorder

Many bipolar patients are maintained for long periods on two or more atypical antipsychotics, a practice for which there is no supporting evidence, researchers say.

Atypical antipsychotics should be used conservatively in the treatment of bipolar disorder, and careful monitoring—especially for weight gain and metabolic syndrome—is essential.

That's the message from the report "Emerging Treatments for Bipolar Disorder: Safety and Adverse Effect Profiles" in the February Annals of Pharmacotherapy.

The authors were Ronald Pies, M.D., a clinical professor of psychiatry at Tufts University School of Medicine, and Patricia Marken, Pharm. D., professor and chair of the division of pharmacy practice and a professor of psychiatry at the schools of pharmacy and medicine at the University of Missouri in Kansas City.

"The take-home message... is that conservative use and careful monitoring are very important when using the atypicals in bipolar disorder."

The review, which was supported by an unrestricted educational grant from GlaxoSmith Kline (GSK), found that some newer antiepileptic drugs may cause less weight gain than older agents and require less therapeutic drug monitoring. GSK manufactures lamotrigine (Lamictal), an antiepileptic.

Pies and Marken conducted a MED-LINE search through July 2005 of randomized controlled trials, open-label studies, and reviews of treatments for bipolar disorder. They reviewed results for atypical antipsychotics—including olanzapine, risperidone, quetiapine, clozapine, ziprasidone, and aripiprazole—as well as antiepileptic drugs such as lamotrigine, topiramate, gabapentin, and oxcarbazepine.

"Our review highlights the many side effects possible with the newer, atypical antipsychotics," Pies told Psychiatric News. "Notwithstanding their antimanic effects and their probable but less established mood-stabilizing effects, I believe that the atypicals should still be used conservatively in bipolar disorder. I find that many bipolar patients are maintained for long periods on two or more atypicals, with or without classical mood stabilizers, and there is practically no controlled evidence to support this practice.

"Such `irrational' polypharmacy definitely increases the risk of side effects and drug interactions," he said. "Weight gain and metabolic syndrome are of particular concern with the atypicals, especially but not exclusively olanzapine. Not every bipolar patient needs to be maintained indefinitely on an atypical antipsychotic, if a mood stabilizer alone—such as lithium, lamotrigine, or divalproex—can do the job. The take-home message, therefore, is that conservative use and careful monitoring are very important when using the atypicals in bipolar disorder."

The review found that new antiepileptic drugs appear to cause less weight gain than older agents, have fewer drug interactions, and require less therapeutic drug monitoring than older antiepileptic drugs.

"Lamotrigine seems to be a bona fide mood stabilizer and maintenance agent in bipolar disorder, though it is more effective for delaying recurrence of depressive episodes than of mania," Pies said. "There is growing, but still preliminary, evidence that lamotrigine is also useful in the acute treatment of bipolar depression, which makes it quite valuable as an alternative to potentially `destabilizing' antidepressants."

But he added that the agent is not a panacea for bipolar disorder and is not risk-free.

"Whereas the fear of serious skin rash is almost certainly overblown when the drug is titrated slowly, it can be associated with headaches in some bipolar patients, and there are rare anecdotal reports of lamotrigine-induced hypomania or overactivation," he said. "Very high lamotrigine doses greater than 400 mg a day may be associated with cognitive side effects, but such high doses are rarely needed for most bipolar patients."

An abstract of "Emerging Treatments for Bipolar Disorder: Safety and Adverse Effect Profiles" is posted at <www.theannals.com/cgi/content/abstract/40/2/276>.

Ann Pharmacother 2005 40 276

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