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
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
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
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
"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>.▪