Rx CARE

Psychotropic-induced weight gain:
Help now available

When it comes to treating psychosis or bipolar illness, health professionals have a hard enough time getting patients to stick with their psychotropic medications. After all, many patients in the throes of a psychiatric illness lack the insight that can motivate them to stay with therapy.

Add to that the fact that a majority of patients gain significant amounts of weight while on antidepressants and mood stabilizers, and you can wind up with a real compliance problem. Six in 10 patients in a recent European survey complained that weight gain was a major hurdle for them when it came to Rx treatment.

But help for drug-associated weight gain in some psychiatric patients may be here, according to Norman Sussman, M.D., a clinical professor of psychiatry at the New York University School of Medicine.

According to Sussman, the anticonvulsant drug topiramate (Topamax, Ortho-McNeil) may help stimulate weight loss when added to the mood-stabilizing cocktails of many patients. And recent evidence also suggests that bupropion (Wellbutrin, Zyban, GlaxoSmithKline) on the market for well over a decade, could aid in weight loss for some psychotic or depressed individuals.

"This has been a dramatic breakthrough for many patients," Sussman said of topiramate at a recent American Medical Association Science Reporters Conference in Washington, D.C.

Between one- and two-thirds of all patients taking common mood stabilizers like divalproex sodium (Depakote, Abbott), lithium, and olanzapine (Zyprexa, Lilly) over extended periods can expect to gain significant weight, he said. "We don't know why it happens, but we know it happens." Then, a recent Canadian study showed that bipolar patients lost an average of 6.2% of their body weight when topiramate was added to their daily medication cocktail. A comparison group gained about 1% when a placebo was added.

A word of caution: Topiramate was approved in late 1996 as an anticonvulsant but is not approved as a mood-stabilizer. And while some clinicians are beginning to talk about the drug as a possible primary treatment for treatment-resistant bipolar illness, no good studies exist to back up the concept. And while preliminary evidence shows that topiramate may cut weight gain, how it works is still a mystery. Some suspect that the drug may interfere with excitatory amino acids, while others have suggested it could disrupt enzymes that help make the taste of food pleasurable.

Somnolence, dizziness, vision problems, and psychomotor slowing are all common side effects reported with use of topiramate. Still, Sussman said that he has used it with success in bipolar patients who are gaining weight. "If someone is being treated for bipolar, I would add topiramate right now, in my practice," he said.

Weight gain can also be a major problem for patients with schizophrenia, especially those taking olanzapine (Zyprexa, Lilly), clozapine (Clozaril, Novartis), or other atypical antipsychotic drugs. The cause may be inherent in the pharmacologic action of atypicals. The drugs target 5-HT_2c serotonin receptors, which, according to recent evidence in the journal Science, help to regulate appetite and metabolism.

Now, evidence suggests that bupropion, marketed as a smoking-cessation agent, may help quell weight gain in some patients. A 2001 study performed at Duke University showed two-thirds of obese women were able to lose at least 5% of their body weight during an eight-week diet when bupropion was added to their daily regimen. Fifteen percent of women managed to lose the weight while taking a placebo. A quarter of the women taking the drug but no women on placebo lost 8% of their body weight. Adding the drug to an antipsychotic regimen may be worth a try, Sussman said.

Significant weight gain can also be a problem in depressed patients taking selective serotonin reuptake inhibitors. "There's a subgroup of patients who take SSRIs who typically gain 20, 30 pounds," according to Sussman. Clinicians tend to "explain it away" by assuming that improved mood leads to a better appetite. But few of these patients report eating more, and most can't lose the weight even with dieting, he said. Part of the problem may be that, like atypical antipsychotics, SSRIs are active at the 5-HT_2c receptor.

Bupropion is an antidepressant, and Sussman said that he would consider switching to it in patients with weight trouble. As an adjunct to SSRIs, however, "it's usually not high-yield," he said.

Todd Zwillich

The author is a writer in Washington, D.C.

Todd Zwillich. Psychotropic-induced weight gain: Help now available.

Drug Topics

2002;21:19.