Antipsychotics and Weight Gain

It is no secret that medications commonly used to treat psychosis can lead to remarkable weight gain. This is particularly true of the second generation antipsychotics clozapine (Leponex, Clozaril) and olanzapine (Zyprexa), but the mechanisms leading to weight gain are poorly understood.

In a recent study Kluge and colleagues from the Max Planck Institute of Psychiatry in Munich, ramdomised 30 patients with schizophrenia, schizophreniform, or schizoaffective disorder in a double-blind, parallel study comparing abnormal eating behavior using a standardized scale to clozapine and olanzapine.

In both treatment groups, there was a significant increase in cravings and in binge eating, whereby the rate of these effects was somewhat higher with olanzepine. Clinical improvements in psychiatric symptoms was comparable.

What the study does not disclose is what one could possibly do to help patients avoid weight gain. The evidence that “lifestyle” interventions are effective in preventing this weight gain is marginal at best. A recent randomized study published in JAMA showed some benefit of prescribing metformin alone or in combination with lifestyle advice.

An earlier double-blind placebo-controlled study in 37 patients on olanzepine showed greater weight loss with sibutramine (Meridia, Reductil) over 12 weeks than on lifestyle alone.

Amantadine, in an even smaller randomised placebo-controlled study in 21 patients, was at least somewhat effective in limiting olanzapine-induced weight gain.

Clearly, addressing weight gain in patients, who need effective antipsychotic medications remains challenging at best.