Medication, Weight Gain and GI Hormones

Bipolar Depression

Bipolar Depression, Weight gain bipolar medicine, side effects olanzapine, gastrointestinal hormones bipolar medicine

This is an 8 week study that compares two medications. One medication is olanzapine (5-20 mg daily) whereas the other medication is an orally disintegrating medication. Both medications are used to treat depressed bipolar patients. The main focus of this study is the comparison of these two medications on gastro-intestinal hormones and weight gain.

Olanzapine is undeniably one of the most effective treatments available for all phases of bipolar disorder. After FDA approval for bipolar mania, the drug became one of the most widely prescribed of treatments for this difficult-to-treat disorder. However, concerns about weight gain and the associated metabolic syndrome/type II diabetes have impacted the use of olanzapine. In fact, weight gain is quite common with olanzapine. For example, in one large scale 8-week placebo-controlled trial of olanzapine in bipolar depression, the olanzapine-treated patients gained an average of 2.59 kg., while placebo patients lost an average of 0.47 kg. Further, weight gain can continue over an extended period of time, mounting to an average of about 6 kg. over one year. It should be noted, however, that in prior studies, no efforts have been made to limit weight gain. More recent data suggest that interventions such as dietary counseling are effective in either preventing or reversing weight gain. Olanzapine is a potent antagonist of serotonin and histamine 1 receptors. Significant and potentially additive weight gain is associated with blockade of serotonin 2C and Histamine 1 receptors. In addition, serotonin and its receptors are significantly involved in the regulation of gastrointestinal (GI) - related hormone secretion. Animal studies suggest significant involvement of other serotonin receptors in the regulation of appetite, satiety, and GI-related hormones. However, the interplay of selective activation or inhibition of these receptor subtypes is complex, and difficult to distinguish from effects on activity and anxiety. Suffice it to say that activation or blockade of these receptors have differential effects on appetite, satiety, metabolic activity, as well as leptin, secretin, insulin, glucagon, ghrelin, neuropeptide Y, and cholecystokinin. Weight gain and the corresponding metabolic syndrome represent a deal killer with regard to the treatment of most patients. However, one recent small study may be highly relevant to this discussion. De Haan et al. investigated the relative effects of standard olanzapine tablets to the orally-disintegrating form (Zydis) in adolescents and young adults who had gained weight with olanzapine. The group randomly assigned 18 patients to continuation olanzapine tablets or Zydis for a 16-week period. The Zydis-treated patients lost an average of 6.6 kg. while the continuation regular olanzapine group gained 3.7 kg. Although small, this study suggests a potential solution to the weight-gain problem associated with olanzapine. Most of the pharmacological effects on weight and hormones are thought to be mediated centrally. However, De Haan et al. (de Haan L, et al. Psychopharmacology (Berl). 2004;175:389-390) proposed that at least some of the difference could be attributable to local effects in the GI tract. In particular, the site of absorption was suggested as a possible explanation, with the orally disintegrating form (Zydis) yielding less exposure of the pylorus to olanzapine than the standard Zyprexa tablets. In this project we will treat 20 patients with bipolar disorder with olanzapine (a widely-used and FDA approved treatment for this condition); patients will be randomly assigned (1:1) to either standard Zyprexa tablets or orally disintegrating Zydis. We will measure symptom improvement and weight gain over the course of the study. Patients will be given dietary counseling prior to initiating either medication. In addition, we will contrast the effects of the treatments on GI-related hormones.

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