The effect of famotidine addition on olanzapine-induced weight gain in first-episode schizophrenia patients: a double-blind placebo-controlled pilot study

Abstract

Olanzapine treatment is associated with substantial weight gain. In this double-blind placebo-controlled study we evaluated whether the H2 antagonist famotidine may prevent/attenuate olanzapine-induced weight gain. Fourteen first-episode DSM-IV schizophrenia patients were randomly allocated to receive either famotidine (40 mg/day, n=7) or placebo (n=7) in addition to olanzapine (10 mg/day) for 6 weeks. All patients completed the trial. Patients in both groups showed a similar increase in body weight (olanzapine/famotidine: 4.8 (3.2) kg and olanzapine/placebo: 4.9 (1.6) kg, respectively; a between-group difference of 0.14 (1.3) kg). Four of seven (57.1%) patients in the olanzapine/famotidine group and three of seven (42.9%) in the olanzapine/placebo group gained at least 7% of their initial body weight, a cut-off for clinically significant weight gain. Famotidine addition was safe and well tolerated and did not interfere with olanzapine's therapeutic effect. In conclusion, famotidine (40 mg/day for 6 weeks) is not effective in preventing/attenuating weight gain in olanzapine-treated first-episode schizophrenia patients.

Introduction

Atypical antipsychotic agents, primarily olanzapine and clozapine, have been associated with significant weight gain (Allison et al., 1999). The mechanism underlying weight gain induced by atypical antipsychotics has not been clarified, though serotonergic, noradrenergic and histaminergic systems have been implicated (Baptista et al., 2002). Within the histaminergic system, the histamine H2 receptor appeared to be one of the possible mediators of feeding behavior and weight regulation (Doi et al., 1994). It was shown that H2 antagonists (cimetidine, ranitidine, famotidine) attenuated weight gain in rats (Stoa-Birketvedt et al., 1997), and cimetidine reduced weight in obese humans Stoa-Birketvedt, 1993, Stoa-Birketvedt et al., 1998. Administration of the H2 antagonist nizatidine was associated with weight reduction in some olanzapine-treated schizophrenia patients Sacchetti et al., 2000, Cavazzoni et al., 2003.

As part of our ongoing project aimed to evaluate the preventing/attenuating weight gain potential of pharmacological agents exerting selective effect at serotonergic, noradrenergic and histaminergic systems Poyurovsky et al., 2002, Poyurovsky et al., 2003, we sought to determine whether famotidine may be effective in limiting weight gain in olanzapine-treated schizophrenia patients. Addition of famotidine to typical antipsychotics in schizophrenia patients had a beneficial adjunctive effect and was safe and well tolerated Kaminsky et al., 1990, Rosse et al., 1996. To the best of our knowledge this is the first study evaluating the putative weight attenuating effect of famotidine in schizophrenia patients treated with the atypical antipsychotic olanzapine. Since young and previously untreated patients seem to be particularly vulnerable to olanzapine-induced weight gain Kinon et al., 2000, Potenza et al., 1999, we evaluated the effect of famotidine on weight gain in first-episode schizophrenia patients.