Betahistine decreases olanzapine-induced weight gain and somnolence in humans

• Published in: Journal of psychopharmacology (Oxford) Vol. 30; no. 3; p. 237
• Main Authors: Barak, Nir, Beck, Yaffa, Albeck, Joseph H
• Format: Journal Article
• Language: English
• Published: United States 01.03.2016
• Subjects: Adult; Antipsychotic Agents - adverse effects; Benzodiazepines - adverse effects; Betahistine - therapeutic use; Brain - drug effects; Brain - metabolism; Double-Blind Method; Female; Histamine Agonists - therapeutic use; Humans; Receptors, Histamine H1 - metabolism; Sleep Initiation and Maintenance Disorders - chemically induced; Sleep Initiation and Maintenance Disorders - metabolism; Weight Gain - drug effects; weight; Olanzapine; histamine; betahistine; somnolence
• ISSN: 1461-7285
• DOI: 10.1177/0269881115626349

Olanzapine's efficacy in schizophrenia is attributed to antagonism of dopamine and serotonin receptors. Olanzapine is also a potent histamine-H1 antagonist that results in weight gain and somnolence. Betahistine is a centrally acting histamine-H1 agonist, and therefore may reduce olanzapine's effect on histamine receptors in the brain. Olanzapine's high affinity for the histamine-H1 receptor warrants the use of high doses of betahistine. Forty-eight healthy women were recruited and randomized to receive either betahistine 144 mg/day or matching placebo for 4 weeks. Due to the high dose of betahistine, olanzapine was started only on the second week and titrated up to 10 mg/day, and co-administration continued for an additional 2 weeks. Only nominal differences in adverse events were noted between the treatment groups. Betahistine caused a 37% reduction in mean weight gain (1.24 kg in the betahistine arm vs. 1.93 kg in the placebo arm; p=.049) and 60% reduction in the mean increase in daytime Epworth sleepiness scores (1.82 units in the betahistine group vs. 3.57 units in the placebo group; p=.042). The present study suggests that betahistine-olanzapine co-administration, in healthy female subjects, yields an acceptable safety profile with mitigation of weight gain and somnolence. This should be further tested in a patient cohort.