title: Betahistine decreases olanzapine-induced weight gain and somnolence in humans.
abstract: 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.
authors.affiliation: Obesity Clinic, Leumit Health Fund, Tel-Aviv, Israel dr.n.barak@gmail.com.
authors.forename: Nir
authors.initials: N
authors.lastname: Barak
authors.affiliation: Private Practice, Tel-Aviv, Israel.
authors.forename: Yaffa
authors.initials: Y
authors.lastname: Beck
authors.affiliation: Private Practice, Belmont, MA, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Albeck
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001569:Benzodiazepines / Q000009:adverse effects*; D001621:Betahistine / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D017442:Histamine Agonists / Q000627:therapeutic use*; D006801:Humans; D000077152:Olanzapine; D011969:Receptors, Histamine H1 / Q000378:metabolism; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced* / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D017442:Histamine Agonists; D011969:Receptors, Histamine H1; D001569:Benzodiazepines; D000077152:Olanzapine; D001621:Betahistine
keywords: Olanzapine; betahistine; histamine; somnolence; weight