Preventing and treating olanzapine-induced obesity with betahistine: a chronic animal model study
Objective : Olanzapine, an atypical antipsychotic drug, is widely prescribed to treat schizophrenia, but induces serious weight gain/ obesity side-effects. Antipsychotic drugs antagonistic affinity for histamine H1 receptors is the main indicator of weight gain side-effects. This study aimed to investigate whether chronic treatment with betahistine (H1 receptor agonist/H3 receptor antagonist) could prevent/ treat olanzapine-induced weight gain at different stages of treatment.
Methods : Female Sprague-Dawley rats were administered under 5 conditions (n=12) : (1) Rats were treated with vehicle (control) during whole experimental period ; (2) ‘‘Obesity treatment group’’ : 5 weeks olanzapine treatment (1 mg/kg, t.i.d.), followed by 6 weeks coadministration of olanzapine with betahistine (9.6 mg/kg, t.i.d.) ; (3) ‘‘Obesity prevention group’’ : 3.5 weeks olanzapine treatment, followed by 2.5 weeks withdrawed, then co-administration of olanzapine and betahistine (4.8 mg/kg, t.i.d.) was introduced ; (4) Sole olanzapine treatment following the same time course as Group 3 ; (5) Rats were treated solely with betahistine (4.8 mg/kg, t.i.d.) during weeks 7–11.
Results : Compared to controls, olanzapine treatment increased body weight (p
Conclusion: This study revealed that chronic co-treatment of olanzapine and betahistine is effective at reducing olanzapineinduced obesity side-effects. These results provide support for further clinical trials to improve of olanzapine-induced obesity side-effects using betahistine co-treatment.