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
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
Results : Compared to controls, olanzapine treatment increased
body weight (p<0.001), food intake (p<0.01), inguinal fat mass
(p<0.05) and liver weight (p<0.01). On the other hand, the ‘‘obesity
treatment group’’ had lower weight gain (p<0.001), food intake and
inguinal fat (p<0.05) than the sole olanzapine treatment group.
The ‘‘Obesity prevention group’’ also showed significantly decreased
weight gain (p<0.05), compared to the olanzapine group.
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.