Effects of second generation antipsychotics on leptin and ghrelin

Weight gain is a major side effect of antipsychotic treatment. Some atypical antipsychotic agents have profound effects on weight. Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that seem to play an important role in the regulation of food intake, energy metabolism, and body weight are leptin and ghrelin. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. In this present study it is aimed to compare the effects of five different atypical antipsychotic medications on leptin and ghrelin.

112 patients who were treated either with clozapine (n=20), olanzapine (n=28), risperidone (n=22), quetiapine (n=20) or amisulpride (n=22) as monotherapy for at least one year and age, gender, and body mass index (BMI) matched control group (n=23) were assessed cross-sectionally. Ghrelin and leptin levels were measured with enzyme-immunoassay.

When fasting serum leptin levels were compared between groups, control group had the highest mean value (9.2+/-6.7) and amisulpride group had the lowest mean value (3.7+/-2.1) but still there was no statistically significant difference between six groups (F=1993, p=0.084). In the comparison of the mean values of fasting serum ghrelin levels there was a statistically significant difference between groups (F=11,473, p=0.00). In post-hoc analysis it was seen that the control group had the lowest ghrelin level (194.5+/-86.8). Quetiapine treated group (378.1+/-260.4) had similar fasting serum ghrelin levels to control group. All the other antipsychotic treatment groups had significantly higher levels of fasting serum ghrelin compared to control group, highest in amisulpride treated group (597.0+/-150.0).

The weight-gain side effect of atypical antipsychotics can be related with the orexigenic effect of elevated serum ghrelin rather than leptin deficit. Among the five widely used atypical antipsychotics quetiapine is the only one which does not elevate the ghrelin level.