Leptin and antipsychotic drugs

There is growing interest in the role of leptin in excessive body weight gain during antipsychotic drug treatment. Herrán et al's (2001) paper is an important contribution to the field. Among other interesting findings they demonstrated that the functioning of the leptin system is preserved during antipsychotic drug administration. However, it is not “the first study analysing the effects of chronic antipsychotic medication on serum leptin levels”, since other authors have published relevant data for humans and rats (Baptista et al, 2000; Lacruz et al, 2000; Melkerson et al, 2000).

An important finding by Herrán et al was that olanzapine— and risperidone— treated patients displayed the highest and lowest leptin levels, respectively, “even after controlling for BMI”. This may support the contention that olanzapine is promoting a deleterious metabolic profile. That finding also prompts speculation that other mechanisms besides body weight gain could be involved in leptin elevation during antipsychotic treatment.

We have proposed elsewhere that insulin may be one of these additional mechanisms. Insulin is a powerful stimulus for leptin synthesis and secretion. Female rats with sulpiride-induced obesity unexpectedly displayed normal serum leptin (and insulin) levels (Lacruz et al, 2000). In addition, serum leptin and insulin levels correlated positively in healthy people and antipsychotic-treated patients (Baptista et al, 2000, 2001). As olanzapine strongly stimulates appetite, it may promote insulin (and leptin) secretion, with relative independence from body weight gain. Surprisingly, Herrán et al reported that treatment with clozapine (another agent with strong appetite-stimulating properties) was associated with leptin levels similar to those found in haloperidol— and phenothiazine-treated patients (in spite of a higher body weight gain). If it were possible for Herrán et al to furnish the information, readers would benefit from knowing (a) the insulin levels in these patients; (b) a comparison of leptin levels between clozapine-, olanzapine— and risperidone-treated patients and their specific matched controls; and (c) the gender distribution in these treatment groups. If olanzapine— and risperidone-treated subjects display higher and lower leptin levels, respectively, than their controls, and if the gender distribution is similar in the three treatment groups, an additional important contribution will have been brought to the field of psychopharmacology.