Are leptin and cytokines involved in body weight gain during treatment with antipsychotic drugs?

Objective: To critically review published literature on the causal association between leptin, cytokines, and excessive body weight gain (BWG) induced by antipsychotic drugs (APs). Methods: We completed a Medline search using the words leptin, cytokines, antipsychotic drugs, neuroleptics, psychotropic drugs, weight gain, and obesity. We also included our empirical research on this topic in the discussion. We examined the relation between leptin, cytokines (mainly tumour necrosis factor alpha [TNF-alpha] and its soluble receptors), and AP-induced BWG, using the biological sciences' current theories of causality. Results: In the general field of weight regulation, there is scarce experimental evidence that leptin or TNF-alpha by themselves can induce obesity. Serum levels of leptin and TNF-alpha rather increase simultaneously as BWG occurs. This has also been reported during AP-induced BWG, with the equivocal exception of a study with clozapine. Some researchers have suggested that the absence of the expected correlation between leptin and body mass index (BMI) or serum insulin levels, and the lack of sex-related differences in leptin levels in AP-treated patients, may point to a causal relation. This contention requires more experimental support. In addition, future clinical studies must carefully control for sex and BMI. Conclusions: No conclusive evidence has been provided that leptin or TNF-alpha may induce obesity either in drug-free subjects or in AP-treated patients. In most cases, the elevated serum levels of these hormones appear to be a consequence rather than a cause of obesity. That does not mean that such an elevation is innocuous, since it may impair blood pressure and also carbohydrate and lipid metabolism regulation. Hence, all efforts should be made to prevent or attenuate BWG during treatment with APs.