Does antidepressant therapy improve glucose metabolism?

Aims: Weight gain is a serious problem with numerous psychotropic drugs including antidepressants such as mirtazapine. Drug-induced weight gain is of clinical importance with respect to subjective discomfort and treatment compliance, and may be associated with the risk for several health problems including type II diabetes. Methods: We investigated changes of weight and cortisol levels and performed glucose tolerance tests, including the assessment of insulin and c-peptide levels in 11 depressed inpatients treated with mirtazapine. Results: During treatment for up to six weeks with mirtazapine subjects gained 2.17kg on average. Unexpectedly, glucose tolerance improved during treatment. This was evidenced by a decrease in basal serum glucose levels (p=0.05) and significant decreases in 120-minutes glucose levels (p=0.048) and the area under the curve (AUC) following glucose intake (p=0.028). The improvement was only partially mirrored by insulin and cortisol levels. Conclusions: We conclude that mirtazapine improves glucose tolerance in depressed patients despite weight gain. Improved glucose tolerance during treatment with mirtazapine may be, at least in part, mediated by a reduction of the increased cortisol secretion of depressed patients. However, the exploratory nature of the present study and the limited number of subjects prohibit firm conclusions regarding causality.