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Improved Insulin Sensitivity in 80 Nondiabetic Patients With MDD After Clinical Remission in a Double-Blind, Randomized Trial of Amitriptyline and Paroxetine

J Clin Psychiatry 2006;67(12):1856-1861

Objective: There is substantial evidence that depression constitutes a risk factor for type 2 diabetes mellitus. A recent study has shown that high salivary cortisol levels are associated with decreased insulin sensitivity in unmedicated, depressed patients. Further, antidepressive treatment might have differential effects on hypothalamus-pituitary-adrenal (HPA) system activity. Therefore, the aim of the present study was to examine whether insulin sensitivity improves during antidepressive treatment in depressed patients with declining HPA system activity.

Method: Eighty inpatients with an episode of major depressive disorder (DSM-IV criteria) were treated in a double-blind, randomized protocol with either amitriptyline or paroxetine over a period of 5 weeks. After 6 drug-free days, an oral glucose tolerance test was performed on day 1 and again 35 days after antidepressive treatment. For quantification of free cortisol levels, saliva was obtained daily at 8:00 a.m. during weeks -1 (washout) and 5. The study was conducted from May 2005 to December 2005.

Results: The insulin sensitivity indexMatsuda increased in only those patients who remitted from major depressive disorder as a result of treatment with either antidepressant (F = 7.0, df = 1,74; p < .01), while correcting for body mass index. Further, cortisol concentrations declined in remitters and responders to amitriptyline (F = 2.1, df = 1,70; p < .05), but not in any other subgroup.

Conclusion: Successful antidepressive treatment with either a selective serotonin reuptake inhibitor or a tricyclic substance increases the sensitivity to insulin in nondiabetic depressed patients. The herein presented longitudinal data do not exclude the HPA system as a major contributor to insulin resistance in depressed patients, but underscore the assumption of additional factors.