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

Bettina Weber-Hamann, M.D.; Maria Gilles, M.D.; Florian Lederbogen, M.D.; Isabella Heuser, M.D., Ph.D.; and Michael Deuschle, M.D.

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 index_Matsuda 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.

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

Received Jan. 31, 2006; accepted May 16, 2006. From the Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany (Drs. Weber-Hamann, Gilles, Lederbogen, Heuser, and Deuschle); and the Department of Psychiatry, Charité-Campus Benjamin Franklin, Berlin, Germany (Dr. Heuser).

This project is supported by the German Ministry for Education and Research within the promotional emphasis "German Research Network on Depression."

Drs. Weber-Hamann, Gilles, Lederbogen, Heuser, and Deuschle report no additional financial or other relationships relevant to the subject of this article.

The authors thank Ms. Angela Heuer for expert technical assistance, Ms. Waltraud VanSyckel for language revision, and Bertram Krumm, Ph.D., for advice in the statistical analyses.

Corresponding author and reprints: Bettina Weber-Hamann, M.D., Central Institute of Mental Health, J5 68159 Mannheim, Germany (e-mail: weber@zi-mannheim.de).