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
© Copyright 2014 Physicians Postgraduate Press, Inc.
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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