Improved insulin sensitivity in 80 nondiabetic patients with MDD after clinical remission in a double-blind, randomized trial of amitriptyline and paroxetine.
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 anti-depressive treatment in depressed patients with declining HPA system activity.


METHODS
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.


CONCLUSIONS
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.
Weber-Hamann
Bettina
B
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany. weber@zi-mannheim.de
Gilles
Maria
M
Lederbogen
Florian
F
Heuser
Isabella
I
Deuschle
Michael
M
D000328:Adult; D000368:Aged; D000639:Amitriptyline / Q000494:pharmacology / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D012307:Risk Factors; D012463:Saliva / Q000737:chemistry
D018687:Antidepressive Agents, Second-Generation; D007004:Hypoglycemic Agents; D007328:Insulin; D000639:Amitriptyline; D017374:Paroxetine; D006854:Hydrocortisone