title: Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  Depression is a prevalent and chronic condition in diabetes and is associated with poor glucose regulation and poor compliance with diabetes treatment. This investigation evaluated the effects of nortriptyline on depression and glycemic control to see whether depression in diabetes is treatable and whether restoring mental health contributes to improved medical outcome.
  
  
  METHODS
  Sixty-eight diabetic patients with poor glycemic control, 28 of whom had active major depression (DSM-IIIR), completed a randomized, placebo-controlled, double-blind trial involving 8 weeks of treatment with nortriptyline targeted to therapeutic plasma levels (50-150 ng/ml). Depression improvement was determined with the Beck Depression Inventory; glucose control was measured by glycated hemoglobin levels. Compliance behavior was assessed using medication dispensing devices and glucometers equipped with electronic memory.
  
  
  RESULTS
  The reduction in depression symptoms was significantly greater in depressed patients treated with nortriptyline compared with those receiving placebo (-10.2 vs -5.8, p = .03). Nortriptyline was not statistically superior to placebo in reducing glycated hemoglobin of the depressed subjects (p = .5). However, path analysis indicated that the direct effect of nortriptyline was to worsen glycemic control whereas depression improvement had an independent beneficial effect on glycated hemoglobin. These findings were not explained by the relationships of nortriptyline treatment to weight change (r = -0.21, p = .31) or depression improvement to compliance with the protocol for self-monitoring of blood glucose (r = 0.01, p = .97).
  
  
  CONCLUSIONS
  Major depression in diabetic patients can be effectively treated with nortriptyline at the expense of a direct hyperglycemic effect. Path analysis demonstrated a treatment-independent effect of depression improvement on glycemic control, suggesting that a more ideal antidepressant agent may both restore mental health and improve medical outcome.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA. lustmanp@psychiatry.wust1.edu
authors.forename: P J
authors.initials: PJ
authors.lastname: Lustman
authors.forename: L S
authors.initials: LS
authors.lastname: Griffith
authors.forename: R E
authors.initials: RE
authors.lastname: Clouse
authors.forename: K E
authors.initials: KE
authors.lastname: Freedland
authors.forename: S A
authors.initials: SA
authors.lastname: Eisen
authors.forename: E H
authors.initials: EH
authors.lastname: Rubin
authors.forename: R M
authors.initials: RM
authors.lastname: Carney
authors.forename: J B
authors.initials: JB
authors.lastname: McGill
mesh_terms: D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000523:psychology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000523:psychology*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000009:adverse effects / Q000627:therapeutic use*; D010349:Patient Compliance / Q000523:psychology; D010555:Personality Inventory; D016896:Treatment Outcome
chemical_list: D000929:Antidepressive Agents, Tricyclic; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D009661:Nortriptyline