A randomized, double-blind, placebo-controlled trial of pramipexole augmentation in treatment-resistant major depressive disorder

J Clin Psychiatry. 2013 Jul;74(7):e636-41. doi: 10.4088/JCP.12m08093.

Abstract

Background: Multiple treatments for patients with major depressive disorder (MDD) have demonstrated efficacy, but up to one-third of individuals with MDD do not achieve symptomatic remission despite various interventions. Existing augmentation or combination strategies can have substantial safety concerns that may limit their application.

Method: This study investigated the antidepressant efficacy of a flexible dose of the dopamine agonist pramipexole as an adjunct to standard antidepressant treatment in an 8-week, randomized, double-blind, placebo-controlled trial conducted in a tertiary-level depression center. We randomized 60 outpatients (aged 18 to 75 years) with treatment-resistant nonpsychotic MDD (diagnosed according to DSM-IV) to either pramipexole (n = 30) or placebo (n = 30). Treatment resistance was defined as continued depression (Montgomery-Asberg Depression Rating Scale [MADRS] score ≥ 18) despite treatment with at least 1 prior antidepressant in the current depressive episode. Patients were recruited between September 2005 and April 2008. The primary outcome measure was the MADRS score.

Results: The analyses that used a mixed-effects linear regression model indicated a modest but statistically significant benefit for pramipexole (P = .038). The last-observation-carried-forward analyses indicated that 40% and 33% of patients randomized to augmentation with pramipexole achieved response (χ(2) = 1.2, P = .27) and remission (χ(2) = 0.74, P = .61), respectively, compared to 27% and 23% with placebo; however, those differences were not statistically significant. Augmentation with pramipexole was well-tolerated, with no serious adverse effects identified.

Conclusion: For patients who have failed to respond to standard antidepressant therapies, pramipexole is a safe and potentially efficacious augmentation strategy.

Trial registration: ClinicalTrials.gov identifier: NCT00231959.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents* / administration & dosage
  • Antidepressive Agents* / adverse effects
  • Benzothiazoles* / administration & dosage
  • Benzothiazoles* / adverse effects
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Treatment-Resistant / diagnosis
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Dopamine Agonists / administration & dosage
  • Dopamine Agonists / adverse effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Monitoring
  • Drug Synergism
  • Drug Therapy, Combination / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pramipexole
  • Psychiatric Status Rating Scales
  • Remission Induction
  • Treatment Outcome

Substances

  • Antidepressive Agents
  • Benzothiazoles
  • Dopamine Agonists
  • Pramipexole

Associated data

  • ClinicalTrials.gov/NCT00231959