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


METHODS
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.


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


BACKGROUND
ClinicalTrials.gov identifier: NCT00231959.
Depression Clinical and Research Program, Massachusetts General Hospital, One Bowdoin Square, Ste 630, Boston, MA 02114, USA. ccusin@partners.org
Cristina
C
Cusin
Nadia
N
Iovieno
Dan V
DV
Iosifescu
Andrew A
AA
Nierenberg
Maurizio
M
Fava
A John
AJ
Rush
Roy H
RH
Perlis
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D052160:Benzothiazoles / Q000008:administration & dosage / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000175:diagnosis / Q000188:drug therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077487:Pramipexole; D011569:Psychiatric Status Rating Scales; D012074:Remission Induction; D016896:Treatment Outcome
D000928:Antidepressive Agents; D052160:Benzothiazoles; D018491:Dopamine Agonists; D000077487:Pramipexole