title: Combining a dopamine agonist and selective serotonin reuptake inhibitor for the treatment of depression: a double-blind, randomized pilot study.
abstract: BACKGROUND
  Antidepressants that act on two or more amine neurotransmitters may confer higher remission rates when first-line agents affecting a single neurotransmitter have failed. Pramipexole, a dopamine agonist, has antidepressant effects in patients with major depressive disorder (MDD). This pilot study examined the efficacy and safety of combination therapy with pramipexole and the selective serotonin reuptake inhibitor (SSRI) escitalopram in MDD.
  
  
  METHODS
  In this double-blind, controlled, pilot study, 39 patients with DSM-IV MDD who had failed to respond to a standard antidepressant treatment trial were randomized to receive pramipexole (n=13), escitalopram (n=13), or their combination (n=13) for six weeks. Pramipexole was started at 0.375 mg/day and titrated weekly up to 2.25 mg/day; escitalopram dosage remained at 10 mg/day. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS).
  
  
  RESULTS
  Subjects receiving pramipexole monotherapy had significantly lower MADRS scores than the combination group (p=0.01); no other primary drug comparisons were significant. The combination group had a substantially higher dropout rate than the escitalopram and pramipexole groups (69%, 15%, 15%, respectively). Only 15% of patients in the combination group tolerated regularly scheduled increases of pramipexole throughout the study, compared with 46% of patients in the pramipexole group.
  
  
  CONCLUSIONS
  Group size was small and the treatment phase lasted for only six weeks.
  
  
  CONCLUSIONS
  The combination of an SSRI and a dopamine agonist was not more effective than either agent alone, nor did it produce a more rapid onset of antidepressant action. Combination therapy with escitalopram and pramipexole may not be well-tolerated.
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Franco-Chaves
authors.forename: Camilo F
authors.initials: CF
authors.lastname: Mateus
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.forename: Pedro E
authors.initials: PE
authors.lastname: Martinez
authors.forename: Alan G
authors.initials: AG
authors.lastname: Mallinger
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D052160:Benzothiazoles / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D000077487:Pramipexole; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D052160:Benzothiazoles; D015283:Citalopram; D018491:Dopamine Agonists; D000077487:Pramipexole; D017367:Selective Serotonin Reuptake Inhibitors