Pramipexole for bipolar II depression: a placebo-controlled proof of concept study.
BACKGROUND
The original serotonergic and noradrenergic hypotheses do not fully account for the neurobiology of depression or mechanism of action of effective antidepressants. Research implicates a potential role of the dopaminergic system in the pathophysiology of bipolar disorder. The current study was undertaken as a proof of the concept that dopamine agonists will be effective in patients with bipolar II depression.


METHODS
In a double-blind, placebo-controlled study, 21 patients with DSM-IV bipolar II disorder, depressive phase on therapeutic levels of lithium or valproate were randomly assigned to treatment with pramipexole (n = 10) or placebo (n = 11) for 6 weeks. Primary efficacy was assessed by the Montgomery-Asberg Depression Rating Scale.


RESULTS
All subjects except for one in each group completed the study. The analysis of variance for total Montgomery-Asberg Depression Rating Scale scores showed a significant treatment effect. A therapeutic response (>50% decrease in Montgomery-Asberg Depression Rating Scale from baseline) occurred in 60% of patients taking pramipexole and 9% taking placebo (p =.02). One subject on pramipexole and two on placebo developed hypomanic symptoms.


CONCLUSIONS
The dopamine agonist pramipexole was found to have significant antidepressant effects in patients with bipolar II depression.
Zarate
Carlos A
CA
Laboratory of Molecular Pathophysiology, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institute of Health, Department of Human and Health Services, Bethesda, Maryland, USA.
Payne
Jennifer L
JL
Singh
Jaskaran
J
Quiroz
Jorge A
JA
Luckenbaugh
David A
DA
Denicoff
Kirk D
KD
Charney
Dennis S
DS
Manji
Husseini K
HK
D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage*; D018692:Antimanic Agents / Q000627:therapeutic use*; D052160:Benzothiazoles; D001714:Bipolar Disorder / Q000188:drug therapy*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000008:administration & dosage; D010865:Pilot Projects; D000077487:Pramipexole; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D013844:Thiazoles / Q000008:administration & dosage*; D014635:Valproic Acid / Q000627:therapeutic use
D000928:Antidepressive Agents; D018692:Antimanic Agents; D052160:Benzothiazoles; C493593:DRD3 protein, human; D018491:Dopamine Agonists; D009414:Nerve Growth Factors; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013844:Thiazoles; D014635:Valproic Acid; D000077487:Pramipexole; D008094:Lithium