Addition of the alpha2-antagonist yohimbine to fluoxetine: effects on rate of antidepressant response.
Electrophysiological studies suggest that alpha2-adrenoceptors profoundly affect monoaminergic neurotransmission by enhancing noradrenergic tone and serotonergic firing rates. Recent reports suggest that alpha2-antagonism may hasten and improve the response to antidepressant medications. To test this hypothesis, a randomized double-blind controlled trial was undertaken to determine if the combination of an alpha2-antagonist (yohimbine) with a selective serotonin reuptake agent (SSRI) (fluoxetine) results in more rapid onset of antidepressant action than an SSRI agent alone. In all, 50 subjects with a DSM-IV diagnosis of major depressive disorder confirmed by SCID interview were randomly assigned to receive either fluoxetine 20 mg plus placebo (F/P) or fluxetine 20 mg plus a titrated dose of yohimbine (F/Y). The yohimbine dose was titrated based on blood pressure changes over the treatment period, in a blind-preserving manner. Hamilton depression scale ratings (HDRS) and clinical global impression (CGI) ratings were obtained weekly over a period of 6 weeks. The rate of achieving categorical positive responses was significantly more rapid in the F/Y group compared to the F/P group using both the HDRS and the CGI scales as outcome measures in a survival analysis using a log-rank test (chi2(1) = 5.86, p = 0.016 and chi2(1) = 5.29, p = 0.021, respectively). At the last observed visit, 18 (69%) of the 26 F/Y subjects met the response criteria for CGI compared to 10 (42%) of 24 F/P subjects. Using the HDRS criteria, 17 (65%) of 26 F/Y subject vs 10 (42%) of 24 F/P subjects were responders. The addition of the alpha2-antagonist yohimbine to fluoxetine appears to hasten the antidepressant response. There is also a trend suggesting an increased percentage of responders to the combined treatment at the end of the 6-week trial.
Sanacora
Gerard
G
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. gerard.sanacora@yale.edu
Berman
Robert M
RM
Cappiello
Angela
A
Oren
Dan A
DA
Kugaya
Akira
A
Liu
Nianjun
N
Gueorguieva
Ralitza
R
Fasula
Donna
D
Charney
Dennis S
DS
D000293:Adolescent; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D015016:Yohimbine / Q000627:therapeutic use*
D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D005473:Fluoxetine; D015016:Yohimbine