Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects.
BACKGROUND
This study was designed to evaluate the effect of combining bupropion sustained release (SR) with venlafaxine, paroxetine, or fluoxetine in patients who reported unacceptable sexual dysfunction when treated with monotherapy with the latter 3 agents.


METHODS
Following a minimum of 6 weeks of antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI) or venlafaxine (a serotonin-norepinephrine reuptake inhibitor), eligible subjects received a further 8 weeks of monitored combination therapy with bupropion SR at a dose of 150 mg/day with no alterations to index antidepressant dosing.


RESULTS
There was a clinically significant benefit in 14 (78%) of 18 partial responders or nonresponders, and 33% (N = 6) achieved a full response (chi2= 8.06, df = 2, p = .017). Sexual dysfunction, particularly a decrease in orgasmic delay, was also significantly improved with combination therapy (men: paired t = -2.1, df = 6, p = .08; women: paired t = -3.0, df = 7, p = .02). Plasma monitoring of drugs and their metabolites revealed a statistically significant increase in venlafaxine levels (F = 6.89, df = 4,24; p = .001) accompanied by a decrease in O-desmethylvenlafaxine (F = 14.26; df = 4,24; p < .0005) during combined treatment with bupropion SR. There were no statistically significant changes in plasma levels of SSRIs (paroxetine and fluoxetine) during the trial.


CONCLUSIONS
Bupropion had an effect on the pharmacokinetics of venlafaxine but not those of the SSRIs. Further investigation of combination treatments under randomized, double-blind conditions is recommended.
Kennedy
Sidney H
SH
Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Ontario, Canada.
McCann
Sonia M
SM
Masellis
Mario
M
McIntyre
Roger S
RS
Raskin
Joel
J
McKay
Gordon
G
Baker
Glen B
GB
D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D016642:Bupropion / Q000494:pharmacology* / Q000627:therapeutic use; D003511:Cyclohexanols / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012725:Sexual Behavior / Q000187:drug effects*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D016642:Bupropion; D003511:Cyclohexanols; D019389:Cytochrome P-450 CYP2D6; D018765:Dopamine Uptake Inhibitors; D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride