Neural correlates of antidepressant-related sexual dysfunction - a placebo-controlled fMRI study on healthy males under subchronic paroxetine and bupropion
Résumé
Sexual dysfunction is a common side effect of serotonin reuptake inhibitors like paroxetine in the treatment of depression imposing a considerable risk on medication adherence and hence therapeutic success. Bupropion, a norepinephrine and dopamine reuptake inhibitor is recommended as an alternative treatment without adverse effects concerning sexual arousal and libido. We investigated the neural bases of paroxetine-related subjective sexual dysfunction as compared to bupropion and placebo. We scanned 18 healthy, heterosexual males in a randomized double-blind within-subjects design while watching video clips of erotic and non-erotic content under steady state conditions after taking 20 mg of paroxetine, 150 mg of bupropion and placebo for 7 days each. Under paroxetine, ratings of subjective sexual dysfunction increased compared to placebo or bupropion. Activation along the anterior cingulate cortex including subgenual, pregenual and midcingulate cortices, in the ventral striatum and midbrain was decreased as compared to placebo. By contrast, bupropion let subjective ratings and ACC activations unchanged and increased activity of brain regions including posterior midcingulate cortex, mediodorsal thalamus and extended amygdala relative to placebo and paroxetine. Brain regions that have been related to the processing of motivational (ventral striatum), emotional, and autonomic components of erotic stimulation (anterior cingulate) in previous studies showed reduced responsiveness under paroxetine in our study. Drug effects on these regions may be part of the mechanism underlying SSRI-related sexual dysfunction. Increased activation under bupropion may point to an opposite effect that may relate to the lack of impaired sexual functioning.
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