Which selective serotonin reuptake inhibitor (SSRI) is less likely to cause sexual dysfunction in men?

SSRIs and Sexual Dysfunction in Men: Medication Selection

Bupropion is significantly less likely to cause sexual dysfunction in men compared to SSRIs and should be considered as a first-line alternative when sexual side effects are a concern. 1

Comparative Sexual Side Effect Profiles

SSRIs and Sexual Dysfunction

• Sexual dysfunction is a common side effect of SSRIs, with significant differences in incidence among medications 1
• Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 1
• According to FDA data, paroxetine is associated with ejaculatory disturbance rates of 13-28% and decreased libido in 6-15% of male patients 2
• Sertraline causes ejaculation failure in approximately 14% of men and decreased libido in 6% of patients 3

Bupropion as a Superior Alternative

• Bupropion has a significantly lower rate of sexual adverse events than fluoxetine or sertraline 1
• In a double-blind comparison study, only 15% of men taking bupropion SR developed sexual dysfunction compared to 63% of men taking sertraline 4
• Bupropion's mechanism as a dopamine-norepinephrine reuptake inhibitor likely contributes to its favorable sexual side effect profile 5, 6

Neurobiological Basis for Differences

• Brain imaging studies show that paroxetine reduces activation in regions associated with sexual motivation (ventral striatum) and emotional/autonomic components of sexual arousal (anterior cingulate cortex) 5
• Bupropion increases activation in regions including posterior midcingulate cortex, mediodorsal thalamus, and extended amygdala compared to paroxetine 5
• These neurobiological differences likely explain the clinical observations of reduced sexual dysfunction with bupropion 5

Management Options

First-line Approach

• For patients requiring antidepressant therapy where sexual dysfunction is a significant concern, bupropion should be considered as a first-line agent 1
• Bupropion is as effective as SSRIs for treating depression while causing significantly fewer sexual side effects 6

For Patients Already on SSRIs

• Adding bupropion to an existing SSRI regimen can effectively treat SSRI-induced sexual dysfunction in 66-75% of male patients 7, 8
• Bupropion can be used either as a scheduled daily medication or on an as-needed basis 1-2 hours before sexual activity 7
• Starting doses of 75-150mg of bupropion taken 1-2 hours before sexual activity can be effective, with potential increase to 75mg three times daily if needed 7

Important Caveats and Considerations

• While bupropion has fewer sexual side effects, it may be associated with an increased risk for seizures compared to SSRIs 1
• Venlafaxine may be associated with increased cardiovascular risks 1
• Sexual dysfunction is likely underreported in clinical trials and may be more prevalent than documented 1
• When switching medications, patients should be monitored for discontinuation symptoms and potential changes in depressive symptoms 1
• For patients with comorbid anxiety disorders, SSRIs may still be preferred despite sexual side effects, as bupropion has less established efficacy for anxiety 1

Monitoring and Follow-up

• Assess patient response and adverse effects within 1-2 weeks of initiating therapy 1
• Physicians should routinely inquire about sexual side effects, as patients may be reluctant to report them spontaneously 3, 2
• If inadequate response to initial therapy occurs within 6-8 weeks, consider medication adjustment 1