What SSRI (Selective Serotonin Reuptake Inhibitor) or SNRI (Serotonin-Norepinephrine Reuptake Inhibitor) is least associated with sexual dysfunction side effects?

SSRI/SNRI with Least Sexual Dysfunction: Bupropion is the Clear Winner

Bupropion should be your first-line choice when sexual dysfunction is a concern, as it has dramatically lower rates of sexual side effects (8-10%) compared to all SSRIs and SNRIs. 1, 2

Evidence-Based Ranking of Sexual Dysfunction Risk

Lowest Risk (Preferred)

• Bupropion (not technically an SSRI/SNRI) has sexual dysfunction rates of only 8-10%, making it significantly superior to all SSRIs and SNRIs 1, 2
• Bupropion was associated with significantly less sexual dysfunction than both fluoxetine and sertraline in direct comparisons 3, 4

Among True SSRIs (if bupropion is contraindicated)

• Escitalopram and fluvoxamine cause the lowest rates of sexual dysfunction among SSRIs, though exact rates are not specified 2
• Sertraline has moderate sexual dysfunction rates (14% ejaculatory failure in males, 6% decreased libido overall) 2
• Fluoxetine and citalopram have intermediate rates of sexual dysfunction 2
• Paroxetine has the highest rates at 70.7% and should be avoided when sexual function is a concern 1, 2

SNRIs

• Venlafaxine and duloxetine both impair sexual function and should be avoided when libido is a concern 1
• SNRIs are associated with higher discontinuation rates due to adverse effects (including sexual dysfunction) compared to SSRIs as a class 3

Clinical Decision Algorithm

Step 1: Consider Bupropion First

• Start with bupropion 150-400 mg/day when sexual function is a priority 1
• Bupropion has comparable antidepressant efficacy to SSRIs but with dramatically fewer sexual side effects 5, 4, 6

Step 2: Screen for Bupropion Contraindications

• Do not use bupropion in patients with seizure disorders, eating disorders (bulimia/anorexia), or those who are agitated 1, 2
• Seizure risk increases at doses above 300 mg/day 1, 2
• Avoid in patients with abrupt alcohol or benzodiazepine discontinuation 1

Step 3: If Bupropion is Contraindicated, Choose Among SSRIs

• First choice: Escitalopram or fluvoxamine (lowest sexual dysfunction among SSRIs) 2
• Second choice: Sertraline or citalopram (intermediate rates) 2
• Avoid: Paroxetine (70.7% sexual dysfunction rate—the worst offender) 1, 2

Step 4: Consider Mirtazapine as Alternative

• Mirtazapine has lower rates of sexual dysfunction than SSRIs 2
• However, it causes significant sedation and weight gain, which may limit tolerability 3, 2

Critical Caveats and Pitfalls

Underreporting of Sexual Dysfunction

• Sexual dysfunction rates in clinical trials are vastly underreported—real-world incidence is likely much higher than published figures 1, 2
• Proactively ask patients about sexual side effects within 1-2 weeks of starting treatment 1

Anxiety Comorbidity

• Bupropion has less established efficacy for anxiety disorders compared to SSRIs 1
• If significant anxiety is present, you may need to balance sexual side effects against anxiety control 7
• Psychiatrists often avoid prescribing bupropion for patients with high anxiety, despite limited evidence supporting differential response 7

Special Population: Breast Cancer Patients on Tamoxifen

• Avoid paroxetine and fluoxetine in patients on tamoxifen due to CYP2D6 inhibition reducing tamoxifen efficacy 2
• Prefer venlafaxine, citalopram, or bupropion in this population 3, 2

Dose-Related Effects

• Sexual side effects of SSRIs are strongly dose-related—higher doses increase both efficacy and sexual dysfunction 2
• Consider using the minimum effective dose to balance depression control with sexual function 2

Monitoring Requirements

• Assess sexual function and other adverse effects within 1-2 weeks of initiating therapy 1, 2
• If inadequate response or intolerable side effects occur within 6-8 weeks, modify treatment 1, 2
• About 40% of patients discontinue antidepressants within 12 months due to side effects, including sexual dysfunction 2