What SSRI (Selective Serotonin Reuptake Inhibitor) or SNRI (Serotonin-Norepinephrine Reuptake Inhibitor) has the least sexual side effects?

SSRI/SNRI with Least Sexual Side Effects

Bupropion has significantly fewer sexual side effects compared to SSRIs and SNRIs and should be considered as a first-line agent when sexual dysfunction is a concern. 1

Comparative Sexual Side Effect Profiles

• Bupropion has a significantly lower rate of sexual adverse events than fluoxetine or sertraline 2, 1
• Paroxetine is associated with higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 2, 1
• Sexual dysfunction is a common side effect of SSRIs and SNRIs, with studies showing significantly higher rates in SSRI-treated patients (63% of men and 41% of women) compared to bupropion-treated patients (15% of men and 7% of women) 3
• Sexual side effects with SSRIs can occur as early as day 7 of treatment, even at low doses (50 mg/day of sertraline) 3

Medication Selection Algorithm

1. First choice: Bupropion

   • Least likely to cause sexual dysfunction among antidepressants 1, 4
   • Efficacy comparable to SSRIs for depression treatment 5
   • Consider as first-line when sexual function is a priority 1

2. If bupropion is contraindicated:

   • Consider SSRIs with lower rates of sexual dysfunction:
     • Sertraline has lower rates than paroxetine 2
     • Fluoxetine and fluvoxamine have lower rates than paroxetine 2

3. For patients already on SSRIs with sexual dysfunction:

   • Adding bupropion (100-300 mg/day) can improve SSRI-induced sexual side effects 6, 7
   • Most improvement occurs within the first 2 weeks and at low doses (100-200 mg/day) 6

Important Considerations and Caveats

• While bupropion has fewer sexual side effects, it may be associated with an increased risk for seizures compared to SSRIs 2, 1
• Common side effects of bupropion include nervousness, insomnia, and dry mouth 4, 5
• Venlafaxine (an SNRI) may be associated with increased cardiovascular risks 2, 1
• Sexual dysfunction is likely underreported in clinical trials and may be more prevalent than documented 2, 1
• Vilazodone (an SSRI) also carries warnings about sexual dysfunction, including ejaculatory delay, decreased libido, and erectile dysfunction in men, and decreased libido and delayed or absent orgasm in women 8
• 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 Recommendations

• Assess sexual function prior to initiating antidepressant therapy to establish baseline 8
• Specifically inquire about changes in sexual function during treatment, as patients may not spontaneously report these issues 8
• When evaluating sexual dysfunction, obtain a detailed history including timing of symptom onset to differentiate medication effects from symptoms of depression 8
• Monitor for other potential side effects specific to the chosen medication 2