What antidepressant has the lowest sexual side effects?

Antidepressant Selection for Minimal Sexual Side Effects

Bupropion is the clear first-line choice when sexual side effects are a concern, with significantly lower rates of sexual dysfunction compared to SSRIs and SNRIs. 1

Primary Recommendation

• Bupropion should be considered as the first-line antidepressant when sexual dysfunction is a significant concern, with recommended dosing of 150-400 mg/day 1
• The American College of Physicians explicitly states that bupropion has lower rates of sexual adverse events than fluoxetine and sertraline, and this should be discussed before medication selection 1
• In head-to-head comparisons, bupropion causes no more sexual dysfunction than placebo, while SSRIs commonly cause sexual complications 2

Comparative Sexual Dysfunction Rates

SSRIs (Highest Risk)

• Paroxetine has the highest rates of sexual dysfunction among all SSRIs—significantly worse than fluoxetine, fluvoxamine, or sertraline 1
• Fluoxetine causes sexual dysfunction in 57.7-62.9% of patients 3
• Sertraline causes sexual dysfunction in 63% of men and 41% of women, appearing as early as day 7 at doses of 50 mg/day 4

SNRIs (High Risk)

• Venlafaxine, desvenlafaxine, and duloxetine all impair sexual function and should be avoided when libido is a concern 1
• SNRIs reduce libido and cause anorgasmia 1

Bupropion (Lowest Risk)

• Bupropion causes sexual dysfunction in only 15% of men and 7% of women 4
• In healthy men, bupropion does not affect subjective sexual function or nocturnal erections 5

Vortioxetine (Serotonergic - Moderate Risk)

• The FDA label for vortioxetine (Trintellix) warns that it may cause ejaculatory delay/failure, decreased libido, and erectile dysfunction in men, and decreased libido with delayed/absent orgasm in women 6

Critical Safety Considerations for Bupropion

• Seizure risk is increased with bupropion, particularly at doses above 300 mg/day 1
• Contraindicated in patients with seizure disorders, bulimia, or anorexia nervosa 1
• Use caution in patients with history of seizures, eating disorders, or abrupt alcohol/benzodiazepine discontinuation 1

Clinical Decision Algorithm

Step 1: Assess for bupropion contraindications

• History of seizures, eating disorders, or bipolar disorder 1

Step 2: If no contraindications exist

• Start bupropion 150 mg/day, can increase to 300-400 mg/day 1
• Most improvement occurs within first 2 weeks at low doses (100-200 mg/day) 7

Step 3: If comorbid anxiety disorder is present

• SSRIs may still be preferred despite sexual side effects, as bupropion has less established efficacy for anxiety 1
• In this scenario, consider starting an SSRI with lower sexual dysfunction rates (avoid paroxetine) 1

Step 4: Monitor response

• Assess within 1-2 weeks of initiating therapy 1
• If inadequate response within 6-8 weeks, consider medication adjustment 1

Important Clinical Caveats

• Sexual dysfunction rates are substantially underreported in clinical trials, so real-world incidence is likely higher than published rates 1
• Always inquire about sexual function before starting treatment and specifically ask about changes during treatment, as patients rarely report this spontaneously 6
• When evaluating sexual dysfunction, obtain detailed history including timing of symptom onset, as symptoms may have other causes including the underlying psychiatric disorder 6
• Cognitive behavioral therapy should be considered as an alternative to pharmacotherapy entirely, as it has similar efficacy with no sexual side effects and lower relapse rates 1