Antidepressants with the lowest sexual side effects

Bupropion, mirtazapine, vortioxetine, vilazodone, and trazodone have the lowest rates of sexual dysfunction among antidepressants. Which drug to choose when preserving sexual function is a priority, and how the mechanisms differ.

Medically reviewed by Shariq Refai, MD, MBA Last reviewed: July 2026

Ranking (lowest to highest sexual side effect rates)

Very low (may improve sexual function):

Bupropion (Wellbutrin, Zyban): Dopamine and norepinephrine reuptake inhibitor, no serotonergic activity. Sexual side effect rates in trials comparable to placebo. Sometimes added to SSRIs specifically for sexual side effects with modest evidence of benefit. Sometimes improves libido or sexual function in patients who previously had SSRI-induced dysfunction.

Low:

Mirtazapine (Remeron): 5-HT2A and 5-HT2C antagonism plus H1 antagonism. Sexual side effects uncommon. Trade-off: significant weight gain (see weight gain) and sedation.
Vortioxetine (Trintellix): Multimodal serotonergic drug with 5-HT1A partial agonism, 5-HT1B partial agonism, 5-HT3, 5-HT7 antagonism, plus SERT inhibition. Sexual side effect rates in trials lower than standard SSRIs, particularly at 5 to 10 mg (rates increase somewhat at 20 mg).
Vilazodone (Viibryd): SSRI plus 5-HT1A partial agonism. Sexual side effect rates in trials lower than standard SSRIs.
Trazodone: Serotonin modulator. Low sexual side effect rates but priapism risk in men (rare but medical emergency). Rarely used as primary antidepressant due to sedation.

Moderate (but variable):

Fluoxetine (Prozac): Among SSRIs, possibly slightly lower rates than paroxetine or citalopram, but studies vary.
Nefazodone (Serzone): Serotonin modulator similar mechanism to trazodone. Low sexual side effects but very limited use due to hepatotoxicity black box warning.

Higher (standard SSRI/SNRI range):

Sertraline (Zoloft)
Escitalopram (Lexapro)
Citalopram (Celexa)
Duloxetine (Cymbalta)
Venlafaxine (Effexor)
Desvenlafaxine (Pristiq)

Highest:

Paroxetine (Paxil): Consistently highest sexual side effect rates among SSRIs.
TCAs (amitriptyline, imipramine, clomipramine): via serotonergic effect plus anticholinergic effect.
MAOIs (phenelzine, tranylcypromine): substantial sexual side effects.

Why bupropion works differently

Sexual response requires dopamine (motivation, arousal, orgasm) and nitric oxide (genital arousal). Bupropion enhances dopamine transmission by blocking DAT and increasing dopamine release. It does not affect serotonin, so it avoids the 5-HT2A activation that dampens sexual response with SSRIs.

The proposed benefit of bupropion for sexual function has been studied. Trials of bupropion added to SSRIs for sexual dysfunction show modest but statistically significant improvement in about 30 to 40 percent of patients. As monotherapy, bupropion has sexual side effect rates comparable to placebo.

When to consider these drugs first

Depression with priority on preserving sexual function: bupropion is first-line for most patients. Mirtazapine, vortioxetine, or vilazodone as second-line if bupropion causes activation, insomnia, or seizure concerns.

Post-SSRI sexual dysfunction (PSSD): See sexual dysfunction page. No consistently effective treatment, but anecdotal reports of benefit from bupropion, vortioxetine, or low-dose aripiprazole.

Depression with sexual dysfunction as a primary complaint: sexual dysfunction is a symptom of depression itself. Treating the depression can improve sexual function even before switching drugs. Bupropion, vortioxetine, or mirtazapine may hit both problems simultaneously.

Switching from an SSRI that caused sexual dysfunction: cross-taper to bupropion, mirtazapine, or vortioxetine typically resolves the sexual side effects within 4 to 8 weeks after the SSRI is fully discontinued.

Trade-offs

Bupropion:

Pros: no sexual side effects, no weight gain (may cause modest weight loss), no sedation
Cons: seizure threshold lowering (contraindicated in seizure disorder, eating disorders); can cause insomnia and activation; not effective for anxiety-predominant presentations

Mirtazapine:

Pros: no sexual side effects, good for insomnia, may help appetite loss
Cons: significant weight gain (see weight gain), sedation, dry mouth

Vortioxetine:

Pros: low sexual side effects, may have modest cognitive benefit, well tolerated
Cons: expensive (branded, no generic yet); modest antidepressant effect size in some studies

Vilazodone:

Pros: low sexual side effects, 5-HT1A partial agonism may have anxiolytic effect
Cons: nausea (must be taken with food), expensive

Common questions

Which antidepressant is the least likely to cause sexual dysfunction? Bupropion. Rates of sexual dysfunction in bupropion trials are comparable to placebo. It may actually improve sexual function in some patients.

Does bupropion help SSRI-induced sexual dysfunction? Yes, modestly. Adding bupropion 150 to 300 mg per day to an SSRI improves sexual function in about 30 to 40 percent of patients in trials. Effect size is not large but real.

Is vortioxetine better than SSRIs for sexual side effects? Yes, at 5 to 10 mg dose. Rates increase somewhat at 20 mg. Direct comparisons with SSRIs show meaningfully lower sexual side effect rates.

What about mirtazapine? Mirtazapine has low sexual side effect rates. The main trade-off is significant weight gain (average 3 to 4 kg in first year) and sedation. For patients where weight is not a concern, it's a strong option.

Does trazodone cause sexual problems? Not typically. Trazodone has low sexual side effect rates. But it carries priapism risk in men, which is rare but a medical emergency requiring emergency care.

Are there differences among SSRIs for sexual side effects? Paroxetine consistently causes the most sexual side effects. Citalopram is next. Sertraline, escitalopram, and fluoxetine cluster together in the middle. The differences among SSRIs are modest compared to the difference between SSRIs and bupropion.

What if bupropion doesn't work for me? Bupropion is less effective for anxiety-predominant depression. If bupropion is inadequate or causes activation, insomnia, or is contraindicated, mirtazapine, vortioxetine, or vilazodone are the alternatives with low sexual side effect profiles.

Should I add bupropion or switch to bupropion? Depends on whether the current antidepressant is working. If it's working for depression but causing sexual side effects, adding bupropion 150 to 300 mg is a reasonable strategy. If it's not working well or causing multiple side effects, switching to bupropion monotherapy is the cleaner option.

Sources

Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol. 2009;29(3):259-266.
Clayton AH, Croft HA, Handiwala L. Antidepressants and sexual dysfunction: mechanisms and clinical implications. Postgrad Med. 2014;126(2):91-99.
Jacobsen PL, Mahableshwarkar AR, Chen Y, Chrones L, Clayton AH. Effect of vortioxetine vs. escitalopram on sexual functioning in adults with well-treated major depressive disorder experiencing SSRI-induced sexual dysfunction. J Sex Med. 2015;12(10):2036-2048.
Clayton AH, Kennedy SH, Edwards JB, Gallipoli S, Reed CR. The effect of vilazodone on sexual function during the treatment of major depressive disorder. J Sex Med. 2013;10(10):2465-2476.
Zisook S, Rush AJ, Haight BR, et al. Use of bupropion in combination with serotonin reuptake inhibitors. Biol Psychiatry. 2006;59(3):203-210.

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