How do I manage a patient with depression on a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) who is experiencing loss of libido and erectile dysfunction, addressing both the psychogenic cause and the medication‑induced sexual side effect?

Managing Depression with SSRI/SNRI-Induced Sexual Dysfunction

Switch to bupropion as the first-line strategy when a patient on an SSRI or SNRI develops sexual dysfunction, as it maintains antidepressant efficacy while having markedly lower rates of sexual side effects (8–10%) compared to SSRIs. 1

Primary Management Algorithm

Step 1: Confirm the Diagnosis

• Directly inquire about sexual dysfunction, as patients rarely volunteer this information and clinical trial data substantially underreport the true incidence (real-world rates are 40–90% versus published figures of 14–70%). 1, 2
• Rule out contributing medical factors including diabetes, cardiovascular disease, hyponatremia (from SIADH), low testosterone (<300 ng/dL morning level), and concomitant medications that impair sexual function. 1, 2
• Distinguish the specific dysfunction: decreased libido, erectile dysfunction, ejaculatory delay/failure, or anorgasmia, as this guides targeted intervention. 1, 2

Step 2: Switch Antidepressants (Preferred Strategy)

Bupropion is the evidence-based first choice because it addresses both the psychogenic depression and eliminates medication-induced sexual dysfunction simultaneously. 1

• Switching protocol: Taper the current SSRI/SNRI gradually over 10–14 days (longer for fluoxetine due to its 1–3 day half-life) to prevent withdrawal syndrome (dizziness, nausea, headache, flu-like symptoms). 1, 2
• Bupropion contraindications: Do not use in patients with seizure disorders, eating disorders, or those who are highly agitated. 1
• Expected outcome: A prospective FDA trial demonstrated that switching from SSRIs to vortioxetine (another low-sexual-dysfunction agent) produced a 2.2-point improvement on validated sexual function scales while maintaining antidepressant response. 3 Bupropion shows similar or superior sexual tolerability.

Step 3: Alternative Antidepressants if Bupropion is Contraindicated

• Mirtazapine (15–30 mg/day): Lower sexual dysfunction rates than SSRIs, but causes significant sedation and weight gain—advantageous for patients with insomnia or poor appetite, problematic otherwise. 1
• Among SSRIs, if one must be used: Escitalopram, fluvoxamine, sertraline, or citalopram have lower sexual dysfunction rates than paroxetine (which has a 70.7% incidence and should be avoided entirely). 1, 2

Step 4: Dose Reduction (If Switching is Not Feasible)

Reduce the SSRI/SNRI to the minimum effective dose for depression control, as sexual side effects are strongly dose-dependent—higher doses increase both antidepressant efficacy and sexual dysfunction frequency. 1, 2

• Monitor closely: Assess for both maintained antidepressant response and improvement in sexual function within 1–2 weeks, modifying treatment if no adequate response within 6–8 weeks. 1

Step 5: Adjunctive Pharmacotherapy for Specific Dysfunctions

For Erectile Dysfunction (Men)

Add a phosphodiesterase-5 inhibitor (sildenafil or tadalafil) if erectile dysfunction persists despite addressing libido. 1, 4

• Evidence: Sildenafil improved ability to achieve erections by 1.04 points and maintain erections by 1.18 points on validated scales (equivalent to frequency improvement from "sometimes" to "most times"). 4
• Tadalafil: Men were 11.5 times more likely to report improved erectile function versus placebo. 4
• Caveat: PDE5 inhibitors address erectile function but not libido; they are adjunctive, not primary treatment. 1

For Decreased Libido (Men and Women)

Bupropion augmentation at 150 mg twice daily (not once daily) shows benefit, with a standardized mean difference of 1.60 versus placebo. 1, 4

• Dose matters: Studies using 150 mg once daily showed no significant benefit (RR 0.62,95% CI 0.09–4.41), so the higher twice-daily dosing is essential. 4

For Anorgasmia or Ejaculatory Delay

Switching remains the most effective strategy, as adjunctive agents have limited evidence. 1, 5

• Avoid buspirone: The American College of Physicians explicitly recommends against buspirone for SSRI-induced sexual dysfunction due to lack of efficacy. 1

Non-Pharmacologic Adjuncts

Integrate these alongside medication management, not as standalone treatments:

• Vibratory therapy: Enhances orgasm intensity and achievement in patients with SSRI-induced genital sensory loss. 1
• Sex therapy or couples counseling: Helps patients adapt to sensory changes and develop compensatory strategies. 1
• Pelvic floor physical therapy: Addresses co-existing pelvic dysfunction that may compound sexual problems. 1

Critical Safety Considerations

• Monitor for serotonin syndrome when combining serotonergic agents (symptoms: tremor, hyperreflexia, agitation, diaphoresis, fever; severe cases: seizures, rhabdomyolysis). 2
• Never combine SSRIs with MAOIs: Allow 14 days after stopping an MAOI before starting an SSRI, and 21 days after stopping vortioxetine before starting an MAOI. 3
• Screen patients under age 24 for suicidal ideation during dose changes or medication switches, as this subgroup has modestly increased risk. 2
• Check serum sodium in older adults or those with cognitive complaints (confusion, headache, weakness), as SSRIs can precipitate SIADH-induced hyponatremia. 1

Common Pitfalls to Avoid

• Do not wait for spontaneous remission: Sexual dysfunction typically emerges within the first week of SSRI treatment and rarely resolves without intervention. 1, 2
• Avoid paroxetine entirely when sexual function is a concern—it has the highest dysfunction rate (70.7%) among all antidepressants. 1, 2
• Do not use "drug holidays" (weekend interruptions) as a primary strategy—evidence is insufficient and risks SSRI withdrawal syndrome. 1, 2
• Recognize that depression itself causes sexual dysfunction: Approximately 50% of patients with untreated major depression have sexual problems, so maintaining antidepressant efficacy is essential. 6

Special Population: Breast Cancer Patients on Tamoxifen

Use venlafaxine, citalopram, or bupropion instead of paroxetine or fluoxetine, as the latter two inhibit CYP2D6 and reduce tamoxifen conversion to its active metabolite. 1