How do you manage sexual side effects from Selective Serotonin Reuptake Inhibitors (SSRIs)?

Management of SSRI-Induced Sexual Dysfunction

When sexual dysfunction occurs with SSRIs, first-line management includes switching to bupropion, mirtazapine, or adding mirtazapine 7.5-30 mg at bedtime as adjunctive therapy, as these agents have significantly lower rates of sexual adverse effects. 1, 2

Assessment and Documentation

• Actively assess sexual function at baseline, at regular intervals during treatment, and after discontinuation — patients rarely volunteer this information spontaneously 2, 3
• Sexual dysfunction occurs in 50% or more of SSRI-treated patients, substantially higher than rates reported in package inserts because patients must be questioned directly 3
• The FDA label for sertraline documents ejaculation failure in 14% of male patients (versus 1% placebo), decreased libido in 6% (versus 1% placebo), and these figures likely underestimate true incidence 4

Risk Stratification by Agent

SSRIs and SNRIs carry the highest risk of sexual dysfunction, with paroxetine associated with the greatest rate among SSRIs 2, 5:

• Highest risk: SSRIs (especially paroxetine) and SNRIs 2, 5
• Moderate risk: Tricyclic antidepressants except clomipramine 2
• Lower risk: Mirtazapine 2
• Lowest risk: Bupropion, moclobemide, agomelatine, reboxetine 2

Management Algorithm

First Strategy: Switch Antidepressants

Switch to bupropion, which has significantly lower rates of sexual adverse events compared to SSRIs like fluoxetine and sertraline 1:

• Bupropion is the preferred alternative when sexual dysfunction is intolerable 3, 5
• Other alternatives include mirtazapine, nefazodone, vilazodone, and vortioxetine 3, 5
• Avoid switching to other SSRIs or SNRIs as they carry similar risk 2

Second Strategy: Adjunctive Mirtazapine

If the patient responds solely to SSRIs and cannot switch, add mirtazapine 7.5-15 mg at bedtime, titrating to 30-45 mg daily as needed 1:

• Mirtazapine can mitigate SSRI-induced sexual dysfunction while maintaining antidepressant efficacy 1
• Common side effects include initial sedation, irritability, and potential weight gain 1
• The sedation and appetite stimulation may be undesirable for some patients 1

Third Strategy: Dose Reduction

• Reduce the SSRI dose, as sexual dysfunction appears strongly dose-related 6, 7
• This strategy balances sexual function improvement against potential loss of antidepressant efficacy 6

Fourth Strategy: Drug Holidays

• Consider scheduled "drug holidays" (temporary discontinuation before sexual activity) 6, 3
• Caution: Patients should avoid sudden cessation or rapid dose reduction of daily SSRIs as this may precipitate SSRI withdrawal syndrome 8
• This approach is less reliable and may compromise antidepressant efficacy 6

Fifth Strategy: Watchful Waiting

• Some patients develop tolerance to sexual side effects over time 3, 7
• This is the least reliable strategy and risks medication non-adherence 2

Critical Warnings

Post-SSRI Sexual Dysfunction (PSSD): A rare but important adverse effect where sexual dysfunction persists after antidepressant discontinuation 2:

• Consider PSSD when sexual dysfunction was absent before starting antidepressants but develops during treatment and persists after drug cessation 2
• This occurs even after remission from depression 2

Serotonin Syndrome Risk: When adding adjunctive agents, monitor for serotonin syndrome (clonus, tremor, hyperreflexia, agitation, diaphoresis, fever) 8:

• Most often occurs with simultaneous use of multiple serotonergic drugs 8
• Treatment includes cessation of serotonergic agents; benzodiazepines may manage acute symptoms 8

Impact on Treatment Adherence

Sexual dysfunction is a leading cause of antidepressant non-adherence 2, 7:

• Approximately 63% of patients on second-generation antidepressants experience at least one adverse effect 8
• Sexual side effects significantly impact quality of life and treatment compliance 7
• Proactive discussion and management prevent treatment abandonment 2, 6