For an adult patient on a selective serotonin reuptake inhibitor (SSRI) or serotonin‑norepinephrine reuptake inhibitor (SNRI) experiencing loss of libido and erectile dysfunction, would flibanserin be a better treatment option?

Flibanserin is NOT the Appropriate Treatment for SSRI/SNRI-Induced Sexual Dysfunction

For patients experiencing loss of libido and erectile dysfunction from SSRI/SNRI therapy, switching to bupropion is the evidence-based first-line intervention, not adding flibanserin. 1

Why Flibanserin is the Wrong Choice

Flibanserin is FDA-approved exclusively for primary hypoactive sexual desire disorder in premenopausal women—not for antidepressant-induced sexual dysfunction in either sex. 2 The drug has several critical limitations in your clinical scenario:

• Flibanserin does not address erectile dysfunction, which is a primary concern in your patient. It targets female sexual desire through central neurotransmitter modulation (increasing dopamine/norepinephrine, decreasing serotonin). 3

• No evidence supports flibanserin for male patients with sexual dysfunction of any etiology. 2

• Flibanserin has not been studied specifically for SSRI/SNRI-induced sexual dysfunction—the ASCO guidelines explicitly note it "has not been evaluated in women with a history of cancer or those on endocrine therapy," and the risk/benefit ratio remains uncertain even in the approved population. 2

• Significant adverse effects include dizziness, somnolence, nausea, and fatigue in clinical trials, with these side effects being substantial enough that the NCCN considers the FDA approval "controversial" and requiring future confirmatory studies. 2

The Evidence-Based Treatment Algorithm

First-Line: Switch to Bupropion

The American College of Physicians recommends bupropion as first-line therapy when sexual dysfunction occurs with SSRIs/SNRIs, with sexual dysfunction rates of only 8-10% compared to 70.7% for paroxetine and 14-20% for other SSRIs. 1

• Bupropion addresses both decreased libido and erectile dysfunction through dopaminergic and noradrenergic mechanisms without serotonergic effects. 1

• This switch directly removes the causative agent while maintaining antidepressant efficacy. 1

• Critical caveat: Bupropion should not be used in agitated patients or those with seizure disorders due to increased seizure risk. 1

Second-Line: Consider Mirtazapine

If bupropion is contraindicated or ineffective, mirtazapine 15-30 mg at bedtime has minimal to no sexual side effects and may actually improve sexual function. 4

• Mirtazapine causes sedation and weight gain, which can be therapeutic for patients with insomnia or poor appetite but undesirable for others. 1, 4

Adjunctive Treatment for Erectile Dysfunction

If erectile dysfunction persists after antidepressant switch, PDE5 inhibitors (sildenafil, tadalafil, vardenafil) are the evidence-based first-line treatment for erectile dysfunction itself. 2

• The European Association of Urology guidelines identify PDE5 inhibitors as first-line pharmacotherapy for erectile dysfunction, with sildenafil revolutionizing management since 1998. 2

• These agents can be safely combined with non-serotonergic antidepressants like bupropion. 2

Management of Persistent Libido Issues

If libido remains impaired after optimizing antidepressant therapy:

• Ensure testosterone levels are normal (total morning testosterone >300 ng/dL), as low testosterone contributes to decreased libido independent of medication effects. 2, 1

• Referral to a sexual health specialist is recommended for persistent symptoms despite medication optimization. 2, 1

• Psychosocial interventions including sexual skills training and cognitive behavioral therapy can complement pharmacological management. 2

Common Pitfalls to Avoid

• Do not add flibanserin to ongoing SSRI/SNRI therapy—while one small trial (n=73) suggested safety when combining flibanserin with serotonergic antidepressants, this does not establish efficacy for treating antidepressant-induced dysfunction, and the study was terminated early by the sponsor. 5

• Do not use buspirone—the American College of Physicians explicitly recommends against buspirone for managing SSRI-induced sexual side effects, as there is no evidence supporting its effectiveness. 1

• Avoid "drug holidays" or dose reduction as primary strategies—these compromise depression control and have inconsistent efficacy. The definitive solution is switching to an antidepressant with lower sexual dysfunction liability. 1

• Monitor for discontinuation syndrome when tapering SSRIs/SNRIs—venlafaxine particularly requires slow discontinuation to avoid "brain zaps," worsening symptoms, and other neurological effects. 4