What antidepressants have a low risk of decreasing libido in patients?

Bupropion is the Clear First-Line Choice for Antidepressants with Minimal Libido Impact

Bupropion should be your primary antidepressant selection when sexual function preservation is a concern, as it has significantly lower rates of sexual dysfunction compared to SSRIs and may even enhance sexual function in some patients. 1, 2

Evidence-Based Medication Selection

Bupropion: The Optimal Choice

• Bupropion demonstrates dramatically lower sexual dysfunction rates compared to SSRIs: only 15% in men and 7% in women versus 63% and 41% respectively with sertraline. 3
• The American College of Physicians explicitly recommends bupropion as having lower rates of sexual adverse events than fluoxetine and sertraline. 1
• Beyond simply avoiding sexual side effects, 77% of bupropion-treated patients reported at least one aspect of heightened sexual functioning, including increased libido, arousal intensity, and orgasm quality. 4
• Effective dosing ranges from 150-400 mg/day, with sustained-release formulations preferred. 1

SSRIs to Avoid When Libido is a Priority

• Paroxetine has the highest rates of sexual dysfunction among all SSRIs and should be specifically avoided. 5, 1
• Sertraline and fluoxetine cause sexual dysfunction in the majority of patients (41-63%), with effects appearing as early as day 7 of treatment at even the lowest doses (50 mg/day sertraline). 3
• SNRIs (venlafaxine, desvenlafaxine, duloxetine) also significantly impair sexual function and should be avoided when libido preservation is important. 1

If SSRIs Are Necessary (e.g., comorbid anxiety)

Among SSRIs, the hierarchy from best to worst for sexual side effects is:

1. Sertraline or fluoxetine (moderate risk)
2. Fluvoxamine or nefazodone (moderate-high risk)
3. Paroxetine (highest risk - avoid) 1

Critical Safety Considerations for Bupropion

Seizure Risk Management

• Bupropion carries an increased seizure risk, particularly at doses above 300 mg/day. 1, 2
• Absolute contraindications include: seizure disorders, bulimia, anorexia nervosa, and abrupt discontinuation of alcohol or benzodiazepines. 1
• Use caution in patients with predisposing factors: head trauma history, CNS tumors, or concurrent medications that lower seizure threshold. 1

Other Common Side Effects

• Dry mouth occurs more frequently with bupropion (19%) than sertraline (14%). 6
• Headache is common (30-40%) but similar across all antidepressants. 6
• Bupropion causes significantly less nausea (18% vs 31%), diarrhea (7% vs 26%), and somnolence (3% vs 17%) compared to sertraline. 6

Management Algorithm for Existing SSRI-Induced Sexual Dysfunction

If a patient is already on an SSRI with sexual side effects:

1. First-line: Switch to bupropion - 24 of 28 patients (86%) with SSRI-induced sexual dysfunction had complete resolution when switched to bupropion. 7

2. Alternative: Add a PDE5 inhibitor (sildenafil or tadalafil) if switching is not feasible, particularly for erectile dysfunction in men. 1

3. Consider buspirone augmentation (off-label) for low libido, though evidence is limited. 1

Important Clinical Caveats

• Sexual dysfunction is substantially underreported in clinical trials - real-world incidence is likely higher than published rates, so proactive screening is essential. 5, 1
• The four patients who failed to improve sexually on bupropion had either diabetes or lifelong sexual dysfunction unrelated to medications, suggesting bupropion's failure rate is minimal in otherwise healthy patients. 7
• Efficacy for treating depression is equivalent between bupropion and SSRIs, so choosing bupropion involves no compromise in antidepressant effectiveness. 2, 6
• For patients with comorbid anxiety disorders, SSRIs may still be preferred despite sexual side effects, as bupropion has less established efficacy for anxiety. 1