Which Selective Serotonin Reuptake Inhibitor (SSRI) has the least sexual side effects?

SSRI with Least Sexual Side Effects

Bupropion has significantly lower rates of sexual side effects compared to SSRIs and should be considered when sexual dysfunction is a concern. 1

Comparison of Sexual Side Effects Among SSRIs

When selecting an SSRI, the following hierarchy exists regarding sexual side effects:

1. Paroxetine (highest risk): Has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 2. FDA labeling shows sexual side effects including decreased libido (0-9% in females, 6-15% in males), ejaculatory disturbance (13-28% in males), and impotence (2-9%) 3.

2. Sertraline (moderate risk): Shows lower rates of sexual dysfunction than paroxetine but still significant 2. FDA data indicates ejaculation failure (14% vs 1% placebo) and decreased libido (6% vs 1% placebo) 4.

3. Fluoxetine (moderate risk): Has lower rates of sexual dysfunction than paroxetine but higher than bupropion 2.

4. Fluvoxamine (moderate risk): Has lower rates of sexual dysfunction than paroxetine 2.

5. Citalopram/Escitalopram: Limited comparative data in guidelines, but research suggests similar profiles to other SSRIs except paroxetine.

Non-SSRI Alternatives with Lower Sexual Side Effects

• Bupropion: Has significantly lower rates of sexual adverse events than fluoxetine or sertraline 2. Often considered first-line when sexual dysfunction is a major concern.

• Mirtazapine: Shows lower incidence of sexual dysfunction (24.4%) compared to SSRIs (58-73%) 5.

• Vortioxetine: Recent evidence shows significantly less treatment-emergent sexual dysfunction compared to paroxetine and was not significantly different from placebo in healthy adults 6. In patients with SSRI-induced sexual dysfunction, switching to vortioxetine showed greater improvements in sexual functioning compared to escitalopram 7.

Mechanism of Sexual Side Effects

Sexual dysfunction with SSRIs is related to:

• Serotonergic effects (primary mechanism)
• Dopamine reuptake inhibition (less with more selective agents)
• Anticholinergic effects (particularly with paroxetine)
• Nitric oxide synthetase inhibition

Management Strategies for SSRI-Induced Sexual Dysfunction

If an SSRI must be used despite sexual side effects:

1. Dose adjustment: Lower doses may reduce sexual side effects while maintaining efficacy 1

   • Example: Fluoxetine at doses as low as 5 mg/day may still provide clinical benefit with fewer side effects

2. Situational dosing: Taking medication only at specific times

   • Example: Sertraline 50 mg taken 4-8 hours before intercourse rather than daily dosing 1

3. Switch to an alternative agent:

   • Switching to vortioxetine has shown effectiveness in improving sexual function in 83.8% of patients with previous antidepressant-related sexual dysfunction 8

Important Clinical Considerations

• Sexual side effects are often underreported - absolute rates are likely higher than documented in clinical trials 2
• Different phases of sexual response may be affected differently based on gender 1
• Sexual dysfunction is a common reason for antidepressant discontinuation, with >35% of patients discontinuing treatment due to this side effect 8
• Only 15-30% of sexual side effects are spontaneously reported by patients, highlighting the importance of direct questioning 8

Pitfalls to Avoid

• Assuming all SSRIs have equivalent sexual side effect profiles
• Failing to specifically ask about sexual side effects during follow-up visits
• Overlooking the impact of sexual dysfunction on medication adherence and quality of life
• Ignoring that sexual dysfunction may be part of depression itself, not just medication-related

When sexual functioning is a priority concern, bupropion should be considered first, followed by mirtazapine or vortioxetine. If an SSRI is required, fluoxetine or fluvoxamine would be preferred over sertraline or paroxetine.