What antidepressant can be prescribed with minimal impact on libido?

Antidepressant Selection When Libido is a Concern

Bupropion is the first-line antidepressant when sexual function or libido is a concern, with sexual dysfunction rates of only 8-10% compared to 63-70% with SSRIs. 1, 2

Evidence-Based Ranking of Sexual Dysfunction Risk

The American College of Physicians has established clear hierarchies of sexual dysfunction risk among antidepressants:

Lowest Risk:

• Bupropion: 8-10% incidence - significantly lower than all SSRIs 1, 2
• Mirtazapine: lower rates than SSRIs, though causes sedation and weight gain 3

Moderate Risk:

• Sertraline: 14% ejaculatory failure, 6% decreased libido 1
• Fluoxetine: intermediate rates 3
• Citalopram: intermediate rates 3
• Venlafaxine: 37-61% reduction in hot flashes but can affect sexual function, though libido may actually increase in some breast cancer patients 3

Highest Risk:

• Paroxetine: 70.7% incidence - highest of all antidepressants 1, 3

Clinical Decision Algorithm

Step 1: Initial Prescription

• Prescribe bupropion SR 100-150 mg daily, titrating to 300 mg/day as needed for patients where sexual function is a priority 1, 2, 4
• Bupropion demonstrates equivalent antidepressant efficacy to SSRIs while preserving sexual function 4

Step 2: Important Contraindications to Bupropion

• Do NOT use bupropion in patients with:
  • Seizure disorders or conditions that lower seizure threshold 2, 5
  • Agitated patients 1
  • Eating disorders (bulimia/anorexia) 5
  • Abrupt discontinuation of alcohol or benzodiazepines 5

Step 3: Alternative if Bupropion is Contraindicated

• Consider mirtazapine 15-30 mg/day, though this causes sedation and weight gain 3
• If an SSRI must be used, choose sertraline or citalopram over paroxetine or fluoxetine 3, 1

Step 4: If Patient Already on an SSRI with Sexual Dysfunction

• Switch to bupropion rather than augmenting 1
• Taper the SSRI appropriately (fluoxetine requires 10-14 days) 1

Critical Mechanism Differences

Bupropion works through norepinephrine and dopamine reuptake inhibition rather than serotonin, which explains its favorable sexual profile 6:

• Preserves activation in the anterior cingulate cortex, ventral striatum, and midbrain - regions critical for sexual motivation and arousal 6
• SSRIs (particularly paroxetine) decrease activation in these same regions, correlating with subjective sexual dysfunction 6
• Bupropion may even enhance sexual function in some individuals, with 70% reporting improvement in libido, arousal, or orgasmic function 7

Important Caveats

Underreporting of Sexual Dysfunction:

• Published rates of sexual dysfunction in clinical trials are likely significantly underestimated 1
• Real-world rates may be substantially higher than reported figures 1

Drug Interactions:

• Bupropion inhibits CYP2D6, which can increase levels of other antidepressants, antipsychotics, beta-blockers, and Type 1C antiarrhythmics 5
• May reduce tamoxifen efficacy in breast cancer patients by inhibiting conversion to active metabolite, though this effect is less pronounced than with paroxetine or fluoxetine 3, 5

Monitoring Requirements:

• Begin monitoring within 1-2 weeks of initiation for therapeutic response and adverse effects 3
• If no adequate response within 6-8 weeks, modify treatment 3

Special Consideration for Tamoxifen Users:

• If SSRI/SNRI required in breast cancer patients on tamoxifen, choose venlafaxine or citalopram over paroxetine or fluoxetine due to less CYP2D6 inhibition 3
• Bupropion also inhibits CYP2D6 but remains preferable to strong SSRI inhibitors 5