Antidepressants with Least Effect on Sexual Drive
Bupropion is the antidepressant with the least effect on sexual drive and should be considered as a first-line option when sexual dysfunction is a concern for patients requiring antidepressant therapy. 1
Comparative Sexual Side Effect Profiles
- Bupropion has significantly lower rates of sexual adverse events compared to SSRIs (selective serotonin reuptake inhibitors) and other second-generation antidepressants 1, 2
- Sexual dysfunction is a common side effect of SSRIs, with significant differences in incidence among medications 1
- Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 2
- In clinical studies, bupropion demonstrated sexual dysfunction rates of only 7-15% compared to 41-63% with sertraline 3
- Sexual side effects can occur as early as day 7 of treatment with SSRIs, even at low doses 3
Evidence Supporting Bupropion's Favorable Sexual Profile
- Bupropion is relatively free of adverse sexual effects compared to other antidepressants 4
- In controlled trials, bupropion did not affect sexual function or nocturnal erections in healthy men 5
- When patients with SSRI-induced sexual dysfunction were switched to bupropion, 46% of women and 75% of men experienced improvement in sexual function 6
- In long-term clinical use, sexual dysfunction resolved in 24 of 28 patients (p<0.001) when they were transferred from other antidepressants to bupropion 7
Other Antidepressants with Lower Sexual Side Effects
- Vilazodone may cause sexual dysfunction, but the FDA label specifically mentions the importance of discussing potential management strategies for sexual side effects, suggesting awareness of this concern 8
- Mirtazapine has a faster onset of action than some SSRIs but may have different side effect profiles 2
Important Clinical Considerations
- While bupropion has fewer sexual side effects, it may be associated with an increased risk for seizures compared to SSRIs 1, 4
- Common side effects of bupropion include nervousness and insomnia 4
- Bupropion undergoes metabolic transformation through hepatic CYP2B6 and has inhibitory effects on CYP2D6, raising concern for drug interactions 4
- For patients with comorbid anxiety disorders, SSRIs may still be preferred despite sexual side effects, as bupropion has less established efficacy for anxiety 1
- Sexual dysfunction is likely underreported in clinical trials and may be more prevalent than documented 1, 9
Monitoring and Management
- Assess patient response and adverse effects within 1-2 weeks of initiating therapy 1
- If inadequate response to initial therapy occurs within 6-8 weeks, consider medication adjustment 1
- When switching medications, patients should be monitored for discontinuation symptoms and potential changes in depressive symptoms 1
- It is important for prescribers to inquire about sexual function prior to initiation of antidepressant therapy and to inquire specifically about changes in sexual function during treatment 8