What is the best course of action for a patient experiencing low libido and extreme fatigue while taking Buspar (buspirone), Wellbutrin (bupropion), and Zoloft (sertraline)?

Management of Low Libido and Fatigue in a Patient on Buspar, Wellbutrin, and Zoloft

The most likely culprit is Zoloft (sertraline), and you should either switch to a different antidepressant with lower sexual side effects or augment with additional bupropion (Wellbutrin) at higher doses to counteract the SSRI-induced sexual dysfunction.

Identifying the Problem Medication

The combination of low libido and extreme fatigue in this patient is almost certainly caused by the sertraline (Zoloft), not the buspirone or bupropion:

• SSRIs like sertraline cause sexual dysfunction in 41-63% of patients, including decreased libido, orgasmic dysfunction, and arousal problems 1, 2
• Sexual dysfunction from sertraline can appear as early as day 7 of treatment at doses as low as 50 mg/day and typically persists throughout treatment 1
• Bupropion (Wellbutrin) is associated with significantly lower rates of sexual dysfunction (7-15%) compared to SSRIs 1, 2
• Buspirone itself does not typically cause sexual dysfunction and may actually help treat it 3

Treatment Algorithm

First-Line Strategy: Augment with Higher-Dose Bupropion

Increase the bupropion dose to 300 mg/day (if not already at this level) to counteract SSRI-induced sexual dysfunction:

• Bupropion SR at doses of 150-300 mg/day added to ongoing SSRI therapy improves sexual dysfunction with response rates of 46% in women and 75% in men 4
• Most improvement (>50%) occurs within the first 2 weeks at doses of 100-200 mg/day 4
• Bupropion augmentation improves all categories of sexual side effects including libido, arousal, and orgasmic function 4
• The activating properties of bupropion may also help address the extreme fatigue 5

Important caveat: Ensure the second bupropion dose is given before 3 p.m. to minimize insomnia risk 5

Second-Line Strategy: Add Buspirone for Sexual Dysfunction

If bupropion augmentation is insufficient or not tolerated, increase buspirone to therapeutic doses (up to 20 mg three times daily):

• Buspirone has emerging evidence for treating SSRI-induced sexual dysfunction, though the data are less robust than for bupropion 3
• Buspirone may take 2-4 weeks to become effective for this indication 5
• This strategy allows you to maintain the effective antidepressant regimen while addressing the sexual side effects

Third-Line Strategy: Switch from Sertraline

If augmentation strategies fail, switch from sertraline to an antidepressant with lower sexual side effect rates:

• Continue bupropion (already on board) as monotherapy if depression severity allows 1, 2
• Consider mirtazapine if sedation would be beneficial for sleep (though it may worsen fatigue during the day) 5
• Avoid switching to other SSRIs (fluoxetine, paroxetine, citalopram, escitalopram) as they have similar sexual dysfunction profiles 5

Addressing the Extreme Fatigue

The fatigue component requires consideration of multiple factors:

• SSRI-related fatigue is common and may improve with the strategies above 5
• Rule out SSRI-induced apathy syndrome or hypoactive symptoms that can mimic fatigue
• Bupropion's activating properties should help counter fatigue once optimized 5
• Consider whether the patient is experiencing residual depressive symptoms (fatigue is a core symptom of depression) that require overall treatment optimization

Critical Monitoring Points

• Do not discontinue sertraline abruptly - taper over 10-14 days if switching to limit withdrawal symptoms 5
• Monitor for worsening depression when making any medication changes 6
• Assess response to augmentation strategies within 2-4 weeks before declaring treatment failure 4
• Screen for other causes of fatigue (thyroid dysfunction, anemia, sleep disorders) if symptoms persist despite medication optimization

What NOT to Do

• Do not add sildenafil or other PDE5 inhibitors as first-line - these are effective for erectile dysfunction in men but have limited evidence for libido or female sexual dysfunction 5, 6
• Do not simply wait and see - sexual dysfunction rarely resolves spontaneously with continued SSRI use and leads to medication non-adherence 6, 3
• Do not assume all three medications are equally responsible - the evidence clearly implicates sertraline as the primary culprit 1, 2