In a patient taking escitalopram 20 mg and cariprazine 3 mg who reports decreased libido, should the next step be to add bupropion (Wellbutrin)?

Managing Decreased Libido in a Patient on Escitalopram 20mg and Cariprazine 3mg

Yes, adding bupropion is the recommended next step, as it has significantly lower rates of sexual dysfunction (8-10%) compared to escitalopram and can be used as augmentation therapy without discontinuing the current regimen. 1

Understanding the Problem

Your patient is experiencing a well-documented adverse effect of SSRI therapy. Escitalopram causes sexual dysfunction through serotonergic mechanisms, affecting libido, arousal, and orgasm in over 50% of patients. 2, 3 While cariprazine (Vraylar) can contribute to decreased libido through dopamine modulation and potential prolactin elevation, the SSRI is the more likely primary culprit. 2

Critical point: Sexual dysfunction from SSRIs is vastly underreported in clinical trials, with actual rates likely much higher than published figures. 4, 1

Evidence-Based Treatment Algorithm

First-Line Strategy: Add Bupropion

• Bupropion augmentation is the preferred initial approach because it addresses sexual dysfunction while maintaining antidepressant efficacy from the existing SSRI. 1, 5

• The American College of Physicians recommends bupropion as first-line therapy when sexual function is a major concern, with sexual dysfunction rates of only 8-10% versus the much higher rates seen with SSRIs. 4, 1, 5

• Bupropion works through noradrenergic and dopaminergic mechanisms, directly counteracting the serotonergic sexual side effects without compromising mood stability. 6

Dosing: Start bupropion SR 150mg daily, increasing to 150mg twice daily after one week if tolerated. 6

Important Contraindications for Bupropion

• Do not use bupropion in patients with seizure disorders (including history of seizures, eating disorders, or abrupt alcohol/benzodiazepine withdrawal), as it lowers seizure threshold. 1

• Avoid in highly agitated patients, as bupropion can worsen agitation. 1

Second-Line Strategy: Switch to Mirtazapine

If bupropion augmentation fails, is contraindicated, or causes intolerable side effects:

• Switch from escitalopram to mirtazapine 15-30mg at bedtime, which has minimal to no sexual side effects and may actually improve sexual function. 1, 5

• Mirtazapine works through noradrenergic and specific serotonergic mechanisms (not broad serotonin reuptake inhibition), avoiding the sexual dysfunction pathway. 1

• Major caveat: Mirtazapine causes significant sedation and weight gain, which can be therapeutically beneficial for patients with insomnia and poor appetite, but problematic for others. 4, 1

Third-Line Strategy: Switch to Different SSRI

If neither bupropion nor mirtazapine are options:

• Consider switching to sertraline or citalopram, which have moderate sexual dysfunction rates (14% in males, 6% in females for sertraline) compared to escitalopram. 5

• Never switch to paroxetine, which has the highest sexual dysfunction rate among all SSRIs at 70.7%. 4, 1, 5

Addressing the Cariprazine Component

• Evaluate whether cariprazine is contributing by checking a prolactin level—elevated prolactin from dopamine blockade can independently cause decreased libido. 2

• If prolactin is elevated and mood is stable, consider reducing cariprazine dose or switching to an antipsychotic with lower prolactin elevation (aripiprazole, brexpiprazole). 2

Monitoring and Timeline

• Begin monitoring for improvement in sexual function within 1-2 weeks of adding bupropion or switching medications. 1, 5

• Modify the treatment plan if no adequate response within 6-8 weeks. 1, 5

• When switching from escitalopram, taper gradually over 10-14 days to limit withdrawal symptoms. 1

Critical Pitfalls to Avoid

• Do not use buspirone for SSRI-induced sexual dysfunction—there is no evidence supporting its effectiveness for this indication despite its common off-label use. 1

• Do not assume sexual dysfunction will resolve spontaneously while continuing the SSRI—in rare cases, sexual dysfunction can persist even after SSRI discontinuation. 7

• Always directly inquire about sexual side effects, as patients rarely volunteer this information and clinical trials vastly underreport these adverse events. 4, 1

Special Considerations

• If your patient has comorbid breast cancer and is taking tamoxifen, bupropion may reduce tamoxifen efficacy through CYP2D6 inhibition (though less than paroxetine or fluoxetine). In this scenario, venlafaxine or citalopram would be preferred alternatives. 1, 5

• Ensure testosterone levels are normal (total morning testosterone >300 ng/dL), as low testosterone can contribute to decreased libido independent of medication effects. 1