Optimal Anxiety Medication to Combine with Bupropion
Buspirone is the best anxiety medication to pair with bupropion (Wellbutrin) when avoiding weight gain and sexual dysfunction, as it is weight-neutral and actually improves sexual function rather than impairing it.
Primary Recommendation: Buspirone
Buspirone stands out as the ideal anxiolytic for this clinical scenario because it addresses all three concerns simultaneously:
Sexual function preservation: Buspirone normalized sexual function in 8 of 10 patients with generalized anxiety disorder after 4 weeks of treatment, offering a clinical advantage over other anxiolytics that typically impair sexual function 1
Weight neutrality: Unlike benzodiazepines and many other psychotropic medications, buspirone does not cause weight gain 2
Compatibility with bupropion: There are no significant pharmacokinetic interactions between buspirone and bupropion, making them safe to combine 2
Dosing Strategy
- Initial dose: 5 mg twice daily 2
- Maximum dose: 20 mg three times daily 2
- Important caveat: Buspirone requires 2 to 4 weeks to become effective and is most useful in patients with mild to moderate agitation 2
Why Other Options Are Less Favorable
SSRIs (Generally Not Recommended for This Scenario)
While some SSRIs might be considered, they have significant drawbacks:
Paroxetine: Associated with the highest risk for sexual dysfunction among SSRIs and the greatest risk for weight gain within its class 2
Fluoxetine and Sertraline: Weight-neutral with long-term use 2, but both still carry risk of sexual dysfunction, with bupropion showing significantly lower rates of sexual adverse events than both 2
Sexual dysfunction rates: Paroxetine had higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 2
Medications to Explicitly Avoid
Mirtazapine: Closely associated with weight gain and would counteract bupropion's weight-neutral profile 2, 3
Benzodiazepines: While effective for anxiety, they typically impair sexual function 1
Critical Clinical Consideration
A key caveat about bupropion itself: Bupropion is activating and can exacerbate anxiety, making it potentially inappropriate for patients with significant anxiety disorders 2. This creates a clinical paradox where the patient may already be experiencing anxiety worsening from the bupropion itself. If anxiety symptoms are severe or worsening on bupropion, reassessing whether bupropion is the appropriate antidepressant should be considered before adding an anxiolytic 2.