Can a patient with a history of taking Addyi (flibanserin) safely use Wellbutrin (bupropion)?

Can a Patient Use Wellbutrin (Bupropion) with Addyi (Flibanserin)?

Yes, bupropion can be safely used with flibanserin (Addyi) based on available evidence, as there are no documented contraindications or significant drug interactions between these medications. 1

Evidence Supporting Concurrent Use

A randomized, placebo-controlled trial specifically evaluated the safety of flibanserin in premenopausal women taking serotonergic antidepressants (SSRIs and SNRIs), demonstrating that flibanserin was generally safe and well tolerated when added to stable antidepressant regimens. 1 While this study did not specifically include bupropion, the safety profile supports the concept that flibanserin can be combined with antidepressants without increased risk. 1

Key Safety Considerations Before Prescribing

Absolute Contraindications for Bupropion (Screen First)

Before initiating or continuing bupropion with flibanserin, verify the patient does NOT have:

• Seizure disorders or conditions predisposing to seizures (brain tumor, stroke, head trauma) - bupropion lowers seizure threshold with approximately 0.1% risk at 300 mg/day 2
• Current or recent MAOI use (within 14 days) 2
• Eating disorders (bulimia or anorexia nervosa) - significantly increases seizure risk 2
• Uncontrolled hypertension - bupropion can elevate blood pressure and heart rate 2, 3
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs - dramatically increases seizure risk 2
• Moderate to severe hepatic impairment - maximum dose 150 mg daily 2
• Moderate to severe renal impairment (GFR <90 mL/min) - reduce dose by 50% 2

Critical Monitoring Parameters

When using bupropion with flibanserin, monitor:

• Blood pressure and heart rate - especially during the first 12 weeks, as bupropion can cause elevations 2, 3
• Neuropsychiatric symptoms - including mood changes, anxiety, agitation, and suicidal ideation, particularly in patients under 24 years old 2, 3
• Depression symptoms - assess within 1-2 weeks of initiation and throughout treatment 3
• Seizure risk factors - any new conditions or medications that lower seizure threshold 2

Dosing Considerations

Maximum Safe Bupropion Dose

The maximum safe dose of bupropion is 450 mg/day - exceeding this substantially increases seizure risk beyond the baseline 0.1% at therapeutic doses. 2, 3

For depression treatment:

• Bupropion SR: Start 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total) 2
• Bupropion XL: Start 150 mg once daily, increase to 150-300 mg once daily 2
• Maximum dose: 400 mg/day for SR, 450 mg/day for XL 2

Important Timing Consideration

Administer the second dose of bupropion SR before 3 PM to minimize insomnia risk, as bupropion has activating properties. 2

Special Clinical Scenarios

If Patient is on Contrave (Naltrexone-Bupropion)

This is a critical distinction: If the patient is taking Contrave (naltrexone-bupropion combination), the full maintenance dose contains 360 mg of bupropion daily. 3 Adding additional bupropion would exceed the 450 mg/day maximum safe dose and substantially increase seizure risk. 3 In this scenario, do not add separate bupropion - the patient is already receiving therapeutic bupropion doses through Contrave. 3

Flibanserin-Specific Considerations

The most common adverse events when flibanserin was combined with serotonergic antidepressants included dry mouth (5.5%), insomnia (5.5%), back pain (4.1%), and dizziness (4.1%). 1 Importantly, there were no serious adverse events and no instances of suicidal ideation or behavior in the trial. 1

Common Pitfalls to Avoid

• Do not combine bupropion with other medications that lower seizure threshold without extreme caution - this includes clozapine, which when combined with bupropion has documented cases of seizures even without prior seizure history 4
• Do not exceed 450 mg/day total bupropion from all sources combined 2, 3
• Do not prescribe bupropion to patients with uncontrolled hypertension - stabilize blood pressure first 2, 3
• Do not abruptly discontinue bupropion - taper gradually to minimize withdrawal symptoms 2

Clinical Advantages of This Combination

Bupropion may be particularly beneficial when combined with flibanserin because:

• Lower sexual dysfunction rates compared to SSRIs - bupropion has significantly lower rates of sexual dysfunction, which is relevant for patients taking flibanserin for hypoactive sexual desire disorder 2
• Minimal weight gain or weight loss - unlike many other antidepressants 2
• Activating properties - beneficial for patients with low energy, apathy, or hypersomnia 2

The combination of bupropion and flibanserin is safe when proper screening for contraindications is performed and appropriate monitoring is maintained. 1