Wellbutrin (Bupropion): Dosing, Contraindications, and Side Effects
FDA-Approved Indications
Bupropion is FDA-approved for major depressive disorder, seasonal affective disorder, and smoking cessation. 1 The medication is not approved for anxiety disorders and may worsen anxiety symptoms, particularly at higher doses. 2
Dosing Regimens
Major Depressive Disorder
Start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily dose). 3 For bupropion XL, initiate at 150 mg once daily in the morning, with a maintenance dose of 150–300 mg once daily. 3
- The maximum dose for SR formulation is 400 mg per day; for XL formulation, it is 450 mg per day. 3
- Administer the second SR dose before 3 PM to minimize insomnia risk. 3
- Allow 6–8 weeks at therapeutic doses before assessing treatment response. 3
Smoking Cessation
Begin bupropion SR 150 mg once daily for days 1–3, then increase to 150 mg twice daily (300 mg total) starting 1–2 weeks before the target quit date. 4, 3 The maximum dose for smoking cessation is 300 mg per day to maintain seizure risk at approximately 0.1%. 4, 3
- Continue treatment for 7–12 weeks after the quit date, with formal efficacy assessment after this period. 4, 3
- Bupropion may be combined with nicotine replacement therapy (NRT) for enhanced efficacy, achieving 12-month abstinence rates of 35.5% versus 30.3% with bupropion alone. 3
Special Populations
For older adults (≥65 years), start with 37.5 mg every morning and increase by 37.5 mg every 3 days as tolerated, targeting a maximum of 150 mg twice daily (300 mg total). 3 This lower starting dose reduces the risk of adverse reactions in elderly patients. 3
In moderate to severe hepatic impairment, limit bupropion to 150 mg every other day. 3, 1 For mild hepatic impairment, reduce the dose and/or frequency. 1
In moderate to severe renal impairment (GFR <90 mL/min), reduce the total daily dose by 50%. 3 Bupropion should be avoided entirely in end-stage renal disease because metabolites accumulate and hemodialysis does not effectively clear hydroxybupropion. 3
Absolute Contraindications
Bupropion is absolutely contraindicated in patients with:
- Seizure disorder or any history of seizures (including stroke, brain tumor, head trauma, or brain metastases). 4, 1
- Current or prior diagnosis of bulimia or anorexia nervosa due to elevated seizure risk. 1
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs because withdrawal lowers seizure threshold. 4, 1
- Current or recent MAOI use (within 14 days of discontinuation) due to hypertensive crisis risk. 4, 1
- Concurrent tamoxifen therapy because bupropion inhibits CYP2D6 and reduces tamoxifen efficacy. 4
- Uncontrolled hypertension, as bupropion can elevate blood pressure and heart rate. 3
- Known hypersensitivity to bupropion, with severe reactions occurring in approximately 1 per 1,000 to 1 per 10,000 patients. 3
Common Side Effects
The most common adverse effects (incidence ≥5%; ≥2× placebo) include dry mouth, nausea, insomnia, dizziness, headache, agitation, anxiety, tremor, and sweating. 1, 5
- Sexual dysfunction is significantly lower with bupropion compared to SSRIs. 3
- Bupropion is associated with minimal weight gain or modest weight loss, unlike many other antidepressants. 3
- Seizure risk at 300 mg/day is approximately 0.1% (1 in 1,000 patients). 4, 5
Critical Safety Monitoring
Black Box Warning
All antidepressants, including bupropion, carry an FDA black-box warning for increased risk of suicidal thoughts and behaviors in patients younger than 24 years, with the greatest risk during the first 1–2 months of therapy. 3, 1
- Monitor for suicidal ideation, agitation, irritability, or unusual behavioral changes during weeks 1–2 after initiation or dose changes. 3
- Discontinue bupropion immediately if serious neuropsychiatric symptoms emerge. 4
Cardiovascular Monitoring
Measure blood pressure and heart rate at baseline and periodically during treatment, especially in the first 12 weeks, as bupropion can cause elevations in both parameters. 3 Uncontrolled hypertension is a contraindication to bupropion use. 3
Neuropsychiatric Safety
High-quality evidence from the EAGLES trial (n=8,144) demonstrates no statistically significant increase in neuropsychiatric adverse events with bupropion compared to nicotine patch or placebo, even among participants with pre-existing psychiatric disorders. 4, 3
Drug Interactions
Bupropion inhibits CYP2D6 and can increase concentrations of antidepressants (venlafaxine, SSRIs, tricyclics), antipsychotics (haloperidol, risperidone), beta-blockers (metoprolol), and Type 1C antiarrhythmics (propafenone, flecainide). 1 Consider dose reduction of these agents when co-prescribed with bupropion. 1
CYP2B6 inducers (ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, phenytoin) may require bupropion dose increases, but do not exceed the maximum recommended dose. 1
Clinical Advantages
Bupropion offers unique dual benefits for patients with both depression and nicotine dependence, addressing both conditions simultaneously. 4, 3 It is particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia due to its activating dopaminergic and noradrenergic properties. 3
Bupropion demonstrates efficacy comparable to SSRIs (42–49% remission rates) while offering significantly lower rates of sexual dysfunction and weight gain. 3
Common Pitfalls to Avoid
- Do not exceed 450 mg/day total dose to maintain seizure risk at 0.1%. 3
- Do not prescribe bupropion to patients with eating disorders (bulimia, anorexia) due to markedly elevated seizure risk. 6, 1
- Do not skip the 1–2 week lead time before the quit date when using bupropion for smoking cessation, as therapeutic drug levels must be established. 3
- Do not combine bupropion with MAOIs or initiate within 14 days of MAOI discontinuation. 1
- Do not use naltrexone-bupropion combination products in patients on opioid therapy, as naltrexone will precipitate severe opioid withdrawal. 3