Bupropion SR (Sustained-Release) is the Recommended Formulation for Smoking Cessation
Bupropion SR (sustained-release) at 150 mg twice daily (300 mg total daily dose) is the standard formulation recommended for smoking cessation, not the ER (extended-release) formulation. 1, 2
Standard Dosing Protocol for Smoking Cessation
The established regimen for bupropion SR in smoking cessation follows this specific titration schedule: 1, 2
- Days 1-3: 150 mg orally once daily
- Day 4 through 7-12 weeks: 150 mg orally twice daily (if tolerated)
- Maximum dose: 300 mg per day
- Treatment initiation: Begin 1-2 weeks prior to the target quit date 1, 2
- Treatment duration: 7-12 weeks, with efficacy assessment after this period 1, 2
Why SR Formulation Over ER
The evidence base and regulatory approvals specifically support bupropion SR for smoking cessation. 1, 3, 4 The SR formulation was the version studied in the pivotal clinical trials that demonstrated efficacy, achieving abstinence rates 9-10 percentage points above placebo at 12 months when combined with behavioral support. 4, 5
Bupropion ER/XL formulations are FDA-approved for depression, not smoking cessation. 6 While bupropion XL is typically dosed as 300 mg once daily for depression, this formulation has not been validated in smoking cessation trials. 2
Critical Timing Considerations
The twice-daily dosing of bupropion SR requires specific timing to minimize adverse effects: 2
- First dose: Morning administration
- Second dose: Before 3 PM to minimize insomnia risk 2
This timing is essential because bupropion has activating properties that can interfere with sleep if taken late in the day. 2
Efficacy Data
The landmark trial by Jorenby et al. demonstrated that bupropion SR achieved 30.3% abstinence at 12 months compared to 15.6% with placebo. 5 Combination therapy with bupropion SR plus nicotine patch achieved 35.5% abstinence, though this was not statistically superior to bupropion SR alone. 5
Safety Profile and Contraindications
The most common adverse events with bupropion SR at 300 mg/day include: 3, 5
- Insomnia (most common, often transient)
- Dry mouth
- Headache
- Nausea
Critical contraindications include: 1, 6, 4
- Seizure disorders or conditions increasing seizure risk (brain metastases, stroke, severe head injury)
- Eating disorders (anorexia nervosa, bulimia)
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
- Current use of MAO inhibitors or within 14 days of discontinuation
- Concurrent use with tamoxifen 1
The seizure risk with bupropion SR at 300 mg/day is approximately 0.1% (1 in 1,000) when patients are properly screened. 3, 4
Special Population Considerations
Renal impairment: For any degree of renal impairment (GFR <90 mL/min), reduce the total daily dose by half to 150 mg once daily. 2, 7
Hepatic impairment: For moderate to severe hepatic impairment, do not exceed 150 mg daily total. 2
Neuropsychiatric Monitoring
Although bupropion carries a black box warning for neuropsychiatric events, a large multicenter RCT (EAGLES trial) found that rates of neuropsychiatric adverse events with bupropion were not significantly increased relative to nicotine patches or placebo in patients with or without psychiatric disorders. 1 Nevertheless, monitor patients for: 1, 6
- Depression and suicidal ideation/behavior
- Hostility, agitation, or behavioral changes
- Discontinue if serious neuropsychiatric symptoms develop
Clinical Pearls
- Bupropion SR may be particularly beneficial for patients with comorbid depression who want to quit smoking, addressing both conditions simultaneously. 2
- The gradual titration schedule is necessary to minimize seizure risk while achieving therapeutic drug levels. 2
- Combining bupropion SR with behavioral therapy significantly enhances outcomes compared to medication alone. 1
- Treatment may be extended beyond 12 weeks (up to 6 months to 1 year) to promote continued cessation, though longer periods should be avoided if possible. 1