What is the best approach for a patient with a history of opioid use disorder, currently taking Suboxone (buprenorphine and naloxone) and bupropion (Wellbutrin) for depression and smoking cessation, to quit smoking using bupropion and nicotine replacement therapy (NRT)?

How to Quit Smoking When Starting Wellbutrin and Nicotine Patches

Timing and Dosing Strategy

Start bupropion (Wellbutrin) SR 150 mg once daily for 3 days, then increase to 150 mg twice daily, beginning 1-2 weeks before your target quit date, and combine with nicotine patches starting on your quit date. 1, 2

Bupropion Initiation Protocol

• Begin bupropion SR at 150 mg once daily in the morning for the first 3 days to assess tolerability and minimize side effects 2
• After 3 days, increase to 150 mg twice daily (300 mg total daily dose) if tolerated 1, 2
• Take the second dose before 3 PM to minimize insomnia risk, as bupropion has activating properties 2
• Start this medication 1-2 weeks before your planned quit date to allow therapeutic drug levels to build up before attempting cessation 1, 3
• The maximum dose for smoking cessation is 300 mg per day—do not exceed this to maintain seizure risk at 0.1% 1, 4

Nicotine Patch Protocol

• Begin nicotine patches on your actual quit date (not when starting bupropion) 1
• Use a 21 mg/24-hour patch if you smoke ≥10 cigarettes per day 3
• Consider adding short-acting nicotine replacement (gum, lozenges) for breakthrough cravings 3
• Continue patch therapy for at least 12 weeks 3

Treatment Duration and Assessment

• Continue bupropion for 7-12 weeks after your quit date 1, 4
• Assess efficacy formally after this 7-12 week period 1, 4
• Nicotine withdrawal symptoms typically peak within 1-2 weeks of quitting and then subside 4
• Longer duration of bupropion treatment may help prevent relapse in those who successfully quit 1

Evidence for Combination Therapy

The combination of bupropion plus nicotine replacement therapy shows the highest abstinence rates, though the difference compared to bupropion alone is not statistically significant. 1

• A double-blind RCT showed 12-month abstinence rates of 35.5% with bupropion plus NRT compared to 30.3% with bupropion alone 1
• This combination is particularly beneficial for patients with comorbid depression and nicotine dependence 2
• All participants should receive behavioral counseling support in addition to pharmacotherapy for optimal outcomes 1, 3

Critical Safety Considerations for Your Specific Situation

Suboxone Compatibility

Bupropion monotherapy is safe to use with Suboxone (buprenorphine/naloxone)—there is no contraindication. 2

• The contraindication only applies to naltrexone-bupropion combination products (like Contrave), which you are NOT taking 2
• Bupropion for depression or smoking cessation operates through different mechanisms and does not interact with opioid medications 2
• Continue your Suboxone as prescribed without adjustment 5

Seizure Risk Management

• The seizure risk with bupropion at 300 mg/day is approximately 0.1% (1 in 1,000) 1, 4, 6
• Avoid bupropion if you have: a history of seizures, epilepsy, brain metastases, eating disorders (bulimia/anorexia), or are abruptly discontinuing alcohol, benzodiazepines, or antiepileptic drugs 1, 2, 4
• Do not exceed 300 mg per day for smoking cessation 1, 4

Monitoring Requirements

• Monitor for neuropsychiatric symptoms during the first few weeks, including agitation, restlessness, or behavioral changes 2, 4
• Recent large-scale trials show no significant increase in neuropsychiatric events with bupropion compared to nicotine patch or placebo 4
• Monitor blood pressure periodically, especially in the first 12 weeks, as bupropion can elevate blood pressure 2
• Watch for worsening depression or suicidal ideation, particularly if you are under 24 years old 2

Common Side Effects and Management

• Most common side effects include disturbed sleep, dry mouth, headaches, and nausea 1
• These side effects are typically more common with bupropion than with NRT alone 1
• Taking the second dose before 3 PM helps minimize insomnia 2
• Side effects often resolve within 4-5 days after starting the medication 7
• Bupropion may cause minimal weight gain or even weight loss, unlike many other antidepressants 2

Additional Benefits for Depression

• Bupropion may be particularly beneficial for smoking cessation in persons with depression, addressing both conditions simultaneously 1, 3
• A trend toward improved efficacy was noted in patients with a history of depression 1
• There is no evidence of emergent depression when bupropion is added to existing antidepressant therapy 8
• Some patients report improvement in sexual dysfunction when bupropion is added to SSRI therapy 8

Drug Interactions to Avoid

• Do not take bupropion if you are currently taking or have taken MAOIs within the past 14 days 2, 4
• Use caution with other medications that lower seizure threshold 2
• Avoid abrupt discontinuation of alcohol or benzodiazepines while on bupropion 2

What to Expect

• You may notice improvement in energy levels within the first few weeks of bupropion treatment 2
• Full antidepressant effect typically occurs at 4-6 weeks 7
• Smoking cessation efficacy should be assessed after 7-12 weeks of treatment 1, 4
• Combining pharmacotherapy with behavioral counseling significantly improves outcomes 4