What is the proper protocol for prescribing Zyban (bupropion)?

Zyban (Bupropion) Prescribing Protocol

For smoking cessation, initiate bupropion 1-2 weeks before the target quit date at 150 mg once daily for 3 days, then increase to 150 mg twice daily (maximum 300 mg/day) for 7-12 weeks, with mandatory screening for seizure risk factors, psychiatric history, and contraindicated medications before prescribing. 1, 2, 3

Pre-Prescription Screening Requirements

Before prescribing bupropion, you must screen for absolute contraindications:

• Seizure disorders or conditions lowering seizure threshold (stroke, brain metastases, eating disorders, abrupt alcohol/benzodiazepine withdrawal) 1, 2, 3
• Current or recent MAOI use (within 14 days) due to hypertensive crisis risk 1, 2, 3
• Concurrent tamoxifen use (bupropion reduces tamoxifen efficacy) 1
• Closed-angle glaucoma 1
• Uncontrolled hypertension 2
• Moderate to severe hepatic cirrhosis 4
• History of bipolar disorder 4

Additionally, obtain psychiatric history and assess suicide risk, particularly in patients under 24 years old, as antidepressants increase suicidal thoughts and behaviors in this age group. 2, 3

Standard Dosing Protocol

Initiation Phase (1-2 Weeks Before Quit Date)

Begin dosing 1-2 weeks prior to the target quit date to establish therapeutic drug levels before cessation attempts. 1, 2

• Days 1-3: 150 mg orally once daily in the morning 1, 2
• Day 4 through end of treatment: 150 mg orally twice daily (total 300 mg/day) if tolerated 1, 2
• Second dose timing: Administer before 3 PM to minimize insomnia risk 2, 5

Treatment Duration

• Standard course: 7-12 weeks of treatment 1, 2
• Extended therapy: May continue for 6 months to 1 year to promote continued cessation, though longer periods should be avoided if possible 1
• Efficacy assessment: Evaluate progress at 7-12 weeks; if no significant progress toward abstinence, reassess treatment 2

Maximum Dosing

Never exceed 300 mg per day for smoking cessation to minimize seizure risk (approximately 1 in 1000). 1, 2

Dose Adjustments for Special Populations

Hepatic Impairment

• Moderate to severe impairment (Child-Pugh 7-15): Maximum 150 mg every other day 2, 3
• Mild impairment (Child-Pugh 5-6): Consider reducing dose and/or frequency 3

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by half due to accumulation of bupropion and metabolites 2, 5, 3

Older Adults

• Starting dose: 37.5 mg once daily in the morning 5
• Titration: Increase by 37.5 mg every 3 days as tolerated 5
• Maximum: 150 mg twice daily (300 mg total daily) 5

Administration Instructions

• Swallow tablets whole—do not crush, divide, or chew, as this alters the sustained-release mechanism 3
• Take in the morning with or without food 3
• If dose missed: Do not double the next dose due to seizure risk; take the next scheduled dose 3

Critical Drug Interactions

Absolute Contraindications

• MAOIs: Allow at least 14 days between MAOI discontinuation and bupropion initiation 1, 2, 3
• Other bupropion-containing products: Do not combine with Wellbutrin, Wellbutrin SR, Aplenzin, or other bupropion formulations 3

Medications Requiring Caution

• CYP2D6 substrates: Bupropion inhibits CYP2D6, potentially increasing levels of drugs metabolized by this enzyme 6
• Drugs lowering seizure threshold: Use extreme caution with medications that reduce seizure threshold 4

Neuropsychiatric Monitoring

Monitor closely for development or worsening of serious neuropsychiatric symptoms, including depression, suicidal ideation/behavior, hostility, and agitation, even in patients without previous psychiatric history. 1, 2, 3

• Discontinue immediately if these signs occur 1
• Highest risk period: First few months of treatment, especially in patients under 24 years 3
• Recent evidence: A multicenter RCT (N=8,058) found that neuropsychiatric adverse event rates with bupropion were not significantly increased relative to nicotine patches or placebo in patients with or without psychiatric disorders 1

However, the FDA black box warning remains in effect, and the substantial benefits of immediate smoking cessation must be weighed against risks of increased hostility, depression, or suicidal behavior. 1, 3

Common Side Effects

The most frequently reported events (by incidence density) are:

• Insomnia (most common—administer second dose before 3 PM to minimize) 2, 7
• Dry mouth 4
• Nausea/vomiting 7
• Dizziness 7
• Nervousness 6

Sexual dysfunction is notably less common than with SSRIs. 6

Serious Adverse Events

• Seizures: Risk approximately 1 in 1000, similar to other antidepressants 1, 2, 8
• Allergic/anaphylactic reactions: Risk 1 in 1,000 to 1 in 10,000 1, 2
• Angle-closure glaucoma: Rare but serious; patients with untreated narrow-angle glaucoma should undergo prophylactic iridectomy before treatment 3

Meta-analyses did not detect a statistically significant increase in serious adverse events (33 trials, N=9,631, RR 1.30,95% CI 1.00-1.69), though the confidence interval narrowly missed significance. 8

Behavioral Support Integration

Combine bupropion with behavioral counseling for optimal outcomes. 2, 4

• Evidence for bupropion efficacy comes primarily from trials including medium to heavy smokers (≥15 cigarettes/day) receiving frequent behavioral counseling 1, 2
• Brief counseling (even 5-10 minutes) significantly improves outcomes when combined with pharmacotherapy 9
• Comprehensive programs with individualized counseling plus bupropion can increase 6-month cessation rates from 6.8% to 21.3% compared to verbal advice alone 2

Efficacy Data

• Bupropion as sole pharmacotherapy: Significantly increases long-term cessation (44 trials, N=13,728, RR 1.62,95% CI 1.49-1.76) 8
• 12-month abstinence improvement: 9-10 percentage points over placebo 4
• Comparison to varenicline: Bupropion is less effective (4 trials, N=1,810, RR 0.68,95% CI 0.56-0.83) 2, 8
• Comparison to NRT: Similar efficacy (8 trials, N=4,096, RR 0.96,95% CI 0.85-1.09) 8
• Adding to NRT: Insufficient evidence for additional benefit (12 trials, N=3,487, RR 1.19,95% CI 0.94-1.51) 8

Discontinuation Protocol

When discontinuing bupropion 300 mg daily, taper to 150 mg once daily before complete discontinuation to minimize withdrawal symptoms. 3

For seasonal affective disorder prevention (if applicable), taper and discontinue in early spring. 3

Cost-Effectiveness

The estimated cost per life-year saved from bupropion use is approximately £1,000 (UK) or $1,500 (US), making it a cost-effective intervention. 4

Pregnancy Considerations

• Advise patients to notify their healthcare provider if they become pregnant during treatment 3
• A pregnancy exposure registry monitors outcomes in women exposed to bupropion during pregnancy 3
• Limited data: 12 first-trimester exposures with 8 known outcomes—5 live births without congenital abnormalities, 2 therapeutic terminations, 1 intrauterine death 7