What is the recommended approach for prescribing Wellbutrin (bupropion) to a patient for either depression or smoking cessation, considering their medical history and potential risks?

Prescribing Wellbutrin (Bupropion): Clinical Approach

Start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (maximum 300 mg/day) for either depression or smoking cessation, but only after screening for absolute contraindications including seizure disorders, eating disorders, uncontrolled hypertension, abrupt alcohol/benzodiazepine discontinuation, and MAOI use. 1, 2, 3

Critical Pre-Treatment Screening

Before prescribing bupropion, you must identify absolute contraindications:

Absolute Contraindications 3

• Seizure disorder or any condition increasing seizure risk (severe head injury, arteriovenous malformation, CNS tumor, stroke, brain metastases) 1, 3
• Current or prior bulimia or anorexia nervosa 3
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1, 3
• Current MAOI use or within 14 days of discontinuing MAOIs 1, 2, 3
• Uncontrolled hypertension 2
• Known hypersensitivity to bupropion 3

High-Risk Situations Requiring Extreme Caution 2

• Moderate to severe hepatic impairment: Maximum dose 150 mg every other day 2
• Moderate to severe renal impairment (GFR <90 mL/min): Reduce total daily dose by 50% 2
• Concomitant medications that lower seizure threshold 3
• Patients taking tamoxifen (bupropion contraindicated) 2
• Closed-angle glaucoma 1

Indication-Specific Dosing

For Major Depressive Disorder 2, 3

• Days 1-3: 150 mg once daily in the morning
• Day 4 onward: 150 mg twice daily (300 mg total)
• Maximum dose: 450 mg/day for XL formulation, 400 mg/day for SR formulation
• Second dose timing: Must be given before 3 PM to minimize insomnia risk 2

For Smoking Cessation 1, 2

• Initiate 1-2 weeks BEFORE target quit date (critical for establishing therapeutic drug levels) 1, 2
• Days 1-3: 150 mg once daily
• Days 4 through week 7-12: 150 mg twice daily (300 mg total)
• Maximum dose: 300 mg/day for smoking cessation (do NOT exceed to maintain seizure risk at 0.1%) 1, 2
• Treatment duration: 7-12 weeks, with efficacy assessment after this period 1, 2

Special Populations 2

• Older adults: Start 37.5 mg every morning, increase by 37.5 mg every 3 days as tolerated, maximum 150 mg twice daily 2
• Hepatic impairment (moderate to severe): 150 mg every other day maximum 2
• Renal impairment: Reduce dose by 50% 2

Critical Monitoring Parameters

Initial Monitoring (Weeks 1-2) 2, 3

• Suicidal ideation and behavior (especially in patients <24 years old—highest risk in first 1-2 months) 2, 3
• Blood pressure and heart rate (bupropion can elevate both) 2
• Neuropsychiatric symptoms: agitation, anxiety, panic attacks, insomnia, irritability, hostility, aggression, depression worsening 3
• Energy levels and sleep patterns 2

Ongoing Monitoring 2

• Blood pressure monitoring: Especially during first 12 weeks 2
• Treatment response assessment: Allow 6-8 weeks at adequate dose before determining efficacy 2
• Seizure risk factors: Monitor continuously 3

Clinical Advantages and Patient Selection

Bupropion is Particularly Beneficial For 2, 4

• Patients with depression AND low energy, apathy, or hypersomnia (due to activating properties) 2
• Patients concerned about sexual dysfunction (significantly lower rates than SSRIs) 2
• Patients concerned about weight gain (associated with minimal weight gain or weight loss) 2
• Patients with comorbid depression and smoking (addresses both conditions simultaneously) 1, 2, 5
• Patients with history of major depression or alcoholism attempting smoking cessation (efficacy maintained in these populations) 5

Combination Therapy Considerations

Smoking Cessation with Nicotine Replacement 1, 2

• Bupropion plus NRT shows highest abstinence rates (35.5% at 12 months vs 30.3% with bupropion alone, though not statistically significant) 2
• Start nicotine patches on the actual quit date, NOT when starting bupropion 2

Augmentation for Treatment-Resistant Depression 2

• Adding bupropion to SSRIs decreases depression severity more than buspirone augmentation 2
• Lower discontinuation rates due to adverse events (12.5% vs 20.6% with buspirone) 2
• May counteract SSRI-induced sexual dysfunction 2, 4

Patients on Multiple Psychotropic Medications 2

• Start at 37.5 mg every morning, increase by 37.5 mg every 3 days 2
• Monitor for increased agitation (bupropion is activating) 2
• Combination with SSRIs addresses complementary mechanisms (noradrenergic/dopaminergic vs serotonergic) 2

Common Pitfalls and How to Avoid Them

Seizure Risk Management 1, 3, 6

• The seizure risk is approximately 0.1% (1 in 1,000) at 300 mg/day 2, 6
• Never exceed 300 mg/day for smoking cessation 1, 2
• Never exceed 450 mg/day for any indication 2, 3
• Gradual dose titration is mandatory to minimize seizure risk 3
• Screen rigorously for predisposing factors 6

Timing Errors 2

• Second dose must be before 3 PM to prevent insomnia 2
• For smoking cessation, start 1-2 weeks BEFORE quit date—do not start on quit date 1, 2

Premature Treatment Discontinuation 2

• Do not discontinue before 6-8 weeks unless significant adverse effects occur 2
• Response rates may be as low as 50%, with 38% not achieving response 2
• Allow adequate time for therapeutic effect 2

Neuropsychiatric Safety Considerations

Black Box Warning 3

• Increased risk of suicidal thinking and behavior in children, adolescents, and young adults 3
• Monitor for worsening depression, suicidal thoughts, and unusual behavior changes 3
• Risk is highest during first 1-2 months of treatment 2

Smoking Cessation-Specific Neuropsychiatric Events 1, 3

• Postmarketing reports include: depression, mania, psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempt, and completed suicide 3
• However, a large multicenter RCT (EAGLES trial) found no significant increase in neuropsychiatric adverse events with bupropion compared to nicotine patches or placebo in patients with or without psychiatric disorders 1
• Instruct patients to discontinue and contact provider immediately if these symptoms occur 3

Comparative Safety Data 7

• Varenicline shows substantially higher risk of suicidal/self-injurious behavior or depression compared to bupropion (OR 8.4 vs 2.9 compared to nicotine replacement) 7
• Bupropion for smoking cessation had smaller increased risks than varenicline 7

Common Adverse Effects 3, 6, 8

• Most common (≥5% and ≥2× placebo): dry mouth, nausea, insomnia, dizziness, headache, anxiety 3, 6
• Only insomnia and dry mouth occurred significantly more frequently than placebo 6
• Most adverse events are transient and resolve without intervention 6
• Discontinuation rate due to adverse events is low (6-12%) 6
• Weight gain during smoking cessation is inversely related to bupropion dose (2.9 kg with placebo vs 1.5 kg with 300 mg/day) 8

Drug Interactions 3

• CYP2D6 inhibition: Bupropion increases concentrations of antidepressants (venlafaxine, nortriptyline, SSRIs), antipsychotics (haloperidol, risperidone), beta-blockers (metoprolol), and Type 1C antiarrhythmics—consider dose reduction 3
• CYP2B6 inducers (ritonavir, carbamazepine, phenobarbital): May require bupropion dose increase 3
• False-positive urine amphetamine tests can occur 3

Efficacy Data

Depression 2, 8

• Response rates similar to other second-generation antidepressants (42-49% remission rates) 2
• No significant difference compared to sertraline or venlafaxine 2

Smoking Cessation 1, 8

• End of treatment (7 weeks): 44.2% abstinence with 300 mg/day vs 19.0% with placebo 8
• One year: 23.1% abstinence with 300 mg/day vs 12.4% with placebo 8
• With intensive behavioral support: 9% above baseline abstinence rates 2
• Efficacy maintained in patients with history of major depression or alcoholism 5