What is the recommended starting dose and titration schedule for Wellbutrin SR (bupropion sustained‑release) in adults, including dose limits, contraindications, and adjustments for hepatic impairment or elderly patients?

Wellbutrin SR Dosing for Adults

Start Wellbutrin SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total) if tolerated, with the second dose administered before 3 PM to minimize insomnia risk. 1

Standard Dosing Protocol

Initial Titration

• Begin with 150 mg once daily in the morning for days 1–3 1
• Increase to 150 mg twice daily (300 mg total) from day 4 onward if the initial dose is well tolerated 1, 2
• Administer the second dose before 3 PM to prevent sleep disturbances 1, 2

Maximum Dose Limits

• Maximum daily dose for Wellbutrin SR is 400 mg/day (200 mg twice daily) 1
• For smoking cessation specifically, do not exceed 300 mg/day (150 mg twice daily) to maintain seizure risk at 0.1% 1

Response Assessment

• Evaluate clinical response after 6–8 weeks at therapeutic doses before considering treatment modifications 1, 2
• If no adequate response by 6–8 weeks, modify treatment by increasing dose (up to maximum), switching agents, or adding augmentation 1

Special Population Adjustments

Hepatic Impairment

• Moderate to severe hepatic impairment: maximum 150 mg daily (one tablet total) 1
• Mild hepatic impairment: reduce dose and/or frequency 1

Renal Impairment

• GFR <90 mL/min: reduce total daily dose by 50% 1, 2
• Avoid in end-stage renal disease 1

Elderly Patients

• Start with 37.5 mg once daily in the morning 1
• Increase by 37.5 mg every 3 days as tolerated 1
• Maximum dose: 150 mg twice daily (300 mg total) 1
• Second dose must be given before 3 PM 1

This gradual titration in older adults minimizes the risk of adverse reactions due to age-related pharmacokinetic changes 1.

Absolute Contraindications

Seizure-Related

• Current or past seizure disorder 1, 2
• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk 1, 2
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1, 2
• Any condition that lowers seizure threshold (brain tumor, stroke, head trauma) 1

Drug Interactions

• Current MAOI use or within 14 days of MAOI discontinuation 1, 2
• Concurrent tamoxifen therapy (due to CYP2D6 inhibition) 1

Medical Conditions

• Uncontrolled hypertension 1, 2
• Chronic opioid therapy (applies only to naltrexone-bupropion combination products) 1

Critical Safety Monitoring

Baseline Assessment

• Measure blood pressure and heart rate before initiation 1
• Screen for seizure risk factors and contraindications 1, 2
• Assess for suicidal ideation, especially in patients <24 years 1

Ongoing Monitoring

• Monitor blood pressure and heart rate periodically, especially during the first 12 weeks, as bupropion can cause elevations 1
• Assess for neuropsychiatric symptoms (agitation, irritability, behavioral changes) during weeks 1–2, when suicide risk is highest 1
• Watch for signs of acute dystonia (neck stiffness, jaw clenching, TMJ pain), which can occur within 24–48 hours of dose increases 3

Seizure Risk

• At 300 mg/day, seizure incidence is approximately 0.1% (1 in 1,000 patients) 1, 4
• Risk increases significantly above 450 mg/day or with rapid dose escalation 1
• Do not crush, divide, or chew SR tablets, as this increases seizure risk by altering drug release 2

Administration Guidelines

Timing and Food

• First dose: morning 1
• Second dose: before 3 PM 1, 2
• May be taken with or without food 2

Formulation Considerations

• Wellbutrin SR requires twice-daily dosing (versus once-daily for XL formulation) 1
• Monitor closely when switching between brand and generic formulations due to historical bioequivalence issues 1

Common Pitfalls to Avoid

1. Do not skip the 3-day initial titration period at 150 mg once daily—this gradual increase minimizes seizure risk 1
2. Do not administer the second dose after 3 PM—this causes insomnia 1, 2
3. Do not exceed 300 mg/day for smoking cessation or 400 mg/day for depression 1
4. Do not discontinue treatment before 6–8 weeks unless significant adverse effects occur 1
5. Do not combine with MAOIs or initiate within 14 days of MAOI discontinuation 1, 2

Clinical Advantages

• Significantly lower rates of sexual dysfunction compared to SSRIs 1
• Associated with minimal weight gain or modest weight loss 1
• Lower rates of sedation than SSRIs 1
• Particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia due to activating properties 1
• Dual benefit for patients requiring both depression treatment and smoking cessation 1