What are the dosage and potential side effects of Wellbutrin (bupropion)?

Wellbutrin (Bupropion) Dosing and Side Effects

Dosing for Major Depressive Disorder

For depression, start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily), with the second dose given before 3 PM to minimize insomnia risk. 1

Standard Dosing Regimens

Bupropion SR (Sustained Release):

• Initial: 150 mg once daily for 3 days 1
• Maintenance: 150 mg twice daily (300 mg/day total) 1
• Maximum: 400 mg per day 1
• Timing: First dose in morning, second dose before 3 PM 1

Bupropion XL (Extended Release):

• Initial: 150 mg once daily in the morning 1
• Maintenance: 150-300 mg once daily 1
• Maximum: 450 mg per day 1
• Timing: Single morning dose 1

Dosing for Smoking Cessation

Begin bupropion SR 150 mg twice daily (300 mg total) 1-2 weeks before the target quit date and continue for 7-12 weeks. 1

• Standard dose: 150 mg twice daily 1
• Start timing: 1-2 weeks before quit date 1
• Treatment duration: 7-12 weeks 1
• Efficacy assessment: After 7-12 weeks 1

Special Population Dosing

Older Adults:

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

Hepatic Impairment:

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

Renal Impairment:

• Moderate to severe (GFR <90 mL/min): Reduce total daily dose by half 1

Timeline for Clinical Response

Allow 6-8 weeks at an adequate therapeutic dose before determining treatment response or considering modification. 1

• Begin monitoring within 1-2 weeks for adverse effects and worsening depression 1
• Energy levels may improve within first few weeks 1
• Full antidepressant response: 6-8 weeks 1
• Highest suicide risk: First 1-2 months of treatment 1

Common Side Effects

The most common side effects include dry mouth, insomnia, agitation, nausea, constipation, and dizziness. 2

Frequent Adverse Effects:

• Dry mouth 2
• Trouble sleeping/insomnia 2
• Feeling anxious/agitation 2
• Stuffy nose 2
• Nausea 2
• Constipation 2
• Dizziness 2
• Joint aches 2

Favorable Side Effect Profile:

• Significantly lower rates of sexual dysfunction compared to SSRIs 3
• Lower risk of weight gain 1
• Minimal anticholinergic effects 4
• Lower cardiovascular risk compared to some alternatives 3

Serious Side Effects and Seizure Risk

The most medically significant adverse effect is seizure, occurring at approximately 1 in 1,000 at standard doses (≤450 mg/day). 1, 4

Seizure Risk Factors:

• Dose-dependent: Risk increases above 450 mg/day 1, 4
• Approximately 0.1% (1 in 1,000) at doses ≤300 mg/day 1
• Approximately 1 in 100 at higher inpatient doses 5
• One-third of overdose cases involve seizures 2

Overdose Manifestations:

• Seizures (most common serious effect) 2
• Hallucinations, loss of consciousness 2
• Mental status changes 2
• Cardiac effects: Sinus tachycardia, arrhythmias, conduction disturbances 2
• Severe cases: Rhabdomyolysis, respiratory failure, cardiac arrest 2
• Doses ≥2.7 grams can cause seizures and encephalopathy 6

Critical Contraindications

Absolute contraindications include seizure disorders, eating disorders (bulimia/anorexia), abrupt discontinuation of alcohol/benzodiazepines/antiepileptics, and concurrent MAOI use. 1, 3

Absolute Contraindications:

• Any seizure disorder or history of seizures 1, 3
• Current or history of bulimia or anorexia nervosa 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
• Concurrent MAOI use or within 14 days of MAOI discontinuation 1, 3
• Severe hepatic cirrhosis 1

Relative Contraindications/High-Risk Situations:

• Uncontrolled hypertension (bupropion can elevate blood pressure) 1
• Brain metastases or conditions predisposing to seizures 3
• Pregnancy (especially naltrexone/bupropion combinations) 1
• Concurrent tamoxifen use 1

Black Box Warning and Monitoring

The FDA requires a black box warning for increased risk of suicidal thoughts and behavior in patients younger than 24 years, requiring close monitoring especially during the first few months of treatment. 1

Critical Monitoring Parameters:

• Suicidal ideation, especially in patients <24 years old 1
• Blood pressure and heart rate, particularly first 12 weeks 1
• Mental status changes and behavioral changes 1
• Neuropsychiatric adverse effects 1

Important Administration Instructions

Swallow bupropion XL tablets whole—never chew, cut, or crush them, as this releases the medication too quickly and increases seizure risk. 2

Key Administration Points:

• Take XL formulation at least 24 hours apart 2
• SR formulation: Doses separated appropriately throughout day 1
• Can be taken with or without food 2
• Tablets may have an odor (this is normal) 2
• Insoluble shell may appear in stool 2
• Never crush or inject (associated with seizures and death) 2

Clinical Pearls

Bupropion is particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia due to its activating properties. 1

• Ideal for patients concerned about sexual dysfunction or weight gain 1
• Useful for comorbid depression and smoking cessation 1
• Can be combined with SSRIs for augmentation (more effective than buspirone) 1
• Should not be combined with MAOIs 1
• Monitor for bioequivalence issues when switching between brand and generic formulations 1
• May cause false-positive amphetamine screening on urine drug tests 2