What are the common side effects of bupropion (Wellbutrin)?

Side Effects of Bupropion

Bupropion commonly causes insomnia, dry mouth, headache, nausea, and constipation, with seizures being the most serious adverse effect occurring at a rate of approximately 0.1% (1 in 1,000) when proper dosing and patient screening are followed. 1, 2

Common Side Effects

The most frequently reported adverse effects include:

• Neurological effects: Insomnia, headache, dizziness, and tremor are among the most common complaints 1, 2
• Gastrointestinal effects: Dry mouth, nausea, constipation, and vomiting occur frequently 1, 2
• Psychiatric effects: Anxiety and feeling anxious are reported, though these may overlap with nicotine withdrawal symptoms in smoking cessation patients 2, 3
• Other effects: Stuffy nose and joint aches are also documented 2

Clinical Pearl: Insomnia and dry mouth are the only side effects that occur significantly more frequently with bupropion compared to placebo 3. These effects are generally transient and often resolve without intervention, though they can be managed by dose reduction if necessary 3.

Serious Side Effects

Seizure Risk

The most critical serious adverse effect is seizures, occurring at approximately 0.1% (1 in 1,000) when patients are properly screened and dosing guidelines are followed. 1, 4, 2

Risk factors that increase seizure probability include:

• Prior history of seizures from any cause 1, 4
• Structural brain lesions (stroke, tumor, trauma) 1
• Eating disorders (bulimia or anorexia nervosa) 1, 5
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1, 4, 5
• Concomitant medications that lower seizure threshold 1
• Exceeding maximum recommended doses (450 mg/day for XL formulation, 400 mg/day for SR formulation) 5, 6

Critical Warning: The FDA label emphasizes that crushing, cutting, or chewing extended-release tablets releases medication too quickly and significantly increases seizure risk 2.

Cardiovascular Effects

• Tachycardia and tachyarrhythmias can occur 1
• Blood pressure elevations may develop, particularly problematic in patients with uncontrolled hypertension 1, 5
• Heart rate increases are documented 4, 5

Monitoring requirement: Blood pressure and heart rate should be checked periodically, especially during the first 12 weeks of treatment 1, 4, 5.

Hypersensitivity Reactions

• Severe hypersensitivity reactions occur at approximately 0.1% incidence 3
• Delayed allergic reactions can appear 2 or more weeks after initiation, presenting as pruritus and urticaria 7
• Risk may be highest in males aged 17-40 years with a history of allergic reactions 7

Clinical Pitfall: Because hypersensitivity reactions can be delayed beyond 2 weeks, clinicians may not immediately recognize bupropion as the causative agent 7.

Psychiatric Effects

• Black box warning: Increased risk of suicidal thoughts and behavior in patients younger than 24 years with depression 5
• Risk for suicide attempts is greatest during the first 1-2 months of treatment 5
• Agitation may occur, particularly given bupropion's activating properties 5, 6

Absolute Contraindications

Bupropion must be avoided in:

• History of seizures or any condition predisposing to seizures 1, 4, 5
• Eating disorders (bulimia or anorexia nervosa) 1, 5
• Abrupt discontinuation of alcohol in dependent patients 4, 5
• Current or recent (within 14 days) use of MAOIs due to hypertensive crisis risk 1, 5
• Pregnancy (for weight management formulations) 5

Special Precautions

Alcohol Interaction

• Patients should minimize or avoid alcohol consumption entirely during treatment 4
• Abrupt alcohol discontinuation in dependent patients is an absolute contraindication 4
• Chronic alcohol use may require dose reduction to maximum 150 mg daily due to hepatic impairment 4

Cardiovascular Disease

• Use with caution in patients with cardiovascular disease 1
• Uncontrolled hypertension should preclude bupropion use 5

Hepatic and Renal Impairment

• Moderate to severe hepatic impairment: maximum 150 mg daily 5
• Moderate to severe renal impairment: reduce total daily dose by half 5

Comparative Tolerability

• Discontinuation rates due to adverse events in clinical trials range from 6-12%, indicating generally good tolerability 3
• Bupropion has lower rates of sexual dysfunction compared to SSRIs 5
• No significant changes in mean heart rate, blood pressure, or routine laboratory parameters when used alone at recommended doses 3

Management Strategies

For insomnia: Administer the second dose of SR formulation before 3 PM; avoid taking XL formulation too close to bedtime 5, 2

For transient side effects: Most common effects (insomnia, dry mouth) resolve quickly without intervention but can be managed with dose reduction if needed 3

For seizure prevention: Never exceed maximum daily doses (300 mg for smoking cessation, 450 mg for XL depression treatment), screen all patients for risk factors, and ensure proper tablet administration (swallow whole, never crush) 1, 5, 2.