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

Side Effects of Wellbutrin (Bupropion)

The most common side effects of Wellbutrin include dry mouth (occurring in up to 20% of patients), insomnia, headache, nausea, constipation, dizziness, and tremor, with the most serious concern being seizures occurring at a rate of approximately 1 in 1,000 patients. 1, 2

Most Common Side Effects

The side effect profile is well-established across multiple authoritative sources:

• Dry mouth is the most frequently reported side effect, affecting up to 20% of patients 3, 1, 2
• Insomnia occurs commonly and is dose-dependent; taking the medication too close to bedtime should be avoided 1, 2, 4
• Headache is among the most frequently reported neurological effects 1, 4, 5
• Nausea occurs commonly but appears slightly less frequent than with SSRI antidepressants 1, 2, 6
• Constipation is a common gastrointestinal effect 1, 2, 4
• Dizziness and tremor are frequently reported neurological side effects 1, 2, 6
• Anxiety can occur, though it may also represent nicotine withdrawal symptoms in smoking cessation patients 2, 4

Important clinical note: Only insomnia and dry mouth occur significantly more frequently with bupropion compared to placebo in controlled trials 4

Serious Side Effects Requiring Immediate Attention

Seizures

Seizures represent the most serious risk, occurring at approximately 0.1% (1 in 1,000) when proper screening and dosing guidelines are followed. 1, 4

Risk factors that absolutely contraindicate bupropion use include: 1, 7

• Prior history of seizures
• Structural brain lesions (from stroke, tumor, or trauma)
• Eating disorders (anorexia nervosa or bulimia nervosa)
• Alcohol abuse or abrupt alcohol discontinuation
• Recent discontinuation of benzodiazepines, barbiturates, or antiepileptic drugs
• Concomitant medications that lower seizure threshold

Critical dosing requirement: The maximum daily dose must not exceed 450 mg/day (or 300 mg/day for extended-release formulations), and doses must be spaced at least 24 hours apart for XL formulations to maintain seizure risk at 0.1% 2, 4, 7

Hypersensitivity Reactions

• Severe hypersensitivity reactions occur in approximately 0.1% of patients 4
• Delayed allergic reactions can appear 2 or more weeks after initiation, presenting as pruritus and urticaria, with highest risk in males aged 17-40 years 8
• If rash, hives, or itching develops, bupropion should be discontinued and antihistamines initiated 8

Neuropsychiatric Effects

• Suicidal thoughts require monitoring, particularly in young adults 1
• The medication should not be stopped abruptly at higher doses (15 mg/92 mg combination formulations require tapering over at least 1 week) 3

Cardiovascular Effects

Blood pressure monitoring is essential, particularly during the first 12 weeks of treatment. 1

• Tachycardia and elevated heart rate can occur 3, 1
• Palpitations and tachyarrhythmias are possible 3
• However, bupropion is 10 to 100 times less likely to cause cardiac conduction problems than tricyclic antidepressants 7
• Orthostatic hypotension is rare 7
• No significant changes in mean blood pressure values have been reported in clinical trials when used alone 4

Drug Interactions and Contraindications

Absolute contraindications include: 1, 2

• Use within 14 days of monoamine oxidase inhibitors (MAOIs) due to hypertensive crisis risk
• Current seizure disorder or conditions predisposing to seizures
• Eating disorders (anorexia or bulimia)
• Abrupt discontinuation of alcohol or sedatives

Important drug interaction: Bupropion inhibits cytochrome P450 2D6, requiring caution when co-prescribing with drugs metabolized by this enzyme 5, 6

Management of Side Effects

Most common side effects (insomnia and dry mouth) are generally transient and resolve without intervention: 4

• If insomnia persists, avoid taking doses close to bedtime 2
• Dose reduction can manage persistent side effects 4
• The discontinuation rate due to adverse events in clinical trials is low (6-12%) 4

Special Warnings

• Do not crush, cut, or chew extended-release tablets as this releases medication too quickly and increases seizure risk 2
• Limit or avoid alcohol during treatment; abrupt alcohol cessation increases seizure risk 2
• The medication may cause false-positive urine drug screens for amphetamines 2
• Sexual dysfunction is the least common among all antidepressants 6
• Minimal anticholinergic effects make it generally well-tolerated compared to tricyclic antidepressants 7