bupropion
Norepinephrine-dopamine reuptake inhibitor (NDRI); antidepressant· Brands: Wellbutrin, Zyban, Aplenzin, Forfivo XLPO
Mechanism of action
Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI). It selectively inhibits the reuptake of norepinephrine and dopamine by blocking the respective transporters, increasing synaptic concentrations of these neurotransmitters. It has little to no effect on serotonin. It also acts as a non-competitive antagonist at nicotinic acetylcholine receptors, which is thought to contribute to its efficacy in smoking cessation. The exact mechanism of its antidepressant action is not fully understood.
Pharmacokinetics
Bupropion is well absorbed after oral administration, with peak plasma concentrations within 2 hours. It undergoes extensive hepatic metabolism primarily through cytochrome P450 2B6, producing three active metabolites: hydroxybupropion, erythrohydrobupropion, and threohydrobupropion. The parent compound has a terminal half-life of approximately 20 hours, while metabolites have longer half-lives (up to 30 hours or more). Bupropion is an inhibitor of CYP2D6. It is excreted in urine as metabolites. Food can affect the rate of absorption, and smoking may induce CYP2B6, altering exposure.
Indications & dosing
Major depressive disorder
Start 150 mg once daily, increase after 4 days. Usual maintenance 300 mg/day.
- adult · PO: 150 mg twice daily · Start 150 mg once daily, increase after 4 days. Usual maintenance 300 mg/day.
Smoking cessation
Start 150 mg once daily for 3 days, then 150 mg twice daily for 7-12 weeks.
- adult · PO: 150 mg twice daily · Start 150 mg once daily for 3 days, then 150 mg twice daily for 7-12 weeks.
Seasonal affective disorder
Use extended-release (XL). Start 150 mg daily in autumn, increase to 300 mg daily if needed.
- adult · PO: 150–300 mg once daily · Use extended-release (XL). Start 150 mg daily in autumn, increase to 300 mg daily if needed.
Contraindications & precautions
- Hypersensitivity to bupropion or any component of the formulation · Discontinue if rash or other signs of hypersensitivity occur.
- Current or prior history of seizures · Bupropion lowers the seizure threshold; risk is dose-related.
- Bulimia or anorexia nervosa · History increases the risk of seizures.
- Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs · May increase the risk of seizures.
- Concomitant use of monoamine oxidase inhibitors (MAOIs) · At least 14 days must elapse between MAOI use and bupropion initiation.
- Severe hepatic cirrhosis · Increases risk of seizures and bupropion toxicity.
- Monitor blood pressure, particularly in patients with hypertension or those receiving concomitant antihypertensive therapy.
- Use with caution in hepatic or renal impairment; consider dose reduction in moderate impairment.
- Advise patients about the increased risk of seizures, especially with high doses, concurrent alcohol use, or other predisposing factors.
- Monitor for psychiatric symptoms, particularly in patients with a history of bipolar disorder or depression.
Adverse effects
- Dry mouth
- Insomnia
- Nausea
- Headache
- Seizuresserious
- Hypertensionserious
- Mania or hypomaniaserious
- Suicidal ideation or behaviourserious
Renal & hepatic adjustment
- eGFR 0–29: Avoid in severe renal impairment. If considered necessary, use with extreme caution and reduce dose (e.g., max 150 mg every other day) with close monitoring. (avoid)
- eGFR 30–59: Reduce dose and/or frequency. Consider a maximum dose of 150 mg per day, and increase dosing interval if required.
- Hepatic impairment (mild): No adjustment required. Use with caution.
- Hepatic impairment (moderate): Reduce dose to 150 mg per day. Use with caution.
- Hepatic impairment (severe): Avoid use. Consider alternative treatment. (avoid)
Monitoring, pregnancy & toxicity
- Blood pressure · Baseline and during dose titration
- Mood, behaviour, and suicidal ideation · Regularly, especially at start of treatment or dose changes
- Seizure risk (e.g., history, concurrent medications, alcohol use) · Before and during treatment
- Neurological signs (e.g., tremor, agitation, insomnia) · At each clinic review
- Pregnancy: In pregnancy, weigh potential benefit against risk. Limited human data; consider alternative antidepressant if possible. If used, use the lowest effective dose and monitor closely.
- Toxicity: Seizures (dose-related; higher risk in overdose, epilepsy, or with drugs that lower seizure threshold) · Manage as per ALS guidelines; give benzodiazepines (e.g., lorazepam) early; avoid stimulants and drugs that increase seizure risk.
- Toxicity: Tachycardia and hypertension · Monitor ECG and blood pressure; treat symptomatically; consider beta-blockers for tachyarrhythmias if required.
- Toxicity: Agitation, hallucinations, confusion · Supportive care; consider benzodiazepines if agitation is severe.
- Toxicity: Cardiac arrhythmias and cardiovascular collapse (in severe overdose) · Supportive care; continuous ECG monitoring; treat arrhythmias per guidelines; consider activated charcoal within 1 hour if large overdose.
Clinical notes
Bupropion is used for major depressive disorder, seasonal affective disorder, and as an aid for smoking cessation. It is generally well tolerated but can cause insomnia, dry mouth, headache, and agitation. It lowers the seizure threshold; therefore, it is contraindicated in patients with a history of seizures, eating disorders such as bulimia or anorexia nervosa, alcohol or benzodiazepine withdrawal, and in those taking other drugs that lower the seizure threshold. It should not be used with MAOIs due to an increased risk of hypertensive reactions. Available in immediate-release, sustained-release, and extended-release formulations, and dosing depends on the formulation. Prescribers should be aware of the risk of hypertension, particularly when used for smoking cessation in patients with cardiovascular disease. Monitor for neuropsychiatric symptoms.
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BNF; local formulary; SmPC