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Bupropion

Bupropion

Wellbutrin Zyban Aplenzin Forfivo XL

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Updated: December 06, 2025

Overview

Bupropion is an atypical antidepressant and smoking cessation aid that acts as a norepinephrine-dopamine reuptake inhibitor (NDRI). First approved by the FDA in 1985, it has a unique pharmacological profile distinct from selective serotonin reuptake inhibitors (SSRIs), with minimal effects on serotonin transmission. Bupropion is particularly valuable for patients who cannot tolerate SSRI side effects like sexual dysfunction or weight gain. It also has stimulant-like properties and is occasionally used off-label for attention deficit hyperactivity disorder (ADHD) and seasonal affective disorder (SAD).

Drug Class

Aminoketone class antidepressant Norepinephrine-dopamine reuptake inhibitor (NDRI) Therapeutic categories: • Antidepressant • Smoking cessation agent

Mechanism of Action

Bupropion primarily inhibits neuronal reuptake of dopamine and norepinephrine with minimal effect on serotonin receptors. Its active metabolites (hydroxybupropion) contribute to therapeutic effects. At molecular level: • Blocks dopamine transporter (DAT) • Inhibits norepinephrine transporter (NET) • Acts as a non-competitive antagonist at nicotinic acetylcholine receptors (nAChRs) - key for smoking cessation

Pharmacokinetics

Absorption: Well absorbed orally (87%), food increases Cmax by 11-35% Distribution: Vd 19-21 L/kg, 84% protein bound Metabolism: Hepatic via CYP2B6 to active metabolites (hydroxybupropion) Excretion: Renal (87%), fecal (10%) Half-life: Parent drug 12-30 hours, metabolites 20-37 hours (dose/formulation dependent)

Pharmacodynamics

• Increases synaptic dopamine and norepinephrine levels • Mild psychostimulant effects • Lower risk of weight gain vs SSRIs • Minimal anticholinergic or antihistaminergic effects • May lower seizure threshold at high doses

Indications

• Major depressive disorder (MDD): For treatment of depression in adults • Seasonal affective disorder (SAD): Extended-release form for prevention of winter depression • Smoking cessation (Zyban): As part of comprehensive cessation program • Adjunctive treatment in ADHD (off-label)

Contraindications

Absolute: • Seizure disorders • Current/past diagnosis of bulimia or anorexia nervosa • MAOI use within 14 days Relative: • Severe hepatic cirrhosis • Bipolar disorder • Recent myocardial infarction • CNS tumors

Dosage & Administration

Major depressive disorder: • Initial: 100 mg IR twice daily or 150 mg SR/XL once daily • Max: 450 mg/day (400 mg SR/XL) Smoking cessation: • Start 150 mg daily x 3 days, then 150 mg twice daily • Duration: 7-12 weeks Seasonal affective disorder: • 150 mg XL daily starting in autumn • May increase to 300 mg XL daily after 1 week

Special Populations

Pediatric: Not FDA-approved under age 18 Geriatric: Use lower initial doses, monitor closely Renal impairment: Reduce dose in severe impairment (CrCl <30 mL/min) Hepatic impairment: Reduce dose/frequency in severe cirrhosis

Adverse Effects

Common (>10%): • Dry mouth (28%) • Insomnia (18-33%) • Headache (25%) • Nausea (13-22%) Serious (<1%): • Seizures (0.1-0.4%) • Hypertensive crisis • Angle-closure glaucoma • Severe skin reactions (SJS/TEN)

Drug Interactions

• MAOIs: Risk of hypertensive crisis • Other antidepressants: Increased seizure risk • CYP2B6 inhibitors (e.g., ticlopidine): Increase bupropion levels • Alcohol: Lower seizure threshold • Nicotine replacement: May increase hypertension risk

Warnings & Precautions

• Black box warning: Antidepressants may increase suicidal thoughts/behaviors in young adults • Seizure risk dose-dependent (avoid >450 mg/day) • May induce manic episodes in bipolar disorder • Monitor blood pressure • Risk of false-positive amphetamine urine screens

Pregnancy & Lactation

Pregnancy: Category C - Use only if potential benefit justifies risk Limited human data, possible cardiovascular malformations Lactation: Excreted in breast milk AAP considers compatible with breastfeeding Monitor infant for irritability/feeding issues

Monitoring Parameters

• Mood changes/suicidal ideation, especially in first few weeks • Seizure risk factors • Blood pressure • Weight changes • Hepatic function in liver disease

Patient Counseling

• Take exactly as prescribed (do not crush/cut XL tablets) • Avoid alcohol consumption • Report mood changes or suicidal thoughts immediately • May cause insomnia - take morning doses early • Do not suddenly stop medication • Smoking cessation requires behavioral support

Storage & Stability

Store at 20-25°C (68-77°F) Protect from light and moisture Keep in original container with dessicant Do not transfer to pill boxes (moisture sensitive)

Clinical Pearls

• First-line for depression with comorbid ADHD or fatigue • Often combined with SSRIs to counteract sexual side effects • Lower weight gain risk makes it preferred in metabolic syndrome • Smoking cessation efficacy independent of antidepressant effect • May improve cognitive symptoms of depression

References

• Stahl SM. Stahl's Essential Psychopharmacology. 5th ed. 2020 • Wellbutrin PI. FDA Prescribing Information. 2023 • Hughes JR et al. Antidepressants for smoking cessation. Cochrane Database. 2014 • Fava M et al. 15 years of clinical experience with bupropion HCl. Prim Care Companion J Clin Psychiatry. 2005