Bupropion: NDRI Antidepressant and Smoking Cessation Aid
Bupropion (Wellbutrin, Zyban) is a norepinephrine-dopamine reuptake inhibitor (NDRI) antidepressant. It does not affect serotonin, making it distinctive among antidepressants — no sexual dysfunction, no weight gain.
Approved for major depressive disorder, seasonal affective disorder, and smoking cessation (as Zyban). Also widely used off-label for ADHD in adults and bipolar depression.
Mechanism of Action
Blocks reuptake of norepinephrine and dopamine at presynaptic terminals. Also a nicotinic acetylcholine receptor antagonist, which underlies its efficacy in smoking cessation by reducing nicotine craving and withdrawal.
Indications & Use
MDD (particularly with fatigue, hypersomnia, or sexual dysfunction from other antidepressants), seasonal affective disorder (SAD), smoking cessation. Off-label: adult ADHD, bipolar depression (with a mood stabiliser), weight management.
Dosage
Immediate-release: 100 mg twice daily (max 450 mg/day). Sustained-release (SR): 150 mg once daily, increase to 150 mg twice daily. Extended-release (XL): 150 mg once daily, may increase to 300–450 mg. Smoking cessation: 150 mg SR once daily for 3 days, then twice daily for 7–12 weeks.
Side Effects
Common: dry mouth, insomnia, headache, agitation. Important: lowers seizure threshold — dose-dependent (risk highest >450 mg/day or with immediate-release). No sexual dysfunction. No weight gain (often causes weight loss).
Drug Interactions
MAOIs: contraindicated (hypertensive crisis). CYP2D6 substrate: inhibited by paroxetine/fluoxetine. Lowers seizure threshold — additive with other drugs that lower it. Alcohol: avoid (increases seizure risk).
Contraindications
Seizure disorder, eating disorders (bulimia, anorexia — high seizure risk), concurrent MAOI use (or within 14 days), abrupt alcohol or benzodiazepine discontinuation, hypersensitivity.
Frequently Asked Questions
Does bupropion cause sexual dysfunction?
No — bupropion is one of the few antidepressants that does not cause sexual dysfunction. It is sometimes added to SSRIs specifically to counteract SSRI-induced sexual side effects.
What is the seizure risk with bupropion?
At doses up to 300 mg/day XL, risk is ~0.1% (similar to other antidepressants). Above 450 mg/day or with immediate-release formulations, risk increases significantly. Avoid in eating disorders and with alcohol.
Can bupropion be used for ADHD?
Yes, off-label. While not first-line (stimulants preferred), bupropion has evidence for adult ADHD, particularly when depression or substance use co-occurs. It has no abuse potential.
References
- NICE NG222 Depression 2022
- Stahl SM: Stahl's Essential Psychopharmacology, 5th ed.
- EMA/FDA Wellbutrin/Zyban SPC
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.