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.