Pharmacology · Atypical antidepressants
Bupropion !
An antidepressant that acts on norepinephrine and dopamine, not serotonin. It also helps people stop smoking and does not cause sexual dysfunction.
Updated 2026-11-01
The figure shows bupropion bound to human NET in an inward-open state.
Mechanism of action
Bupropion is a relatively weak inhibitor of norepinephrine and dopamine reuptake; it does not block serotonin reuptake or inhibit MAO. Its active metabolite hydroxybupropion reaches much higher levels than the parent drug. The dopaminergic and noradrenergic actions are thought to explain both its antidepressant effect and its help with nicotine craving.
- Bupropion and hydroxybupropion bind NET and DAT
- Norepinephrine and dopamine reuptake is reduced
- Reward and arousal circuits are strengthened; serotonin is not affected
- Mood improves and nicotine craving and withdrawal ease
Pharmacokinetics
- Absorption
- By mouth, with or without food; sustained-release tablets
- Metabolism
- CYP2B6 forms hydroxybupropion, the main active metabolite; bupropion inhibits CYP2D6
- Half-life
- About 21 hours for bupropion with chronic use and about 20 hours for hydroxybupropion
Indications
- Major depressive disorder
- Help to stop smoking (nicotine dependence, WHO list)
- Seasonal affective disorder
Adverse effects
Common
- Insomnia, agitation, tremor
- Dry mouth, nausea
- Headache
- Weight loss rather than gain
Contraindications
- Seizure disorder
- Current or past bulimia or anorexia nervosa
- Abrupt withdrawal of alcohol, benzodiazepines, barbiturates or antiepileptic drugs
- MAO inhibitors, or within 14 days of stopping either drug (hypertensive reactions); not started during linezolid or intravenous methylene blue
Key interactions
- Drugs that lower the seizure threshold (other bupropion products, antipsychotics, antidepressants, theophylline, systemic corticosteroids)
- Higher seizure risk
- CYP2D6 substrates (venlafaxine, nortriptyline, imipramine, paroxetine, fluoxetine, sertraline and others)
- Higher levels of those drugs
- CYP2B6 inducers or inhibitors
- Changes bupropion exposure
- Levodopa or amantadine
- CNS toxicity (restlessness, agitation, tremor, ataxia), as all three have dopaminergic effects
- MAO inhibitors
- Hypertensive reactions
What is monitored
- Blood pressure
- Seizure risk factors before starting
- Mood, sleep and neuropsychiatric symptoms, especially during smoking cessation
- Suicidal thoughts
Administration and safety
- Sustained-release tablets are not chewed, cut or crushed
- Dose changes are gradual because seizure risk rises with dose
- The same molecule is sold for depression and for smoking cessation: two bupropion products are not given together
Nursing care
- Ask about seizures, eating disorders, head injury and recent stopping of alcohol or sedatives before the first dose
- Measure blood pressure at baseline and follow-up
- Teach that insomnia is common and to report mood changes, agitation or unusual thoughts, especially while quitting smoking
- Teach that sexual dysfunction and weight gain are not typical, which helps adherence
Pregnancy and breastfeeding
First-trimester studies have not shown a higher overall risk of malformations; untreated depression also carries risks for the mother.
Test yourself
Think of the answer, then tap the question to see it.
Why is bupropion contraindicated in bulimia and anorexia nervosa?
These patients had a higher rate of seizures on bupropion; it lowers the seizure threshold, more so with electrolyte disturbances.
Which antidepressant is also used to help people stop smoking and has no serotonergic action?
Bupropion, a norepinephrine and dopamine reuptake inhibitor.
A patient wants an antidepressant without sexual dysfunction or weight gain. Which one fits, and what history must be checked?
Bupropion. Seizures, eating disorders and abrupt withdrawal from alcohol or sedatives must be ruled out.
Related drugs
← Back to the class: Atypical antidepressants
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - BUPROPION HYDROCHLORIDE SR- bupropion hydrochloride tablet, film coated, extended release (DailyMed (U.S. National Library of Medicine), 2026); Bupropion: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); eEML - Electronic Essential Medicines List (World Health Organization, 2025); 8HFL: Cryo-EM structure of human norepinephrine transporter NET in the presence of the antidepressant bupropion in an inward-open state at resolution of 3.0 angstrom. (RCSB Protein Data Bank, 2024).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.