bupropion

Brand: Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban, Aplenzin

⚠ BBW Prototype Drug

Drug Class: antidepressant / smoking cessation

Drug Family: antidepressant

Subclass: norepinephrine-dopamine reuptake inhibitor (NDRI)

Organ Systems: cns

Mechanism of Action

Inhibits neuronal reuptake of dopamine and norepinephrine; also a nicotinic acetylcholine receptor antagonist, which contributes to smoking cessation efficacy; no serotonergic activity.

dopamine reuptake transporter (DAT)norepinephrine reuptake transporter (NET)

Indications

major depressive disorder
seasonal affective disorder
smoking cessation (Zyban)
ADHD (off-label)
sexual dysfunction from SSRIs (off-label)

Contraindications

seizure disorder
anorexia nervosa or bulimia nervosa
abrupt alcohol or benzodiazepine discontinuation
concurrent MAOIs
patients on other bupropion-containing products

Adverse Effects

Common

dry mouth
headache
insomnia
nausea
constipation
tachycardia
agitation

Serious

seizures (dose-dependent; risk 0.1–0.4%)
suicidal ideation
neuropsychiatric symptoms (in smoking cessation use)
hypertension

Pharmacokinetics (ADME)

Absorption	Rapid absorption; extensive first-pass metabolism; bioavailability ~5–20%
Distribution	Protein binding ~84%; Vd ~19 L/kg
Metabolism	CYP2B6 to active hydroxybupropion (primary metabolite; higher levels than parent); also threohydrobupropion and erythrohydrobupropion
Excretion	Renal (~87%)
Half-life	21 hours (parent); 20–37 hours (hydroxybupropion)
Onset	Antidepressant: 2–4 weeks
Peak	3 hours (IR); 5 hours (SR); 5 hours (XL)
Duration	12–24 hours depending on formulation
Protein Binding	84%
Vd	~19 L/kg

Drug Interactions

Drug / Agent	Mechanism	Severity
MAOIs	hypertensive crisis risk	major
drugs that lower seizure threshold	additive seizure risk	major
tamoxifen	CYP2D6 inhibition by bupropion may reduce tamoxifen's active metabolite endoxifen	major

Nursing Considerations

Never exceed 450 mg/day total dose and avoid individual doses >200 mg (IR) or >300 mg (SR); dose-dependent seizure risk increases significantly above threshold
Contraindicated in eating disorders — purging behavior and nutritional compromise increase seizure risk
Advantage over SSRIs/SNRIs: no sexual dysfunction and no weight gain; can be used as add-on to SSRI when sexual dysfunction is problematic
For smoking cessation (Zyban): begin 1–2 weeks before quit date; combination with nicotine replacement therapy improves quit rates

Clinical Pearls

Bupropion is the only commonly-used antidepressant that facilitates weight loss and lacks sexual side effects — key differentiating factors when selecting an antidepressant
The ceiling dose limit exists strictly for seizure prevention; splitting doses and using the SR/XL formulations are pharmacokinetically designed to keep peak levels below seizure threshold

Safety Profile

Pregnancy use-with-caution

Lactation use-with-caution

Renal Adjustment Required

Hepatic Adjustment Required

TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

ADHD (off-label) Antidepressant / Smoking Cessation Major Depressive Disorder Seasonal Affective Disorder Sexual Dysfunction From SSRIs (off-label) Smoking Cessation (Zyban)

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