Bupropion
WELLBUTRIN
Pronunciation: byoo-PROE-pee-on (WEL-byoo-trin)
“Boop ropin’ Well booty”
Strong CYP2D6 inHibitor
Skinny → weight loss possible
What it isNorepinephrine-dopamine reuptake inhibitor; depression. Smoking cessation is the SR product ZYBAN, and SAD prevention is WELLBUTRIN XL.
Why this oneFar less sexual dysfunction and weight gain than SSRIs; hence use as an addition or substitute.
What limits itLowers the seizure threshold, so avoid in eating disorders and with alcohol withdrawal. A strong CYP2D6 inhibitor.
Pearls
- Best when anxiety is not prominent; agitation and insomnia common.
- Smoking cessation: start 7–14 days before quit date; SR equals single NRT.
- Raises blood pressure; contraindicated within 14 days of an MAOI.
- Blunts 2D6-activated prodrugs (tamoxifen, codeine); CYP2B6 substrate.
Bupropion prescription history
Animated chart of estimated U.S. prescriptions per year, Antidepressants (1957–2026). Bupropion enters in 1989 (estimated).
FDA-approved for
- depression (1985)
- smoking cessation, as ZYBAN (SR) (1997)
- seasonal affective disorder (prevention), as WELLBUTRIN XL (2006)
Off-label
- ADHD
- antidepressant sexual dysfunction
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityDose-related seizures and delayed cardiotoxicity are prominent in overdose, especially with extended-release products.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Major depressive disorder | Adults | 100 mg BID | 100 mg TID (300 mg/day) | 450 mg/day (≤150 mg per dose) |
Titration After 3 days may increase to 300 mg/day; increases ≤100 mg/day per 3-day period
Renal GFR <90 mL/min: consider reduced dose and/or frequency
Hepatic Moderate–severe (Child-Pugh 7–15): max 75 mg/day; mild (Child-Pugh 5–6): consider reduced dose and/or frequency
Not approved for smoking cessation; pediatric safety and effectiveness not established.
Instructions
- Swallow whole; do not crush, divide, or chew
- With or without food
- At least 6 h between doses
- Above 300 mg/day use 75- or 100-mg tablets; max 450 mg/day as 150 mg TID (≤150 mg per dose, ≥6 h apart); 100-mg tablet 4 times daily = 400 mg/day, not 450
Available strengths
- tab 75, 100 mg
Contraindications
- Seizure disorder
- Current or prior bulimia or anorexia nervosa
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
- MAOIs (psychiatric) concurrently or within 14 days; starting in patients on linezolid or IV methylene blue — hypertensive reactions
Cautions
- Suicidal thoughts and behaviors in children, adolescents, young adults
- Neuropsychiatric adverse events in smoking cessation
- Seizure (dose-related; ≤450 mg/day, titrate gradually)
- Hypertension
- Activation of mania/hypomania
- Psychosis and other neuropsychiatric reactions
- Angle-closure glaucoma
- Hypersensitivity reactions
Adverse reactions
- Agitation
- Dry mouth
- Constipation
- Headache/migraine
- Nausea/vomiting
- Dizziness
- Excessive sweating
- Tremor
- Insomnia
- Blurred vision
- Tachycardia
- Confusion, rash, hostility, cardiac arrhythmias, auditory disturbance
Pregnancy First-trimester epidemiologic data show no increased overall malformation risk; weigh risks of untreated depression.
Lactation Bupropion and metabolites present in milk (~2% of maternal weight-adjusted dose); seizures reported in breastfed infants (relationship unclear).
Cost
| Strength | #/mo | generic $/mo | CostPlus | |
|---|---|---|---|---|
| 75 mg | tab | 30 qd | $2.78 | offered |
| 100 mg | tab | 30 qd | $3.39 | offered |
Other forms: Bupropion hydrobromide ER (APLENZIN) · Bupropion SR (WELLBUTRIN SR) · Bupropion XL (WELLBUTRIN XL) · Bupropion XL 450 mg (FORFIVO XL)
Available combined with: dextromethorphan / bupropion · naltrexone / bupropion
Generic entry1999
Serotonicity
This drug is routinely called serotonergic. By Gillman’s human-effect criteria it does not raise serotonin in the synapse.
No clinically significant SRI activity.
Label contraindicationMAOIs (psychiatric) concurrently or within 14 days; starting in patients on linezolid or IV methylene blue — hypertensive reactions. The label governs prescribing; Gillman’s point concerns serotonin toxicity only.
Gillman’s four human testsA measurable SERT affinity that fails all four is not clinical serotonicity.
- Retarded orgasm
- Efficacy in OCD and cataplexy
- Clonus and hyperreflexia in single-drug overdose
- Serotonin toxicity when combined with an MAOI
Non-elevating actionNone recorded
Evidence confidenceHigh
Background: what serotonicity is · what is and is not an SRI · what counts as a relevant MAOI.
Active metabolites
Open Bupropion in the interactive console ↗
Memory aids: interaction avatars
Open Bupropion in the interactive console ↗
Self-check
- Which enzyme does bupropion strongly inhibit?
CYP2D6. - Which two settings should avoid bupropion because of seizure risk?
Eating disorders and alcohol withdrawal.