Generic Name

Bupropion

Mechanism

Bupropion, the active ingredient in *Wellbutrin*, is a norepinephrine‑dopamine reuptake inhibitor (NDRI).
• Inhibits the dopamine and norepinephrine transporters (DAT & NET), increasing synaptic dopamine and norepinephrine.
• Minimal serotonin activity reduces risk of serotonin syndrome.
• Partial agonist at nicotinic acetylcholine receptors → explains its efficacy in smoking cessation (Janssen product *Zyban*).

Pharmacokinetics

• Absorption: Oral bioavailability ~20 %; peak plasma concentration at ≈2–4 h.
• Metabolism: Primarily CYP2B6 → hydroxy‑bupropion (active metabolite). Genetic polymorphisms affect plasma levels.
• Half‑life: ~21 h (bupropion); hydroxy‑bupropion 20–27 h.
• Excretion: Renal (≈20 %) and fecal elimination.
• Food effect: Minimal; can be taken with or without food.

Indications

• Major depressive disorder (MDD) – first‑line or adjunctive.
• Seasonal affective disorder (SAD).
• Smoking cessation (*Zyban*).
• Adjunctive therapy for depressive episodes in bipolar disorder (under supervision).

Contraindications

• Seizure disorders – lowers seizure threshold (dose‑dependent).
• Current alcohol or substance abuse – increases relapse risk.
• Intoxication (e.g., overdose).
• Pregnancy category C – limited data; use only if benefit outweighs risk.
• Concurrent use of MAOIs – avoid.

Warnings
• Seizure risk ↑ with doses >450 mg/day.
• Hypertension – may slightly elevate BP; monitor in hypertensives.
• QT prolongation uncommon but noted at high doses.
• Psychosis – rare; monitor emerging symptoms.

Dosing

• Split‑dose may reduce seizure risk and improve tolerability.
• Taper slowly to prevent discontinuation syndrome (headache, irritability).

Adverse Effects

Common (≥10 %)
• Dry mouth, insomnia, anxiety, jitteriness.
• Loss of appetite → weight loss (beneficial in some cases).

Serious (≤3 %)
• Seizures, hypertension, angina, serious arrhythmias.
• Severe allergic reactions (rash, swelling).

Rare (<1 %)
• Severe psychiatric reactions (mania, suicidality).

Monitoring

• Baseline: BP, HR, BMI.
• Follow‑up: BP & HR every 2–4 weeks during titration.
• Seizure monitoring: patient education; consider EEG in high‑risk patients.
• Therapeutic drug monitoring rarely required but useful in CYP2B6 polymorphisms.
• Pregnancy & lactation: monitor infant if nursing.

Clinical Pearls

• Non‑serotonergic profile → lower risk of sexual dysfunction compared to SSRIs.
• Smoking cessation synergy: use *Zyban* to boost bupropion’s antidepressant effect.
• Titration with 150 mg BID: reduces seizure incidence vs. single daily dose.
• Patient selection: ideal for patients with ADHD or smoking history requiring antidepressant.
• CYP2B6 inhibitors (e.g., clopidogrel) ↑ bupropion levels—consider dose adjustment.
• Rapid detox: abrupt discontinuation can precipitate withdrawal; taper 2–4 weeks.

--
• *This drug card is educational; always cross‑check with current clinical guidelines and institutional protocols before prescribing.*