Generic Name

Bupropion

Brand Names

“Zyban” or generic).

Mechanism

• NDRI Activity: Inhibits the presynaptic transporters NET and DAT, increasing extracellular concentrations of norepinephrine and dopamine.
• Antagonism of α‑Adrenergic Receptors: Mild blockade of α1‑adrenergic receptors contributes to sympathomimetic side effects.
• Partial Agonist at α2‑Adrenergic Sites: Modulates neuronal firing, aiding in mood stability.
• Cytotoxic Metabolite: Its metabolite Hydroxybupropion contributes to most clinical effects and toxicity profile.

The overall pharmacodynamic profile exhibits less serotonergic activity, reducing the risk of serotonin syndrome and sexual dysfunction.

Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentrations in ~2–3 h.
• Distribution: Widely distributed; plasma protein binding ~85 %.
• Metabolism: Primarily hepatic through CYP2B6 (→ hydroxybupropion) and to a lesser extent CYP2C19, CYP2D6, and CYP3A4.
• Elimination: Renal excretion of metabolites; half‑life ~20 h (steady‑state ≈ 36 h).
• Drug Interactions: Inhibits CYP2B6; can increase plasma levels of other CYP2B6 substrates.
• Special Populations:
• Renal impairment: minimal adjustment needed.
• Hepatic impairment: dose reduction recommended.
• Elderly: may require lower initial dose.

Indications

• Major Depressive Disorder (MDD)
• Seasonal Affective Disorder (SAD) (approved as a mono‑dose or adjunct).
• Smoking Cessation (common brand name “Zyban” or generic).
• Adjunct for Bipolar depression (off‑label; caution in mania).
• Adjunct for ADHD (in combination with stimulants) – off‑label, evidence limited.

Contraindications

• Seizure disorder (lowered seizure threshold).
• Episodic catatonia – risk of precipitating catatonic episodes.
• History of hypersensitivity to bupropion or trimethoprim.
• Rapid weight loss or fasting – exacerbates seizure risk.
• Concurrent use of MAOIs (within 14 days).
• Pregnancy Category C – minimal data; use only if benefits outweigh risks.
• Concurrent use of CYP2B6 inhibitors (e.g., clopidogrel) may increase plasma bupropion levels.

Dosing

• Titration: Increase cautiously; reduce if seizure activity or QTc prolongation detected.
• Stopping: Abrupt cessation can precipitate withdrawal headaches; taper over 1–2 weeks if needed.

Adverse Effects

• Common:
• Dry mouth, insomnia, tremor, anxiety, headache, nausea, constipation.
• Serious:
• Seizures: dose‑dependent, especially >450 mg/day.
• QTc prolongation (rare with fixed schedules).
• Suicidal ideation: monitor as with other antidepressants.
• Hyponatremia (rare).
• Allergic reactions: rash, anaphylaxis.

Monitoring

• Baseline:
• Seizure history, weight, vital signs, ECG (if risk factors).
• During Therapy:
• Weight, blood pressure (for hypertension or tachycardia), complete blood count if preceding metabolic issues, thyroid function tests (if clinically relevant).
• Therapeutic Drug Monitoring: Not routinely required unless concomitant CYP2B6 inhibitors or hepatic function altered.

Clinical Pearls

• Seizure Threshold: *Bupropion* lowers the seizure threshold; limit total daily dose to ≤450 mg in patients with a history of seizures or on antiepileptic drugs.
• Smoking Cessation Synergy: When used for smoking cessation, *bupropion* should be coupled with behavioral counseling for maximal success rates.
• Portion of Dosing: Splitting doses in the night can reduce insomnia – particularly useful in depressed patients with sleep disturbance.
• CYP2B6 Polymorphism: Patients with *CYP2B6* slow‑metabolizer genotype may have higher plasma levels and increased side‑effect risk; consider early dose reduction.
• Adjunct Use in Depression: *Bupropion* as an add‑on to SSRIs can mitigate sexual dysfunction due to its non‑serotonergic profile.
• Drug Interaction Caution: *Bupropion*’s interaction with clopidogrel may blunt antiplatelet activity; monitor platelet function if both drugs are prescribed.

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• > References & Further Reading:

> 1. FDA prescribing information for Bupropion (Zyban, Wellbutrin).

> 2. Goodman & Gilman's: *The Pharmacological Basis of Therapeutics* – Chapter on antidepressants.

> 3. JAMA Internal Medicine: “Bupropion as a serotonin‑modulating agent.”

> 4. American Psychiatric Association Practice Guideline on Smoking Cessation.

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