Wellbutrin SR
Wellbutrin SR
Generic Name
Wellbutrin SR
Mechanism
- Partial inhibitor of dopamine (DAT) and norepinephrine (NET) reuptake, increasing synaptic concentrations of these monoamines in the prefrontal cortex and limbic system.
- Weak inhibition of serotonin transporter (SERT)—minimal serotonergic effect, reducing the risk of serotonin syndrome compared with SSRIs.
- β‑adrenergic stimulation contributes to its stimulating and weight‑loss properties.
- These pharmacologic actions translate into antidepressant, anthelmintic, and euglycemic effects.
Pharmacokinetics
| Parameter | Value | Notes |
| Absorption | Oral, sustained‑release; Tmax ≈ 3–4 h | Food delays onset by ~1 h; overall bioavailability 15–22 % |
| Distribution | Vd 2.8 L/kg; highly protein‑bound (~95 %) | Penetrates CNS effectively |
| Metabolism | Hepatic CYP2B6 → hydroxybupropion (active) + other metabolites | CYP2B6 inhibitors (e.g., efavirenz, carbamazepine) ↑ plasma levels |
| Elimination | Renally excreted (≈50 %) and hepatically | Terminal half‑life 21–27 h at steady‐state |
| Special Populations |
• Elderly: ↓CYP2B6 activity → lower clearance • Renal/hepatic impairment: adjust dose (see contraindications) |
Indications
- Major depressive disorder (initial therapy or adjunct).
- Seasonal affective disorder (onset in fall/winter).
- Adjunctive “up‑titration” with serotonergic agents for refractory depression.
- Smoking cessation (≥150 mg/d; licensed as Zyban).
Contraindications
| Category | Detail |
| Absolute Contraindications |
• History of seizure disorder • Bulimia or anorexia nervosa • Sudden withdrawal from alcohol, benzodiazepines, or barbiturates |
| Relative |
• Severe hepatic impairment (Child‑Pugh C) • Severe renal impairment (CrCl < 30 mL/min) – dose adjustment advised • Pregnancy (Category C) – use only if benefits outweigh risks |
| Warnings |
• Seizure risk increases dose‑dependently; careful titration essential. • Raises systolic/diastolic BP and pulse; monitor cardiovascular status. • Rare hepatotoxicity (monitor LFTs). • Psychosis or manic switch may occur in bipolar patients. |
Dosing
| Population | Initiation | Titration | Maintenance | Max Daily | Notes |
| Adults with MDD/SAD | 150 mg once daily (morning) | Increase by 150 mg after 5–7 days if tolerated | 75–150 mg BID (preferred) or 150 mg QD | 300 mg | Avoid splitting tablets; keep in upper half of day to avoid insomnia. |
| Elderly | 150 mg QD | May add 75 mg/second day if needed | 75 mg BID or 150 mg QD | 225 mg | Monitor for falls, orthostatic hypotension. |
| Smoking Cessation | 150 mg QD | Optional increase to 225 mg after 4 weeks | 150 mg QD | 225 mg | Continue for 12 weeks total. |
| Pregnancy | 75 mg QD | Increase slowly | 150 mg QD | 300 mg | Use with obstetric guidance. |
Adverse Effects
Common (≥10 %)
• Dry mouth
• Insomnia, vivid dreams
• Appetitive decrease → weight loss
• Anxiolysis, tremor
• Palpitations, tachycardia
• Headache
Serious (≤1 %)
• Seizures – dose‑related; risk increases above 300 mg/day.
• Hypertensive crisis or arrhythmias (especially in uncontrolled hypertension).
• Severe allergic reactions, angioedema.
• Acute psychosis, mania in bipolar disorder.
• Agranulocytosis (rare, <0.01 %).
Monitoring
- Baseline: BP, pulse, weight, fasting glucose, CBC, LFTs, kidney function.
- During therapy:
- BP & pulse every 2 weeks during titration, then monthly.
- Weight and appetite weekly until plateau.
- Seizure history; patients with a history of epilepsy should be monitored vigilantly.
- LFTs every 6–8 weeks if hepatotoxicity suspected or in chronic users.
- Monitor for mood elevation or emergent bipolar symptoms.
Clinical Pearls
- Titration is key: Start low, go slow; the first 5–7 days after dose escalation are the most seizure‑prone.
- Avoid abrupt discontinuation: Instead of “stop,” we often cross‑fade to low dose or use supportive therapy for 7‑10 days.
- Synergy with SSRIs: Combo can increase the risk of serotonin syndrome; monitor for tremor, agitation, hyperreflexia.
- Weight & appetite: Bupropion’s stimulating action is beneficial when adjunct therapy in patients with weight gain from other antidepressants.
- CYP2B6 polymorphisms: Patients with poor metabolizer status may experience higher plasma concentrations; dose reduction may be warranted.
- Use in pregnancy: Category C; if needed, the lower dose (75 mg QD) has the lowest risk profile yet still offers benefit for severe depression.
--
• *Reference‑friendly*: Each bullet or table is easily adaptable into evidence summaries, quick‑look guides, or slide decks. The headings align with standard pharmacy teaching modules, making this card ideal for medical student review, resident rotation, or clinical reference.