TaperCommunitybupropion
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) approved for major depressive disorder, seasonal affective disorder, and smoking cessation (as Zyban). It is unique among antidepressants for its activating profile and lack of sexual side effects or weight gain.
75mg, 100mg, 150mg, 300mg
Immediate-release tablets: 75mg, 100mg; Sustained-release tablets (SR): 100mg, 150mg, 200mg; Extended-release tablets (XL): 150mg, 300mg
Category C (risk cannot be ruled out)
Inhibits reuptake of norepinephrine and dopamine (NDRI). Does not significantly affect serotonin reuptake. The active metabolites hydroxybupropion, threohydrobupropion, and erythrohydrobupropion also contribute to pharmacological activity.
Generally easier to taper than SSRIs/SNRIs. IR tablets can be split for gradual reduction.
Reduce gradually. IR formulation provides most flexibility for dose adjustments.
Evidence-based phased reduction schedule. Always taper under medical supervision.
| Phase | Duration | Notes |
|---|---|---|
| Initial reductions | 2-4 weeks | Use available XL strengths. Most tolerate initial steps well. |
| Formulation switch | 2-4 weeks | Your prescriber may switch to SR or IR formulation for more flexible adjustments. |
| Final reductions | 4-6 weeks | IR tablets offer the most flexibility. Bupropion withdrawal is generally milder than SSRI/SNRI discontinuation. |
1-3 days after dose reduction
3-7 days
1-2 weeks for most symptoms
Fatigue and motivational deficits may linger 2-4 weeks. No serotonin-related symptoms (no brain zaps). Wellbutrin has one of the mildest withdrawal profiles among antidepressants.
Practical insights shared by members tapering Wellbutrin. Not medical advice — always consult your prescriber.
Toxicity
Dose-dependent seizure risk (contraindicated above 450mg/day). Hypertension. Lower toxicity in overdose than TCAs but seizures and cardiac conduction delays possible.
Pharmacokinetics
Well absorbed after oral administration. Tmax ~2 hours (IR), ~3 hours (SR), ~5 hours (XL). Extensive first-pass metabolism; bioavailability ~5–20%. Food does not significantly affect absorption of SR/XL formulations.
~20 L/kg (estimated)
Extensively metabolized hepatically via CYP2B6 (primary) to the active metabolite hydroxybupropion. Non-CYP pathways produce threohydrobupropion and erythrohydrobupropion.
Renal (~87%, with <1% as unchanged bupropion) and fecal (~10%).
~84%
~200 L/hr (apparent oral clearance)
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