bupropion

General Information

Bupropion is an atypical antidepressant (NDRI) used for major depressive disorder, bipolar depression augmentation, and smoking cessation, valued for weight neutrality and low sexual side effects.

Because it is not serotonergic, SSRI-style sexual dysfunction is often less prominent; the trade-off is a more activating profile that can worsen anxiety or insomnia in susceptible patients.

The compare tool can help contrast activation, weight change, and sexual side-effect profiles, and drug-specific evidence summaries can support augmentation and cessation decisions.

The bipolar disorder hub can support mania-prevention planning when bupropion is used in bipolar depression, and the bupropion print view provides patient-friendly counselling sheets.

Activating profile can be useful for fatigue and low motivation, but it is contraindicated in seizure disorders and in current/prior eating disorders; screening for risk factors (alcohol withdrawal, electrolyte disturbances) is important before initiation.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Inhibits norepinephrine and dopamine reuptake and antagonizes nicotinic acetylcholine receptors.

• Norepinephrine-dopamine reuptake inhibitor with nicotinic receptor antagonism.

Metabolism and Pharmacokinetics

• Metabolized by CYP2B6 to active hydroxybupropion; parent half-life ~14 h, metabolite half-life 20–37 h.
• Exposure can shift with strong CYP2B6 inhibitors/inducers; interaction checks are particularly important when carbamazepine or ritonavir are in a regimen.

Dosing and Administration

• XL: start 150 mg qAM for 3–7 days, increase to 300 mg qAM; may increase to 450 mg qAM if needed.
• SR: 150 mg qAM ×3 days then 150 mg BID (≥8 h apart).
• For smoking cessation (SR), a common approach is 150 mg daily for several days, then 150 mg twice daily; coordinate quit date planning and behavioral supports.
• SR/XL tablets should not be crushed, split, or chewed; dose timing (often morning dosing) can help limit insomnia, and staying within labeled maximums helps reduce seizure risk.

Monitoring & Labs

• Blood pressure at baseline and after dose changes, especially when nicotine replacement is used.
• Seizure risk factors (eating disorder history, alcohol/benzodiazepine withdrawal, electrolyte disturbances) before initiation and at follow-up.
• Sleep and anxiety during early titration; dose timing and titration speed are common levers for tolerability.
• Mood elevation or agitation in bipolar-spectrum illness; coordinate prevention plans via the bipolar disorder hub.
• Medication list review to ensure only one bupropion-containing product is active (to reduce accidental dose escalation across brands).

Bupropion’s activating profile can be helpful for low energy, but tolerability depends heavily on seizure-risk screening and on a predictable titration plan. Alcohol reduction and minimizing abrupt sedative withdrawal reduce seizure risk; document plans when alcohol use disorder is present. SR/XL tablets should remain intact, and gradual dose changes can reduce insomnia and seizure risk.

Adverse Effects

Interactions

• CYP2B6 inhibitors (clopidogrel, ticlopidine) raise levels; CYP2B6 inducers (carbamazepine, ritonavir) lower levels.
• As a strong CYP2D6 inhibitor, bupropion can increase concentrations of coadministered CYP2D6 substrates (antidepressants, antipsychotics).
• Contraindicated with MAO inhibitors; a 14-day washout is used to reduce hypertensive crisis risk.

Other Useful Information

• Combination with SSRIs for augmentation is sometimes used; anxiety and insomnia are common early tolerability issues to watch.
• Alcohol moderation can reduce seizure risk.
• Duplicate bupropion across products (e.g., antidepressant plus smoking-cessation brand) can lead to accidental dose escalation; a medication list review helps prevent this.

References

1. WELLBUTRIN XL (bupropion hydrochloride) prescribing information — DailyMed (2026)
2. Clinical efficacy of bupropion in the management of smoking cessation — Drugs (2002)
3. Seasonal affective disorder and its prevention by anticipatory treatment with bupropion XL — Biological Psychiatry (2005)
4. APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
5. Comparative efficacy and acceptability of 21 antidepressant drugs for major depressive disorder — The Lancet (2018)Meta-analysisdepressionefficacy