Atypical antidepressants · Psychiatry
Bupropion
Wellbutrin® · Zyban®(brand names vary by market)
Activating, weight-neutral, no sexual side effects, and it lowers the seizure threshold.
Also: modified release
Mechanism
Noradrenaline and dopamine reuptake inhibition with essentially no serotonergic activity, which is why its side-effect profile is so different from the rest.
Indications
- Major depressive disorder
- Seasonal affective disorder
- Smoking cessation
Formulations
Dosing concepts
Seizure threshold
Risk is dose-related and rises sharply above defined ceilings, which is why extended-release formulations and dose limits matter more here than with most antidepressants.
Double prescribing
It is marketed under different names for depression and for smoking cessation. A patient can end up on both, which is a genuine and checkable error.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- Extensive first-pass; active metabolites contribute substantially
- Half-life
- ~21 h; hydroxybupropion around 20 h and accumulates
- Elimination
- hepatic: CYP2B6 substrate; a potent CYP2D6 inhibitor itself
- Protein binding
- ~84%
Adverse effects
- Insomnia and agitationcommon
- Dry mouth, headachecommon
- SeizureseriousDose-related; the reason for the eating-disorder and epilepsy contraindications.
- Hypertensionserious
- Neuropsychiatric symptomsserious
Contraindications & precautions
Contraindications
- Seizure disorder
- Eating disorder, current or past
- Abrupt alcohol or benzodiazepine withdrawal
- Concurrent or recent MAO inhibitor
Precautions
- Head injury or CNS lesion
- Hypertension
- Bipolar disorder
- Concurrent CYP2D6 substrates
Interactions
Monitoring
Blood pressure
It rises, particularly in combination with nicotine replacement
Sleep and agitation
Its activating profile
Any history that raises seizure risk
The contraindications are absolute and easy to miss on a busy clinic day
Counselling points
- Take the second dose earlier rather than at bedtime; it can keep you awake.
- Swallow extended-release tablets whole.
- Tell us if you have ever had a seizure, or an eating disorder.
- It is also sold as a stop-smoking medicine; make sure you are not taking both.
Clinical pearls
- It is the antidepressant of choice when sexual dysfunction ended the last one, and it can be added to an SSRI for the same reason.
- The eating-disorder contraindication exists because purging and electrolyte disturbance compound the seizure risk. It is not a soft caution.
References & review
- Bupropion product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.