Buprobion: spelling variant of the antidepressant bupropion

Buprobion is a common spelling variant of the substance bupropion. The correct name is bupropion (brand names Wellbutrin, Elontril, Zyban), a noradrenaline-dopamine reuptake inhibitor (NDRI). Confusion arises because the order of letters is easily transposed. Pharmacologically the substance is identical.

Bupropion was approved in the USA in 1989 and later in Europe for the treatment of depression. In smoking cessation (Zyban) bupropion has been established since 1997. Compared with SSRIs bupropion has a different side-effect profile: less sexual dysfunction, less weight gain, often more drive-enhancing, but a higher risk of sleep disturbance and seizures.

Mechanism of action

Bupropion and its active metabolite hydroxybupropion inhibit reuptake of noradrenaline and dopamine at the presynaptic neuron. Unlike SSRIs, bupropion has no relevant action on serotonin. This produces characteristic clinical effects:

• Antidepressant effect with focus on drive, concentration, anhedonia
• Reduction of nicotine craving and withdrawal symptoms via the dopaminergic component
• Less impact on sexual function and weight
• Weak nicotinic acetylcholine receptor antagonism, presumably supporting smoking cessation

Bupropion is metabolised hepatically via CYP2B6. Full antidepressant effect develops over 2 to 4 weeks.

Indications

• Major depression: acute and maintenance therapy, especially in patients with reduced drive, apathy or SSRI-induced sexual dysfunction
• Smoking cessation: in combination with behavioural interventions, particularly effective in heavily dependent smokers
• Seasonal affective disorder (SAD): approved in some countries, effective in studies
• Off-label uses: adult ADHD, sexual dysfunction under SSRIs (augmentation), obesity (naltrexone-bupropion combination), reduction of negative schizophrenia symptoms

Dosing and administration

Major depression (bupropion XR): start 150 mg in the morning, after 1 week increase to 300 mg in the morning.

Smoking cessation (Zyban): 150 mg in the morning for 6 days, then 150 mg twice daily, at least 8 hours apart. Start 1 to 2 weeks before the quit date, treatment duration 7 to 9 weeks.

Maximum dose: 300 mg per day with sustained-release preparations, up to 400 mg in exceptional cases.

Take in the morning, or with twice-daily dosing morning and afternoon, to reduce sleep disturbance. Sustained-release tablets must not be split or chewed.

Patients at increased seizure risk: do not exceed 300 mg per day, prefer the sustained-release form.

Side effects

Very common: sleep disturbance, dry mouth, headache, nausea, dizziness, tremor, sweating.

Common: constipation, taste changes, tinnitus, rash, pruritus, tachycardia, hypertension, concentration problems, irritability, anxiety.

Uncommon: seizures (dose-dependent, around 0.1 % at standard dose), psychotic symptoms, hallucinations, depersonalisation-like sensations.

Rare and very rare: Stevens Johnson syndrome, anaphylaxis, hepatitis, suicidal thoughts, serotonin syndrome in combination with serotonergic substances.

Important safety points:

• Seizure threshold is lowered, hence contraindicated in seizure disorders, bulimia, anorexia, alcohol or benzodiazepine withdrawal
• Watch for new suicidal thoughts in the first weeks, especially in young patients
• With hypertension, regular blood pressure monitoring, since bupropion can raise blood pressure
• With acute psychotic symptoms, pause therapy

Interactions

• MAO inhibitors: risk of hypertensive crisis, combination contraindicated; minimum 14-day interval
• CYP2D6 substrates (metoprolol, codeine, tamoxifen, tricyclics, antipsychotics): levels raised by bupropion-induced CYP2D6 inhibition; caution or dose adjustment
• CYP2B6 inhibitors and inducers: level changes
• Other serotonergic substances: combination possible but monitor closely
• Alcohol: increased seizure risk
• Levodopa, amantadine: additive dopaminergic effects, possible psychotic symptoms

Special considerations

Pregnancy: data limited, avoid in the first trimester if possible. If clinically required, individual judgement.

Breastfeeding: small passage into milk, individual decision possible.

Contraindications: seizure disorder, history of bulimia or anorexia, acute alcohol or benzodiazepine withdrawal, concurrent MAO inhibitor therapy, severe hepatic cirrhosis.

Older patients: increased sensitivity, low starting doses.

Renal and hepatic impairment: dose adjustment; in severe cirrhosis maximum 150 mg every other day.

Smoking cessation strategy: bupropion is a pillar of pharmacological smoking cessation. Combined with behavioural measures and possibly nicotine replacement therapy, the success rate rises markedly. A realistic goal is roughly doubling abstinence rates versus placebo at 12 months.

Patient counselling: the drive-enhancing effect can be perceived paradoxically as restlessness or insomnia at first. Honest counselling about the first weeks, possible mood changes and seizure risk strengthens trust and adherence.

Related substances

• Bupropion, correct spelling of the substance
• Agomelatine, melatonergic antidepressant
• Desvenlafaxine, SNRI
• Paroxetine, SSRI with different profile
• Buspirone, anxiolytic for augmentation

Frequently asked questions

Sources

• EMA European Medicines Agency
• BfArM Federal Institute for Drugs and Medical Devices
• AWMF guidelines depression and tobacco cessation
• Gelbe Liste bupropion monograph