Other antidepressants (NDRI)
ATC code: N06AX12 (Bupropion)
Brand names
Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban
Selective norepinephrine and dopamine reuptake inhibitor (NDRI). Does not affect serotonin. Unlike SSRIs, does not cause sexual dysfunction or weight gain — some patients lose weight. Lowers seizure threshold dose-dependently — contraindicated in epilepsy and seizure-risk states. Active metabolite hydroxybupropion has a longer half-life and accounts for much of the pharmacological effect.
First line
Per 2023 and NG222, bupropion is a first-line agent for major depression. Efficacy comparable to SSRIs, with a different side-effect profile: less sexual dysfunction, less sedation, no weight gain. Often chosen for depression with hypersomnia or increased appetite, or in SSRI patients with sexual side effects — as switch or augmentation. Not registered in Russia; available via individual import.
First line
Per 2021 and Cochrane 2023, bupropion (Zyban 150 mg twice daily) is first-line for smoking cessation alongside varenicline and nicotine replacement therapy. Doubles the chance of sustained abstinence vs placebo. Start 1–2 weeks before quit date; continue for 7–12 weeks.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Bupropion monotherapy is widely used for weight loss in people without nicotine dependence or major depression, primarily on the back of the naltrexone+bupropion fixed-dose combination (Contrave/Mysimba) approved for obesity. Bupropion alone has never been approved for obesity by the , , or Russian Ministry of Health. Endocrine Society (2015), AACE/ACE (2016), and EASO (2021) obesity-pharmacotherapy guidelines list only registered weight-loss agents (semaglutide, liraglutide, phentermine-topiramate, naltrexone-bupropion, orlistat); bupropion monotherapy is not among them.
24 pairs found. Sorted from critical to minor.
Mechanism
Bupropion inhibits dopamine and norepinephrine reuptake. Linezolid reversibly inhibits MAO. Combined action raises monoamine levels, risking hypertensive crisis and seizures (bupropion lowers seizure threshold on its own).
Symptoms
Hypertension, tachycardia, tremor, agitation, headache. Seizures may occur, particularly in patients with prior epilepsy or eating disorders. Serotonin syndrome is less common unless other serotonergics are added.
Management
The combination is not prescribed. Stop bupropion 14 days before linezolid. As a smoking-cessation bridge during antibiotic therapy, use nicotine replacement or varenicline. Alternative antibiotics: vancomycin, daptomycin.
Mechanism
IV methylene blue is a potent reversible MAO-A inhibitor. Bupropion inhibits dopamine and norepinephrine reuptake. Combined action raises monoamines sharply, risking hypertensive crisis and seizures.
Symptoms
Hypertension, tachycardia, tremor, agitation, headache. Seizures may occur (bupropion lowers seizure threshold). Serotonin syndrome is less common unless other serotonergics are involved.
Management
Avoid the combination. IV methylene blue is reserved for emergencies with bupropion withdrawn 14 days in advance. If unavoidable for methaemoglobinaemia on bupropion, give for life-threatening indications with blood pressure monitoring and anticonvulsants ready.
Mechanism
Bupropion is a potent CYP2D6 inhibitor, the main amitriptyline metabolic route. TCA plasma levels rise 2- to 5-fold. Both drugs lower the seizure threshold. Plus additive cardiotoxicity.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
Avoid the combination. For neuropathic pain, replace amitriptyline with gabapentin or pregabalin. Alternative antidepressants if bupropion is needed: sertraline or escitalopram.
Mechanism
Ciprofloxacin blocks CYP1A2 and lowers seizure threshold itself. Bupropion is a potent proconvulsant. Ciprofloxacin also weakly blocks CYP2B6 (a minor bupropion route).
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
Avoid the combination, especially in patients with prior epilepsy. Alternative antibiotics: a cephalosporin, nitrofurantoin, or fosfomycin (no effect on seizure threshold).
Mechanism
Additive seizure threshold reduction (both drugs do this). Weak additional serotonergic risk (bupropion has minimal serotonergic activity). Citalopram itself prolongs QT.
Symptoms
Seizures (especially with prior epilepsy or eating disorders), QT prolongation on ECG, dizziness. Serotonin syndrome when other serotonergics are added.
Management
The combination is used for antidepressant augmentation (bupropion added to SSRI). Cap citalopram at 20 mg, bupropion at 300 mg/day. Avoid in prior epilepsy or eating disorders.
Mechanism
Dexamethasone is a potent CYP3A4 inducer and weak CYP2B6 inducer (which metabolises bupropion). Bupropion levels may fall, giving partial loss of antidepressant effect. The glucocorticoid itself also lowers the seizure threshold.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
For prolonged dexamethasone therapy, bupropion may be increased by 50% with clinical monitoring. For short courses, no adjustment is usually needed. After dexamethasone stops, induction persists for 1–2 weeks.
Mechanism
Additive seizure threshold reduction plus elevated synaptic norepinephrine (bupropion is a norepinephrine-dopamine reuptake inhibitor; duloxetine is an SNRI). Tachycardia and hypertension may emerge.
Symptoms
Tachycardia, hypertension, tremor, agitation. Seizures may occur, especially with prior epilepsy or eating disorders.
Management
The combination is possible for antidepressant augmentation with careful blood pressure and pulse monitoring. Cap bupropion at 300 mg and duloxetine at 60 mg/day. Avoid with prior epilepsy or eating disorders.
Mechanism
Escitalopram is a citalopram enantiomer with the same effects. Additive seizure threshold reduction (bupropion + escitalopram). High-dose escitalopram prolongs QT.
Symptoms
Seizures (especially with prior epilepsy or eating disorders), QT prolongation on ECG, dizziness.
Management
The combination is used for antidepressant augmentation. Cap escitalopram at 10 mg and bupropion at 300 mg/day. Avoid in prior epilepsy or eating disorders.
Mechanism
Fluoxetine is a potent CYP2D6 inhibitor. Levels of bupropion's active metabolite (hydroxybupropion) rise. Both drugs lower the seizure threshold.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
The combination is possible for augmentation with careful monitoring. Keep doses low: fluoxetine 20 mg, bupropion 300 mg/day. Avoid with prior epilepsy or eating disorders.
Mechanism
Fluvoxamine is a weak CYP2D6 inhibitor but a strong CYP2C19 and CYP1A2 inhibitor. Bupropion levels may rise. Both drugs lower the seizure threshold.
Symptoms
Seizures (especially with prior epilepsy or eating disorders), anxiety, insomnia. Agitation possible.
Management
The combination is possible for augmentation. Keep doses low: bupropion ≤300 mg, fluvoxamine ≤100 mg/day. Avoid with prior epilepsy or eating disorders.
Sources
Mechanism
Haloperidol is a CYP2D6 substrate; bupropion is a potent CYP2D6 inhibitor. Haloperidol plasma levels rise 2- to 3-fold. Risk of extrapyramidal symptoms and QT prolongation emerges. Both drugs also lower the seizure threshold.
Symptoms
Extrapyramidal symptoms (tremor, rigidity, akathisia), QT prolongation on ECG, seizures. Older patients: fall risk.
Management
Avoid the combination. Alternative antipsychotics without CYP2D6 dependence: olanzapine or aripiprazole. Alternative antidepressants without CYP2D6 inhibition: sertraline or escitalopram.
Mechanism
Methylprednisolone (a systemic glucocorticoid) modestly lowers the seizure threshold and induces CYP3A4. Bupropion also lowers the seizure threshold. Combined action raises the risk of episodes, particularly in patients with prior epilepsy or eating disorders.
Symptoms
Seizures (generalised tonic-clonic or focal). In patients without prior epilepsy: isolated episodes; with epilepsy: more frequent seizures. Agitation, anxiety possible.
Management
Avoid the combination in patients with prior epilepsy or eating disorders. If unavoidable, do not increase bupropion dose and discontinue methylprednisolone as soon as possible. Alternative antidepressants without seizure threshold reduction: sertraline, escitalopram.
Mechanism
Bupropion is a potent CYP2D6 inhibitor, the main metoprolol metabolic route. Metoprolol plasma levels rise 4- to 5-fold. Risk of marked bradycardia and hypotension emerges.
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope, orthostatic hypotension. In heart failure: worsening dyspnoea and oedema.
Management
Reduce metoprolol 2- to 3-fold when combined; monitor pulse and blood pressure. Alternative beta-blockers without CYP2D6 dependence: bisoprolol or carvedilol.
Mechanism
Mirtazapine lowers the seizure threshold less than bupropion, but the effect is additive. Both drugs may also cause insomnia and anxiety in combination.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
The combination is possible for augmentation. Keep doses low: bupropion 300 mg, mirtazapine 30 mg/day. Avoid with prior epilepsy.
Mechanism
High morphine doses cause opioid-induced myoclonus, raising seizure risk. Bupropion lowers the seizure threshold. Particularly dangerous in chronic pain patients on high opioid doses.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
Avoid bupropion on long-term opioid therapy. Alternative antidepressants in chronic pain: duloxetine or sertraline (no proconvulsant effect). For smoking cessation on morphine: nicotine replacement or varenicline.
Mechanism
Prednisolone (a systemic glucocorticoid) modestly lowers the seizure threshold; bupropion also lowers it. The effect is clinically significant during prolonged high-dose prednisolone, especially with prior epilepsy.
Symptoms
Seizures (generalised tonic-clonic or focal). Agitation, anxiety, insomnia from both drugs are possible.
Management
Avoid the combination in patients with prior epilepsy. If unavoidable, do not increase bupropion dose and use prednisolone at the minimum effective dose. Alternative antidepressants without seizure threshold reduction: sertraline, escitalopram.
Mechanism
Quetiapine lowers the seizure threshold, especially at doses above 300 mg/day. Bupropion is a potent proconvulsant. Additive seizure risk.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
Avoid the combination, especially with quetiapine above 300 mg. Alternative antipsychotics: olanzapine or aripiprazole (minimal seizure threshold effect). Alternative antidepressants: sertraline or escitalopram.
Mechanism
Additive seizure threshold reduction. Sertraline is a weak CYP2D6 inhibitor with minimal effect on bupropion. Real risk is limited to patients with risk factors (prior epilepsy, eating disorders).
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
The combination is widely used for augmentation. Without risk factors, no special measures are needed. Standard doses. Avoid with prior epilepsy or eating disorders.
Mechanism
Theophylline at toxic doses causes seizures by itself. Bupropion lowers the seizure threshold. High risk even at therapeutic theophylline concentrations.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
Avoid the combination, especially in COPD or asthma patients. Alternative antidepressants: sertraline or escitalopram. Alternative bronchodilators: inhaled β2-agonists with anticholinergics.
Mechanism
Bupropion blocks CYP2D6 – the route converting tramadol to its active M1 metabolite. Analgesia falls but parent tramadol accumulates, raising seizure risk. Both drugs also lower the seizure threshold.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
Avoid the combination. For analgesia on bupropion, use paracetamol, an NSAID, or morphine/oxycodone. For neuropathic pain, gabapentin or pregabalin.
Mechanism
Additive seizure threshold reduction plus elevated synaptic norepinephrine. Venlafaxine prolongs QT at high doses.
Symptoms
Tachycardia, hypertension, tremor, agitation. Seizures (especially with prior epilepsy) and QT prolongation at high venlafaxine doses are possible.
Management
The combination is possible for augmentation. Cap bupropion at 300 mg and venlafaxine at 150 mg/day. ECG at 2 weeks; monitor blood pressure and pulse. Avoid with prior epilepsy.
Mechanism
Bupropion lowers seizure threshold, especially at high doses (above 300 mg/day) or in predisposition. Abrupt alprazolam withdrawal further raises seizure risk via GABAergic rebound.
Symptoms
Tremor, jitters, severe cases: seizures. Symptoms appear with bupropion up-titration or abrupt alprazolam withdrawal. In epilepsy or prior head trauma, risk is maximal.
Management
Avoid in epilepsy and prior head trauma. If unavoidable (nicotine dependence with anxiety), start bupropion at 150 mg in the morning and do not exceed 300 mg/day. Do not stop alprazolam abruptly — taper over 4–8 weeks.
Mechanism
Bupropion blocks CYP2D6. Amlodipine is minorly metabolised via CYP2D6 (main route is CYP3A4). The effect is weak – possible mild amlodipine level rise without clinically significant effect.
Symptoms
Minimal changes. Mild additional hypotension or ankle oedema possible in some patients.
Management
No dose adjustment is usually needed. In older patients and reduced ejection fraction, check blood pressure and pulse 2 weeks after starting bupropion.
Mechanism
Bupropion blocks CYP2D6. Bisoprolol is metabolised 50% via CYP3A4 and 50% renally, so the effect is clinically minor, unlike metoprolol (fully CYP2D6).
Symptoms
Minimal changes: mild additional bradycardia possible. Older patients: rare symptomatic hypotension.
Management
Dose adjustment is usually unnecessary. In older patients and reduced ejection fraction, check pulse and blood pressure 2 weeks after start.
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Boxed warning
FDA boxed warning (antidepressants): increased suicidal ideation risk in children, adolescents, and adults under 25. In 2016, the FDA removed the separate neuropsychiatric black box for smoking-cessation use after the EAGLES RCT, but mood monitoring on bupropion is still recommended.
Data are mixed; large meta-analyses show no teratogenicity signal. Use is individualized. In pregnant patients with depression, SSRIs with larger safety datasets (sertraline) are preferred.
Transfers into milk. Per LactMed, use is acceptable with monitoring.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Bupropion is evaluated for the following indications with varying evidence strength: Smoking cessation (evidence tier A), Major depressive disorder (evidence tier A), Weight loss (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Bupropion (≥ 1 in 100): Dry mouth, Insomnia, anxiety (especially first 1–2 weeks), Headache, Tremor, nausea, Decreased appetite, weight loss, Sweating. See the Safety section for uncommon and serious reactions.
FDA category C. Data are mixed; large meta-analyses show no teratogenicity signal. Use is individualized. In pregnant patients with depression, SSRIs with larger safety datasets (sertraline) are preferred.
Transfers into milk. Per LactMed, use is acceptable with monitoring.
Bupropion is contraindicated in: Epilepsy or seizure history; Eating disorders (anorexia, bulimia) — increased seizure risk; Abrupt alcohol or benzodiazepine withdrawal — seizure risk; Concurrent or recent (14 days) MAOI; Hypersensitivity. Full list in the Safety section.
FDA boxed warning (antidepressants): increased suicidal ideation risk in children, adolescents, and adults under 25. In 2016, the FDA removed the separate neuropsychiatric black box for smoking-cessation use after the EAGLES RCT, but mood monitoring on bupropion is still recommended.