Bupropion

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 IV methylene blue is reserved for emergencies with bupropion withdrawn 14 days in advance.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

The combination works along two lines. Kinetics: bupropion and its metabolite hydroxybupropion inhibit CYP2D6 (bupropion SmPC), an enzyme that clears amitriptyline. The amitriptyline SmPC names bupropion as a potent CYP2D6 inhibitor that can markedly raise tricyclic levels. With another tricyclic, desipramine, bupropion increased peak concentration and AUC 2- to 5-fold, and the enzyme stayed inhibited for at least 7 days after the last bupropion dose (bupropion SmPC). Seizures: bupropion seizure risk is dose-related and rises with drugs that lower the seizure threshold, antidepressants included (bupropion labels).

Symptoms

Seizures: their risk rises when bupropion is combined with antidepressants (bupropion labels). Signs of amitriptyline excess: drowsiness, dry mouth, constipation, urinary retention, dilated pupils, fast heartbeat and dizziness on standing. High amitriptyline levels can cause arrhythmias, QT prolongation and marked hypotension (amitriptyline SmPC). Bupropion itself can cause insomnia and dry mouth (bupropion SmPC).

Management

Use the combination only when it is clinically justified. The bupropion SmPC for smoking cessation says bupropion should not be used in patients taking antidepressants unless there is a justified clinical reason, and then a maximum of 150 mg a day should be considered for the rest of the course. The FDA bupropion label asks for extreme caution, a low starting dose of bupropion and gradual increases, up to 300 mg a day. Assess seizure risk factors in every patient before starting. Bupropion is contraindicated with a current or past seizure disorder, a central nervous system tumour, bulimia or anorexia nervosa. If a seizure occurs, stop bupropion and do not restart it (bupropion labels). When bupropion is added to amitriptyline, consider a lower amitriptyline dose based on response and monitoring of its plasma level (amitriptyline SmPC). Bupropion keeps inhibiting the enzyme for at least 7 days after it is stopped, which matters when doses are changed (bupropion SmPC).

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

Start bupropion at a low dose and increase it gradually (FDA label). Bupropion raises citalopram exposure: AUC by 40% and Cmax by 30%. So when bupropion is added to citalopram, the Spanish bupropion SmPC calls for reviewing whether the citalopram dose should be lowered. If bupropion is prescribed for smoking cessation to someone taking an antidepressant, the Zyntabac SmPC advises considering a ceiling of 150 mg/day. Bupropion is contraindicated with a history of seizures, bulimia or anorexia nervosa.

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 to augment antidepressant response, but bupropion is contraindicated in patients with a seizure history per the label. Start bupropion at a low dose and titrate gradually. Start escitalopram at the low end of its dose range when bupropion is already on board, and if bupropion is added to an established escitalopram regimen, consider reducing the escitalopram dose. When bupropion is prescribed for smoking cessation in a patient taking an antidepressant, the label advises a maximum of 150 mg a day. Watch for agitation, tremor, myoclonus and fever (serotonin syndrome) during the first weeks and after dose increases.

Mechanism

Bupropion and its metabolite hydroxybupropion inhibit CYP2D6, which metabolises fluoxetine, so fluoxetine exposure can rise. Bupropion itself is not a CYP2D6 substrate: hydroxybupropion is formed by CYP2B6. Both drugs lower the seizure threshold, and together they can cause serotonin syndrome.

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 used to augment antidepressant response, but bupropion is contraindicated in patients with a seizure history, bulimia or anorexia nervosa per the label. Start bupropion at a low dose and titrate gradually. Start fluoxetine at the low end of its dose range when bupropion is already on board, and if bupropion is added to fluoxetine, consider reducing the fluoxetine dose. When bupropion is prescribed for smoking cessation in a patient taking an antidepressant, the label advises a maximum of 150 mg a day. Watch for agitation, tremor, myoclonus and fever during the first weeks and after dose increases.

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.

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 and its metabolite hydroxybupropion inhibit CYP2D6 (bupropion SmPC), the main enzyme that clears metoprolol (metoprolol labels). The Spanish metoprolol SmPC lists bupropion among potent CYP2D6 inhibitors that raise metoprolol plasma levels. The FDA metoprolol label reports that strong CYP2D6 inhibitors doubled metoprolol concentrations; the documents give no figure for bupropion itself. Higher levels reduce the cardioselectivity of metoprolol (FDA metoprolol label). Bupropion keeps inhibiting the enzyme for at least 7 days after the last dose (bupropion SmPC).

Symptoms

Stronger metoprolol effect: slow pulse, dizziness, weakness, low blood pressure, including on standing, and fainting. Marked metoprolol excess can cause severe bradycardia, atrioventricular block, heart failure and bronchospasm (FDA metoprolol label). Because cardioselectivity is reduced, bronchospasm is a particular concern in asthma and chronic obstructive pulmonary disease.

Management

If metoprolol is started in a patient on bupropion, begin at the lower end of the dose range. If bupropion is added to metoprolol, assess whether the metoprolol dose needs lowering and weigh the expected benefit of bupropion against the risk (Spanish bupropion SmPC). The FDA bupropion label also notes that the metoprolol dose may need to be decreased. The FDA metoprolol labels ask for close monitoring when a CYP2D6 inhibitor cannot be avoided, above all of heart rate and blood pressure. Bupropion keeps inhibiting the enzyme for at least 7 days after it is stopped, which matters when doses are changed (bupropion SmPC).

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

Bupropion is a strong CYP2D6 inhibitor. Endoxifen falls 60%.

Symptoms

Tumour progression.

Management

For smoking cessation – nicotine replacement or varenicline (not a CYP2D6 inhibitor).

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.