Bupropion

GENERAL PRINCIPLES

• Bupropion is an antidepressant that is also used for smoking cessation and weight loss.

• Bupropion is available in the US in three formulations: immediate-release, sustained-release (dosed twice daily), and extended-release (dosed once daily).

• Bupropion is misused recreationally, especially by people with limited access to other recreational substances, such as prisoners.

Pathophysiology

• Bupropion is a cathinone, which is an amphetamine derivative with a ketone group on the alpha­carbon. Bupropion is the only cathinone in pharmaceutical use—all other cathinones are illicit recreational drugs (sometimes referred to as “bath salts”).

• Bupropion has amphetamine-like properties: it inhibits the reuptake of dopamine and norepinephrine and enhances their release.

Bupropion is not directly serotonergic but may enhance serotonin signaling by indirect mechanisms and has been implicated in the development of serotonin syndrome.

• In overdose, bupropion is profoundly cardiotoxic—it is thought to antagonize myocardial gap junctions and may cause takotsubo-like myocardial stunning.

DIAGNOSIS

Clinical Presentation

• Bupropion poisoning produces a sympathomimetic toxidrome (see above, amphetamines).

• Bupropion poisoning causes seizures.

î Seizures may be delayed in onset (up to 24 hours postingestion in the extended-release formulation) and may occur in patients with minimal or no other symptoms of poisoning.

î Seizures may occur even after minimal overdose, including accidental double doses in some cases.

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o Status epilepticus may occur in severe poisoning.

• Severe bupropion poisoning may cause shock and cardiovascular collapse.

Diagnostic Testing

LABORATORIES

Have a low threshold to obtain a BMP, troponin, and/or creatinine kinase to evaluate for end-organ damage, including renal injury, myocardial ischemia, and rhabdomyolysis.

ELECTROCARDIOGRAPHY

• ECG may demonstrate sinus tachycardia or ventricular dysrhythmias.

• Bupropion may prolong the QRS duration due to gap junction antagonism. ³⁰

TREATMENT

• The mainstay of treatment is benzodiazepines or other directly GABAergic sedatives, titrated to control of agitation, improvement of vital signs, and control of seizures if present.

• It is critically important to observe patients in a medical setting for seizures and cardiovascular complications for an adequate time period postingestion. For extended-release bupropion, most experts recommend a full 24-hour observation period before medical clearance.

• Patients with severe poisoning causing cardiovascular instability may require treatment with vasopressors, inotropes, and mechanical ventilation.

• Sodium bicarbonate is generally not effective in reversing QRS prolongation due to bupropion. ³⁰

• Administration of intravenous lipid emulsion (bolus of 1.5 cc/kg, max 100 cc, followed by infusion of 0.25 cc/kg/min for 20 minutes) may be reasonable in patients with status epilepticus, significant cardiovascular instability, or cardiac arrest.

• VA ECMO is lifesaving in severe poisoning. Have a low threshold to transfer patients with severe bupropion poisoning to an ECMO-capable center.