There are some overdoses where the patient walks into the ED looking surprisingly well, their vitals aren’t particularly alarming, and you start to wonder whether this whole thing might turn out to be pretty uneventful. Bupropion is not the medication to make that assumption about.
A patient can look okay early after an ingestion and then develop seizures, conduction abnormalities, ventricular dysrhythmias, or cardiogenic shock hours later. Extended-release formulations make this especially tricky because toxicity can be delayed, turning an initially reassuring encounter into what toxicologists sometimes describe as a ticking time bomb.¹
Bupropion already stands apart from many other antidepressants pharmacologically. It is an aminoketone related structurally to cathinones and primarily inhibits norepinephrine and dopamine reuptake. It also has antagonistic activity at nicotinic acetylcholine receptors.¹,²
That pharmacology helps explain why overdose can look distinctly sympathomimetic. Early findings can include tachycardia, hypertension, agitation, anxiety, tremor, restlessness, hallucinations, confusion, and seizures. In one Canadian poison-center study of 1,065 bupropion overdoses, 17.3% of patients experienced a seizure, 51.9% developed tachycardia, and 23.9% had ECG abnormalities.² In adolescents, bupropion overdose has also been associated with substantially more serious toxicity than selective serotonin reuptake inhibitor overdose, including more seizures and major medical interventions.³
Persistent tachycardia, agitation, tremor, altered mental status, restlessness, hallucinations, and even mydriasis may signal evolving neurotoxicity. Tachycardia and altered mental status have been associated with increased seizure risk.¹ That doesn’t mean every mildly tachycardic patient will seize. It means those findings deserve attention. Bedside nurses reassessing these patients may be the first to notice when something has shifted: the heart rate keeps climbing, the patient suddenly becomes more restless, or their conversation seems a little less organized than it did an hour ago.
Bupropion comes in immediate-release, sustained-release, and extended-release formulations. All can cause serious toxicity, but modified-release products add another problem: time. Extended-release bupropion can produce seizures as late as 24 hours after ingestion.¹ That means a normal neurologic exam two or three hours after ingestion does not establish medical clearance.
When taking the history, find out as much as you can:
The formulation
Estimated dose
Time of ingestion
Intent
Possible coingestants
Baseline seizure risk
Current or earlier symptoms
Start with the basics: ABCs, point-of-care glucose, electrolytes, an ECG, and continuous cardiac monitoring. Watch for progressive QRS widening, QTc prolongation, ventricular ectopy, and dysrhythmias. Correct abnormalities that could make seizures or dysrhythmias worse, including hypoglycemia, hypokalemia, hypomagnesemia, and acidemia.¹
Serum bupropion and hydroxybupropion concentrations do exist, but they generally aren’t available quickly enough to guide acute emergency management.¹
This is also an excellent time to call your regional poison center. Early consultation can help with risk assessment, decontamination decisions, observation duration, and escalation when the patient starts moving in the wrong direction.
If seizures occur, benzodiazepines are first-line therapy. For recurrent seizures or status epilepticus, management may require repeated benzodiazepines, airway control, and escalation of GABAergic therapy. Once the airway is secured, propofol may be added, with barbiturate therapy considered in refractory cases.
Traditional antiseizure medications are not necessarily the next automatic step in toxin-induced seizures because the physiology differs from typical epilepsy. This is another moment when a toxicologist or poison center can be especially useful.
Bupropion-associated QRS widening appears to result primarily from impaired myocardial gap-junction communication rather than classic fast sodium-channel blockade. A small retrospective cohort evaluating sodium bicarbonate in bupropion overdose found no significant narrowing of the QRS after treatment.⁴ That doesn’t mean bicarbonate should never be given. If the history is uncertain or a sodium-channel-blocking coingestant is possible, trying it can be reasonable.
Severe bupropion toxicity can progress to recurrent seizures, coma, hypotension, ventricular dysrhythmias, cardiogenic shock, and cardiac arrest.¹ Treat hypotension using standard resuscitation principles. Norepinephrine is a reasonable initial vasopressor, while bedside echocardiography can help identify severe myocardial dysfunction and guide additional vasoactive support. For refractory cardiovascular collapse, intravenous lipid emulsion has been used as rescue therapy, although evidence is largely observational and case-based. It is not routine therapy for uncomplicated seizures, tachycardia, or isolated ECG abnormalities. If the patient is progressing toward refractory cardiogenic shock or recurrent cardiac arrest, start thinking about VA-ECMO early rather than after every other option has failed. Successful rescue with ECMO has been reported in severe bupropion cardiotoxicity.¹
Observation after immediate-release exposure should be individualized based on dose certainty, intent, symptoms, coingestants, and poison-center guidance. Extended-release overdoses generally warrant at least 24 hours of observation because seizures can be significantly delayed.¹
Persistent tachycardia, agitation, tremor, altered mental status, seizures, hypotension, or ECG abnormalities should push the patient toward monitored admission. Recurrent seizures, significant conduction abnormalities, ventricular dysrhythmias, shock, or escalating cardiovascular support belong in the ICU.
References
Alberter AA, Chambers AJ, Schaffer DH. Bupropion Toxicity. In: StatPearls. StatPearls Publishing; updated June 8, 2026.
Stewart E, Grewal K, Hudson H, Thompson M, Godwin J. Clinical characteristics and outcomes associated with bupropion overdose: a Canadian perspective. Clin Toxicol (Phila). 2020;58(8):837-842. doi:10.1080/15563650.2019.1699658.
Overberg A, Morton S, Wagner E, Froberg B. Toxicity of bupropion overdose compared with selective serotonin reuptake inhibitors. Pediatrics. 2019;144(2):e20183295. doi:10.1542/peds.2018-3295.
Simpson M, et al. Sodium bicarbonate treatment for QRS widening in bupropion overdoses. Clin Toxicol (Phila). 2023.