Bupropion, sold under brand names like Wellbutrin and Zyban, is a commonly prescribed medication used primarily to treat major depressive disorder and aid in smoking cessation. The drug is classified as an aminoketone that works by inhibiting the reuptake of norepinephrine and dopamine in the brain. Bupropion has a relatively narrow therapeutic window, meaning the difference between a therapeutic dose and a toxic dose is small. Overdose carries potential for severe central nervous system and cardiovascular complications.
Understanding Bupropion Toxicity and Lethal Dose Variability
The question of how many bupropion tablets constitute a fatal dose does not have a single, fixed answer. Toxicity is highly dependent on individual biological factors, such as metabolism, body weight, overall health, and tolerance. Serious adverse events can occur even at relatively low supratherapeutic levels, as toxicity begins immediately when the prescribed dosage is exceeded.
The risk of life-threatening events, particularly seizures, increases significantly with higher doses. Overdoses exceeding 3 grams carry a higher risk of seizures, and ingestions above 9 to 10 grams are associated with severe cardiovascular effects and fatality. Bupropion’s toxic effects are amplified by its extended-release (XL) and sustained-release (SR) formulations.
When modified-release tablets are involved, the drug continues to be absorbed for a prolonged period, causing a delayed onset of severe symptoms. Bupropion is metabolized in the liver into active compounds that can be more toxic than the parent drug itself, contributing to this delayed toxicity. The risk of toxicity is also increased when bupropion is taken alongside other medications that lower the seizure threshold, such as certain antidepressants or antipsychotics. Co-ingestion with drugs that inhibit bupropion’s metabolism can increase the concentration of the drug in the bloodstream, raising the risk.
Identifying the Signs of Overdose
Bupropion overdose primarily affects the central nervous system and the cardiovascular system, often presenting with symptoms that resemble a sympathomimetic toxidrome. A generalized seizure is the most common life-threatening symptom, which can occur suddenly and without warning, sometimes progressing to status epilepticus. Seizures are often preceded by symptoms such as agitation, severe tremors, confusion, or visual and auditory hallucinations.
Cardiovascular effects frequently manifest as tachycardia, an abnormally high heart rate. Blood pressure may initially be elevated, but severe toxicity can lead to hypotension and cardiogenic shock. Severe ingestions can cause changes in the heart’s electrical activity, visible on an electrocardiogram as QRS or QTc prolongation, which increases the risk for life-threatening arrhythmias. Other common symptoms include nausea, vomiting, dizziness, and excessive sweating.
Immediate Emergency Action Steps
Any suspected or confirmed bupropion overdose requires immediate medical attention, regardless of how stable the individual appears. If the person has collapsed, is having a seizure, is having trouble breathing, or cannot be awakened, call 911 immediately. These symptoms indicate a rapidly progressing and potentially fatal emergency.
For any non-life-threatening but suspected ingestion, immediately call the national Poison Control Center at 1-800-222-1222. This free and confidential hotline connects callers with experts in toxicology who provide case-specific guidance. When calling, it is helpful to provide information including the exact name of the medication, the strength, the estimated number of tablets taken, and the approximate time of ingestion.
If the individual is conscious and having a seizure, try to protect them from injury by moving objects away from them. If possible, gently roll the person onto their side to prevent them from inhaling vomit or saliva. Do not attempt to restrain the person or place anything in their mouth during the seizure.
Clinical Treatment and Management Protocols
Once a patient arrives at a medical facility, treatment for bupropion overdose is primarily supportive. The immediate goals are to stabilize the airway, breathing, and circulation, with continuous cardiac monitoring initiated upon arrival. An electrocardiogram is routinely performed to check for electrical abnormalities in the heart.
Seizures are the most common complication and are treated using intravenous benzodiazepines, which are the first-line medication for controlling bupropion-induced seizures. For large ingestions, especially of modified-release formulations, decontamination measures may be employed to limit further drug absorption. This often involves administering activated charcoal if the patient presents soon after ingestion and can protect their airway.
Patients who have ingested extended-release bupropion require prolonged observation, often for a minimum of 24 hours, even if they initially appear asymptomatic. This monitoring is necessary due to the risk of delayed seizure onset, which can occur up to a full day after ingestion. For severe cases involving cardiac instability, such as persistent hypotension or cardiogenic shock, medical staff may use advanced interventions like vasopressors or intravenous lipid emulsion therapy.