06-24-2019 Why are Bupropion Overdoses Dangerous?

Toxicology Question of the Week

June 24, 2019

Why are Bupropion Overdoses Dangerous?

What clinical effects occur following bupropion overdoses?

Bupropion is an overdose commonly reported to poison centers. Bupropion has a small therapeutic window– even a small dosage error can potentially cause complications. The maximum daily dose is 450mg. Seizures can occur with accidental and intentional overdoses, and occasionally even with therapeutic ingestion.  After an overdose common clinical effects include vomiting, tachycardia, tremor, agitation, and seizures.

Clinical Use:

Bupropion is an antidepressant used to treat major depressive disorder (MDD), Seasonal Affective Disorder (SAD), and smoking cessation. Bupropion is also used off-label to treat anxiety, bipolar disorder (can increase the risk of mania), and attention deficit/hyperactivity disorder.

How it is supplied:

Bupropion trade names include Wellbutrin®, Zyban®, Aplenzin®, Forfivo®, Buproban®, and Brudeprion®. It is available in immediate release (IR), sustained release (SR), and extended release formulas (XL).

Dosage strength:

Immediate release:75mg and 100 mg

Sustained and extended release: 100mg, 150mg, 174mg, 200mg, 300mg, 348mg, 450mg, (Aplenzin 522 mg)

Mechanism of action:

Bupropion works by inhibiting the reuptake of dopamine and norepinephrine. It is structurally similar to amphetamines and can cause a false positive on urine drug screens-which means it has a structure like an amphetamine but is not actually an amphetamine.  Confirmation on the urine drug screen would be negative for amphetamines. It also antagonizes acetylcholine at nicotinic receptors. Bupropion crosses the blood brain barrier and is metabolized in the liver producing three major active metabolites (hydroxybupropion, threohydrobupropion, erythrohydrobupropion) which are present in higher concentrations in the plasma than the parent compound. It is the high concentration of active metabolite that causes delayed seizures. 

Toxic clinical effects:

Nausea and vomiting can occur. Tachycardia is one of the most common side-effects. Other possible cardiovascular effects include QRS widening, QT prolongation, hypertension, and hypotension. Seizures are the primary neurologic effect. Confusion, agitation, hallucination, and coma also occur. Studies suggest that patients who ingest 4.5 to 9 grams of buproprion are at a greater risk of seizures, but doses as low as 600mg in adults have resulted in seizure activity. Seizures usually occur within 6 to 8 hours after IR overdose and are delayed up to 19 to 24 hours in SR and XL formulations. Agitated and tachycardic patients are at greater seizure risk. Seizures can occur with no previous CNS symptoms

Treatment:

Treatment is primarily supportive care. If a large ingestion of SR or XL tablets present within the first 5 hours of ingestion, whole bowel irrigation (WBI) can be considered. Benzodiazepines are the treatment of choice for tremors, agitation, and seizures. Cardiac monitoring with EKG is required. Recommended observation time is 23 hours due to the active metabolites increasing the risk for delayed seizures.

If you have questions or concerns about bupropion exposure, the poison center has certified specialists in poison information waiting 24/7 to assist you. Please, don’t hesitate to call 1-800-222-1222.

This question was prepared by: Donna Sainato RN, CSPI

The main question we have following buproprion overdose is why 23-hour admission is indicated in asymptomatic patients.  The peak concentration of the active metabolite peaks 12-18 hours after the initial ingestion-this is the metabolite which causes seizures. Seizures are usually self-limited and can occur in asymptomatic patients.  ds

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vumc.org.

Donna Seger, MD

Executive Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222