Bupropion toxicity with unintentional exposure or abuse: More common than you think

The BC Drug and Poison Information Centre handled 95 cases of bupropion (Wellbutrin, Zyban) exposure in 2013. Eighty-one cases involved adults, with 22 therapeutic errors, 47 cases of suspected suicide, and 9 cases of misuse or abuse. Sixty-four cases were referred to hospital and 22 were admitted to critical care. There was one death. There were 11 exposures in older children and adolescents, including 9 suicide attempts. More than half experienced moderate to severe effects and two patients were admitted to critical care. There were three unintentional exposures in children 5 years and younger; all were referred to hospital for observation.

Pharmacology
Bupropion has antidepressant effects and reduces nicotine craving by stimulating release and blocking reuptake of dopamine and norepinephrine, and antagonizing nicotinic receptors. Bupropion is a cathinone derivative, a class of amphetamine-like chemicals that includes the recreational substances referred to as bath salts.

Unintentional exposures
US poison control centres reported 6000 bupropion exposures over a 7-year period in young children. Tachycardia, irritability, drowsiness, ataxia, hallucinations, lethargy, and tremor were seen with doses of bupropion up to 10 mg/kg.[1] A single patient in this dose range developed seizures. The occurrence of seizures or coma increased with higher doses. Buehler and colleagues recommended referral to a health care facility if the ingested dose was greater than 10 mg/kg (a single tablet in a small child) or if the dose was unknown.

In a review of adult medication errors involving bupropion, the median dose ingested was 300 mg (mostly sustained release).[2] Frequent adverse effects were agitation, dizziness, tremor, GI upset, drowsiness, and tachycardia, occurring in 6% to 8% of patients, with seizures in 0.8% and hallucinations in 0.4%. Almost 25% of patients were evaluated at a health care facility. Multiple brand names and indications contributed to errors. In one case report, a patient developed confusion, agitation, and a seizure after unknowingly taking Wellbutrin, Zyban, and generic bupropion for a total of 600 mg bupropion per day.[3]

Bupropion abuse
While bupropion’s abuse potential is low for most patients, reports of recreational use by ingestion and insufflation or snorting began appearing on the popular user experience website, Erowid.org, in 2001.[4] The first report of recreational use of bupropion in medical literature appeared in 2002 and involved ingestion of 600 mg bupropion.[5] This was followed soon after by reports of nasal insufflation, with users reporting amphetamine- or cocaine-like highs, and adverse effects ranging from nasal pain to irritability, aggression, hallucinations, and seizures. Most patients had a history of substance abuse.[6,7] Snorting the substance, referred to as welbyswelliesdubs, or barnies (due to the purple color), has led to the removal of bupropion from some US prison formularies.[8,9]

Intravenous abuse has also been reported and has resulted in severe skin lesions, vascular complications, and death.[10]

Summary
Bupropion toxicity following unintentional exposures in young children and adults or following abuse by insufflation or injection may be more common than previously thought.

If you suspect an overdose, call the BC Drug and Poison Information Centre at 604 682-5050 or 1 800 567-8911.
—Raymond Li, BSc(Pharm), MSc
BC Drug and Poison Information Centre

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This article is the opinion of the BC Centre for Disease Control and has not been peer reviewed by the BCMJ Editorial Board.


References

1.    Beuhler MC, Spiller HA, Sasser HC. The outcome of unintentional pediatric bupropion ingestions: A NPDS database review. J Med Toxicol 2010;6:4-8.
2.    Shepherd G. Adverse effects associated with extra doses of bupropion. Pharmacoetherapy 2005;25:1378-1382.
3.    Grissinger M. A medication-error trifecta! P&T 2006;31:244.
4.    Erowid Center. Defined and memorable: Bupropion (Wellbutrin). Accessed 29 September 2014. www.erowid.org/experiences/exp.php?ID=7185.
5.    McCormick J. Recreational bupropion abuse in a teenager. Br J Clin Pharmacol 2002;53:214.
6.    Kim D, Steinhart B. Seizures induced by recreational abuse of bupropion tablets via nasal insufflation. CJEM 2010;12:158-161.
7.    Reeves RR, Ladner ME. Additional evidence of the abuse potential of bupropion. J Clin Pyschopharmacol 2013;33:584-585.
8.    Hilliard WT, Barloon L, Farley P, et al. Bupropion diversion and misuse in the correctional facility. J Correct Health Care 2013;19:211-217.
9.    Phillips D. Wellbutrin®: Misuse and abuse by incarcerated individuals. J Addict Nurs 2012;23:65-69.
10.    Baribeau D, Araki KF. Intravenous bupropion: A previously undocumented method of abuse of a commonly prescribed antidepressant agent. J Addict Med 2013;7:216-217.

Raymond Li, BSc(Pharm), MSc. Bupropion toxicity with unintentional exposure or abuse: More common than you think. BCMJ, Vol. 56, No. 9, November, 2014, Page(s) 445 - BCCDC.



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