Bupropion Overdose: Factors Associated with Seizures

Background

Bupropion ingestions are one of the scarier poisonings due to a relatively narrow therapeutic index and the numerous adverse effects that may occur. Medical toxicologist Dr. Dan Rusyniak details his hatred of this drug in overdose in a Tox & Hound blog post aptly-titled Illbutrin. When bupropion was first approved in the 1980s, the max dose was 600 mg/day [1]. However, reports of seizures, particularly in patients with bulimia, caused its temporary removal from the market [2]. It was reintroduced a few years later with a max dose of 450 mg/day [3]. Common signs and symptoms noted in overdose include seizures, agitation, sinus tachycardia, and QRS/QTc prolongation. Seizures occur in up to 40% of overdose cases, are often refractory to initial therapy, and can happen as long as 24 hours after an overdose with extended release formulations [4, 5].

Evidence

A study of 256 patients from the Toxicology Investigators Consortium (ToxIC) Registry identified three factors associated with seizure development after bupropion overdose [6, 7].

1. QTc prolongation > 500 msec (OR = 3.4, 95% CI: 1.3-8.8)
2. Tachycardia (heart rate > 140) (OR = 1.9, 95% CI: 1-3.6)
3. Age 13–18 years (OR = 2.4, 95% CI: 1.3-4.3)

Agitation and tremors are more common in patients who develop seizures with bupropion compared to those who do not [4]. Additionally, presence of tachycardia (heart rate >100 bpm) has a sensitivity of 91% and a negative predictive value of 93% for development of seizures [4].

Bottom Line

• Seizures are common following bupropion overdose and patients who seize are generally tachycardic.
• Patients should be observed at least 24 hours after a extended release bupropion overdose, as seizures can be significantly delayed.

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References

1. Davidson J. Seizures and bupropion: a review. J Clin Psychiatry. 1989;50(7):256-261. PMID: 2500425.
2. Horne RL, Ferguson JM, Pope HG, et al. Treatment of bulimia with bupropion: a multicenter controlled trial. J Clin Psychiatry. 1988;49(7):262-266. PMID: 3134343.
3. Huecker MR, Smiley A, Saadabadi A. Bupropion. In: StatPearls. StatPearls Publishing; 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470212/.
4. Starr P, Klein-Schwartz W, Spiller H, Kern P, Ekleberry SE, Kunkel S. Incidence and onset of delayed seizures after overdoses of extended-release bupropion. Am J Emerg Med. 2009;27(8):911-915. doi: 10.1016/j.ajem.2008.07.004. PMID: 19857406.
5. Al-Abri SA, Orengo JP, Hayashi S, Thoren KL, Benowitz NL, Olson KR. Delayed bupropion cardiotoxicity associated with elevated serum concentrations of bupropion but not hydroxybupropion. Clin Toxicol (Phila). 2013;51(10):1230-1234. doi: 10.3109/15563650.2013.849349. PMID: 24131328.
6. Wax PM, Kleinschmidt KC, Brent J, ACMT ToxIC Case Registry Investigators. The toxicology investigators consortium (Toxic) registry. J Med Toxicol. 2011;7(4):259-265. doi: 10.1007/s13181-011-0177-z. PMID: 21956161.
7. Rianprakaisang TN, Prather CT, Lin AL, Murray BP, Hendrickson RG, Toxicology Investigators Consortium (ToxIC). Factors associated with seizure development after bupropion overdose: a review of the toxicology investigators consortium. Clin Toxicol (Phila). Published online April 21, 2021:1-5. doi: 10.1080/15563650.2021.1913180. PMID: 33878992.

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