Alcohol significantly lowers the seizure threshold in mice when co-administered with bupropion hydrochloride

Abstract

Background: Bupropion HCl is a widely used antidepressant that is known to cause seizures in a dose-dependent manner. Many patients taking antidepressants will consume alcohol, even when advised not to. Previous studies have not shown any interactions between bupropion HCl and alcohol. However, there have been no previous studies examining possible changes in seizure threshold induced by a combination of alcohol and bupropion HCl.

Methods: Experimentally naïve female Swiss albino mice (10 per group) received either single doses of bupropion HCl (ranging from 100 mg/kg to 120 mg/kg) or vehicle (0.9% NaCl) by intraperitoneal (IP) injection in a dose volume of 10 ml/kg, and single-dose ethanol alone (2.5 g/kg), or vehicle, 5 min prior to bupropion dosing. The presence or absence of seizures, the number of seizures, the onset, duration and the intensity of seizures were all recorded for 5 h following the administration of ethanol.

Results: The results show that administration of IP bupropion HCl alone induced seizures in mice in a dose-dependent manner, with the 120 mg/kg dose having the largest effect. The percentage of convulsing mice were 0%, 20%, 30% and 60% in the 0 (vehicle), 100, 110, and 120 mg/kg dose groups, respectively. Pretreatment with ethanol produced a larger bupropion HCl-induced convulsive effect at all the doses (70% each at 100, 110 and 120 mg/kg) and a 10% effect in the ethanol + vehicle only group. The convulsive dose of bupropion HCl required to induce seizures in 50% of mice (CD50), was 116.72 mg/kg for bupropion HCl alone (CI: 107.95, 126.20) and 89.40 mg/kg for ethanol/bupropion HCl (CI: 64.92, 123.10).

Conclusion: These results show that in mice alcohol lowers the seizure threshold for bupropion-induced seizures. Clinical implications are firstly that there may be an increased risk of seizures in patients consuming alcohol, and secondly that formulations that can release bupropion more readily in alcohol may present additional risks to patients.

Figure 1

Dose-response curves of the percentage of convulsing mice following the administration of bupropion HCl alone (closed circles) and the effect of ethanol pretreatment on bupropion HCl-induced seizures (open circles) in the Swiss albino mice. The 50% convulsing dose (CD₅₀) values, the convulsant doses of bupropion HCl required to induce seizures in 50% of mice were 116.72 (CI: 107.95, 126.20) and 89.40 (CI: 64.92, 123.10) mg/kg for the dose-response curves for bupropion alone and ET + bupropion HCl, respectively. Doses of bupropion HCl administered intraperitoneally (IP) were 0 (vehicle or ET + vehicle only), 100, 110, and 120 mg/kg. Ethanol pretreatment was with 2.5 g/kg IP 5 min prior to administration of bupropion HCl. Each data point is the percentage of convulsing mice in n = 10 mice. ET, ethanol + vehicle; S, vehicle (0.9% NaCl).