Acute pharmaceutical poisoning as a cause of seizure events: a database analysis (2011-2023)

Supratherapeutic exposures to pharmaceuticals are a considerable cause of seizures, often leading to severe complications. This study aimed to identify the drugs most frequently associated with seizures in overdose and to evaluate their seizure potential, focusing on dosage and age-related differences.

A retrospective analysis of single-agent pharmaceutical exposures, mostly overdoses, reported to Tox Info Suisse from 1 January 2011 to 31 December 2023 was conducted. Cases with seizures were compared to all cases ("seizure rate") and to all cases involving the same substance ("seizure potential"). The median ingested dose was compared to the maximum approved daily dosage ("relative overdose"), and relative overdose in seizure versus non-seizure cases with the same substance was compared ("seizure overdose ratio").

There were 20,176 single-agent pharmaceutical exposures, with seizures reported in 233 cases (1.2%). Antidepressants were the most frequently implicated drug class (34.3%). Mefenamic acid (15.7%), quetiapine (10%), and bupropion (10%) were most commonly associated with seizures. Cefepime (37.5%) and bupropion (23.7%) showed the highest seizure potentials. Seizures occurred at low relative overdoses for clozapine, chlorprothixene, and trimipramine (1.3×, 2.0×, 2.8×, respectively). Tricyclic antidepressants (notably trimipramine), mefenamic acid, tolperisone, and bupropion exhibited low seizure overdose ratios (1.4, 2.0, 2.1, 2.1, respectively). Age-related seizure rates did not differ significantly between adolescents (1.7%) and adults (1.5%).

Besides the established seizure association of antidepressants, this analysis confirmed the high seizure risk of overdoses of mefenamic acid and bupropion. A comparative assessment using relative overdoses and seizure overdose ratios revealed that even mild overdoses of clozapine or chlorprothixene induce seizures. For mefenamic acid, tolperisone and bupropion, seizures occurred at overdoses only about twice those not associated with seizures. Seizures from intravenously administered cefepime were caused by not adapting the posology to decreased kidney function.

Overdoses of mefenamic acid, quetiapine, bupropion, venlafaxine and tramadol, respectively, were most commonly associated with seizures. Cefepime exhibited the highest seizure potential, in patients with impaired renal function. Tricyclic antidepressants (trimipramine, amitriptyline), tolperisone, mefenamic acid and bupropion were associated with seizures at relatively small overdoses compared to respective non-seizure cases.