Seizures after single-agent overdose with pharmaceutical drugs: Analysis of cases reported to a poison center

Abstract

CONTEXT Seizures during intoxications with pharmaceuticals are a well-known complication. However, only a few studies report on drugs commonly involved and calculate the seizure potential of these drugs. OBJECTIVES To identify the pharmaceutical drugs most commonly associated with seizures after single-agent overdose, the seizure potential of these pharmaceuticals, the age-distribution of the cases with seizures and the ingested doses. METHODS A retrospective review of acute single-agent exposures to pharmaceuticals reported to the Swiss Toxicological Information Centre (STIC) between January 1997 and December 2010 was conducted. Exposures which resulted in at least one seizure were identified. The seizure potential of a pharmaceutical was calculated by dividing the number of cases with seizures by the number of all cases recorded with that pharmaceutical. Data were analyzed using descriptive statistics. RESULTS We identified 15,441 single-agent exposures. Seizures occurred in 313 cases. The most prevalent pharmaceuticals were mefenamic acid (51 of the 313 cases), citalopram (34), trimipramine (27), venlafaxine (23), tramadol (15), diphenhydramine (14), amitriptyline (12), carbamazepine (11), maprotiline (10), and quetiapine (10). Antidepressants were involved in 136 cases. Drugs with a high seizure potential were bupropion (31.6%, seizures in 6 of 19 cases, 95% CI: 15.4-50.0%), maprotiline (17.5%, 10/57, 95% CI: 9.8-29.4%), venlafaxine (13.7%, 23/168, 95% CI: 9.3-19.7%), citalopram (13.1%, 34/259, 95% CI: 9.5-17.8%), and mefenamic acid (10.9%, 51/470, 95% CI: 8.4-14.0%). In adolescents (15-19y/o) 23.9% (95% CI: 17.6-31.7%) of the cases involving mefenamic acid resulted in seizures, but only 5.7% (95% CI: 3.3-9.7%) in adults ( 20y/o; p < 0.001). For citalopram these numbers were 22.0% (95% CI: 12.8-35.2%) and 10.9% (95% CI: 7.1-16.4%), respectively (p = 0.058). The probability of seizures with mefenamic acid, citalopram, trimipramine, and venlafaxine increased as the ingested dose increased. CONCLUSIONS Antidepressants were frequently associated with seizures in overdose, but other pharmaceuticals, as mefenamic acid, were also associated with seizures in a considerable number of cases. Bupropion was the pharmaceutical with the highest seizure potential even if overdose with bupropion was uncommon in our sample. Adolescents might be more susceptible to seizures after mefenamic acid overdose than adults. "Part of this work is already published as a conference abstract for the Reichert, C; Reichert, P; Monnet-Tschudi, F; Kupferschmidt, H; Ceschi, A; Rauber-Lüthy, C (2014 However, only a few studies report on drugs commonly involved and calculate the seizure potential of these drugs. Objectives. To identify the pharmaceutical drugs most commonly associated with seizures after single-agent overdose, the seizure potential of these pharmaceuticals, the age-distribution of the cases with seizures and the ingested doses. (11), maprotiline (10) and quetiapine (10). Antidepressants were involved in 136 cases. D...

Morbidity and Mortality Associated With Medications Used in the Treatment of Depression: An Analysis of Cases Reported to U.S. Poison Control Centers, 2000–2014

“…Case reports and case series suggest that certain secondgeneration agents, notably citalopram, venlafaxine, and bupropion, as well as selected antipsychotic medications, might be more hazardous in overdose (11)(12)(13)(14)(15)(16)(17)(18)(19). However, few reports have systematically compared the morbidity and mortality of the array of agents used to treat depression.…”

Acute toxicity profile of tolperisone in overdose: Observational poison centre-based study

“…The remarkable potential of tolperisone to cause seizures in overdose was also described in another study from our centre, and was shown to be comparable with that of tramadol, mefenamic acid, citalopram, and venlafaxine. 16 The observed cardiovascular symptoms were predominantly mild, although there was a case of relevant prolongation of the QTc-interval (500 ms), and this has not been previously reported in the literature. The product information reports a case of unspecified QT-interval prolongation, which was observed in combination with a supraventricular and ventricular arrhythmia after the ingestion of 750 mg of tolperisone in a 11-month-old child.…”

Comparative Toxicity of Tapentadol and Tramadol Utilizing Data Reported to the National Poison Data System

“…There are human cases and animal models that attempt to characterize this adverse effect. 7,[14][15][16][17][18][19][20] In a rat and a mouse model, TRA, its enantiomers, and active metabolite were shown to induce seizures in rats with a lowered seizure threshold and at a seizure dose to antinociceptive dose ratio similar to that of codeine. 14,15 TRA has structural similarities and may possess some antidepressant activity similar to venlafaxine, which has been associated with seizures in several studies.…”