Topiramate overdose: A case report of a patient with extremely high topiramate serum concentrations and nonconvulsive status epilepticus

Abstract

SUMMARYWe report the case of a 21-year-old man with idiopathic generalized epilepsy who ingested about 8,000 mg of topiramate (TPM) in a suicide attempt. On admission to the hospital he had a nonconvulsive status epilepticus and received 4 mg lorazepam i.v. He recovered rapidly despite an initial TPM concentration of 144.6 lg/ml. To our knowledge, this is the first report of a patient who survived such a high TPM concentration. The case indicates that nonconvulsive status epilepticus could be a manifestation of TPM intoxication.KEY WORDS: Topiramate, Overdose, Intoxication, Nonconvulsive status epilepticus, Suicide attempt.Topiramate (TPM) is an antiepileptic drug (AED) that is rapidly absorbed (peak plasma concentrations 2 h following intake). Bioavailability is 81-95%. TPM is excreted primarily as unchanged drug, It showed linear steady-state pharmacokinetics, and its elimination half-life in monotherapy ranged from 19 to 25 h in healthy volunteers after single-dose oral administration (May et al., 2002). Typical TPM dosing and serum concentrations (trough) in adults range from 150-400 mg/day and from 2-8 lg/ml, respectively. Case ReportA 21-year-old, 108-kg Caucasian man with a history of epilepsy was found in a confused state of mind in his room in the boarding home of a vocational training center and had wet his clothes. It was suspected that he had had a generalized tonic-clonic seizure (GTCS), and he was admitted to the hospital. On admission he was drowsy and disoriented, initially responded inappropriately, and then became unresponsive. Vital signs were the following: pulse, 81/min; blood pressure, 110/60 mm Hg; normal respiratory rate; body temperature, 36.9°C (measured in the ear), and oxygen saturation 100% (measured by pulse oximetry). Electroencephalography (EEG) revealed nonconvulsive status epilepticus (NCSE, details below). Lorazepam (4 mg) was injected intravenously (1 mg/min), and the EEG pattern of status epilepticus was terminated within <1 min after the end of the injection. The patient fell asleep and showed, when awakened by the staff, inappropriate verbal response again.The patient has a history of idiopathic generalized epilepsy (IGE) with absence seizures since childhood. He had a single GTCS in 2004, a few days after a tonsillectomy in general anesthesia. In 1999, depressive conduct disorder was diagnosed. In 2004, TPM was introduced into his therapy. He was frequently noncompliant and withdrew the drug several times on his own for up to several months, but reintroduced TPM in monotherapy 3 weeks before the suicide attempt, again on his own and immediately in a dose of 400 mg/day.On the day of admission (day 1, 11:06 a.m.), a TPM concentration of 144.6 lg/ml revealed an overdose. In hindsight, it was discovered that after an argument with his girlfriend he had ingested about 40, 200-mg tablets of TPM in a suicide attempt the night before. The patient did not receive gastrointestinal decontamination or hemodialysis, as more than 24 h had passed since ingestion of TPM and as he was reco...

Levetiracetam and topiramate poisoning: Two overdoses on those drugs with no lasting effects

“…In the current case, however, a metabolic imbalance was not noted when the patient was brought in the second time. Christian et al and Anand et al reported seizures after a topiramate overdose (4,9), but the current patient remained absolutely normal.…”

“…It is also indicated in the treatment of psychiatric illnesses. Several cases of an accidental overdose in children or an intentional or suicidal overdose in older individuals have been reported (6,9). At therapeutic levels, topiramate is benign, and the most prevalent adverse reactions are dizziness, somnolence, and ataxia.…”

Therapeutic drug monitoring of newer antiepileptic drugs / Therapeutic drug monitoring bei neueren Antiepileptika

“…So, from the available data, no proposal for routine use of TDM of TPM can be made. A case report has shown TDM to be helpful in differentiating non-convulsive status from severe TPM intoxication [42] .…”

Topiramate, a concealed cause of severe metabolic acidosis

“…Less commonly a variety of gastrointestinal symptoms have also been described [6]. Several reports describe toxicity at varying doses of ingestion when used for migraine and epilepsy (Table 2) [4,5,[7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Based on a retrospective review of 567 cases of topiramate toxicity (during 2000-2001), the American Association of Poison Control revealed that: 39% were adults, mild mental status changes were common, and severe respiratory depression or persistent NAGMA were infrequent yet other reports confirm their occurrence [5,[10][11][12].…”