Seizures associated with tiagabine overdose: A case series

Tiagabine (TG) (Gabitril super(TM)) was approved in 1997 as adjunctive therapy in the treatment of partial seizures. It has also been used to treat patients with bipolar disorder and other psychiatric illness. Recently there was a change in the labeling of TG to warn prescribers of the risk of seizures in patients without epilepsy, treated with TG. This alert described seizures in patients in a non-overdose setting at doses as low as 4 mg/day. The therapeutic dose of TG is 32-56 mg/day for use as an antiepileptic agent. A previous retrospective review of 57 TG ingestions described seizure in 16, with status-epilepticus (SE) in 3. The mean dose for patients with seizure was 224 mg with the lowest dose for seizures 96 mg. We report 4 patients experiencing a seizure(s) with doses ranging from 36-480 mg. Case 1: A 47 year-old female with bipolar disorder ingested a maximum of 36 mg of TG. She appeared to be post-ictal with tremor and flexure posturing of her upper extremities. Symptoms resolved after lorazepam 3 mg IV. Case 2: A 49 year-old female prescribed TG for insomnia experienced a self-limited seizure after ingesting a maximum of 68 mg of TG. Case 3: A 42-year-old male reported ingesting approximately 72 mg of TG. Shortly after presentation he developed convulsive SE refractory to lorazepam. The seizures were eventually terminated with additional phenobarbital (1600 mg bolus and 180 mg/2 hours x 3) and propofol. Case 4: A 45 year-old male ingested approximately 480 mg of TG and subsequently experienced a generalized seizure, which responded to midazolam. Later, the patient was found obtunded with "twitching eyelids." Neurology diagnosed non-convulsive status epilepticus (NCSE). This patient required additional phenobarbital after lorazepam for termination of seizure. We describe four patients who experienced seizures of varying intensity and duration including SE and NCSE refractory to single agent treatment. Previous reports of TG ingestion suggest that SE was a strictly dose-dependent phenomenon that was easily avoided. Our experience suggests that further review of TG ingestion is warranted.