Abstract
Tiagabine is a selective GABA-reuptake inhibitor used as adjunctive therapy for patients with partial epilepsy [1]. Symptoms resembling mania following withdrawal of GABA-ergic drugs are accumulating in literature. There are reports of withdrawal-emergent mania as a result of benzodiazepine discontinuation [2], especially lorazepam [3]. In clinical trials, behavioural effects have been noted with tiagabine which comprise of causing depression, nervousness and rarely psychosis [1]. However, to the best of our knowledge, there is no report of tiagabine-associated mania in literature so far. We report tiagabine withdrawal-emergent mania in a patient with complex partial seizures (CPS).
A.P., a 20-year-old male patient with nil contributory past or family history visited our epilepsy clinic in July 2005 with history suggestive of temporal lobe CPS for past 2 years. His CT scan of brain (contrast study) was normal and electroencephalogram showed frequent bitemporal spike and slow waves. His seizures were inadequately controlled with carbamazepine 900 mg day−1 with serum level being 11.5 μg mL−1. He was started on oral tiagabine 4 mg day−1 and when the dose reached 12 mg day−1 after 2 months, his seizures were fully controlled. Repeat electroencephalogram at this point revealed occasional left temporal spikes. He was brought for follow-up after 3 months with 20 days history suggestive of elation, overactivity, abusiveness and decreased sleep, without doing any productive work. Treatment review revealed that he had abruptly discontinued tiagabine 2 days before the onset of symptoms but continued carbamazepine at the same dose. We initiated treatment with oral olanzapine 10 mg day−1. On next fol-low-up after 2 weeks he became euthymic. Fortunately, he did not have any episode of CPS.
In our case, manic symptoms quickly emerged upon abrupt discontinuation of tiagabine and remitted with addition of olanzapine indicating a potential association. Carbamazepine is unlikely to be the offending agent as it was continued in the same dose. The possible relation between CPS episodes and onset of mania is also bleak considering the fact that A.P. had already remained seizure free over past 2 months. A negative family history of mood disorder further strengthened the association.
Trimble et al. noted an association between suppression of right-sided seizure discharges with antiepileptic drugs and the onset of the psychiatric symptoms [4]. Interestingly, there was suppression of right-sided temporal discharges upon introduction of tiagabine in our case too. It appears that this could be one independent electrophysiological predictor of an imminent adverse psychiatric event for anticonvulsants.
Another notable point in our case was the abrupt onset of manic symptoms. One possible explanation could be the sudden release of catecholamines following abrupt cessation of a short half-life GABA-ergic drug like tiagabine. These hypotheses need to be empirically tested.