Abstracts

RATIONALE: Levetiracetam (LEV) is a recently introduced AED, that appears to be well tolerated in most patients. The potential association between behavioral disturbances and LEV has not been well described in the literature. Similar adverse effects have been reported with other AEDs.
METHODS: A series of 15 patients, seen in a tertiary care epilepsy clinic, that appear to display treatment-emergent behavioral disturbances were studied.
RESULTS: The patients ranged from 25 to 81 years (mean= 38.2 years)and were two-thirds female. LEV was being used as adjunctive treatment for the following seizure types: complex partial seizures (n=12), mixed seizures (n=2), and simple partial seizures (n=1). Concomitant AEDs included: lamotrigine, carbamazepine, divalproex, topiramate, phenytoin, acetazolamide, and primidone. LEV daily doses ranged from 1000 to 3500 mg. In the majority of patients, LEV was initiated at the recommended rate of 500 mg twice daily for 2 weeks, then 1000 mg twice daily and some were increased to 1500 mg twice daily 2 weeks later. None exceeded this rate and some had LEV introduced more slowly or remained on lower doses. Reported behavioral symptoms included significant irritability and aggressiveness, mood lability, physical and emotional displays of anger, sleep disturbances and increases in depressive symptoms. Onset of symptoms occurred approximately 4 to 8 weeks following LEV initiation. There was no clear evidence that the onset of these symptoms was related to acute changes in patient reported seizure frequency. 4 of the 15 patients were receiving psychotropic medications for pre-existing mood disturbances. 12 patients had symptom improvement or return to pre-treatment baseline within 4 to 8 weeks following discontinuation of LEV treatment. It remains unclear if these patients would have experienced less behavioral disturbances at lower doses. One patient continued LEV treatment since there was a significant reduction in seizure frequency. Two patients were treated with antidepressants with some improvement.
CONCLUSIONS: This case series suggests a temporal relationship between the emergence of behavioral irritability and aggressiveness and LEV treatment. These effects may be therapy-limiting in some patients. Given the anecdotal nature of these observations, we are unable to establish direct causality between LEV use and these adverse effects. Future prospective, well-controlled studies are warranted to confirm these observations, identify any relationships between LEV dose and these adverse effects, and establish possible risk factors.
Disclosure: Consulting - UCB-Pharma
Elan; Honoraria - UCB-Pharma
Elan