SEATTLE, Wash -- December 7, 2008 -- Children treated for epilepsy with levetiracetam may develop psychiatric adverse events as a result of the treatment if they have certain risk factors, according to new research presented here at the American Epilepsy Society (AES) 62nd Annual Meeting.
A causal relationship between levetiracetam and psychiatric adverse events was supported by the fact that psychiatric adverse events appeared once levetiracetam therapy started and disappeared following cessation or dose reduction of the medication.
Alexandra Faber, MD, University of British Columbia, Vancouver, British Columbia, and colleagues analysed records of 207 patients registered at the British Columbia Children's Hospital in Vancouver as taking levetiracetam. Of these 207 children, 8 were identified as having developed acute psychiatric adverse events at a median levetiracetam dose of 17.37 mg/kg/day (minimum dose 13.82 mg/kg/day, maximum dose 103.42 mg/kg/day).
The median duration of treatment before symptoms appeared was 83 days (minimum 20 days, maximum 517 days), and the patients ranged in age from 21 months to 22 years. Epilepsy aetiology was varied, and all 8 of the patients with psychiatric adverse events were receiving 2 or more antiepileptic drugs in addition to levetiracetam. These 8 patients had failed on an average of 5.4 (95% confidence interval, 3.2-7.6) antiepileptic drugs. Prior to the study, all 8 patients received from 2 to 8 antiepileptic drugs with levetiracetam.
The psychiatric adverse events noted in the study, presented here on December 6, included aggression/agitation in 87.5% (7/8) of the children, behavioural changes in 87.5% (7/8), mood changes in 50.0% (4/8), hallucinations in 37.5% (3/8), suicidal ideation in 25.0% (2/8), paranoia in 25.0% (2/8), and sleep disturbance in 25.0% (2/8). The prevalence of psychiatric adverse events in this study was 2.4%. Of particular concern, said Dr. Faber, was the appearance of suicidal ideation.
The most common risk factors in this group, each occurring in 5 out of 8 children (62.5%), were psychiatric history, abnormal magnetic resonance imaging, and learning disability. Other risk factors were developmental delay occurring in 2 out of 8 children (25.0%), behavioural issues in 3 out of 8 children (37.5%), family psychiatric history in 2 out of 7 children (28.6%), and febrile seizures in 1 child (12.5%). All of these risk factors are consistent with prior reports.
Dr. Faber's group believes there is a "threshold dosage" of levetiracetam above which psychiatric adverse events may develop. While levetiracetam was discontinued in 6 of the 8 patients when symptoms occurred, the dose was merely reduced in the other 2 patients. Symptoms resolved in these 2 children as well, lending support to the theory of threshold dosage.
Dr. Faber said she hopes to follow up this study with a larger prospective study. When asked if physicians should change anything about the way they prescribe levetiracetam, she stressed that the medication is safe, but physicians should watch children with the above risk factors more carefully when treating with levetiracetam.
[Presentation title: Acute Psychiatric Adverse Events Associated With Levetiracetam Therapy in Children With Epilepsy. Abstract 1.201]
