Amelioration of levetiracetam- induced behavioral side effects by pyridoxine

Adel Mahmoud, Sadia Tabassum, Shoaa Al Enazi, Nahed Lubbad, Ali Al Wadei, Ali Al Otaibi, Lamya Jad and Ruba Benini. Amelioration of Levetiracetam- induced behavioral side effects by Pyridoxine-Randomized double blinded controlled study. Article in Press: Pediatric Neurology.

Abstract

Background

Levetiracetam is a relatively new generation antiseizure drug approved for the treatment of focal and generalized seizures. Despite its favorable side effect profile and minimal drug-drug interactions, neuropsychiatric side effects are reported in up to 13% of children. A few case series have suggested that supplementation of pyridoxine may mitigate these side effects, but controlled trials are lacking. To address this issue, a randomized interventional study was carried out in a pediatric tertiary hospital to qualify and quantify the potential beneficial effect of pyridoxine in attenuating the neuropsychiatric side effects of Levetiracetam in children. 

Methods

A total of 105 children with epilepsy on levetiracetam (as a monotherapy or an adjunct) who showed behavioral symptoms coinciding with the start of levetiracetam, were included. Patients randomly and blindly received either a therapeutic (pyridoxine group, 46/105, 44%) or a homeopathic dose of pyridoxine (placebo, 59/105, 56%). A 30-item behavioral checklist was used to qualify and quantify the behavioral side effects at baseline and at different time points following initiation of treatment. 

Results

Both Placebo and pyridoxine groups experienced a statistical reduction in behavioral scores as compared to baseline. Our study indicated that although there was a placebo effect, the improvement in neuropsychiatric symptoms was more prominent in children who received therapeutic doses of pyridoxine. 

Conclusion

This data provides clinicians with pertinent evidence-based information that suggests that a trial of pyridoxine in patients who experience behavioral side effects due to the use of levetiracetam may avoid unnecessary change of antiseizure medications.

KEY POINTS

• Epilepsy is a common neurological disorder in children in pediatrics worldwide.

• Levetiracetam is an antiseizure drug that has broad spectrum of action with good efficacy, low side effect profile and minimal drug-drug interactions.

• Behavioral side effects are the commonest with the use of levetiracetam.

• Pyridoxine is claimed to ameliorate behavioral side effects due to levetiracetam.

• This prospective randomized controlled trial provides evidence for the efficacy of pyridoxine in mitigating the behavioral side effects of levetiracetam.

• No adverse side effects were reported with pyridoxine use in the recommended doses.