Pyridoxine Add-On Treatment for the Control of Behavioral Adverse Effects Induced by Levetiracetam in Children: A Case-Control Prospective Study

Ann Pharmacother. 2018 Jul;52(7):645-649. doi: 10.1177/1060028018759637. Epub 2018 Feb 14.


Background: Few studies on adult and pediatric patients have shown pyridoxine efficacy as additional therapy for those receiving levetiracetam (LEV) to prevent and mitigate behavioral adverse effects (BAEs).

Objective: The aim of our study was to analyze the safety and efficacy of pyridoxine supplementation in the prevention of LEV adverse effects, including suicidal ideation.

Methods: This randomized, case-control trial included patients receiving LEV as monotherapy treatment. Patients were subdivided into 2 groups, according to whether they were treated with LEV only (group 1) or LEV with supplemental pyridoxine (group 2).

Results: In both cohorts, the most frequent BAEs were irritability/aggression followed by depression and confusion. Those patients (92%) who initiated pyridoxine after 1 month of LEV treatment did not need to change or suspend LEV ( P < 0.001), and BAE improved after 9.06 ± 3.05 days of pyridoxine supplementation. None of the patients complained of symptoms of pyridoxine toxicity, and no new adverse effects of LEV off-label were reported.

Conclusions: In our study, we found pyridoxine to be safe and effective in controlling LEV-induced BAEs in children.

Keywords: behavioral adverse effects; child; levetiracetam; pyridoxine.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aggression / drug effects
  • Anticonvulsants / adverse effects*
  • Child
  • Child Behavior / drug effects*
  • Child, Preschool
  • Confusion / drug therapy
  • Depression / drug therapy
  • Drug Therapy, Combination
  • Female
  • Humans
  • Irritable Mood / drug effects
  • Levetiracetam / adverse effects*
  • Male
  • Pyridoxine / administration & dosage*
  • Treatment Outcome


  • Anticonvulsants
  • Levetiracetam
  • Pyridoxine