Levetiracetam-associated irritability and potential role of vitamin B6 use in veterans with epilepsy

OBJECTIVES: Levetiracetam, a commonly prescribed antiseizure medication (ASM), may cause irritability, depression, and anger. The mechanisms underlying these behavioral effects and individual risk factors remain unknown. Mitigation strategies are limited, including discontinuation, supplementation with vitamin B6, or switching to an alternative ASM. Several retrospective studies and anecdotal reports, primarily in pediatric populations, suggest vitamin B6 supplementation may be helpful in reducing levetiracetam-associated irritability. Although data in adult patients is limited, and no data is available for Veterans. The objective of this project was to describe our preliminarily experience with vitamin B6 supplementation for alleviating levetiracetam-associated irritability in male Veterans with epilepsy. METHODS: Retrospective chart reviews were completed for patients who had an active prescription for levetiracetam from the William S. Middleton Memorial Veterans Hospital from January 1, 2015 to June 1, 2020. A total of 26 charts were screened. Patients were excluded if not using vitamin B6 supplementation or if deceased at end of data collection. Baseline characteristics were compared, including age, sex, comorbidities, and concomitant medications. Charts were then reviewed to identify any clinical description of irritability, including subjective assessment of change in symptoms across multiple visits, and scores from standardized instruments including the patient health questionnaire (PHQ-9), generalized anxiety disorder questionnaire (GAD-7), and/or irritability in adult patients with epilepsy (I-EPI) questionnaire. These symptoms and scores were then compared pre- and post-B6 supplementation. RESULTS: Of 22 patients, data was available for 20 (91%). For patients with data available, 9 (45%) showed improved irritability following supplementation with vitamin B6 and 11 (55%) showed no improvement. CONCLUSIONS: This project suggests that vitamin B6 supplementation may have a role in mitigating levetiracetam-associated irritability in a male Veteran population. These results support future prospective controlled studies to assess further the efficacy of this approach and characteristics associated with successful treatment in veterans.