A 2022 systemic review evaluated the efficacy of vitamin B6 as an adjunctive treatment for levetiracetam-associated neuropsychiatric adverse events (NPAEs) in patients being treated for epilepsy. Among the 7 studies included in the analysis, study populations were composed of both adult and pediatric patients being treated with levetiracetam (LVT) and evaluated on the incidence of LVT-associated behavioral adverse events (BAEs) following concomitant vitamin B6 treatment. One pediatric trial (N= 105) evaluated the use of vitamin B6 following the development of BAEs with LVT treatment initiation and showed that vitamin B6 (10-15 mg/kg/day) significantly reduced BAE severity from baseline to 6 months compared to control (p<0.001). The remaining studies, mostly retrospective, reported positive outcomes with vitamin B6 use in patients with LV-associated NPAEs; though the validity of these study results is limited by low-quality data. Notably, these available analyzed studies do not report the efficacy of vitamin B6 for the treatment or prevention of sedation associated with levetiracetam use. [1], [2]
A clinical review of drug titration methods for patients receiving antiepileptic drugs (AEDs) also highlighted the importance of patient-specific parameters for AED titration in regard to the incidence and severity of adverse effects. Central nervous system (CNS) adverse effects, such as sedation and dizziness, are commonly dose-related, occur early during initial treatment, and are likely to diminish over time while on therapy. Adverse effects upon treatment initiation may be diminished by using a low dose at initiation and gradually titrating to allow for pharmacodynamic tolerance to AED to develop over time; ultimately preventing CNS adverse effects and potential treatment failure. These recommendations are specific to the tolerability and safety of AED use in patients being treated for epilepsy but do not highlight the use of additional agents for the management of CNS adverse effects commonly seen with AED use. [1], [2]
Available studies evaluating the potential role of vitamin B6 for improving tolerance of levetiracetam in epilepsy treatment do not specifically analyze the effects of vitamin B6 for improving levetiracetam-associated sedation, but rather its effects on behavioral adverse events as a whole. In one retrospective chart review of 22 veterans with epilepsy receiving levetiracetam and concomitant vitamin B6, 9 (45%) patients showed improved irritability following supplementation with vitamin B6, while 11 (55%) showed no improvement. In another retrospective study of 240 children receiving levetiracetam, 83 (35%) reported side effects while taking levetiracetam alone or with other anti-seizure medications, with behavioral and mood concerns being the most frequently reported side effects at 50% and 24%, respectively. Of the patients who reported side effects, 71% were taking concomitant vitamin B6 (n= 59), and the rate of levetiracetam discontinuation was reported to be significantly lower for children receiving concomitant vitamin B6 versus children not receiving vitamin B6 (49% vs. 88%; p= 0.001). Again, despite these findings, conclusions regarding the use of vitamin B6 for management of levetiracetam-associated sedation cannot be made. [3], [4]