Abstracts

Rationale: Levetiracetam, a commonly prescribed antiseizure drug, is known to cause both behavioral and mood changes, the most notable being irritability, depression, and anger. Currently, the mechanisms underlying these behavioral effects remains unknown. Individual risk factors for these adverse effects are poorly understood. As there is a lack of evidence regarding strategies to mitigate the irritability, often an efficacious medication must be discontinued.Vitamin B6 (pyridoxine) has been studied in various settings suggesting that it plays a role in reducing the prevalence of tardive dyskinesia in patients with schizophrenia, reducing PMS symptoms including irritability, moodiness, and anxiety, as well as potentially leading to improvement of depression symptoms in elderly patient. Several retrospective studies and anecdotal reports have suggested that pyridoxine supplementation may be helpful in reducing or reversing the irritability that often occurs with levetiracetam therapy. These reports are primarily in children, and it is still unknown as to how this vitamin might mitigate these behavioral changes. It has been hypothesized that its effectiveness in PMS-related mood changes could be related to its role as a cofactor in neurotransmitter biosynthesis and there is speculation that elevated levels of homocysteine plays a role in these mood changes and pyridoxine may be helping to reduce those levels. As mentioned, while some data suggest benefit in certain pediatric populations, there is a paucity of data in adult patients. Moreover, there is a lack of use of standardized mood assessments in many of the existing reports. Given that these mood symptoms may be therapy-limiting, it would be valuable to understand whether co-medication with this inexpensive and safe vitamin can ameliorate adverse mood effects. Our objective therefore was to quantify the use of levetiracetam and pyridoxine co-medication for patients who were experiencing irritability, and use of standardized mood assessment scales in a Veterans Administration epilepsy clinic.  Methods: To accomplish our primary objective, we performed an initial retrospective chart review to identify patients who had received levetiracetam for the specific treatment of seizures, and who were concomitantly receiving pyridoxine at the William S Middleton Memorial Veterans Hospital Epilepsy Center of Excellence clinic. To be eligible for review, objective measures of irritability, anxiety or depression and a clinical assessment of benefit were required to be documented. Baseline characteristics were collected, including age, sex, comorbidities and concomitant medications. Clinical descriptions of irritability were identified, including assessment of change in symptoms across multiple visits, as well as scores from standardized instruments including the patient health questionnaire (PHQ9), generalized anxiety disorder questionnaire (GAD7), and/or irritability in patients with epilepsy (I-EPI) questionnaire. These data were then compared pre- and post-pyridoxine treatment. Patients were excluded from analysis if they were using over-the-counter vitamin B6, given the difficulty to confirm both the dose as well as adherence through objective records.  Results: Fourteen patients with active prescriptions for both levetiracetam and pyridoxine were identified (100% male, 78% White/22% African American, mean age=60 yo, LEV mode dose=1000mg/day, pyridoxine dose=100mg/day) Of those 14 patients, thus far, n=6 have completed full evaluation. Four showed subjective irritability improvement, while two patients did not show improvement between baseline and end of the data collection time frame. Of the four patients who endorsed subjective improvement, three of them also had corroborating objective improvement shown with the symptom assessment questionnaires  PHQ9 (median 8 vs 5)  and/or GAD7 (median 9 vs 1).  Of the two patients who did not endorse subjective improvement, one of these individuals had corroborating objective anxiety or depression as evidenced by the questionnaires, and both patients had comorbid mental health diagnoses. Eight patients are awaiting clinical follow-up and assessment. Conclusions: These pilot data suggest that a standardized approach to identify and quantify levetiracetam-associated irritability, treatment with and follow-up evaluation of irritability using standardized assessments, can be implemented in an epilepsy clinic setting. The preliminary findings further suggest that co-medication with pyridoxine may show benefit in mitigating the irritability often associated with levetiracetam therapy in some adult patients. The influence of psychiatric comorbidities on subjective/objective response to pyridoxine is still unclear.  Funding: No funding