Risk factors for adverse events in patients with antiepileptic polypharmacy: Large-scale cohort study

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08483
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders
• Principal Investigator: Yoshiaki Yamamoto 独立行政法人国立病院機構(静岡・てんかん神経医療センター臨床研究部), その他部局等, その他 (60596245)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: てんかん / ポリファーマシー / 薬物相互作用

Outline of Final Research Achievements

The aim of this study was to evaluate the risk factors and prevalence of adverse events among epilepsy patients. We retrospectively reviewed 25,419 epilepsy patients. The incidence of severe hyponatremia, thrombocytopenia, pancytopenia, liver injury was 1.6% (N=453), 2.0 % (N=516), 0.67 % (N=171), and 1.2 % (N=316), respectively. When severe hyponatremia was defined as a serum sodium level < 130 mEq/L, old age, low body weight, and concomitant use of phenobarbital, benzodiazepines, or antipsychotics were risk factors for hyponatremia. Also, the sodium level decreased as the carbamazepine dose increased. In patients receiving carbamazepine and valproate, there was 17-fold higher prevalence of hyponatremia. When a platelet count less than 100,000/ mm was defined as thrombocytopenia, the risk factors were a antiepileptic polypharmacy, concomitant use of valproate and rufinamide. Our findings can help clinicians to avoid adverse events in patients with epilepsy.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

近年，日本の医療現場では多剤併用（ポリファーマシー）が問題となっている．てんかん患者のうち30～40％は薬剤抵抗性の難治てんかんで，発作を抑制するために複数の抗てんかん薬を長期間服用する必要がある．一方，多剤併用は相互作用や有害事象の発生頻度を増加させ，医療費を増大させる要因となる．本研究は，てんかん患者の大規模コホートを構築し，抗てんかん薬多剤併用時における重篤な有害事象の発現率とリスク因子を明らかにしたものであり，有害事象の発症を予測する上で極めて有用な知見を提供すると考えられる．