Carbamazepine versus valproate monotherapy for epilepsy

  • Review
  • Intervention




Carbamazepine and valproate are drugs of first choice for epilepsy. Despite the lack of hard evidence from individual randomized controlled trials, there is strong clinical belief that valproate is the drug of choice for generalized epilepsies and carbamazepine for partial epilepsies.


To overview the best evidence comparing carbamazepine and valproate monotherapy

Search methods

We searched the Cochrane Epilepsy Group's Specialized Register (27 July 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007), and MEDLINE (1966 to July 2007). No language restrictions were imposed. We also contacted pharmaceutical companies and researchers in the field.

Selection criteria

Randomized controlled trials comparing carbamazepine and valproate monotherapy for epilepsy.

Data collection and analysis

This was an individual patient data review. Outcome measures were time to withdrawal of allocated treatment, time to 12-month remission, and time to first seizure post randomization. Data were analysed using the stratified logrank test with results expressed as hazard ratios (HR) with 95% confidence intervals (CIs), where HR > 1 indicates an event is more likely on valproate. A test for an interaction between treatment and epilepsy type (partial versus generalized) was also undertaken.

Main results

Results data were available for 1265 participants from five trials, representing 85% of the participants recruited into the eight trials that met our inclusion criteria. The main overall results (HR) were: time to treatment withdrawal 0.97 (95% CI 0.79 to 1.18); 12 month remission 0.87 (95% CI 0.74 to 1.02); first seizure 1.09 (95% CI 0.96 to 1.25) suggesting no overall difference for these outcomes. The test for an interaction between treatment and epilepsy type was non significant for time to treatment withdrawal and 12-month remission, but significant for time to first seizure. The age distribution of adults classified as having a generalized epilepsy indicate that significant numbers of individuals may have had their epilepsy misclassified.

Authors' conclusions

We have found some evidence to support the policy of using carbamazepine as the first treatment of choice in partial epilepsies, but no evidence to support the choice of valproate in generalized epilepsies, but confidence intervals are too wide to confirm equivalence. Misclassification of people with epilepsy may have confounded our results, and has important implications for the design and conduct of future trials.








我們搜尋了Cochrane Epilepsy Group's Specialized Register (2007年7月27日)以及Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library,2007年第3期), MEDLINE (1966年2007年7月)。沒有設定任何語言限制。 我們也聯繫了醫藥公司和該領域的研究人員。




本研究是取自臨床試驗中個別病人資料的回顧。治療成果的收集包括開始治療後至停止試驗用藥的時間,開始治療後至達成連續12個月緩解的時間,開始隨機分配治療後至首次癲癇發作的時間等。我們使用tratified logrank test來分析資料,將結果呈現為hazard ratios (HR) 和95% confidence intervals (CIs),其中HR>1表示該事件較可能發生在使用valproate時。我們也檢驗了治療藥物和發作類型(局部發作型癲癇症對比全盤發作型癲癇症)之間的相互影響。


我們從5個試驗中取得其中1265位受試者的相關資料,佔所有8個符合我們選擇條件的試驗中所有病患的85%。各項治療成果的HR如下:開始治療後至停止試驗用藥的時間為0.97 (95% CI 0.79 – 1.18);開始治療後至達成連續12個月緩解的時間為0.87 (95% CI 0.741.02); 開始隨機分配治療後至首次癲癇發作的時間為1.09 (95% CI 0.96−1.25),以上皆顯示兩種藥物治療間沒有明顯差異。至於治療藥物和發作類型之間的相互影響方面,在開始治療後至停止試驗用藥的時間和開始治療後至達成連續12個月緩解的時間等治療成果上無顯著差異,但於開始隨機分配治療後至首次癲癇發作的時間上則明顯有別。然而因有許多成人病患被歸類在全盤發作型癲癇症,這代表可能有相當數目的病患其癲癇分類並不正確。�




此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。



Plain language summary

Carbamazepine versus valproate monotherapy for epilepsy

No reliable evidence to distinguish between carbamazepine and valproate for partial onset seizures and generalized onset tonic-clonic seizures.

Epilepsy is a disorder where recurrent seizures are caused by abnormal discharges from the brain. Carbamazepine is commonly used to treat partial seizures while valproate is used for generalized seizures. The review of trials found no evidence to support the belief that valproate is superior to carbamazepine for generalized tonic-clonic seizures. While it was found that younger people fared better on valproate and older people on carbamazepine, this may be because generalized epilepsy is more common in childhood and adolescence.