Clonazepam add-on therapy for refractory epilepsy in adults and children

Review question

This review aimed to evaluate the efficacy and tolerability of clonazepam when used as an add-on therapy for adults and children with refractory focal onset or generalised onset epileptic seizures, when compared with placebo or another antiepileptic agent.

Background

Epilepsy affects about 50 million people worldwide, nearly a quarter of whom have drug-refractory epilepsy. Clonazepam is one of the 1,4-benzodiazepine drugs commonly used in epilepsy management, and recommended for second-line adjunctive treatment for various types of seizures. Previous studies have shown that clonazepam is effective in comparison with placebo when used as a supplement to previous medication for people with an insufficient response to conventional antiepileptic treatment.

Review methods

We searched different databases that contain both published and unpublished results of medical studies. We included only randomised controlled studies (i.e. studies in which participants are randomly allocated to one or more treatments), which are considered the gold-standard of experimental studies in research literature. Two review authors independently selected studies for inclusion, extracted relevant data, and assessed trial quality.

Key results

We found no double-blind randomised controlled trials that considered clonazepam as an add-on therapy for adults and children with refractory focal or generalised onset epileptic seizures, thus its efficacy and safety could not be analysed in this review. There is a need for double-blind randomised controlled trials of clonazepam as an add-on therapy for refractory epilepsy.

The evidence is current to September 2017.

Authors' conclusions: 

There is no evidence from double-blind randomised controlled trials for or against the use of clonazepam as an add-on therapy for adults and children with refractory focal or generalised onset epileptic seizures.

Read the full abstract...
Background: 

Epilepsy affects about 50 million people worldwide, nearly a quarter of whom have drug-refractory epilepsy. People with drug-refractory epilepsy have increased risks of premature death, injuries, psychosocial dysfunction, and a reduced quality of life.

Objectives: 

To assess the efficacy and tolerability of clonazepam when used as an add-on therapy for adults and children with refractory focal onset or generalised onset epileptic seizures, when compared with placebo or another antiepileptic agent.

Search strategy: 

We searched the following databases on 14 September 2017: Cochrane Epilepsy Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 14 September 2017), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP).

Selection criteria: 

Double-blind randomised controlled studies of add-on clonazepam in people with refractory focal or generalised onset seizures, with a minimum treatment period of eight weeks. The studies could be of parallel or cross-over design.

Data collection and analysis: 

Two review authors independently selected studies for inclusion, extracted relevant data, and assessed trial quality. We contacted study authors for additional information.

Main results: 

No double-blind randomised controlled trials met the inclusion criteria.

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