Sulthiame add-on therapy for epilepsy


Epilepsy is a common neurological (brain) condition that is characterised by recurrent seizures (fits). Most patients respond well to conventional antiepileptic medicines, although about 30% of patients (non responders) will continue to have seizures .

Sulthiame is an antiepileptic drug that is used widely in some European countries and in Israel. Sometimes it is used as an additional (add-on) antiepileptic medicine in non responders, alongside an existing antiepileptic medicine.

What the researchers investigated

A team of Cochrane researchers wanted to investigate how well sulthiame works when it is used as an add-on antiepileptic medicine in non responders.

Randomised controlled trials produce the most reliable evidence for medicines. The team searched the medical literature, up to 11 August 2015, for all randomized controlled trials that compared sulthiame as an add-on therapy against an add-on placebo (fake medicine) or another antiepileptic medicine.

What the researchers found

The researchers found one relevant trial that included 37 participants who were all babies or very young children, aged from two to 15 months. All the participants had a diagnosis of West syndrome, which is a type of epilepsy. All participants were started on an antiepileptic medicine, pyridoxine, three days before they also started to take sulthiame or placebo. The participants did not know the identity of the add-on therapy. The trial lasted for nine days.

This single trial suggested that sulthiame may stop seizures in patients with West syndrome who are non responders to pyridoxine, but the small number of participants in the trial, and its short duration, reduces the confidence the researchers have that this is a reliable effect.

Further randomized controlled trials are required if meaningful conclusions are to be drawn about how well sulthiame works as an add-on therapy in West syndrome and other types of epilepsy, and to establish whether it produces any unwanted or harmful effects.

Authors' conclusions: 

Sulthiame may lead to a cessation of seizures when used as an add-on therapy to pyridoxine in patients with West syndrome. The included study was small and had a significant risk of bias which limits the impact of the evidence. No conclusions can be drawn about the occurrence of adverse drug effects, change in quality of life or mean reduction in seizure frequency. No evidence exists for the use of sulthiame as an add-on therapy in patients with epilepsy outside West syndrome. Large, multi-centre randomized controlled trials are necessary to inform clinical practice if sulthiame is to be used as an add-on therapy for epilepsy.

Read the full abstract...

Epilepsy is a common neurological condition characterised by recurrent seizures. Most patients respond to conventional antiepileptic drugs, however, around 30% will continue to experience seizures despite multiple antiepileptic drugs. Sulthiame, also known as sultiame, is a widely used antiepileptic drug in Europe and Israel. We present a summary of the evidence for the use of sulthiame as add-on therapy in epilepsy.


To compare the efficacy and side-effect profile of sulthiame as add-on therapy compared with placebo or another antiepileptic drug.

Search strategy: 

We searched the Cochrane Epilepsy Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and the WHO ICTRP Search Portal on 11 August 2015. No language restrictions were imposed. We contacted the manufacturers of sulthiame and researchers in the field to seek any ongoing or unpublished studies.

Selection criteria: 

Randomised controlled add-on trials of sulthiame in people of any age with epilepsy of any aetiology.

Data collection and analysis: 

Two review authors independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: 1) reduction in seizure frequency of 50% or greater between baseline and end of follow-up; 2) complete cessation of seizures during follow-up; 3) mean seizure frequency; 4) time to treatment withdrawal; 5) adverse drug effects; and 6) quality of life scoring. Primary analyses were intention-to-treat. We present a narrative analysis.

Main results: 

We included one trial with 37 participants with a new diagnosis of West syndrome. Sulthiame was given as an add-on therapy to pyridoxine. No data were reported for outcomes 1), 3) or 6). Overall risk ratio with 95% confidence intervals (CI) for complete cessation of seizures during a nine-day follow-up period versus placebo was 0.71 (95% CI 0.53 to 0.96). Meaningful analysis of time to treatment withdrawal and adverse drug effects was not possible due to incomplete data.