Background
Epilepsy is a common neurological condition characterised by recurrent seizures. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel.
Review aims
This review aimed to determine the efficacy and side effect profile of STM as monotherapy, when compared with placebo or another antiepileptic drug for people with epilepsy.
Results
We found four randomised controlled trials (studies in which participants are randomly assigned to one of two or more treatment groups) involving a total of 355 participants that looked at the effectiveness and tolerability of sulthiame used as a single treatment in epilepsy. Three studies were conducted on a common form of childhood epilepsy known as benign epilepsy of childhood with centrotemporal spikes, and one study was conducted on generalised tonic-clonic seizures, a type of seizure that starts on both sides of the brain and causes stiffness or twitching throughout the body. Based on the available evidence, we could draw no meaningful conclusions on the effectiveness or tolerability of sulthiame as a single treatment in epilepsy.
Quality of the evidence
The quality of the evidence is limited by small sizes of the groups being studied, significant risk of bias, and incomplete data on important outcome measures, as well as by the lack of an English translation of the full-text manuscript of one study.
Conclusions
Further high-quality research is needed to fully evaluate the effectiveness and tolerability of sulthiame as a single treatment in epilepsy.
The evidence is current to April 2020.
This review provides insufficient information to inform clinical practice. Small sample sizes, poor methodological quality, and lack of data on important outcome measures precluded any meaningful conclusions regarding the efficacy and tolerability of sulthiame as monotherapy in epilepsy. More trials, recruiting larger populations, over longer periods, are needed to determine whether sulthiame has a clinical use.
This is an updated version of the original Cochrane Review published in 2014.
Epilepsy is a common neurological condition characterised by recurrent seizures. Pharmacological treatment remains the first choice to control epilepsy. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we have presented a summary of evidence for the use of STM as monotherapy in epilepsy.
To assess the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug for people with epilepsy.
We searched the following databases on 13 April 2020: the Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 10 April 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies.
Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology.
We followed standard Cochrane methodology. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: treatment withdrawal; seizure-free at six months; adverse effects; and quality of life scoring. We conducted the primary analyses by intention-to-treat where possible, and presented a narrative analysis of the data.
We included four studies involving a total of 355 participants: three studies (209 participants) with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS), and one study (146 participants) with a diagnosis of generalised tonic-clonic seizures (GTCS). STM was given as monotherapy compared with placebo and with levetiracetam in the BECTS studies, and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract.
For the primary outcome, the total number of dropouts caused either by seizure recurrence or adverse reaction was significantly higher in the levetiracetam treatment arm compared to the STM treatment arm (RR 0.32, 95% Cl 0.10 to 1.03; 1 study, 43 participants; low-certainty evidence). For the secondary outcomes for this comparison, results for seizure freedom were inconclusive (RR 1.12, 95% Cl 0.88 to 1.44; 1 study, 43 participants; low-certainty evidence).
Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than participants receiving phenytoin in the GTCS study (RR 0.03, 95% CI 0.00 to 0.58; 1 study, 146 participants; low-certainty evidence). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. The most common adverse events were related to behavioural disturbances when STM was compared with levetiracetam (RR 0.95, 95% Cl 0.59 to 1.55; 1 study, 43 participants; low-certainty evidence), with the same incidence in both groups. No data were reported for quality of life.
Overall, we assessed one study at high risk of bias and one study at unclear bias across the seven domains, mainly due to lack of information regarding study design. Only one trial reported effective methods for blinding. The risk of bias assessments for the other two studies ranged from low to high. We rated the overall certainty of the evidence for the outcomes as low using the GRADE approach.