Results of the search
Our search identified 72 papers and two ongoing studies. After the titles and abstracts were reviewed, 61 papers were rejected, as it was clear that they were not randomised controlled monotherapy studies comparing sulthiame (STM) versus placebo or active control in epilepsy. Three studies from four papers were included, six studies were rejected and two studies are ongoing studies for which we were unable to obtain data. One study (Borggraefe 2013) was identified as potentially eligible for inclusion. We were unable to evaluate its relevance and include it in this version of the review because of time constraints. We will address it in the next update of the review. Further evaluation of the remaining papers is presented below and in the tables Characteristics of included studies and Characteristics of excluded studies.
Three studies (Basnec 2005; Li 2000; Rating 1999) met our inclusion criteria, comprising a total of 246 participants. One study (Rating 1999) accounted for two of the search results: Rating 1999 and Rating 2000. Each publication reported data for the same study.
Rating 1999 was a multi-centre randomised, double-blind, placebo-controlled, parallel-group study. Participants between the ages of three and 10 years, weighing between 10 and 50 kg and with a diagnosis of BECTS with at least two seizures in the past six months were recruited into the study. Participants with severe organic disease, acute porphyria, a history of mental illness, relevant hypersensitivity reactions, relevant renal, thyroid or hepatic dysfunction and somatic signs of puberty or AED treatment after the age of six months (unless treatment was provided for less than six months) were excluded. A total of 66 participants were randomly assigned. Partcipants in the intervention group had a median (range) age of 8.2 years (3.9 to 10.7 years), and participants in the placebo group had a median (range) age of 8.4 years (3.1 to 10.3 years). Interquartile age was not reported. A total of 31 participants received STM, and 35 received placebo. The intervention group consisted of 16 (52%) males and 15 (48%) females. The control group was made up of 24 (69%) males and 11 (31%) females. After a six-month historic baseline period, during which participants kept a seizure diary but received no intervention or placebo, participants were randomly assigned to receive STM (5 mg/kg/d) or placebo during a six-month treatment phase. No titration period was provided. Seizure activity was recorded by participants in a diary, and assessments occurred at screening, on day 14, on day 28, after three months and at the end of the six-month treatment phase. On day 14, assessment consisted of physical and neurological examinations, review of seizure diaries and evaluation of adverse effects, intercurrent illnesses and medications. During subsequent reviews, assessment included laboratory tests such as STM plasma levels and awake and asleep EEG changes.
Li 2000 was a multi-centre randomised, double-blind, active-controlled (PHT), parallel-group study in which an additional third group received STM openly. Participants with generalised tonic-clonic seizures (GTCS) who had experienced a seizure within three to six months of the study start date were recruited into the study. Participants in the intervention group had a mean (standard deviation (SD)) age of 29.53 (15.09) years, and participants in the placebo group had a mean (SD) age of 34.91 (15.12) years. Participants in the open group had a mean (SD) age of 27.69 (16.76) years. In all, 32 participants in the intervention group received STM, and 32 received PHT. A further 82 participants in the open group received STM. The intervention group consisted of 18 (56%) males and 14 (44%) females. The treatment phase lasted for six months; however, no information was provided on loading or titration periods or whether a historic baseline period was included. The control group was made up of 17 (53%) males and 15 (47%) females. The open group included 57 (70%) males and 25 (30%) females. At the start of the trial, participants were randomly assigned to receive STM (100 to 200 mg/d) or PHT (300 mg/d) as a double-blind treatment or STM (100 to 200 mg/d) as an open treatment. Treatment continued for six months, during which seizure frequency and adverse effects were measured on a monthly basis. Laboratory tests were carried out before treatment commenced and after the six-month treatment period had been completed; they consisted of blood count, liver function, kidney function, electrocardiogram (ECG) and EEG.
Providing a robust analysis of Basnec 2005, which was published in Croatian, is difficult because of the lack of a reliable English translation of the full text. We will aim to obtain an English translation of the full text in future updates of this review and will discuss below information that can be obtained from the English translation of the abstract. Basnec 2005 was a multi-centre randomised, double-blind, placebo-controlled, parallel-group study. Details on dosing and study phases were not provided. Participants between the ages of three and 11 years who had experienced a single seizure only and had received no AED treatment were recruited into the study. Participants received STM or placebo, and data were collected on the proportion of participants who withdrew from treatment, the proportion of participants who experienced a second seizure within six months, the proportion of participants who experienced a second seizure after six months and the proportion of participants who experienced status epilepticus.
Three studies (Ingram 1963; Griffiths 1964; Livingston 1967) administered STM to participants with epilepsy but did not include a placebo group. Amongst the excluded studies were two RCTs. One study (Debus 2004) compared STM versus placebo as an add-on therapy in epilepsy. Another study (Groppa 2006) compared STM versus placebo as monotherapy in healthy participants with no history of epilepsy, measuring axonal excitability of cortical neurons as a primary outcome. Two ongoing studies (ISRCTN66730162; ISRCTN97864911) compared STM versus placebo (ISRCTN66730162) or levetiracetam (ISRCTN97864911) as monotherapy in participants with BECTS. At the time of publication of this Cochrane review, data from either of these studies are not available. Future updates of this review will include data from ongoing studies once they become available.