| Methods | Randomised, double‐blinded, three‐period cross‐over study The randomization schedule was generated by the NIH statistician and administered by pharmacy None of the participants, physicians, nurses, social workers, or technicians interacting with the participants knew what treatment they were being given, felbamate or placebo, at any time. 4 treatment sequence: felbamate‐placebo‐felbamate; felbamate‐placebo‐placebo; placebo‐felbamate‐placebo; placebo‐felbamate‐felbamate The treatments were administered over the course of alternating titration and analysis periods, each lasting 2 weeks. |
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| Participants | 30 participants were randomised (10 male), aged 19‐50 years. 8 participants were randomised to felbamate‐placebo‐felbamate sequence, 8 participants were randomised to felbamate‐placebo‐placebo sequence, 7 participants were randomised to placebo‐felbamate‐placebo sequence, 7 participants were randomised to placebo‐felbamate‐felbamate sequence. Simple partial seizures, complex partial seizures, generalised tonic‐clonic seizures Mean baseline seizure frequencies of the participants were unavailable. The other AED was carbamazepine. |
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| Interventions | Add‐on placebo or felbamate 28 participants who completed the study received felbamate dosage of 3000 mg/d. The 2 exceptions who left the study received felbamate dosage of 2400 mg/d. |
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| Outcomes |
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| Notes | 2 participants left the study after randomisation; 1 owing to seizure exacerbation and the other owing to hyponatraemia possibly related to carbamazepine. Both were included in the data analysis. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Selective reporting (reporting bias) | Low risk | The outcomes mentioned in the methods were reported. |
| Random sequence generation (selection bias) | Low risk | We contacted the study author and the reply was as follows: "The randomisation schedule was generated by the NIH statistician and administered by the pharmacy." |
| Allocation concealment (selection bias) | Low risk | We contacted the study author and the reply was as follows: "The randomisation schedule was generated by the NIH statistician and administered by the pharmacy." |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | We contacted the study author and the reply was as follows: "None of the physicians or nurses or patients knew what drug they were being given, felbamate or placebo, at any time." |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Quote: "double blind". Comment: probably done |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Quote: "47 individuals were enrolled, 17 were not randomised, 2 of the 30 randomisation left the study after randomisation." |
AED: antiepileptic drug d: day NIH: National Institutes of Health