Background Ketogenic diets (KDs), being high in fat and low in carbohydrates, have been suggested to reduce seizure frequency in people with epilepsy. At present, such diets are mainly recommended for children who continue to have seizures despite treatment with antiepileptic drugs (AEDs) (drug-resistant epilepsy). Recently, there has been interest in less restrictive KDs, including the modified Atkins diet (MAD), and the use of these diets has extended into adult practice. This is an update of a review first published in 2003 and last updated in 2016. Objectives To assess the e ects of KDs for drug-resistant epilepsy by reviewing the evidence from randomised controlled trials.

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Study characteristics This review examined data from 9 trials including a total of 3327 participants. Study participants were assigned using a random method to take pregabalin, placebo, or another antiepileptic drug in addition to their usual antiepileptic drugs. Key results Participants taking pregabalin were more than twice as likely to have their seizure frequency reduced by 50% or more during a 12week treatment period compared to those taking placebo, and were nearly four times more likely to be completely free of seizures. Pregabalin was shown to be e ective across a range of doses (150 mg to 600 mg), with increasing e ectiveness at higher doses. There was also an increased likelihood of treatment withdrawal with pregabalin. Side e ects associated with pregabalin included ataxia, dizziness, fatigue, somnolence, and weight gain. When pregabalin was compared to three other antiepileptic drugs (lamotrigine, levetiracetam, and gabapentin), participants taking pregabalin were more likely to achieve a 50% reduction in seizure frequency than those taking lamotrigine. We found no significant di erences between pregabalin and levetiracetam or gabapentin as add-on drugs. Certainty of the evidence We rated all included studies as at low or unclear in risk of bias due to missing information about the methods used to conduct the trial and a suspicion of publication bias. Publication bias can occur when studies that report non-significant findings are not published. We suspected publication bias because the majority of included studies showed significant findings and were sponsored by the same drug company. We assessed the certainty of the evidence for the primary outcome of reduction in seizure frequency as low, meaning that we Pregabalin add-on for drug-resistant focal epilepsy (Review)