A systematic review of placebo‐controlled trials of topiramate: How useful is a multiple‐indications review for evaluating the adverse events of an antiepileptic drug?

Abstract

Sarah Donegan is a biostatistician specializing in metaanalysis SUMMARY Objective: Topiramate (TPM) is an antiepileptic drug that is also used for other indications (e.g., migraine). Adverse event (AE) data from epilepsy trials could be supplemented by data from trials in other indications. Combining data across trials and indications is a novel method for evaluating AEs. We conducted a multiple-indications review by systematically reviewing randomized placebo-controlled trials of TPM, to compare the nervous system AEs of TPM in epilepsy with those in other indications. Methods: Randomized placebo-controlled trials of TPM including patients with any indication were included. We searched Cochrane Central Register of Controlled Trials (Issue 2, 2012) and MEDLINE (1966( -February 2012. Two authors assessed eligibility and risk of bias, and extracted data. For each reported nervous system AE, we extracted event rates, applied random-effects inverse-variance meta-analysis (pooling within-indications then across-indications), and assessed within-and across-indication heterogeneity. Results: Ninety trials, including 16 epilepsy trials, were included. A difference was detected between TPM and placebo for three events (i.e., drooling, dysgeusia, and hypoesthesia) that were not reported in epilepsy trials but were reported by other trials. A difference between TPM and placebo was detected for speech disorder using epilepsy trials but not when combining all trials. For two events (i.e., cognitive disorder and "language problems"), no difference was detected between TPM and placebo when using epilepsy trials alone, but a difference was identified using all trials. A difference was detected between TPM and placebo for six events (i.e., ataxia, disturbance in attention, dizziness, memory impairment, paraesthesia, and somnolence) when using epilepsy trials alone, and using all trials. Significance: Including trials of any indication enabled detection of differences that would have been missed using epilepsy trials alone. Multiple-indications reviews can improve the synthesis of AEs for antiepileptic drugs.

Practice guideline recommendations summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders

“…While generally well-tolerated at low doses (25-150 mg/day) it may cause adverse effects, including cognitive and language problems, somnolence, and weight loss, and may increase the risk of renal stones (RELA). [26][27][28]…”

Revisiting the Efficacy and Tolerability of Topiramate for Tic Disorders: A Meta-Analysis

“…It should be noted that the most common side effects for topiramate were language problems, cognitive disorder, kidney stones, and weight loss, while the rare side effects such as fatigure, insomnia, dizziness, diarrhea, and migraine also needed to be considered (Dell'Orto et al 2014). In addition, the well-tolerated dose of topiramate was 25-150 mg/day, but over 200 mg/day, the side effects increased (Donegan et al 2015;Pringsheim et al 2019).…”

The Application of Text Mining Algorithms In Summarizing Trends in Anti-Epileptic Drug Research

“…Topiramate is used as a monotherapy in children of ages two and above and as an adjunctive therapy for adults. Its use is children is specifically indicated for seizures related with Lennox-Gastaut syndrome (LGS) (Crumrine, 2011;Donegan, Dixon, Hemming, Tudur-Smith, & Marson, 2015;Hoy, 2016). Topic modeling showed a strong association of this agent with Lennox-Gastaut syndrome, a disorder which initiates seizures in children (Crumrine, 2011;Singh, 2016;Singh et al, 2016;VanStraten & Ng, 2012).…”