Elisa Bruno, Alessandra Nicoletti, Graziella Filippini, Graziella Quattrocchi, Carlo Colosimo, Mario Zappia

Essential tremor (ET) is one of the most common movement disorders. The treatment is primarily based on pharmacological agents. Although primidone and propranolol are well established treatments in clinical practice, they can be ineffective in 25% to 55% of patients, and can produce serious adverse events in a large percentage of them. For these reasons, it may be worthwhile evaluating the treatment alternatives for ET. Zonisamide has been suggested as a potentially useful agent for the treatment of ET but there is uncertainty about its efficacy and safety. To assess the effect on functional abilities and the safety profile of zonisamide in adults with essential tremor (ET). We carried out a systematic search, without language restrictions to identify all relevant trials. We searched CENTRAL, MEDLINE, Embase, NICE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) to January 2017. We searched BIOSIS Citation Index (2000 to January 2017) for conference proceedings. We handsearched grey literature and examined the reference lists of identified studies and reviews. We included all randomised controlled trials (RCTs) of zonisamide versus placebo or any other treatment. We included studies in which the diagnosis of ET was made according to accepted and validated diagnostic criteria. We excluded studies conducted in patients presenting secondary forms of tremor or reporting only neurophysiological parameters to assess outcomes. Two review authors independently collected and extracted data using a data collection form. We assessed the risk of bias and the quality of evidence.We used inverse variance methods for continuous outcomes and measurement scales. We compared differences between treatment groups as mean differences. We combined results for dichotomous outcomes using Mantel-Haenszel methods and obtained risk differences to compare treatment groups. We used Review Manager 5 software for data management and analysis. We only considered one study eligible for this review (20 participants). Assessments of risk of bias for most domains were unclear or low. Adverse events were only reported in participants from the zonisamide group, making it possible that they were aware of treatment group assignment. We are uncertain as to the effects of zonisamide on motor tasks (mean difference (MD) -0.00, 95% confidence interval (CI) -1.51 to 1.51, very low-quality evidence) and functional disabilities (MD -0.30, 95% CI -1.23 to 0.63, very low-quality evidence) when compared with placebo. Three participants in the zonisamide group (30%) and two participants in the placebo group (20%) discontinued the treatment and withdrew from the study for any reason (very low-quality evidence), however the increased risk of withdrawal in the zonisamide group was statistically non-significant (risk difference (RD) 0.1, 95% CI -0.28 to 0.48). Six participants in the zonisamide group (60%) and none of the participants in the placebo group (0%) developed adverse events (AEs), with a RD of 0.60 (95% CI 0.28 to 0.92; very low quality evidence). The most common AEs, experienced with zonisamide treatment, were headache, nausea, fatigue, sleepiness, and diarrhoea. Quality of life was not assessed in the study included. Based on currently available data, there is insufficient evidence to assess the efficacy and safety of zonisamide treatment for ET.