Use of zonisamide for the treatment of essential tremor

Review question

The authors of this review tried to assess the effectiveness and safety of zonisamide in people (16 years or older) with essential tremor.

Background

Essential tremor is the most common movement disorder. Although benign, in term of its effect on life expectancy, it is typically progressive and potentially disabling. The treatment is primarily based on pharmacological agents (propranolol and primidone as first-line therapy) but these are ineffective in 25% to 55% of participants. Zonisamide has been suggested as a potentially useful agent for the treatment of essential tremor.

Study characteristics

We found one study comparing zonisamide versus placebo, involving a total of 20 randomised participants with essential tremor.

Key results

The impact of zonisamide on functional abilities, risk of treatment discontinuation, and adverse events is uncertain because the quality of evidence is very low. Adverse events were only reported in participants from the zonisamide group, making it possible that they were aware of which treatment they had been receiving. Quality of life was not assessed in the study included.

Quality of evidence

The single study we found was small and the possibility of study participants becoming aware of the treatment group means that we cannot be certain about the risk-benefit profile of this treatment.

Authors' conclusions: 

Based on currently available data, there is insufficient evidence to assess the efficacy and safety of zonisamide treatment for ET.

Read the full abstract...
Background: 

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.

Objectives: 

To assess the effect on functional abilities and the safety profile of zonisamide in adults with essential tremor (ET).

Search strategy: 

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.

Selection criteria: 

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.

Data collection and analysis: 

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.

Main results: 

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.

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