Abstract Background The first International Parkinson and Movement Disorder Society Evidence‐Based Medicine (MDS‐EBM) review for essential tremor (ET) was published in 2019; since then, the modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was adopted by MDS, and new evidence exists. Objective The objective of this study was to update EBM conclusions for medical treatments of ET with a focus on longer follow‐up periods. Methods A systematic literature search was conducted for randomized controlled trials (RCTs) investigating medical interventions for ET with a minimum 1‐month follow‐up, with subsequent appraisal of data using an MDS‐EBM framework. Results Thirty‐one RCTs were included evaluating 16 interventions against placebo. Nine interventions were evaluated by more than one RCT: alprazolam, botulinum toxin type A (BtA), levetiracetam, phenobarbitone, pregabalin, primidone, propranolol, topiramate, and trazodone. The remainder were studied in a single RCT (acetazolamide, flunarizine, gabapentin, mirtazapine, perampanel, progabide, and zonisamide). Trial sample size ranged from 5 to 117 participants, and study duration ranged from 4 to 28 weeks. More than one RCT documented improvement in tremor severity for propranolol, primidone, topiramate, and BtA. Using the modified GRADE framework, we found significant methodological shortcomings in the studies, resulting in insufficient evidence for all interventions. Concerns about risk of bias and imprecision commonly limited the ability to make stronger recommendations for these interventions. Conclusions Current evidence from RCTs with at least 1 month of follow‐up is insufficient to confidently support the efficacy of available medical treatments for ET. There is a need for longer, higher‐quality clinical trials to improve treatment recommendations and guide decision‐making for clinicians and patients with ET. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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