{"doi":"10.1002/14651858.cd004762.pub3","title":"Drug treatment for myotonia","abstract":"BACKGROUND: Abnormal delayed relaxation of skeletal muscles, known as myotonia, can cause disability in myotonic disorders. The main myotonic disorders are non-dystrophic myotonia and myotonic dystrophy. Non-dystrophic myotonia is a genetic muscle channelopathy predominantly causing myotonia. Myotonic dystrophic is a more systemic neuromuscular disorder causing myotonia as well as progressive myopathy and systemic manifestations, such as arrhythmias and cataracts. Myotonia manifests as stiffness, cramps, locking, pain, and fatigue, and can cause marked morbidity and disability. Sodium channel blockers, tricyclic antidepressive drugs, benzodiazepines, calcium antagonists, taurine, and prednisone may reduce myotonia. This is an update of a review first published in 2005 and updated in 2006. OBJECTIVES: To review evidence from randomised controlled trials (RCTs) on the efficacy and tolerability of drug treatment in people with clinical myotonia due to myotonic disorders. SEARCH METHODS: We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and World Health Organization ICTRP on 29 March 2023. We handsearched the grey literature and contacted disease experts and antimyotonic drug manufacturers. SELECTION CRITERIA: We included RCTs involving participants with myotonia treated with any drug treatment versus no therapy, placebo, or any other active drug treatment. We included clinical trials where the reported primary outcome was a participant-reported measure of myotonia. We excluded non-RCTs and where myotonia may have been part of the condition (e.g. paramyotonia or Brody's disease). The primary myotonic conditions were myotonic dystrophy and non-dystrophic myotonia. Our primary outcome was participant-reported improvement in clinical myotonia. Our secondary outcomes were relaxation time, electromyographic relaxation time, adverse events, and quality of life. DATA COLLECTION AND ANALYSIS: Review authors independently extracted the data onto standardised extraction forms. Three review authors independently assessed risk of bias and we collected adverse events data from the included trials. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: This review includes 17 double-blind or single-blind RCTs involving a total of 392 participants, 219 with myotonic dystrophy type 1 and 173 with non-dystrophic myotonia. Seven RCTs were newly identified and included in this update. Four of these RCTs investigated the effect of mexiletine or lamotrigine versus placebo in people with non-dystrophic myotonia. The remaining RCTs explored mexiletine in myotonic dystrophy. Myotonic dystrophy Mexiletine No RCTs reported improvement in clinical myotonia according to validated scales. Mexiletine likely reduces hand grip relaxation time compared to placebo (mean difference (MD) 1.37 seconds better, 95% confidence interval (CI) 0.87 to 1.86; 2 RCTs, 56 participants; moderate-certainty evidence). Low-certainty evidence from four RCTs (91 participants) reported 55 adverse events with placebo and 84 adverse events with mexiletine. The most frequent adverse events with mexiletine were gastrointestinal symptoms, lethargy, and headache. There may be no difference in quality of life measures between mexiletine and placebo (36-item Short Form (SF-36) Physical Component Summary (PCS): MD -1.40, 95% CI -5.56 to 2.76; SF-36 Mental Component Summary (MCS): MD -1.10, 95% CI -6.17 to 3.97; 1 RCT, 38 participants; low-certainty evidence). Non-dystrophic myotonia Mexiletine Mexiletine likely reduces myotonia compared to placebo using the Interactive Voice Response Diary Stiffness score (across both treatment periods: MD -3.12, 95% CI -3.75 to -2.49; 2 cross-over RCTs, 89 participants; moderate-certainty evidence). There is likely no effect on relaxation times with no differences in eye closure or clinical hand grip between mexiletine and placebo (2 RCTs, 89 participants; moderate-certainty evidence). Me","journal":"Cochrane Database of Systematic Reviews","year":2025,"id":540845,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02251457"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1429234,"name":"J. Trip","orcid":null,"position":1,"is_corresponding":false},{"id":1016257,"name":"Jeffrey Balzer","orcid":"0000-0002-3546-4548","position":2,"is_corresponding":false},{"id":292131,"name":"Catharina G. Faber","orcid":"0000-0002-2467-067X","position":3,"is_corresponding":false},{"id":55171,"name":"Michael G. Hanna","orcid":"0000-0003-0825-4075","position":4,"is_corresponding":false},{"id":1193912,"name":"Sarah J Nevitt","orcid":"0000-0001-9988-2709","position":5,"is_corresponding":false},{"id":1040498,"name":"Vinojini Vivekanandam","orcid":"0000-0002-4944-0061","position":6,"is_corresponding":false},{"id":1304200,"name":"Jennifer Spillane","orcid":"0000-0002-9339-0938","position":0,"is_corresponding":true}],"reference_count":132,"raw_metadata":null,"created_at":"2026-07-19T02:52:42.901627Z","pmid":"40197813","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}