Updating the recommendations for treatment of tardive syndromes: A systematic review of new evidence and practical treatment algorithm

Background Management of tardive syndromes (TS) is challenging, with only a few evidence-based therapeutic algorithms reported in the American Academy of Neurology (AAN) guideline in 2013. Objective To update the evidence-based recommendations and provide a practical treatment algorithm for management of TS by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TS treatment? 2) Does switching from typical to atypical DRBAs reduce TS symptoms? 3) What is the efficacy of pharmacologic agents in treating TS? 4) Do patients with TS benefit from chemodenervation with botulinum toxin? 5) Do patients with TS benefit from surgical therapy? Methods Systematic reviews were conducted by searching PsycINFO, Ovid MEDLINE, PubMed, EMBASE, Web of Science and Cochrane for articles published between 2012 and 2017 to identify new evidence published after the 2013 AAN guidelines. Articles were classified according to an AAN 4-tiered evidence-rating scheme. To the extent possible, for each study we attempted to categorize results based on the description of the population enrolled (tardive dyskinesia [TD], tardive dystonia, tardive tremor, etc.). Recommendations were based on the evidence. Results and recommendations New evidence was combined with the existing guideline evidence to inform our recommendations. Deutetrabenazine and valbenazine are established as effective treatments of TD (Level A) and must be recommended as treatment. Clonazepam and Ginkgo biloba probably improve TD (Level B) and should be considered as treatment. Amantadine and tetrabenazine might be considered as TD treatment (Level C). Pallidal deep brain stimulation possibly improves TD and might be considered as a treatment for intractable TD (Level C). There is insufficient evidence to support or refute TS treatment by withdrawing causative agents or switching from typical to atypical DRBA (Level U).