A new era in the diagnosis and treatment of tardive dyskinesia

Abstract

Tardive dyskinesia (TD) is a heterogeneous, hyperkinetic movement disorder induced by dopamine-receptor blocking agents that presents a unique challenge in the treatment of psychosis. Although acceptance of TD as a serious consequence of antipsychotic treatment was resisted initially, subsequent research by many investigators in psychopharmacology contributed to a rich store of knowledge on many aspects of the disorder. While basic neuroscience investigations continue to deepen our understanding of underlying motor circuitry, past trials of potential treatments of TD focusing on a range of theoretical targets were often inconclusive. Development of newer antipsychotics promised to reduce the risk of TD compared to older drugs, but their improved tolerability unexpectedly enabled an expanding market that paradoxically both increased the absolute number of patients at risk and diminished attention to TD which was relegated to legacy status. Fortunately, development and approval of novel vesicular monoamine transporter inhibitors offered evidence-based symptomatic treatment of TD for the first time and rekindled interest in the disorder. Despite recent progress, many questions remain for future research including the mechanisms underlying TD, genetic predisposition, phenomenological diversity, whether new cases are reversible, how to implement best practices to prevent and treat TD, and whether the development of novel antipsychotics free of the risk of TD is attainable. We owe our patients the aspirational goal of striving for zero prevalence of persistent symptoms of TD in anyone treated for psychosis.

Putative role of immune reactions in the mechanism of tardive dyskinesia

“…These forms are also called orofacial and limb-truncal TD. For a more detailed description of the clinical manifestations, reference is made here to some of the numerous review articles ( Van Harten and Tenback, 2011 ; Waln and Jankovic, 2013 ; Savitt and Jankovic, 2018 ; Hirjak et al, 2019 ; Caroff, 2022 ). In respiratory TD, the respiratory muscles and diaphragm are dyskinetic ( Yassa and Lal, 1986 ; Rich and Radwany, 1994 ; Kruk et al, 1995 ; Vorre and Lange, 2019 ).…”

“…It does deserve mention that a large-scale randomized pragmatic study found no significant differences between the classic perphenazine and the second-generation agents studied ( Caroff et al, 2011 ). Some uncertainty exists about having greater susceptibility to motor side effects as a risk factor for getting and having TD ( Kane and Smith, 1982 ; Miller et al, 2005 ; Solmi et al, 2018 ), in part because it may also be related to hereditary pharmacokinetic or other effect-determining factors ( Loonen et al, 2019 ; Caroff, 2022 ). A consistently found risk factor is advanced age ( Miller et al, 2005 ; Carbon et al, 2017 ; O'Brien, 2016 ; Caroff, 2022 ).…”

“…Extrapyramidal disorders include Parkinson's disease and Huntington's disease, but they are also a well-known side effects of drugs used to treat mental illness. The classical antipsychotics in particular are known for it, but the second generation drugs of this pharmacotherapeutic group, contrary to everyone's initial hopes, are certainly not free of these so-called extrapyramidal side effects (EPS) ( Correll and Schenk, 2008 ; Van Harten and Tenback, 2011 ; O'Brien, 2016 ; D'Abreu et al, 2018 ; Caroff, 2022 ). This article will focus on tardive dyskinesia, which is characterized by abrupt, irregular and uneven muscle contractions, of which the patient is often unaware.…”

“…This article will focus on tardive dyskinesia, which is characterized by abrupt, irregular and uneven muscle contractions, of which the patient is often unaware. It typically takes several months to various years for the symptoms to appear, they are usually less prominent after increasing the dosage and become more severe when abstaining from taking the drug ( Kane and Smith, 1982 ; Caroff, 2022 ). These aspects must be taken into account when searching for a pharmacological mechanism for the onset of TD.…”

Neurological Perspectives Should Be Integrated Into the Management of Tardive Dyskinesia—Expert Opinions and Proposed Educational Initiatives in Asia

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227Tardive dyskinesia(TD) is a movement disorder that exhibits a range of clinical manifestations arising as side effects of treatment with dopamine receptor-blocking agents, primarily antipsychotic drugs (APDs) [1,2].Consequently,its management overlaps different disciplines, in particular, psychiatry and neurology.In practice, this canresult ina gap in management whereby patients receive only one aspect of what should ideally bemultidisciplinarycare. Psychiatrists will naturally focus on controllingthe patient'schallenging psychotic symptomsand may not be specialized in the evaluation of the abnormal movements that are a core manifestation of TD [3,4].As a result, exposure of neurologists to TD patients may be limited to when the condition has becomesevere.

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