Tardive dyskinesia update: treatment and management

Abstract

SUMMARYThe development of rational treatments for tardive dyskinesia has been held back by limitations to our understanding of its aetiology, which even now does not extend far beyond its association with centrally acting dopamine-blocking drugs. This article reviews briefly the major aetiological theories and addresses general management and specific treatment options. Primary prevention and early recognition remain the crucial management issues because, once the condition is established, there are no satisfactory treatments. The article considers two newly developed drugs, valbenazine and deutetrabenazine, in some detail as, although they are not yet licensed in Europe, they have largely been responsible for an upsurge in interest in tardive dyskinesia in the North American literature and are likely to be widely promoted in the future. Although possessed of undoubted benefits, the evidence suggests that these represent small steps rather than large leaps forward in treatment.LEARNING OBJECTIVES•Be able to discuss the major aetiological theories on the causation of a common, and sometimes serious, adverse action of antidopaminergic drugs•Understand general management and specific treatment options•Understand the pharmacology and efficacy of two drugs recently approved by the FDA for the treatment of tardive dyskinesiaDECLARATION OF INTERESTD.C.O. is psychiatric commissioner on the Commission on Human Medicines, the UK drug regulator, and chair of its expert advisory group on CNS drugs. He is also a member of the psychiatry Scientific Advisory Group of the European Medicines Agency.

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

“…There is no satisfactory treatment for TD, emphasising the importance of primary prevention. Attempts to modify antipsychotic regimens may be tried, but any changes of type of medication (reducing potency) and/or dose should be undertaken very gradually, over weeks or months, to minimise the risk of withdrawal-emergent exacerbation of disorder which may not entirely resolve (Owens, 2019b). Support for the most advocated treatments springs from small, underpowered studies (Bergman et al, 2017) that, in addition, do not separate out movement types and/or distributions which may respond differentially, or allow for confounding by non-specific (e.g.…”

“…Good quality, independent studies conducted in the 1980s and 1990s reported a prevalence of 20% in younger populations with schizophrenia (Muscettola et al, 1993; Woerner et al, 1991), though this figure is inflated substantially (>50%) with the inclusion of mild abnormality (Owens, 2019b). An annual incidence of 5% was found (Chakos et al, 1996; Morgenstern and Glazer, 1993), which increases by some five to sixfold when first exposure is after middle life (Jeste et al, 1995).…”

“…In Europe, the VMAT2 inhibitor, tetrabenazine, has been approved for many years and should be considered in disabling disorder. It is, however, not an easy drug to use and can be associated with high rates of adverse effects (Owens, 2019b). Newer compounds which maintain the presynaptic depleting action but have enhanced tolerability (valbenazine and deutetrabenazine) are licensed in the USA (Anderson et al, 2017; Fernandez et al, 2017; Hauser et al, 2017), and are likely to become more widely available (Ricciardi et al, 2019).…”

“…There is no satisfactory treatment for TD, emphasising the importance of primary prevention. Attempts to modify antipsychotic regimens may be tried, but any changes of type of medication (reducing potency) and/or dose should be undertaken very gradually, over weeks or months, to minimise the risk of withdrawal-emergent exacerbation of disorder which may not entirely resolve (Owens, 2019b).…”

“…Support for the most advocated treatments springs from small, underpowered studies (Bergman et al, 2017) that, in addition, do not separate out movement types and/or distributions which may respond differentially, or allow for confounding by non-specific (e.g. sedation) effects (Owens, 2019b). Increasing antipsychotic dose may, at least temporarily, suppress disorder but should be restricted to specialist movement disorder settings.…”