Tardive Dyskinesia: Therapeutic Options for an Increasingly Common Disorder

Abstract

Tardive dyskinesia (TD) is a serious, often disabling, movement disorder that is caused by medications that block dopamine receptors (i.e., neuroleptics, anti-emetics). There is currently no standard treatment approach for physicians confronted with such patients. This may be the result of notions that TD is disappearing because of the switch to secondgeneration antipsychotic agents and that it is largely reversible.In this article we demonstrate that second-generation antipsychotics do, indeed, cause TD and, in fact, the frequency is likely higher than expected because of growing off-label uses and a tripling of prescriptions written in the last 10 years. In addition, studies demonstrate that TD actually remits in only a minority of patients when these drugs are withdrawn. Furthermore, neuroleptic agents are often utilized to treat TD, despite prolonged exposure being a risk factor for irreversibility. The outcome of these trends is a growing population afflicted with TD. We review non-neuroleptic agents that have shown positive results in small, early-phase, blinded trials, including tetrabenazine, amantadine, levetiracetam, piracetam, clonazepam, propranolol, vitamin B6, and Ginkgo biloba. Other options, such as botulinum toxin and deep brain stimulation, will also be discussed, and a suggested treatment algorithm is provided. While these agents are reasonable treatment options at this time there is a need, with a concerted effort between neurology and psychiatry, for full-scale drug development, including multicenter, randomized, blinded trials to confirm the effectiveness of the agents that were positive in phase 2 trials and the development of newer ones.

The Effects of Valbenazine in Participants with Tardive Dyskinesia

“…[1][2][3] Evidence suggests that DRBAs up-regulate postsynaptic dopamine receptors, resulting in hypersensitivity and increased dopamine signaling, which in turn, leads to TD. 4 Other pathogenetic hypotheses include GABAergic neuron dysfunction, synaptic plasticity dysfunction, or neurotransmitter system degeneration, which may also contribute to TD by altering basal ganglia pathways or neurons.…”

Antipsychotikainduzierte tardive Syndrome

“…Eine Übersicht zur Pathophysiologie tardiver Syndrome findet sich in dem rezenten Review von Cloud et al [37].…”

“…Bei diesen Patienten wird eine Umstellung der antipsychotischen Therapie auf eine Substanz mit geringerem Risiko für TD oder die symptomatische medikamentöse Therapie der TD empfohlen. In Reviews wird häufig die Umstellung auf Clozapin oder Quetiapin empfohlen [37,49].…”

Editorial: Neurotherapeutics of Movement Disorders

“…The key role of education, support services, and cognitive behavioral therapy are also highlighted. Cloud et al [15] take on the topic of tardive dyskinesia with a comprehensive look at clinical features and pathophysiological mechanisms. A key issue is the rising prevalence rates of this disabling iatrogenic condition because of the increase in the number of antipsychotic prescriptions.…”

“…A key issue is the rising prevalence rates of this disabling iatrogenic condition because of the increase in the number of antipsychotic prescriptions. While no phase III trials have been completed, Cloud et al [15] present data on therapy with a focus on those drugs with evidence from phase II double-blind trials, such as tetrabenazine, amantadine, levetiracetam, clonazepam, and gingko biloba. Comella [16] presents the current status of restless leg syndrome and the evidence for dopaminergic agents and the alpha-2-delta ligands, as well as other older medications, such as opiates and benzodiazepines.…”