Adequately Addressing Tardive Dyskinesia: Clinical Tips and Insights

The use of antipsychotic medications is increasing in Western countries, primarily related to increased nonpsychotic indications and some off-label use.^1-3 There are concerns that clinicians underestimate the risk of potential adverse effects associated with second-generation antipsychotics (SGAs).^4,5 Despite a general perception that SGAs are safer than those in the first generation, data suggest that along with the nearly doubling of use of SGAs, there has been a doubling in the rates of antipsychotic overdoses, with the same level of consequent morbidity and mortality.¹

One of the most troubling adverse effects of antipsychotic medications is tardive dyskinesia (TD). TD is a severe and frequently permanent movement disorder that occurs as a consequence of chronic use of dopamine-blocking agents, which include some antipsychotics and some antiemetics. Concerns over the induction of TD were the main driver of clinicians’ switch from first-generation antipsychotic (FGA) to SGA medications.⁶ Indeed, in a meta-analysis of 57 head-to-head randomized controlled trials, the annualized incidence of TD with SGAs was less than half that with FGAs (2.6%; 95% CI, 2.0%-3.1% vs 6.5%; 95% CI, 5.3%-7.8%; RR = 0.47; 95% CI, 0.39-0.57; P < .0001).⁷ However, TD risk is associated with upregulation of the dopaminergic pathways, and that is related to the extent of blockade of the D2 receptors,⁸ so it is not surprising that the risk of developing TD increases in a dose-dependent manner independent of whether the drug was an FGA or SGA.⁹ This is related to the fact that an increased dose is generally associated with increased D2 receptor occupancy, and if receptor occupancy of a D2 antagonist exceeds 80%, there is a significant increase in parkinsonism and eventual TD.¹⁰

Editor's Note: An updated version of this article will be available shortly.

Dr El-Mallakh is a professor in the Department of Psychiatry and Behavioral Sciences and director of the Mood Disorders Research Program at the University of Louisville School of Medicine in Kentucky.

Ms Woods is a nurse practitioner practicing medicine in Louisville, Kentucky.

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