Epidemiology of Tardive Dyskinesia Implicates Both "Atypical" and Neuroleptic Antipsychotics

AUGUST 09, 2018
Kenneth Bender, PharmD, MA
Anelyssa D'Abreu, MD, PhDAnelyssa D'Abreu, MD, PhDU
Updated 8/9/2018 at 12:45 PM EST.

A recent review of tardive dyskinesia (TD) epidemiology found that the incidence of this often-intractable condition is similar between first- and second-generation antipsychotic drugs (APDs), despite the newer agents having been termed "atypical" for fewer extrapyramidal side effects (EPS) and presumably less liable for TD than older neuroleptics.

For the review, Anelyssa D'Abreu, MD, PhD, co-director, Movement Disorders Program, Rhode Island Hospital and associate professor, The Warren Albert Medical School, Brown University, Providence, Rhode Island, and colleagues marked publications from the early 2000's as the last which attributed a substantially lower incidence of TD to the atypical agents.  They note that 1 recent meta-analysis of 41 studies between 2000 and 2015 comparing typical versus atypical APDs demonstrated an estimated weighted mean prevalence of 25.3% across all treatment groups

"It was hoped that the 'atypical' APDs, or second-generation APDs, would minimize this complication," D'Abreu and colleagues wrote.  "However, later publications failed to confirm these findings."

In addition to a 2.5-year study in patients treated with typical versus atypical APDs in an outpatient psychiatric cohort, the reviewers cite large, prospective studies from the United Kingdom (CUtLASS) and the United States (CATIE) which failed to show that the newer agents reduced the incidence of TD.

The unexpected finding in the CATIE trial was "stunning," according to D'Abreu and colleagues, given that it had been designed and executed on the widely held assumption that second-generation antipsychotics are associated with less TD than first-generation drugs.

Instead, the results of the CATIE trial demonstrated that there was no difference in the incidence of TD between the APDs, "leading to a flurry of papers attempting to understand what went wrong, rather than believing that there were, in fact, no major differences," D'Abreu and colleagues indicated. "The jury is still out," they added.

In 1 of the analyses of movement disorder data from the CATIE trial, Stanley Caroff, MD, professor, department of psychiatry, The Veterans Affairs Medical Center, and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, and colleagues considered that even EPS rates might be comparable between first- and second-generation APDs if lower-potency first-generation drugs were modestly dosed.

"The dichotomy between first- and second-generation drugs may be oversimplified," Caroff and colleagues suggested, "and antipsychotics could be conceptualized as a single drug class with a spectrum of risk for movement disorders depending upon receptor binding affinities and individual patient susceptibility."

The notable exception is clozapine. This first agent of the atypical group remains the only APD substantially devoid of movement disorder effects, albeit it does have hematologic complications that necessitate prescribing restrictions and particular monitoring procedures. Interestingly, although incidents of TD with clozapine have been reported, D'Abreu and colleagues attribute them to the propensity of the disorder to manifest after discontinuing the causative APD (such as those likely to have been used before switching to clozapine).

The "unmasking" of TD when the causative agent is discontinued is one of the factors confounding a clear epidemiology, the reviewers indicate. An additional confounding factor is that patients often need to continue taking the causative APD, as strategies of drug “holiday" or dose reduction have not been shown to either sustain efficacy or reduce the risk of TD.

"TD remains a major challenge and impediment for the treatment of psychotic disorders," D'Abreu and colleagues conclude.

The review, Tardive dyskinesia: Epidemiology, was published in the June issue of the Journal of Neurological Sciences.

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