patient care perspectives

Prevalence Rates of Tardive Dyskinesia With Second-Generation Antipsychotics

by Leslie Citrome, MD, MPH

Overview

The risk of tardive dyskinesia (TD) from second-generation antipsychotics appears to be lower than with first-generation agents, but the full cumulative exposure risk of TD from second-generation agents remains to be defined. Routine TD screening is highly encouraged for all patients who receive dopamine receptor–blocking medications.

Expert Commentary

Leslie Citrome, MD, MPH

Clinical Professor
Department of Psychiatry and Behavioral Sciences
New York Medical College
Valhalla, NY

“When second-generation antipsychotics became available, the hope was that we had done away with drug-induced parkinsonism and, possibly, TD. We believed that we had potentially solved the TD problem with these agents, but that was proven to be untrue.”

Leslie Citrome, MD, MPH

Pharmacoepidemiologic studies have demonstrated that the prevalence of TD is approximately 30% in patients receiving first-generation antipsychotic agents and 20% in patients receiving second-generation agents who may also have previously been on first-generation agents. When second-generation antipsychotics became available, the hope was that we had done away with drug-induced parkinsonism and, possibly, TD. We believed that we had potentially solved the TD problem with these agents, but that was proven to be untrue.

The rate of TD among patients who have only been on second-generation antipsychotics is not zero and has been estimated to be approximately 7%. Moreover, this lower rate may be misleading. If we consider those who have only been exposed to second-generation antipsychotics and have not used first-generation agents, many are relatively young and have been on treatment for relatively briefer periods of time compared with previous cohorts on first-generation medications. We do not yet have second-generation–only exposed patients who have been on treatment for 30 years or longer and are now advanced in age. Therefore, we do not yet really know the cumulative exposure–associated risk of second-generation agents on TD. In my view, 7% is likely an underestimate of what we will eventually see.

Cumulative exposure to dopamine receptor–blocking agents and advanced age are among the strongest risk factors for TD. As one gets older, the risk of developing TD is higher. If a patient begins treatment with an antipsychotic at 60 years of age, their risk of developing TD would be much higher than that of a 20-year-old person who is initiating the same treatment. It will be interesting to know the true prevalence of TD in people who have only been on second-generation agents and have been on them for 30 years or longer.

Anyone on a dopamine receptor–blocking agent must be regularly screened for TD. Guidelines have suggested that the less-frequent use of formal, structured assessments such as the Abnormal Involuntary Movement Scale might, perhaps, be appropriate for those patients on second-generation agents who have no other risk factors for TD, such as advanced age or a history of movement disorders. However, these assessments must still be done.

References

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed, text revision. American Psychiatric Association; 2022.

Carbon M, Hsieh C-H, Kane JM, Correll CU. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. J Clin Psychiatry. 2017;78(3):e264-e278. doi:10.4088/JCP.16r10832

Caroff SN, Yeomans K, Lenderking WR, et al. RE-KINECT: a prospective study of the presence and healthcare burden of tardive dyskinesia in clinical practice settings. J Clin Psychopharmacol. 2020;40(3):259-268. doi:10.1097/JCP.0000000000001201

Correll CU, Leucht S, Kane JM. Lower risk for tardive dyskinesia associated with second generation antipsychotics: a systematic review of 1-year studies. Am J Psychiatry. 2004;161(3):414-425. doi:10.1176/appi.ajp.161.3.414

Donohue J, O'Malley AJ, Horvitz-Lennon M, Taub AL, Berndt E, Huskamp H. Changes in physician antipsychotic prescribing preferences, 2002-2007. Psychiatr Serv. 2014;65(3):315-322. doi:10.1176/appi.ps.201200536

Huskamp HA, O'Malley AJ, Horvitz-Lennon M, Taub AL, Berndt ER, Donohue JM. How quickly do physicians adopt new drugs? The case of second-generation antipsychotics. Psychiatr Serv. 2013;64(4):324-330. doi:10.1176/appi.ps.201200186

Jain R, Correll CU. Tardive dyskinesia: recognition, patient assessment, and differential diagnosis. J Clin Psychiatry. 2018;79(2):nu17034ah1c. doi:10.4088/JCP.nu17034ah1c

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