There’s an irony to the etiology of tardive dyskinesia (TD), as it’s a condition that results from antipsychotic medications used to treat schizophrenia.

Although there’s controversy regarding TD’s diagnosis and definitions, there are FDA-approved treatments for it. According to research, the best treatments are preventive; physicians should prescribe minimal effective doses of antipsychotic medications only when needed.

 

TD prevalence

TD is a persistent, debilitating condition typified by chorea, athetosis, and or dystonia. According to an article published in Movement Disorders, chorea is characterized by random-appearing involuntary movements or movement fragments; athetosis is slow, involuntary, continuous writhing movements; and dystonia is defined as muscle contractions that cause repetitive and twisting movement and/or abnormal postures.

Sanger TD, Chen D, Fehlings DL, et al. Definition and classification of hyperkinetic movements in childhood. Mov Disord. 2010; 25(11): 1538–1549.

Although most common in patients with schizophrenia, these conditions can occur in anybody taking antipsychotic medications.

 

TD first appeared in literature in 1957. Even though there have been clinical advances in the treatment of TD, its pathophysiology and prognosis are not fully understood. However, some experts debate the definitions of TD, considering it either a syndrome or a subset of tardive syndromes.

“A unique opportunity is thus presented by the enhanced focus on TD to resolve fundamental issues with regards to nomenclature and clinical criteria, thereby facilitating more sophisticated surveillance and genetic and epidemiological research into tardive movement disorders related to dopamine receptor blocking agents,” wrote the authors of a study published in the Journal of Neurological Studies.

Meyer JM. Future directions in tardive dyskinesia research. J Neurol Sci. 2018;389:76–80.

 

To further explain the disease’s pathogenesis, researchers publishing in Translational Psychiatry undertook the biggest genome-wide association study to date.

Lim K, Lam M, Zai C, et al. Genome wide study of tardive dyskinesia in schizophrenia. Transl Psychiatry. 2021;11(1):351.

They identified a novel locus and three suggestive loci that pointed to immune-related pathways playing a role. They found that single nucleotide polymorphisms contained in TNFRSF1B and CALCOCO increased TD risk in addition to age of onset and duration of schizophrenia illness.

 

The prevalence of TD in patients with schizophrenia ranges from 15% to 30%. Fortunately, the rate of TD has dropped with second-generation antipsychotics, but these newer medications still present risk.

TD is linked to more severe schizophrenia, decreased quality of life, cognitive impairments, and death. Although this condition subsides in some patients, a return to baseline can take years. For others, TD is a lifelong issue.

 

Treatments for TD

Experts suggest that the burden of TD can be particularly heavy for individuals who are highly functional and able to work. While effective treatments are needed for all TD patients, management in these patients in particular is imperative, as they are keenly aware of their movements and any associated disruption.

According to the treatment algorithm presented by Gregory Pontone, MD, MHS, of The Johns Hopkins University School of Medicine, the best approach to prevent or minimize TD symptoms is to use minimally effective doses of antipsychotics, with reduction of doses or discontinuation whenever possible.

Pontone G. Treating tardive dyskinesia: a clinical conundrum and new approaches. Psychopharmacology Institute. January 3, 2020.

 

First-line treatments include second-generation vesicular monoamine transporter 2 (VMAT2) inhibitors, which are also recommended by the American Psychiatric Association.

Vesicular monoamine transporter 2 (VMAT2) inhibitors. National Institute of Diabetes and Digestive and Kidney Diseases. Updated April 2, 2019.

Other potential treatments include clonazepam and ginkgo biloba.

 

The American Psychiatric Association advises that reversible VMAT2 inhibitors (eg, valbenazine, deutetrabenazine) should be used in moderate or severe TD cases. These agents may be helpful for patients with TD, and factors such as preference, degree of impairment, and effects on social functioning should be considered.

 

Patient perspectives

Given the pervasive aspects of TD, the condition warrants close consideration as to how it affects individuals.

A recent social media listening study was conducted in which information was obtained from social media posts to allow researchers to gain more insight than is typically available in clinical trials. The results identified that patients are indeed concerned with movements linked to TD.

Researchers found that TD-related anger and insecurity were among the most common emotions identified. Furthermore, it was identified that patients often feel unaccepted by society and fear being judged.