New Insights into Tardive Dyskinesia: Pathophysiology, Treatment Recommendations, and Focus on Prevention

Researchers of a study looked at the current knowledge regarding the pathophysiology of tardive dyskinesia (TD) to provide recommendations for prevention and treatment based on a literature search and a roundtable discussion with psychiatrists in Japan.

Most guidelines recommend managing TD by reducing antipsychotic doses, switching to clozapine or other second-generation antipsychotics with a lower association with TD, as well as focusing on prevention and monitoring when prescribing antipsychotics. TD is often irreversible, emphasizing the importance of cautious antipsychotic use at the lowest effective dose and frequent monitoring for TD symptoms. Another promising option is the use of vesicular monoamine transporter 2 (VMAT-2) inhibitors, which interfere with dopamine uptake and storage, counteracting the increased dopaminergic activity associated with prolonged antipsychotic use.

Study Shows Deutetrabenazine’s Significant Impact on TD Symptoms: Reduction in Motor AIMS Score Linked to Clinically Meaningful Improvement

A recent study analyzed the minimal clinically important change (MCIC) in total motor Abnormal Involuntary Movement Scale (AIMS) score in patients with tardive dyskinesia (TD) treated with deutetrabenazine. Deutetrabenazine is an approved medication for TD. The study included 295 patients, with 197 receiving deutetrabenazine and 98 receiving a placebo. The analysis found that the MCIC in deutetrabenazine-treated patients was approximately -2.4 based on the Patient Global Impression of Change (PGIC) and -2.1 based on the Clinical Global Impression of Change (CGIC). In comparison, the MCIC for placebo-treated patients was -1.4 based on the PGIC and -1.5 based on the CGIC. Additionally, a significant proportion of deutetrabenazine-treated patients showed improvement in total motor AIMS score by at least 2 and 3 points. These findings suggest that a reduction in total motor AIMS score of approximately 2 is associated with clinically meaningful improvement in TD symptoms when treated with deutetrabenazine.

Authors Review Impact of Calcium Channel Blockers on Antipsychotic-Induced Tardive Dyskinesia

Authors of a review looked to study the impact of calcium channel blocker therapies (diltiazem, nifedipine, nimodipine, verapamil) in treating patients with neuroleptic-induced tardive dyskinesia (TD) and chronic mental illnesses including schizophrenia and schizoaffective disorder. Researchers used the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017) to gather information for their research. There were no trials included in prior versions of this review. In their 2015 review, there were three cross-over trials that were included by the researchers, but no new relevant studies in the 2017 review. A total of 47 patients were included in the study from the included trials who had chronic mental illness from both the United States and China. Authors did note that, due to the low availability of evidence, no conclusions could be made on the impact of calcium channel blockers in antipsychotic-induced TD.

Clinical Efficacy of the Use or Withdrawal of Anticholinergic Drugs in Tardive Dyskinesia

This study analyzes data regarding the use and withdrawal of anticholinergic drugs (benzhexol, benztropine, biperiden, orphenadrine, procyclidine, scopolamine, or trihexyphenidyl) for the treatment of patients with tardive dyskinesia (TD; among other movement disorders). Researchers sought to determine if the use or removal of these drugs showed clinical effectiveness in treating those with antipsychotic-induced TD. It was determined that further studies are needed on the benefits of both the use and withdrawal of anticholinergic drugs for this population.

Insights on Treating Tardive Dyskinesia Using Telehealth

A panel of six neurologists, three psychiatrists, and three psychiatric nurse practitioners participated in a study to outline a framework to address the use of telehealth to treat tardive dyskinesia. The panel found telehealth to be beneficial primarily for the ease of making and attending appointments for patients but agreed that an in-person assessment should be held at least every six months from telehealth appointments. Additional recommendations are discussed. 

Assessing Minimal Clinically Important Change in Abnormal Involuntary Movement Scale Score in Patients With TD Treated With Deutetrabenazine

Researchers sought to examine the minimal clinically important change (MCIC) in total motor Abnormal Involuntary Movement Scale (AIMS) score in patients with tardive dyskinesia (TD) who were treated with deutetrabenazine. Patients in the pooled analysis population consisted of those who were administered the study drug and had at least 1 postbaseline AIMS evaluation in both the ARM-TD and AIM-TD placebo-controlled studies. The US Food and Drug Administration approval of deutetrabenazine was based on these 2 studies.

Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change (CGIC) were used to conduct MCIC analyses. In the analysis, 295 patients were included (deutetrabenazine, n = 197; placebo, n = 98).  MCIC in patients who were treated with deutetrabenazine was -2.4 based on PGIC and -2.1 based on CGIC at Week 12. In patients who were treated with placebo rated minimally improved, mean change in baseline in total motor AIMS score was -1.4 based on PGIC and -1.5 based on CGIC. It was seen that from baseline to Week 12, about 66% and 55% of patients who were given deutetrabenazine achieved an improvement in total motor AIMS score by ≥2 and ≥3 points, respectively. Approximately 41% and 34% of patients in the placebo group saw improvement in total motor AIMS score by ≥2 and ≥3 points, respectively. From utilizing anchor-based methodology, researchers concluded that a decline in total motor AIMS score of approximately 2 is linked to clinically meaningful improvement in symptoms of TD.

The Complex Spectrum of Tardive Dyskinesia

In a continuing medical education program presented at Psych Congress Regionals 2021, faculty presented on a wide range of topics in tardive dyskinesia (TD). The goals of the presentation were to describe the effect of TD on patient outcomes, barriers to care, and note the prevalence of TD in those who are taking antipsychotic medication. In addition to this, faculty reviewed updated recommendations and screening strategies for better recognition of TD as well as guideline recommendations outlining treatment and best practices.

Treating Tardive Dyskinesia

A meta-analysis showed that approximately 1 in 4 patients who have been on a second-generation antipsychotic after 10 years will develop tardive dyskinesia (TD), while the rate of those on first-generation antipsychotics is 1 in 2. The 2 greatest risk factors for TD are the duration and dose of treatment. Two FDA-approved treatments for TD are VMAT2 inhibitors deutetrabenazine and valbenazine. When using one of these therapies to treat TD, it will likely need to be put in place for the duration that the antipsychotic is being used, or else the TD may come back within a month of discontinuation.