Although "late", Chinese and American experts gathered in Chengdu to discuss the experience of diagnosis and treatment of adult tardive dyskinesia

The first Deuterium Tetrabenazine China-West International Summit Forum ended successfully, and we reviewed the wonderful content
together.

In the field of movement disorders, there is a common direction of neurology and psychiatry, that is, extrapyramidal diseases, in which hypotonia-hyperkinesthesia, with Huntington's disease (HD) and tardive dyskinesia (TD) as the main representative diseases
.

With the approval of deuterated tetrabenazine tablets (trade name: Titan), new treatments have been provided for adult HD-related chorea, adult patients with HD and TD at home and abroad, making it possible
to further improve their quality of life.
On October 29, 2022, the first Deuterium Tetraphenazine China and West International Summit Forum was successfully held in Chengdu, where many experts in psychiatry and neurology at home and abroad shared their experience in TD and HD treatment, opening up a smooth life for
more patients.
This article summarizes and organizes the main hot topics of this summit forum, collects the essence, and shares it with readers
.

Tardive dyskinesia should be identified and monitored early

TD is one of the hot topics of
this summit.
Experts from China and the United States gave wonderful speeches
on the impact of TD on patients, diagnosis, and standardized treatment.

As defined by DSM-5, TD is generally involuntary spasmodic or choreostatic movements of the tongue, lower face, jaw, and extremities (but sometimes muscles involving the pharynx, diaphragm, or trunk) that occur for at least several months after the use of neuroleptic drugs ^[1].

"Late-onset" in TD refers to delayed, especially if it is related to a disease with characteristic symptoms or signs of disease that appears late; And "dyskinesia" refers to a defect in voluntary motor capacity, or any disorder characterized by uncontrolled or involuntary movement ^[2].

The clinical feature of TD is mainly that patients have involuntary, rhythmic repetitive stereotyped movements, which are typically manifested as "mouth-tongue-cheek triad", that is, involuntary movements of the mouth, lips, tongue and face, such as involuntary tongue turning in the mouth, involuntary chewing, etc.
(can also be described by "oral and tongue chorea"); TD can also present with spastic torticollis, other forms of dystonia, tics, and tremors, involuntary limb swings, aimless tics, and torsional movements of the extremities ^{and trunk [3,4].}

TD can be identified and evaluated
clinically by using the Abnormal Involuntary Movement Scale (AIMS), an assessment tool.
AIMS evaluates the presence and severity of involuntary movements in seven major aspects of body, face and oral movement, limb movement and trunk movement, and includes three general criteria, each question is 0-4 points, the higher the score, the more severe the degree of involuntary movement (Figure 1).

Figure 1 AIMS scale

In addition, although the onset of TD is "late", participating experts pointed out that the evaluation of TD cannot be ignored, and should be paid attention to early, identified early, and regularly monitored for the occurrence
of TD during antipsychotic treatment.
This is reflected in several schizophrenia guidelines, such as:

• The second edition of China's 2015 schizophrenia prevention and treatment guidelines pointed out that in long-term treatment, TD and metabolic side effects have the greatest impact on the physical and mental health of patients, and these two side effects need to be continuously monitored, and once they occur, they should be dealt with as soon as possible ^[5].
  
  

• 2020 American Society of Health System Pharmacists (ASHP) Practice Guidelines: All adult schizophrenic patients receiving antipsychotic medications should be monitored for symptoms of dystonia, Parkinson's disease, akathisia, and TD, and evaluated for tardive dyskinesia at least annually ^[6].
  
  

From no drug available to drug available, deuterium tetrabenazine offers new hope for TD patients

The pathophysiology of TD has not been fully elucidated and may be related to DA receptor upregulation and hypersensitivity (Figure 2), abnormal γ-aminobutyric acid (GABA) neuronal function, and cholinergic dysfunction ^[7].

TD is generally considered difficult
.
Studies have shown that lowering or discontinuing antipsychotics has limited effect on relieving TD ^[8], and switching from first-generation antipsychotics to second-generation antipsychotics does not improve TD ^[9].

Fig.
2 Mechanism of postsynaptic dopamine receptor upregulation and hypersensitivity to TD

With the deepening of research and the continuous development of drugs, the treatment of TD has experienced the stage of no drug availability to drug finding, and deuterium tetrabenazine provides a new method
for the treatment of TD.
The 2013 American Academy of Neurological Disorders (AAN) guidelines do not have a Class A recommendation for TD ^[10].

The 2018 updated AAN guidelines state that novel selective vesicle monoamine transporter 2 (VMAT2) inhibitors deuterated tetrabenazine and valbenazine are recommended for the treatment of TD based on significant evidence (Class I) ^{support [11].}

The 2021 American Psychiatric Association (APA) guidelines for schizophrenia recommend (1B) that patients with schizophrenia who develop moderate to severe or disabling TD associated with antipsychotic therapy should be treated
with a VMAT2 reversible inhibitor.
In patients with moderate to severe or disabling TD associated with antipsychotic therapy, VMAT2 inhibitors significantly reduce movement signs and symptoms
of dyskinesia.
These drugs may also be effective against other late-onset ^{syndromes [12].}

Clinical trials of deuterated tetrabenazine have been reported
abroad.
Results of ARM-TD studies (Figure 3) showed that deuterated tetrabenazine significantly reduced AIMS scores for 12 weeks in patients with moderate to severe TD and was well tolerated ^[13].

The AIM-TD study (Figure 4) showed that deuterated tetrabenzazine 24 mg/day and 36 mg/day significantly reduced involuntary activity levels in patients with TD with good safety and tolerability ^[14].

In addition, a study published in 2019 showed that deuterated tetrabenazine reduced AIMS scores at 80 weeks and had a good safety profile (Figure 5) ^[15].

Figure 3 Primary endpoint of the ARM-TD study [13].

Figure 4 Primary endpoint of the AIM-TD study [14].

Fig.
5 Deuterated tetrabenazine can reduce AIMS score after 80 weeks of treatment and has a good safety profile [15].

Based on evidence-based medical evidence, in April 2017, the US FDA approved deuterium tetrabenazine tablets for marketing
.
China continues to pay attention to deuterium tetrabenazine tablets, and in May 2020, it approved the marketing of deuterated tetrabenazine tablets for the treatment of HD-related chorea, as well as TD in adult patients, becoming the second country
to approve the marketing of deuterated tetrabenazine tablets.

The big coffee said, concentrated

At the summit forum, the discussion session of the big coffee pushed the whole meeting to a climax
.
Experts from home and abroad gathered together to discuss
hot topics related to TD and HD.
The panelists emphasized:

(1) Under the background of the current normalization of the COVID-19 epidemic, in view of the difficulty of patients seeking medical treatment offline, HD/TD patients can be managed daily through
online appointment video diagnosis and treatment, high-resolution video condition assessment, etc.

(2) Clinicians should pay more attention to TD, pay attention to early identification of TD, and be proficient in TD assessment tools, early diagnosis and timely use of deuterated tetrabenazine, reduce or stop anti-acetylcholine drugs, which will help patients benefit and promote the improvement
of the overall function of TD patients.

(3) Even the same disease has different manifestations in different systems in the clinic, so the differential diagnosis and treatment of diseases require multidisciplinary collaboration
.
The multidisciplinary diagnosis and treatment model will effectively avoid the situation of "blind people touching elephants" and bring benefits
to HD and TD patients.

(4) According to evidence-based medical recommendations, deuterium tetrabenazine can help improve the symptoms of HD and TD patients, and will comprehensively consider the patient's disease characteristics, socioeconomic factors and other aspects in clinical application, and require doctors and patients to make joint decisions
.

(5) It is necessary to pay attention to patient education, guide patients to have reasonable expectations for disease treatment, communicate with patients and families in detail about the onset time of drugs, encourage patients and their families to adhere to treatment, and improve treatment compliance
.

As a delayed disease, TD is easy to be ignored by doctors and patients, which not only affects patients' treatment compliance, but also affects patients' daily life and social functions
.
The Summit reminded us that TD should be closely monitored throughout the management of the disease, and the use of relevant scales can help detect TD
early.
The emergence of deuterated tetrabenazine has further improved the dilemma of TD patients without a drug, and early application of deuterated tetrabenazine will contribute to the long-term benefit
of TD patients.

[1] Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

[2] Taber’s Online Medical Dictionary.
Accessed April 7, 2020.

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)

[4] GUAN Xiaobo,LU Zheng,WANG Yuhui.
World Journal of Clinical Drugs,2012,33(10):595-598+603.

[5] Psychiatry Branch of Chinese Medical Association.
Guidelines for the prevention and treatment of schizophrenia, second edition.

[6] Noel JM,et al.
Am J Health Syst Pharm.
2020; 77(24):2114-2132.

Sun Zhenxiao,Sun Yuxin,Yu Xiangfen[J].
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)

[8] Mentzel CL, Bakker PR, van Os J,et al.
J Clin Psychiatry.
2017 Mar; 78(3):e279-e285.

[9] Bhidayasiri R, Jitkritsadakul O, Friedman JH, et al.
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[10] Bhidayasiri R, Fahn S, Weiner WJ, et al.
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[11] Bhidayasiri R, Jitkritsadakul O, Friedman JH, et al.
J Neurol Sci.
2018 Jun 15; 389:67-75.

[12] Keepers GA, Fochtmann LJ, Anzia JM, et al.
3rd ed.
American Psychiatric Association Publishing; 2021.

[13] Fernandez HH, Factor SA, Hauser RA,et al.
.
Neurology.
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[14] Anderson KE, Stamler D, Davis MD, et al.
2017 Aug; 4(8):595-604.

[15] Fernandez HH, Stamler D, Davis MD,et al.
J Neurol Neurosurg Psychiatry.
2019 Dec; 90(12):1317-1323.

*This article is for scientific information provided only to healthcare professionals and does not represent the views of the platform