After 7 months of approval, it quickly entered the medical insurance, deuterium tetrabenazine reshapes the new pattern of the treatment of tardive dyskinesia!

*Only for medical professionals to read for reference.
Deuterium tetrabenazine entered medical insurance in the year when it was approved in my country, providing Chinese patients with new and accessible therapeutic drugs.

In 2019, my country’s first "China Mental Health Survey" (CMHS) showed that the lifetime prevalence of mental disorders in my country is as high as 16.
6%, which means that 1 in 6 people suffer from mental disorders.
Among them, long-term medication is required.
The prevalence of schizophrenia and bipolar disorder accounted for more than 1% of the total [1], bringing a heavy social and economic burden to a large number of patients.

However, while taking medication to control the condition, the side effects of antipsychotic drugs may also bring new problems.
Among them, tardive dyskinesia (TD) is a more serious extrapyramidal reaction that may occur after taking antipsychotic drugs.
No effective drug for the treatment of TD has been approved for marketing in my country.

In May 2020, the National Medical Products Administration (NMPA) approved the marketing of the innovative deuterated drug deuterium tetrabenazine for the treatment of chorea related to Huntington’s disease and adult TD, breaking the problem of no medicine available for TD treatment.
In the same year, deuterium tetrabenazine was also included in the list of medical insurance drugs.
Its good efficacy and safety, as well as the significant increase in accessibility of treatment after being included in medical insurance, will make it a new and favored choice in the treatment of TD.

TD has a serious impact on patients, but patients who have been taking antipsychotic drugs for 1-2 years and above are more likely to develop TD, which is manifested by involuntary movements of mouth, lips, tongue and other parts, as well as dance-like movements of limbs and trunk.
And dystonia.

The specific pathogenesis of TD has not yet been elucidated, but TD in most patients is often irreversible and potentially disabling [2].

In patients with mental disorders who develop TD, the quality of life, social function and treatment compliance will be significantly affected [3], but the attention paid to TD in the diagnosis and treatment of mental disorders in my country is still insufficient.
For example, the prevalence analysis is only in 2009.
Studies have shown that the prevalence of TD in patients with schizophrenia is as high as 33.
7% [4], and there is still a lack of analysis of the prevalence of bipolar disorder and severe depression.

Previously, the traditional treatment strategy for TD was mainly to stop, switch or adjust the dose of antipsychotics, but this may lead to problems such as psychotic relapse, worsening of TD symptoms, and withdrawal reactions, and the symptoms of TD are being stopped and switched.
It may still exist after the drug.

In 2015, the second edition of my country's "Guidelines for the Prevention and Treatment of Schizophrenia" recommended that schizophrenia patients with TD should first switch to second-generation antipsychotic drugs with a low probability of triggering TD, and if necessary, use tetrabenazine tablets and other drugs.
.

It can be seen that the existing methods of TD treatment in my country have obvious limitations.
The clinical treatment needs of patients are far from being met.
A safe and efficient new therapy is needed to fill the gap.
The deuterium tetrabenazine approved in 2020 will fill the gap.
After this gap, this approval is only three years after the drug was approved by the US FDA.
The entire process can be said to be very rapid.

In the same year it was approved, it entered medical insurance.
Deuterium tetrabenazine achieved "two hands".
Deuterium tetrabenazine is a new type of vesicle monoamine transporter-2 (VM AT2) inhibitor drug, which is a kind of tetraphenylazine.
Modified form, replacing the two methoxy hydrogen atoms in the tetraphenylazine molecule with deuterium atoms.
This substitution can effectively reduce the rate of drug metabolism, double the half-life, and significantly improve the pharmacokinetic characteristics, thereby reducing drug delivery Frequency, while improving the efficacy, safety and tolerability of the drug [5].

Deuterium tetrabenazine was approved by the U.
S.
FDA in April 2017.
It is the world's first approved deuterium drug.
Since then, it has also been approved for marketing by my country's NMPA according to the priority review procedure.
It is the first and currently the only approved drug in China.
The ability of deuterated drugs to "pass quickly" all the way is obviously related to the excellent mechanism of action of deuterated tetrabenazine and the urgency of filling clinical needs. In the 2020 medical insurance negotiations, deuterium tetrabenazine is one of the 6 rare disease drugs officially included in the "National Basic Medical Insurance, Work Injury Insurance and Maternity Insurance Drug List" (indications for chorea related to Huntington).
The treatment of adult TD indications has also been included in the medical insurance, and the corresponding price reduction policy has been officially implemented on March 1 this year, which greatly improves the accessibility of treatment and reduces the economic burden of patients.

Large-scale clinical studies have shown long-lasting and good efficacy.
Deuterium tetrabenazine is highly recommended by foreign guidelines.
Based on two randomized controlled, multi-center clinical phase III studies of ARM-TD and AIM-TD, the efficacy of deuterium tetrabenazine in the treatment of TD has been established.
Among them, the ARM-TD study is a placebo-controlled flexible dose trial involving 117 patients with moderate to severe TD.
The treatment dose of deuterium tetrabenazine group starts from 12 mg per day and increases by 6 mg every 1 week until TD is satisfactorily controlled.
, There are intolerable side effects or the maximum dose of 48 mg per day is reached, and the optimal therapeutic dose is titrated within 6 weeks.
The main research endpoint is the change in the patient's abnormal involuntary movement scale (AIMS) score from baseline to week 12.

The results of the study showed that at the 12th week of treatment, the AIMS score of the deuterium tetrabenazine treatment group was improved by 3.
0 compared with the baseline, which was significantly better than the placebo group (AIMS score improvement 1.
6, p = 0.
019), secondary endpoint The treatment success rate of the deuterium tetrabenazine group according to the General Clinical Efficacy Rating Scale (CGIC) or the Patient Overall Impression Change Scale (PGIC) also showed an advantage over the placebo group (CGIC: 48.
2% vs 40.
4%, PGIC ：42.
9% vs 29.
8%), but there is no significant difference.
The incidence of adverse reactions worthy of special attention (AESI) in the two groups is relatively low [6].

Figure 1: Trends in the average AIMS scores of the placebo group and the deuterated tetrabenazine treatment group.
The AIM-TD study is a placebo-controlled fixed-dose trial involving 298 adult TD patients at a ratio of 1:1:1:1 Groups receive 12mg/24mg/36mg deuterium tetrabenazine or placebo treatment.
Deuterium tetrabenazine also adopts a therapeutic dose escalation method.
The main efficacy endpoint is also the change in the patient's AIMS score from baseline to week 12.
A total of 222 patients were included in the intention-to-treat population for the main efficacy analysis. The results of the study showed that in the 12th week of treatment, the AIMS scores of the 24mg/36mg deuterium tetrabenazine treatment group were improved by 3.
2 and 3.
3 respectively compared with the baseline period, which was significantly better than that of the placebo group (AIMS score improvement was 1.
4, P = 0.
003/0.
001 ), the proportion of patients in the deuterium tetrabenazine 24mg/36mg treatment group whose AIMS score increased by more than 50% was 35% and 33%, respectively, which were also significantly better than 12% of the placebo group; the deuterium tetrabenazine 24mg/36mg group was based on The treatment success rates assessed by CGIC were 49% and 44%, which were significantly better than the 26% of the placebo group (P=0.
014/0.
059).

The safety of deuterium tetrabenazine treatment in the study is good.
The adverse event rates of the 12mg/24mg/36mg treatment group were 49%, 44%, and 51%, which were similar to the placebo group (47%); there were no serious fatal adverse reactions.
Common adverse reactions include drowsiness, vomiting, inability to sit still, etc.
, which are easy to handle [7].

Figure 2: Changes in AIMS scores and response rates of different groups in the AIM-TD study.
Based on the efficacy and safety of the above studies, the 2018 American Academy of Neurology (AAN) TD diagnosis and treatment guidelines update [8], the 2019 edition of Canadian TD treatment recommendations [9] The 2020 American Psychiatric Association (APA) Schizophrenia Diagnosis and Treatment Guidelines [10] all recommend that new VMAT-2 inhibitors such as deuterium tetrabenazine should be used as the first-line treatment of TD.

my country currently does not have specific guidelines for the diagnosis and treatment of TD, but deuterium tetrabenazine is approved and entered into medical insurance, which will also strongly promote its widespread use in TD clinical diagnosis and treatment.

References: [1]Huang Y, Wang YU, Wang H, et al.
Prevalence of mental disorders in China: a cross-sectional epidemiological study[J].
The Lancet Psychiatry, 2019, 6(3): 211-224.
[2]Zutshi D, Cloud LJ, Factor S A.
Tardive syndromes are rarely reversible after discontinuing dopamine receptor blocking agents: experience from a university-based movement disorder clinic[J].
Tremor and Other Hyperkinetic Movements, 2014, 4.
[3 ]McEvoy J, Gandhi SK, Rizio AA, et al.
Effect of tardive dyskinesia on quality of life in patients with bipolar disorder, major depressive disorder, and schizophrenia[J].
Quality of Life Research, 2019, 28(12): 3303 -3312.
[4]Zhang XY, Qi LY, Wang F, et al.
Gender differences in the prevalence, risk and clinical correlates of tardive dyskinesia in Chinese schizophrenia[J].
Psychopharmacology, 2009, 205(4): 647-654 .
[5]Stahl S M.
Comparing pharmacologic mechanism of action for the vesicular monoamine transporter 2 (VMAT2) inhibitors valbenazine and deutetrabenazine in treating tardive dyskinesia: does one have advantages over the other?[J].
CNS Spectrums, 2018, 23(4): 239-247.
[ 6]Fernandez HH, Factor SA, Hauser RA, et al.
Randomized controlled trial of deutetrabenazine for tardive dyskinesia: the ARM-TD study[J].
Neurology, 2017, 88(21): 2003-2010.
[7]Anderson KE , Stamler D, Davis MD, et al.
Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial[J].
The Lancet Psychiatry, 2017 , 4(8): 595-604.
[8]Bhidayasiri R, Jitkritsadakul O, Friedman JH, et al.
Updating the recommendations for treatment of tardive syndromes:a systematic review of new evidence and practical treatment algorithm[J].
Journal of The Neurological Sciences, 2018, 389: 67-75.
[9]Ricciardi L, Pringsheim T, Barnes TRE, et al.
Treatment recommendations for tardive dyskinesia[J ].
The Canadian Journal of Psychiatry, 2019, 64(6): 388-399.
[10]Keepers GA, Fochtmann LJ, Anzia JM, et al.
The American psychiatric association practice guideline for the treatment of patients with schizophrenia[J] .
American Journal of Psychiatry, 2020, 177(9): 868-872.
Tardive Dyskinesia Diagnosis and Treatment Practice Survey Questionnaire This questionnaire is designed to investigate doctors’ cognitions on the diagnosis and treatment of tardive dyskinesia.
The American psychiatric association practice guideline for the treatment of patients with schizophrenia[J].
American Journal of Psychiatry, 2020, 177(9): 868-872.
Tardive dyskinesia diagnosis and treatment practice questionnaire Cognition of diagnosis and treatment of tardive dyskinesia.
The American psychiatric association practice guideline for the treatment of patients with schizophrenia[J].
American Journal of Psychiatry, 2020, 177(9): 868-872.
Tardive dyskinesia diagnosis and treatment practice questionnaire Cognition of diagnosis and treatment of tardive dyskinesia. Scan the QR code below or click on the bottom of the article to read the original text to participate.
Thank you for your participation.