What are highest quality studies assessing safety and efficacy of valbenazine, tetrabenazine, and deutetrabenazine for treatment of tardive dyskinesia?

Comment by InpharmD Researcher

The highest-quality assessments appear to be the randomized controlled trials and subsequent meta-analyses: valbenazine was studied in KINECT 2, KINECT-3, and a Japanese RCT, while deutetrabenazine was studied in ARM-TD and AIM-TD, with a 2019 indirect comparison pooling these RCTs and a 2018 systematic review/meta-analysis summarizing 20 studies. In contrast, tetrabenazine evidence is much weaker, consisting mainly of open-label cohort studies with nonstandardized outcomes. A 2018 review noted a lack of high-quality double-blind randomized trials and excluded tetrabenazine data from meta-analysis.
Background

A 2019 review examined the efficacy and safety of valbenazine versus deutetrabenazine via indirect comparison in the management of TD. Two valbenazine randomized controlled trials (RCTs; KINECT 2 [NCT01733121] and KINECT-3 [NCT02274558] and two deutetrabenazine RCTs (ARM-TD [NCT02195700] and AIM-TD [NCT02291861] were included. KINECT-2 and ARM-TD were flexible in dosing (once daily valbenazine 25-75 mg versus twice daily deutetrabenazine 12-48 mg). KINECT-3 and AIM-TD used fixed doses (once-daily valbenazine 40 or 80 mg versus twice-daily deutetrabenazine 12, 14, and 36 mg, respectively). The pooled data of AIMS change from baseline from all these individual RCTs favored valbenazine; the difference reached statistical significance for KINECT 3 pooled (40 and 80 mg) at 6 weeks versus AIM-TD pooled (12, 24, and 36 mg) at 8 weeks (mean difference [MD] -1.29; 95% CI: -2.49 to -0.09; p<0.05). There were no significant differences between the two agents in terms of AIMS responses and clinical global impression of change responses. The overall safety outcomes were comparable between the two drugs. The authors suggest that the long-term efficacy and persistence of effect still remained inconclusive. [1], [2]

A 2017 systematic review investigated the efficacy, tolerability, and safety of deutetrabenazine for the treatment of TD. The pooled data revealed a number needed to treat (NNT) of 7 (95 CI 4 to 18) for AIMS response (≥ 50% improvement in AIMS score) when therapeutic doses of deutetrabenazine were compared to those of placebo. Discontinuation rates due to adverse events (AEs) occurred in 3.6% of deutetrabenazine patients vs. 3.1% of placebo patients, resulting in an insignificant difference in the number needed to harm (NNH). The most common AEs related to deutetrabenazine were nasopharyngitis and insomnia. Valbenazine was investigated in another systematic review by the same author, finding a NNT of 4 (95% confidence interval [CI] 3 to 6). The discontinuation rate of valbenazine due to AEs was 2.9% in treated patients vs. 1.6% in placebo patients, again resulting in an insignificant difference in NNH. Somnolence was reported at an incidence rate of ≥ 5% and at a rate twice greater than that of placebo (10.9% valbenazine vs. 4.2% placebo), resulting in a NNH of 15 (95% CI 9 to 52). [3], [4]

A 2018 systematic review and meta-analysis summarized the characteristics, efficacy, and safety of VMAT2 inhibitors for treating TD. Data were compiled from 20 studies. A lack of high-quality, double-blind, randomized trials was noted for tetrabenazine; even available studies contained significant limitations which prevented inclusion of the data in this meta-analysis. For deutetrabenazine and valbenazine, the primary outcome was AIMS scores. A significant decrease in AIMS scores was demonstrated with both deutetrabenazine (standardized mean difference [SMD] −0.40, 95% CI −0.19 to −0.62, p<0.001; weighted mean difference [WMD] −1.44, 95% CI −0.67 to −2.19, p<0.001) and valbenazine (SMD −0.58, 95% CI −0.26 to −0.91, p<0.001; WMD −2.07, 95% CI −1.08 to −3.05, p<0.001) compared to placebo. The NNT for responders (≥ 50% reduction in total AIMS score) was 7 (95% CI 3 to 333, p= 0.046) with deutetrabenazine and 4 (95% CI 3 to 6, p<0.001) with valbenazine. Both valbenazine and deutetrabenazine were considered to be effective in treating TD acutely and long-term, without an increased risk of depression or suicide. [5]

A 2017 review compared tetrabenazine with valbenazine for the treatment of TD in 11 trials. Given the lack of rigorous designs associated with tetrabenazine, primarily open-label cohort studies, a formal meta-analysis evaluating the two agents was not conducted. Compared to tetrabenazine-recipients who received one- to three-times daily with mean doses ranging from 37.5–175 mg/day, patients in the valbenazine group all received once-daily dosing with a more consistent dosing regimen of 40 or 80 mg/day. In general, studies of tetrabenazine lacked standardized outcome measures, such as AIMS, and most studies documented changes in psychiatric status (depression) and secondary movement disorders (parkinsonism, akathisia) as frequent side effects of treatment. Adverse events associated with tetrabenazine were found to be dose-dependent and generally relieved upon dose reduction. Unlike tetrabenazine, which had been used off-label for TD, valbenazine gained FDA approval for the treatment of adults with TD and demonstrated favorable outcomes in AIMS total score in major RCTs. Additionally, change in psychiatric status and occurrence of secondary abnormal movements did not appear to be major concerns in patients treated with valbenazine even with concomitant antipsychotic agents. Overall, a qualitative analysis of current evidence suggests valbenazine is associated with a better safety profile and convenience for administration and presents a higher quality of evidence compared to tetrabenazine in the management of TD. [6]

Background References: [1] Aggarwal S, Serbin M, Yonan C. Indirect treatment comparison of valbenazine and deutetrabenazine efficacy and safety in tardive dyskinesia. J Comp Eff Res. 2019;8(13):1077-1088. doi:10.2217/cer-2019-0059
[2] Patel RS, Mansuri Z, Motiwala F, et al. A systematic review on treatment of tardive dyskinesia with valbenazine and deutetrabenazine. Ther Adv Psychopharmacol. 2019;9:2045125319847882. Published 2019 May 20. doi:10.1177/2045125319847882
[3] Citrome L. Deutetrabenazine for tardive dyskinesia: A systematic review of the efficacy and safety profile for this newly approved novel medication-What is the number needed to treat, number needed to harm and likelihood to be helped or harmed?. Int J Clin Pract. 2017;71(11):10.1111/ijcp.13030.
[4] Citrome L. Valbenazine for tardive dyskinesia: A systematic review of the efficacy and safety profile for this newly approved novel medication-What is the number needed to treat, number needed to harm and likelihood to be helped or harmed?. Int J Clin Pract. 2017;71(7):10.1111/ijcp.12964. doi:10.1111/ijcp.12964
[5] Solmi M, Pigato G, Kane JM, Correll CU. Treatment of tardive dyskinesia with VMAT-2 inhibitors: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2018;12:1215-1238. Published 2018 May 14. doi:10.2147/DDDT.S133205
[6] Caroff SN, Aggarwal S, Yonan C. Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review. J Comp Eff Res. 2018;7(2):135-148. doi:10.2217/cer-2017-0065
[7] Golsorkhi M, Koch J, Pedouim F, Frei K, Bondariyan N, Dashtipour K. Comparative Analysis of Deutetrabenazine and Valbenazine as VMAT2 Inhibitors for Tardive Dyskinesia: A Systematic Review. Tremor Other Hyperkinet Mov (N Y). 2024;14:13. Published 2024 Mar 13. doi:10.5334/tohm.842
[8] Patel AR, Hauser RA, Citrome L, et al. VMAT2 inhibitors for the treatment of tardive dyskinesia: a narrative review. CNS Spectr. 2025;30(1):e90. Published 2025 Oct 22. doi:10.1017/S1092852925100643
[9] Solmi M, Fornaro M, Caiolo S, et al. Efficacy and acceptability of pharmacological interventions for tardive dyskinesia in people with schizophrenia or mood disorders: a systematic review and network meta-analysis. Mol Psychiatry. 2025;30(3):1207-1222. doi:10.1038/s41380-024-02733-z
[10] Ismail O, Albdour K, Jaber Y, Jaber K, Alsaras A. Efficacy and safety of different pharmacological interventions in the treatment of tardive dyskinesia: a systematic review and network meta-analysis. Eur J Clin Pharmacol. 2026;82(5):123. Published 2026 Apr 15. doi:10.1007/s00228-026-04039-1
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

What are highest quality studies assessing safety and efficacy of valbenazine, tetrabenazine, and deutetrabenazine for treatment of tardive dyskinesia?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-5 for your response.

KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia
Design

Phase 3 randomized, double-blind, placebo-controlled trial

N= 225
Objective To evaluate the efficacy, safety, and tolerability of valbenazine as a treatment for tardive dyskinesia
Study Groups

Placebo (n= 78)

Valbenazine 40 mg/day (n= 76)

Valbenazine 80 mg/day (n= 80)
Inclusion Criteria Medically stable, 18–85 years of age, diagnosis of schizophrenia, schizoaffective disorder, or mood disorder for ≥3 months prior to screening, DSM diagnosis of dopamine receptor blocker–induced tardive dyskinesia for ≥3 months prior to screening, moderate or severe tardive dyskinesia based on qualitative assessment of screening videos
Exclusion Criteria Total score ≥50 on the Brief Psychiatric Rating Scale, total score ≥70 on the Positive and Negative Syndrome Scale, total score ≥10 on the Calgary Depression Scale for Schizophrenia, total score ≥10 on the Young Mania Rating Scale, total score >13 on the Montgomery-Åsberg Depression Rating Scale, any clinically significant unstable medical condition, any comorbid involuntary movement disorder more prominent than tardive dyskinesia, a score ≥3 on two or more items of the Simpson-Angus Scale, history of neuroleptic malignant syndrome, significant risk of suicidal or violent behavior
Methods Participants were randomly assigned to once-daily placebo, valbenazine at 40 mg/day, or valbenazine at 80 mg/day. The primary efficacy endpoint was change from baseline to week 6 in the AIMS dyskinesia score. Safety assessments included adverse event monitoring, laboratory tests, ECG, and psychiatric measures. An interactive web response system was used for randomization. Concomitant use of medications for psychiatric and medical conditions was allowed with stable treatment regimen for ≥30 days before baseline.
Duration 6-week double-blind, placebo-controlled period
Outcome Measures Primary: Change from baseline to week 6 in AIMS dyskinesia score Secondary: Clinical Global Impression of Change–Tardive Dyskinesia (CGI-TD) score
Baseline Characteristics   Placebo Group (N=76) Valbenazine 40 mg/day Group (N=72) Valbenazine 80 mg/day Group (N=79) All Participants (N=227)
Age (years) 57.0 ± 10.5 55.3 ± 8.5 56.0 ± 10.1 56.1 ± 9.7
Body mass index 28.0 ± 5.4 28.6 ± 5.5 27.8 ± 5.8 28.1 ± 5.6
Brief Psychiatric Rating Scale score 29.3 ± 7.0 30.6 ± 7.6 29.1 ± 6.6 29.7 ± 7.1
Abnormal Involuntary Movement Scale dyskinesia score (items 1–7) 9.9 ± 4.3 9.7 ± 4.1 10.4 ± 3.6 10.0 ± 4.0
Male 42 (55.3%) 42 (58.3%) 39 (49.4%) 123 (54.2%)
Race - White/Caucasian 43 (56.6%) 41 (56.9%) 44 (55.7%) 128 (56.4%)
Race - Black/African American 29 (38.2%) 26 (36.1%) 32 (40.5%) 87 (38.3%)
Illness category - Schizophrenia/schizoaffective disorder 50 (65.8%) 48 (66.7%) 52 (65.8%) 150 (66.1%)
Illness category - Mood disorder 26 (34.2%) 24 (33.3%) 27 (34.2%) 77 (33.9%)
Results   Placebo (n= 78) Valbenazine 40 mg/day (n= 76) Valbenazine 80 mg/day (n= 80) p-Value
Change in AIMS dyskinesia score -0.1 -1.9 -3.2 <0.001
AIMS response (≥50% improvement) 8.7% 23.8% 40.0% <0.001
Adverse Events Somnolence (5.3% vs. 3.9%), akathisia (3.3% vs. 1.3%), dry mouth (3.3% vs. 1.3%), suicidal ideation (5.3% in placebo vs. 2.6% in valbenazine groups combined)
Study Author Conclusions

Once-daily valbenazine significantly improved tardive dyskinesia in participants with underlying schizophrenia, schizoaffective disorder, or mood disorder. Valbenazine was generally well tolerated, and psychiatric status remained stable. Longer trials are necessary to understand the long-term effects of valbenazine in patients with tardive dyskinesia.
Critique The study demonstrated significant efficacy of valbenazine in reducing tardive dyskinesia symptoms with a favorable safety profile. However, the short duration of the trial limits the understanding of long-term effects. The study's design was robust, but the lack of a validated minimal clinically important difference for AIMS score changes could affect the interpretation of clinical relevance. Future research should explore long-term outcomes and optimal dosing strategies.

 

Table 1 References:
[11] Hauser RA, Factor SA, Marder SR, et al. KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Am J Psychiatry. 2017;174(5):476-484. doi:10.1176/appi.ajp.2017.16091037
Efficacy and safety of valbenazine in Japanese patients with tardive dyskinesia: A multicenter, randomized, double-blind, placebo-controlled study (J-KINECT)
Design

Multicenter, phase II/III, randomized, double-blind, placebo-controlled study

N= 256
Objective To assess the efficacy and safety of valbenazine in Japanese patients with tardive dyskinesia
Study Groups

Valbenazine 40 mg (n= 86)

Valbenazine 80 mg (n= 85)

Placebo (n= 85)
Inclusion Criteria Men and women aged 20–85 years; diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder; diagnosed with moderate to severe tardive dyskinesia; stable maintenance treatment for primary psychiatric disorder for at least 30 days
Exclusion Criteria Active, clinically significant, unstable cerebrovascular, hepatic, renal, endocrine, cardiovascular, gastrointestinal, respiratory, or metabolic disease; presence of other prominent comorbid movement disorder; diagnosis of major neurocognitive disorder; presence of substance abuse disorder; high risk of suicidal or self-injurious behavior
Methods

Patients were randomly allocated to receive placebo or valbenazine (40- or 80-mg) once daily for 6 weeks, followed by a 42-week extension where placebo group switched to valbenazine. Primary endpoint was change from baseline in AIMS total score at Week 6. CGI-TD was also assessed. Compliance was monitored by capsule count.
Duration Study period: June 21, 2017 to September 29, 2020 Double-blind period: 6 weeks Extension period: 42 weeks
Outcome Measures

Primary: Change from baseline in AIMS total score at Week 6

Secondary: Percentage of patients with ≥50% improvement in AIMS total score, CGI-TD score at Week 6
Baseline Characteristics   Valbenazine 40 mg (n = 83) Valbenazine 80 mg (n = 82) Placebo (n = 84)
Age, years 60.0 ± 13.4 58.5 ± 14.0 57.9 ± 13.6
Sex, male 36 (42.9%) 38 (45.8%) 50 (61.0%)
Body mass index, kg/m2 23.75 ± 3.82 23.40 ± 4.00 23.90 ± 4.21
AIMS dyskinesia total score 8.0 ± 4.2 7.7 ± 3.8 7.4 ± 4.3
Results   Valbenazine 40 mg (n= 86) Valbenazine 80 mg (n= 85) Placebo (n= 85) p-Value
Change from baseline in AIMS score at Week 6 -2.3 (-3.0 to -1.7) -3.7 (-4.4 to -3.0) -0.1 (-0.8 to 0.5) <0.001
Percentage of patients with ≥50% improvement in AIMS score 23.9% 47.2% 10.3% <0.001
Adverse Events Incidence of adverse events was highest in the 80-mg group; common events included nasopharyngitis, somnolence, schizophrenia worsening, hypersalivation, insomnia, and tremor
Study Author Conclusions The efficacy/safety profile of valbenazine was similar to that of previous clinical trials, supporting its use for TD treatment in Japanese patients.
Critique The study demonstrated significant improvements in TD symptoms with valbenazine, but the relatively high incidence of adverse events in the 80-mg group raises concerns. The study's short placebo-controlled period and focus on stable psychiatric patients may limit the generalizability of the findings to broader populations.

 

Table 2 References:
[12] Horiguchi J, Watanabe K, Kondo K, et al. Efficacy and safety of valbenazine in Japanese patients with tardive dyskinesia: A multicenter, randomized, double-blind, placebo-controlled study (J-KINECT). Psychiatry Clin Neurosci. 2022;76(11):560-569. doi:10.1111/pcn.13455
Tetrabenazine Treatment for Tardive Dyskinesia: Assessment by Randomized Videotape Protocol
Design

Single-blind, randomized videotape assessment

N= 20
Objective To test the efficacy of tetrabenazine for the treatment of tardive dyskinesia using randomized videotapes scored by raters blind to pre- or posttreatment status
Study Groups All patients (n= 20)
Inclusion Criteria Patients diagnosed with tardive dyskinesia referred to the Baylor College of Medicine Parkinson’s Disease Center and Movement Disorders Clinic. Most had refractory tardive dyskinesia, but this was not a specific inclusion criterion
Exclusion Criteria None specified
Methods Patients were videotaped before and after tetrabenazine treatment. Tetrabenazine was started at 12.5 mg twice a day and titrated to a maximum of 150 mg/day. Videotapes were scored using the motor subset of the AIMS by raters blind to treatment status. Patients stopped other treatments for tardive dyskinesia at least 30 days before the study
Duration Mean of 20.3 weeks
Outcome Measures

Primary: AIMS motor subset score

Secondary: Subjective AIMS score, global impressions, adverse events
Baseline Characteristics   All patients (n= 20)
Mean age, years (SD) 65.2 (10.8)
Gender - Female 15 (75%)
Mean duration of tardive dyskinesia, months (SD) 43.7 (47.1)
Mean exposure to offending agent, months (SD) 52.1 (46.1)
Results   Pre-treatment Post-treatment p-Value
AIMS motor subset score (SD) 17.9 (4.4) 8.2 (5.3) <0.001
Subjective AIMS score (SD) 9.1 (1.5) 3.6 (1.5) <0.001
Adverse Events Sedation was reported by five patients. Mild parkinsonism was found in five patients. No adverse events were rated as more than mild
Study Author Conclusions Tetrabenazine was effective and generally well tolerated for the treatment of tardive dyskinesia, showing significant improvements in AIMS scores. It should be considered for severe and refractory cases
Critique The study's single-blind design and reliance on videotape assessments may limit the detection of subtle movements. The study group may be biased towards more severe cases due to referral patterns. The subjective results are subject to the limitations of open-label trials

 

Table 3 References:
[13] Ondo WG, Hanna PA, Jankovic J. Tetrabenazine treatment for tardive dyskinesia: assessment by randomized videotape protocol. Am J Psychiatry. 1999;156(8):1279-1281. doi:10.1176/ajp.156.8.1279
Randomized controlled trial of deutetrabenazine for tardive dyskinesia
Design

Randomized, double-blind, multicenter trial

N= 117
Objective To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD)
Study Groups

Deutetrabenazine (n= 58)

Placebo (n= 59)
Inclusion Criteria Patients with moderate to severe TD, AIMS score of $6, stable psychiatric illness, stable psychoactive medication treatment
Exclusion Criteria Treatment with tetrabenazine, reserpine, strong anticholinergic medications, metoclopramide, dopamine agonists, levodopa, stimulants within 30 days of screening or baseline; neurologic condition confounding TD assessments; serious untreated psychiatric illness; unstable medical illness; history of suicidal ideation or behavior within 6 months; QTcF >450 ms in men or >460 ms in women
Methods Patients received deutetrabenazine or placebo, starting at 12 mg/d and titrated weekly by 6 mg/d up to 48 mg/d. Efficacy assessed by AIMS score change from baseline to week 12. Secondary endpoints included CGIC and PGIC. Safety monitored through AEs, ECG readings, and various scales
Duration June 2014 to May 2015
Outcome Measures Primary: Change in AIMS score from baseline to week 12 Secondary: Treatment success on CGIC and PGIC, change in mCDQ-24 score
Baseline Characteristics   Deutetrabenazine (n= 58) Placebo (n= 59)
Age (SD), y 55.9 (9.8) 53.3 (10.6)
Female, n (%) 29 (50.0) 32 (54.2)
Male, n (%) 29 (50.0) 27 (45.8)
White, n (%) 37 (63.8) 44 (74.6)
Weight (SD), kg 86.9 (24.1) 85.0 (21.0)
Duration of TD, mo 72.6 (81.7) 76.8 (82.1)
DRA use at baseline, n (%) 45 (77.6) 49 (83.1)
AIMS score, items 1–7 (SD) 9.6 (4.1) 9.6 (3.8)
Results   Deutetrabenazine (n= 58) Placebo (n= 59) p-Value
Change in AIMS score from baseline to week 12 -3.0 (0.45) -1.6 (0.46) 0.019
Treatment success on CGIC 48.2% 40.4% not significant
Treatment success on PGIC 42.9% 29.8% not significant
Adverse Events Patients from the deutetrabenazine and placebo groups reported similar rates of AEs. Common AEs included somnolence, fatigue, insomnia, headache, diarrhea, akathisia, anxiety, dizziness, dry mouth, and upper respiratory tract infection. Serious AEs were reported by 5.2% in the deutetrabenazine group and 8.5% in the placebo group. No deaths occurred
Study Author Conclusions Deutetrabenazine is efficacious for the treatment of abnormal movements in patients with TD, with a favorable safety and tolerability profile that enables the continued use of DRAs and antidepressants for managing chronic psychiatric conditions.
Critique The study provides strong evidence of deutetrabenazine's efficacy in reducing TD symptoms, supported by a robust randomized controlled design. However, the placebo response was notable, potentially affecting the perceived efficacy. The study's reliance on video assessments may not fully capture the dynamic nature of TD, and the lack of significant findings in secondary endpoints suggests variability in symptom appreciation. The study's findings are relevant for clinical practice, especially for patients who cannot discontinue antipsychotic treatment.

 

Table 4 References:
[14] Fernandez HH, Factor SA, Hauser RA, et al. Randomized controlled trial of deutetrabenazine for tardive dyskinesia: The ARM-TD study. Neurology. 2017;88(21):2003-2010. doi:10.1212/WNL.0000000000003960
Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial
Design

Double-blind, randomised, placebo-controlled, phase 3 trial

N=298
Objective To assess the efficacy, safety, and tolerability of fixed doses of deutetrabenazine in patients with tardive dyskinesia
Study Groups

Placebo (n=74)

Deutetrabenazine 12 mg/day (n=75)

Deutetrabenazine 24 mg/day (n=74)

Deutetrabenazine 36 mg/day (n=75)
Inclusion Criteria Patients aged 18–80 years with tardive dyskinesia for at least 3 months before screening and a history of use of dopamine receptor antagonists for at least 3 months (or 1 month in patients aged ≥60 years)
Exclusion Criteria Patients who had received treatment within 30 days of screening with tetrabenazine, reserpine, metirosine, medications with strong anticholinergic properties, dopamine antagonising antiemetics, stimulants, monoamine oxidase inhibitors, levodopa or dopamine agonists, or botulinum toxin within 3 months of screening; and patients with a neurological condition other than tardive dyskinesia that could interfere with dyskinesia assessment
Methods

Patients were started on oral deutetrabenazine 12 mg/day, increased weekly in increments of 6 mg/day until the randomised dose was achieved, then maintained over 8 weeks. The primary efficacy endpoint was change in AIMS score from baseline to week 12. Safety analysis was done in patients who received any study drug.
Duration October 29, 2014, to August 19, 2016
Outcome Measures

Primary: Change in Abnormal Involuntary Movement Scale (AIMS) score from baseline to week 12

Secondary: Treatment response ≥50% improvement
Baseline Characteristics   Placebo (n= 72) Deutetrabenazine 12 mg/day (n= 74) Deutetrabenazine 24 mg/day (n= 73) Deutetrabenazine 36 mg/day (n= 74)
Age, years 54.6 (12.1) 57.0 (10.0) 55.6 (11.3) 58.3 (11.6)
Female 37 (51%) 42 (57%) 41 (56%) 42 (57%)
White race 59 (82%) 58 (78%) 54 (74%) 61 (82%)
Duration of tardive dyskinesia, years 6.0 (5.4) 5.5 (5.4) 5.0 (6.0) 5.9 (5.3)
Use of dopamine receptor antagonists 56 (78%) 56 (76%) 57 (78%) 53 (72%)
Primary psychiatric illness - Schizophrenia 31 (43%) 32 (43%) 42 (58%) 40 (54%)
Primary psychiatric illness - Schizoaffective disorder 11 (15%) 8 (11%) 7 (10%) 4 (5%)
Primary psychiatric illness - Bipolar 17 (24%) 15 (20%) 7 (10%) 12 (16%)
Primary psychiatric illness - Depression 11 (15%) 17 (23%) 11 (15%) 16 (22%)
Results   Placebo (n= 58) Deutetrabenazine 12 mg/day (n= 60) Deutetrabenazine 24 mg/day (n= 49) Deutetrabenazine 36 mg/day (n= 55)
Mean change in AIMS score -1.4 (0.41) -2.1 (0.42) -3.2 (0.45) -3.3 (0.42)
Treatment response ≥50% improvement 12% (n=7) 28% (n=17) 35% (n=17) 33% (n=18)
Adverse Events The rate of adverse events was similar between groups. Serious adverse events were reported in 5% of patients given deutetrabenazine 36 mg/day, 8% of patients given 24 mg/day, and 3% of patients given 12 mg/day, compared with 6% of patients given placebo. Two patients in the safety population died, one each in the deutetrabenazine 24 mg/day and 36 mg/day groups; neither death was deemed related to study drug
Study Author Conclusions

Deutetrabenazine 24 mg/day and 36 mg/day provided a significant reduction in tardive dyskinesia, with favourable safety and tolerability. These findings suggest that dosing regimens could be individualised and tailored for patients on the basis of dyskinesia control and tolerability.
Critique

The study was well-designed with a large sample size and robust methodology, including central video rating to minimise bias. However, the notable placebo response observed could affect the interpretation of efficacy. The study's reliance on patient-reported outcomes may be influenced by the underlying psychiatric conditions of participants, potentially affecting the accuracy of self-assessment. Additionally, the study did not explore long-term effects beyond the 12-week period.

 

Table 5 References:
[15] 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. Lancet Psychiatry. 2017;4(8):595-604. doi:10.1016/S2215-0366(17)30236-5