Expert Opinion on Pharmacotherapy

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Selecting dopamine depleters for hyperkinetic

movement disorders: how do we choose?

Laszlo Szpisjak, Andras Salamon, Denes Zadori, Peter Klivenyi & Laszlo
Vecsei

To cite this article: Laszlo Szpisjak, Andras Salamon, Denes Zadori, Peter Klivenyi & Laszlo
Vecsei (2020) Selecting dopamine depleters for hyperkinetic movement disorders: how do we
choose?, Expert Opinion on Pharmacotherapy, 21:1, 1-4, DOI: 10.1080/14656566.2019.1685980

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Published online: 30 Oct 2019.

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EXPERT OPINION ON PHARMACOTHERAPY
2020, VOL. 21, NO. 1, 1–4
https://doi.org/10.1080/14656566.2019.1685980

EDITORIAL

Selecting dopamine depleters for hyperkinetic movement disorders: how do we choose?

Laszlo Szpisjaka, Andras Salamona, Denes Zadoria, Peter Klivenyia and Laszlo Vecseia,b,c
a
Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary; bMTA-SZTE
Neuroscience Research Group, Szeged, Hungary; cDepartment of Neurology, Interdisciplinary Excellence Centre, University of Szeged, Szeged,
Hungary

ARTICLE HISTORY Received 29 August 2019; Accepted 24 October 2019

KEYWORDS Deutetrabenazine; hyperkinetic; movement disorders; tetrabenazine; valbenazine; VMAT2 inhibitor

1. Introduction 2.1. Tetrabenazine

The group of hyperkinetic movement disorders (MD) is char-
acterized by abnormal involuntary movements including dys-
tonia, chorea, athetosis, ballism, tics, tremors, myoclonus and
stereotypies [1]. The etiology of these MDs can be classified as
acquired (e.g. vascular, inflammatory, tumorous, drug-
induced), hereditary (e.g. Huntington’s disease; HD) and idio-
pathic (e.g. Tourette syndrome) forms. In a few cases of
acquired hyperkinetic MDs, the underlying pathology can be
treated, whereas in the rest of them only symptomatic thera-
pies are available to reduce the amplitude and frequency of
abnormal movements [1].
Symptomatic treatment is aimed at decreasing the hyper-
dopaminergic state of basal ganglia [1]. This can be achieved
by transporter or receptor blockade. The latter approach
includes dopamine receptor blocking agents (antipsychotics
or neuroleptics) which can improve many hyperkinesia, how-
ever these drugs have unfavorable side effects, such as par-
kinsonism and tardive dyskinesia (TD). On the other hand,
vesicular monoamine transporter type 2 (VMAT2) inhibitors
aim to deplete dopamine from the neurons without antagon-
ism of dopamine receptors. These dopamine depleters have
better side effect profiles with minimal or no risk of develop-
ing tardive syndromes.
2. VMAT2 inhibitors
Reserpine, an antihypertensive and antipsychotic agent,
was one of the first VMAT inhibitor drugs, however its
effect was irreversible and nonselective for VMAT2.
Reserpine reduced chorea in Huntington’s disease (HD),
but its irreversible and nonselective action resulted in
unfavorable side effects, including orthostatic hypotension,
gastric dysmotility, depression and extrapyramidal symp-
toms, therefore it was not a well-tolerated compound [2].
Over the next decades, novel, selective VMAT2 inhibitors
were developed, including tetrabenazine, deutetrabenazine
and valbenazine. Table 1. contains the most important
pharmacological features of these agents, whereas Table
2. summarizes the parameters of the most relevant clinical
studies of these drugs.
Tetrabenazine (TBZ) was the first selective VMAT2 inhibitor,
synthesized in 1950 for the treatment of psychosis [3].
However, phenothiazines were more effective antipsycho-
tics, thus TBZ was not significantly used in this indication.
In addition, TBZ has the potential to ameliorate hyperki-
netic MDs, including chorea, TD, dystonia, tics and
Tourette syndrome (TS). On the other hand, in most of
these MDs only non-randomized or retrospective studies
and, in a few cases, randomized, double-blind, placebo-
controlled trials with small numbers of patients, were per-
formed [3,4]. The only exception is the TETRA-HD study,
which was conducted in 2006 by the Huntington Study
Group. This randomized, double-blind, placebo-controlled,
multicentre study demonstrated that TBZ can effectively
reduce chorea in HD and was well-tolerated by all the
participants. Drowsiness, insomnia and fatigue were the
most common side effects, while the most prevalent
dose-limiting symptoms were sedation, akathisia, parkin-
sonism and depression [5]. This side effect profile was
reinforced by a relevant open-label, retrospective, long-
term tolerability study on a variety of hyperkinetic MDs
(TD, dystonia, chorea, tics and myoclonus) treated with
TBZ. Fortunately, all side effects were dose-related and
remitted when the dosage was reduced [6]. Based on the
convincing results of the TETRA-HD study, TBZ was
approved by the US Food and Drug Administration (FDA)
for the treatment of chorea in August 2008.
2.2. Deutetrabenazine
Deutetrabenazine (DTBZ) is the deuterated form of TBZ, which
incorporates six deuterium isotopes, also known as heavy hydro-
gen, because its atomic nucleus contains one neutron plus one
proton, in contrast to the most common hydrogen isotope, pro-
tium, which does not have a neutron [1]. This molecular modifica-
tion creates an 8-times stronger hydrogen (deuterium) carbon
bond, making the agent more resistant to its metabolizing
enzyme, CYP2D6. Therefore, DTBZ has longer plasma half-life
than TBZ, and it enables less frequent daily dosing with the advan-
tage of more constant plasma concentrations with lower peaks

CONTACT Laszlo Vecsei vecsei.laszlo@med.u-szeged.hu Department of Neurology, University of Szeged, Semmelweis u. 6, Szeged H-6725, Hungary
© 2019 Informa UK Limited, trading as Taylor & Francis Group
2 L. SZPISJAK ET AL.
Table 1. Pharmacological features of VMAT2 inhibitors.
Characteristic Tetrabenazine
Approved indication HD
Date of FDA approval 15 August 2008
Starting dose (mg per day) 12.5
Max total dose (mg per day) 100
Dosing TID
Peak plasma concentration (Cmax) 1–1.5 h
Half life 5.5 h
Metabolism CYP2D6
(BID: Bidaily, CYP2D6: Cytochrome P450 2D6, FDA: Food and Drug Administration, HD: Huntington’s Disease, TID: Thrice daily, TD: Tardive Dyskinesia)
and fluctuations [7]. A randomized, short-term, multicentre, dou-
ble-blind, placebo-controlled trial (FIRST-HD) delineated that DTBZ
can effectively reduce chorea in HD, while the adverse event rate
was lower than side effect frequencies of TBZ in the TETRA-HD
study [8,9]. Besides HD, DTBZ was also examined in class I, short-
term studies for the treatment of TD (ARM-TD and AIM-TD). These
two trials showed the efficacy, safety and tolerability of DTBZ in TD,
which was reinforced by a long-term, open-label trial [10–12]. On
this basis, DTBZ was approved by the US FDA for the treatment of
HD in April 2017 and for the treatment of TD in August 2017, and it
was the first deuterated drug to receive FDA approval. Moreover,
an open-label study of 23 patients with TS found DTBZ to be
effective and safe in adolescent patients with tics related to TS
[1,13]. A currently ongoing larger, randomized, double-blind, pla-
cebo-controlled trial is attempting to confirm the hopeful results of
the pilot study (https://clinicaltrials.gov/ct2/show/NCT03452943).
2.3. Valbenazine
Valbenazine (VBZ) is the purified prodrug of α-dihydrote-
trabenazine (α-HTBZ), which is the most active metabolite
of TBZ [1]. α-HTBZ is a highly selective VMAT2 inhibitor and
its half-life of approximately 20 hours permits once daily
dosing [7]. Two randomized, double-blind, placebo-con-
trolled, short-term studies (KINECT 2 and 3) of VBZ in TD
revealed that VBZ has the potential to significantly reduce
abnormal involuntary movements in TD [14,15]. In addition
to efficacy, VBZ showed a favorable side effect profile and
it was well tolerated by patients. A long-term study (KINECT
3 Extension) reinforced these outstanding results about
efficacy, safety and tolerability [16]. The most common
adverse events were headache, urinary tract infection, diar-
rhea, dizziness, suicidal ideation and depression [16].
Moreover, a further analysis of these studies confirmed
the statistically significant improvements in TD severity
both overall and in separate body regions [17]. Based on
these trials, VBZ became the first FDA-approved treatment
for TD in April 2017. Besides TD, VBZ is under investigation
as a treatment for TS, however the results of this trial are
not yet available (https://clinicaltrials.gov/ct2/show/
NCT03325010?term=valbenazine&rank=8).
3. Expert opinion
Currently, VMAT2 inhibitors are the best medications for
treating hyperkinetic MDs. However, as we mentioned
above, results from multicentre, randomized, double-blind,
Deutetrabenazine Valbenazine
HD, TD TD
3 April 2017 for HD 30 August 2017 for TD 11 April 2017
6 40
48 80
BID Once daily
3–4 h 4–10 h
8.6 h 20 h
CYP2D6 CYP2D6
placebo-controlled studies are limited to HD and TD so far,
therefore use of these agents in the treatment of other
hyperkinetic movements are off-label.
Regarding HD, only TBZ and DTBZ have FDA approval
for the treatment of choreiform movements. In the lack of
direct head-to-head studies, the selection between these
drugs may depend on indirect comparisons and good clin-
ical practice. An indirect comparison of TBZ and DTBZ in
HD according to the TETRA-HD and FIRST-HD studies pub-
lished by Claassen et al. demonstrated that DTBZ has
a more favorable tolerability profile than TBZ for the treat-
ment of HD chorea [18]. They found that DTBZ presented
a significantly lower risk for the most prevalent neuropsy-
chiatric side effects compared to TBZ, including drowsiness,
insomnia, depression, akathisia, parkinsonism and agitation.
However, Rodrigues et al. performed the same comparison
using a different statistical method and they demonstrated
that there was no difference between the efficacy and
safety profiles of the two drugs [19]. In light of these
controversial results, and the availability and price of
these two agents, it is suggested to start the treatment
with TBZ, and in the case of remarkable intolerance, a shift
to DTBZ may be recommended. Furthermore, in a case of
severe concomitant neuropsychiatric symptoms with the
possibility of considerable aggravation by TBZ, DTBZ may
come into account as a first choice. Regarding TD, a real-
world study published in 2019 and a review article focused
on TD highlighted that all three VMAT2 inhibitors are
effective and safe for treatment of these abnormal involun-
tary movements [20,21], but only DTBZ and VBZ have FDA
approval. There is only one indirect comparison of these
two agents available which delineated VBZ as statistically
more effective than DTBZ in AIMS score improvements,
whereas there was no relevant difference in safety para-
meters [22]. Although the application of TBZ in TD is off-
label, due to its widespread availability and relatively low
price compared to the other two VMAT2 inhibitors, it may
also be applied in selected cases.
VMAT2 inhibitors do not have FDA approval for other
hyperkinetic MDs, and therefore they can only be applied
off-label in these conditions. Regarding TBZ observational
cohort studies, retrospective investigations and case
reports may support its use in TS, dystonia, myoclonus,
dyskinesia and other hyperkinetic MDs. Some prospective
studies are ongoing without available results. The experi-
ence with DTBZ and VBZ in these disorders is considerably
limited.
Table 2. Characteristics of most relevant clinical trials of VMAT2 inhibitors.
Number of
included Most common side effects (% of patients, only
Drug Disease Study Phase patients Purpose of study Dose Comparator Duration Relevant results those reaching 2% or higher are indicated) References
TBZ HD TETRA-HD III 84 Efficacy, dosing, tolerability 25–100 mg/day PLC 12 weeks Significant reduction in total maximal Drowsiness 31.5, Insomnia 25.9, Fatigue 22.2, Fall [5]
and safety of TBZ in HD (mean: 74.7 mg) chorea of UHDRS in comparison to 16.7, Depression 14.8, Agitation 14.8, Anxiety
PLC (−5 vs. −1.5) and TBZ was 14.8, Nausea 13, Purpura 11.1, Upper
superior to PLC in CGIC Global respiratory tract infection 11.1, Ataxia 9.3,
Improvement Scale (3.0 vs. 3.7) Hyperkinesia 9.3, Nervousness 9.3, Coughing
7.4, Diarrhea 7.4, Vomiting 5.6, Dose-limiting
symptoms: Sedation 27, Akathisia 8,
Parkinsonism 4, Depression 4
TBZ TS Kenney et al. Retrospective 77 Safety and efficacy of TBZ in 6.3–125.0 mg/day – 23.7 ± 41.1 months TBZ was safe and well tolerated. Most Drowsiness 36.4, Nausea 10.4, Depression 9.1, [4]
TS patients (mean: side effects were dose-related and Insomnia 7.8, Parkinsonism 6.5, Nervousness/
50.4 ± 27.0) controlled with dose reducetion. The Anxiety 5.2, Akathisia 3.9, Tremor 2.6, ‘Trance-
efficacy was measured in 5 point like/Zombie’ 2.6, Rash 2.6, Drooling 2.6, Speech
scale (1 means the best, 5 means the difficulties 2.6
worst), in the last visit 83.1% of the
patients have 1 or 2 points
TBZ Hyperkinetic MDs (TD, Kenney et al. Retrospective 448 Long-term efficacy and 12.5–300 mg/day – Mean time on treatment: TBZ was safe and well tolerated. All Drowsiness 25, Parkinsonism 15.4, Depression 7.6, [6]
dystonia, chorea, tics, tolerability of TBZ in (mean: 2.3 ± 3.4 y (up to adverse events were dose-related Akathisia 7.6, Nausea/Vomiting 5.6,
myoclonus) hyperkinetic MDs 60.4 ± 35.7) 21.6 years) and abated when dosage was Nervousness/Anxiety 5.1, Insomnia 4.9,
reduced. TBZ was effective, efficacy Salivation 2.7, Dizziness 2.5
was measured in 5 point scale (1
means the best, 5 means the worst),
in the last visit most of the patients
have 1 or 2 points (TD: 85.7%,
chorea: 81.4%, tics: 76.7%,
myoclonus 71.4%, dystonia: 69.5%)
DTBZ HD FIRST-HD III 90 Efficacy and safety of DTBZ 12–48 mg/day (mean: PLC 12 weeks Significant reduction in total maximal Somnolence 11.1, Dry mouth 8.9, Diarrhea 8.9, [8]
in HD 39.7 mg) chorea of UHDRS in comparison to Irritability 6.7, Insomnia 6.7, Fatigue 6.7, Fall
PLC (−4.4 vs. −1.9) and DTBZ showed 4.4, Dizziness 4.4, Depression or agitated
favorable effect compared to PLC in depression 4.4
CGIC (51 vs. 20%), PGIC (42 vs. 13%)
and improvement in SF-36 (0.7 vs.
−3.6)
DTBZ TD ARM-TD II/III 117 Efficacy and safety of DTBZ 18–48 mg/day (mean: PLC 12 weeks Significant reduction in AIMS scores in Somnolence 13.8, Fatigue 6.9, Insomnia 6.9, [10]
in TD 38.3 mg) comparison to PLC (−3.0 vs. −1.6) Headache 5.2, Diarrhea 5.2, Akathisia 5.2,
Anxiety 3.4, Dizziness 3.4, Dry mouth 3.4, Upper
respiratory tract infection 3.4
DTBZ TD AIM-TD III 298 Efficacy, safety and 3 groups: 12 mg/day, PLC 12 weeks Significant reduction in AIMS scores in Headache 5, Anxiety 4, Diarrhea 4, Nasopharyngitis [11]
tolerability of DTBZ in 24 mg/day and 24 mg/day and 36 mg/day group 4, Fatigue 3, Somnolence 2, Depression 2, Dry
TD 36 mg/day compared to PLC (−3.2 [24 mg/day], mouth 2
−3.3 [36 mg/day] vs. −1.4 [PLC]) and
24 mg/day DTBZ group showed
significantly higher proportion of
‘very much improved’ or ‘much
improved’ on CGIC compared to PLC
(49 vs. 26%)
DTBZ TD Fernandez et al. Open-label 343 Long-term safety and 12–48 mg/day (mean: – 106 weeks DTBZ was safe and effective. Significant Somnolence 9, Depression 9, Anxiety 9, Headache [12]
efficacy of DTBZ in TD 39 mg) reduction in AIMS score (−6.3 at 7, Diarrhea 6, Nasopharyngitis 6, Urinary tract
Week 80) and CGIC was improved or infection 6
very much improved in 70% of the
patients at Week 80. Most AEs were
mild or moderate in severity.
DTBZ TS Jankovic et al. Open-label 23 Efficacy, safety and 18–36 mg/day (mean: – 8 weeks DTBZ was safe and effective. Significant Fatigue 17, Headache 17, Irritability 13, [13]
tolerability of DTBZ in TS 32.1 mg) reduction in YGTSS score (11.6 Somnolence 8, Hyperhidrosis 8, Diarrhea 8,
points, 37.6%) and improvement in Nasopharyngitis 8
TS-CGI score (1.2 points) and TS-PGIC
showed that 76.2% if patients were
much improved or very much
improved compared with baseline.
All AEs were mild to moderate in
severity.
VBZ TD KINECT 2 II 102 Efficacy, safety and 25–75 mg/day PLC 6 weeks Significant reduction in AIMS score Fatigue 9.8, Headache 9.8, Decreased appetite 7.8, [14]
tolerability of VBZ in TD compared to PLC (−3.6 vs. −1.1) and Nausea 5.9, Somnolence 5.9, Dry mouth 5.9,
VBZ was superior to PLC in CGI-TD Vomiting 5.9, Constipation 3.9, Urinary tract
(2.3 vs. 3.1) and PGIC scores (2.2 vs. infection 3.9, Sedation 3.9, Back pain 3.9
2.9)
VBZ TD KINECT 3 III 234 Efficacy, safety and 2 groups: 40 mg/day, PLC 6 weeks Significant reduction in AIMS score Somnolence 5.3, Akathisia 3.3, Dry mouth 3.3, [15]
tolerability of VBZ in TD 80 mg/day compared to PLC (−3.2 [80 mg/day], Suicidal ideation 2.6, Arthralgia 2.6, Headache
−1.9 [40 mg/day], vs. −0.1 [PLC]) 2.6, Vomiting 2, Dyskinesia 2, Anxiety 2,
Insomnia 2, Fatigue 2, Urinary tract infection 2,
Weight increase 2
VBZ TD KINECT 3 Extension III 198 Long-term efficacy, safety 2 groups: 40 mg/day, – 42 weeks Significant reduction in AIMS score (−4.8 Headache 7.1, Urinary tract infection 6.6, Diarrhea [16]
and tolerability of VBZ in 80 mg/day [80 mg/day], −3.0 [40 mg/day] 5.6, Dizziness 5.6, Suicidal ideation 5.1,
EXPERT OPINION ON PHARMACOTHERAPY

TD compared to baseline. VBZ was safe Depression 4

and well-tolerated

AE: adverse event, AIMS: Abnormal Involuntary Movement Scale, CGIC: Clinical Global Improvement of Change, CGI-TD: Clinical Global Improvement of Change TD Scale, DTBZ: Deutetrabenazine, HD: Huntington’s Disease, MD:
3

Movement Disorder, PGIC: Patient Global Impression of Change, PLC: Placebo, SF-36: 36-Item Short Form Healthy Survey, TBZ: Tetrabenazine, TD: Tardive Dyskinesia, TS: Tourette syndrome TS-CGI: TS Clinical Global
Impression, TS-PGIC: TS Patient Global Impression of Change, UHDRS: Unified Huntington’s Disease Rating Scale, VBZ: Valbenazine, YGTTS: Yale Global Tic Severity Scale.
4 L. SZPISJAK ET AL.
Funding
The authors are supported by the Hungarian Brain Research Program
[Grant No. 2017-1.2.1-NKP-2017-00002 NAP VI/4], project GINOP 2.3.2-15-
2016-00034 and by the Ministry of Human Capacities, Hungary grant
[20391-3/2018/FEKUSTRAT]. Dénes Zádori was also supported by the
János Bolyai Research Scholarship of the Hungarian Academy of Sciences.
Declaration of interest
The authors have no other relevant affiliations or financial involve-
ment with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
Reviewer disclosures
One referee declares that they have served as a consultant for Teva
Pharmaceuticals for studies related to deutetrabenazine in tardive
dyskinesia. Peer reviewers on this manuscript have no other relevant
financial relationships or otherwise to disclose.
References
Papers of special note have been highlighted as either of interest (•)
or of considerable interest (••) to readers.
1. Jankovic J. Dopamine depleters in the treatment of hyperki-
netic movement disorders. Expert Opin Pharmacother.
2016;17:2461–2470.
2. Citrome L. Tardive dyskinesia: placing vesicular monoamine
transporter type 2 (VMAT2) inhibitors into clinical perspective.
Expert Rev Neurother. 2018;18:323–332.
3. Kaur N, Kumar P, Jamwal S, et al. Tetrabenazine: spotlight on
drug review. Ann Neurosci. 2016;23:176–185.
4. Kenney C, Hunter C, Mejia NI, et al. Tetrabenazine in the
treatment of Tourette syndrome. J Pediatr Neurol.
2007;05:009–013.
5. Huntington Study Group. Tetrabenazine as antichorea therapy in
huntington disease: a randomized controlled trial. Neurology.
2006;66:366–372.
6. Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabe-
nazine in the treatment of hyperkinetic movement disorders. Mov
Disord. 2007;22:193–197.
• Important long-term observations of tetrabenazine treatment.
7. Scorr LM, Factor SA. VMAT2 inhibitors for the treatment of tardive
dyskinesia. J Neurol Sci. 2018;389:43–47.
8. Huntington Study Group. Effect of deutetrabenazine on chorea
among patients with huntington disease: a randomized controlled
trial. JAMA. 2016;316:40–50.
•• The randomized, double-blind, placebo-controlled trial of deu-
tetrabenazine in Huntington disease.
9. Bashir H, Jankovic J. Deutetrabenazine for the treatment of
Huntington’s chorea. Expert Rev Neurother. 2018;18:625–631.
10. Fernandez HH, Factor SA, Hauser RA, et al. Randomized con-
trolled trial of deutetrabenazine for tardive dyskinesia: the
ARM-TD study. Neurology. 2017;88:2003–2010.
11. 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:
595–604.
12. Fernandez HH, Stamler D, Davis MD, et al. Long-term safety and
efficacy of deutetrabenazine for the treatment of tardive
dyskinesia. J Neurol Neurosurg Psychiatry. 2019. published online
2019 Jul 10. DOI:10.1136/jnnp-2018-319918.
• Important long-term observations of deutetrabenazine treatment.
13. Jankovic J, Jimenez-Shahed J, Budman C, et al.
Deutetrabenazine in tics associated with Tourette syndrome.
Tremor Other Hyperkinet Mov (NY). 2016;6:422.
14. O’Brien CF, Jimenez R, Hauser RA, et al. NBI-98854, a selective
monoamine transport inhibitor for the treatment of tardive
dyskinesia: a randomized, double-blind, placebo-controlled
study. Mov Disord. 2015;30:1681–1687.
•• The randomized, double-blind, placebo-controlled trial of
valbenazine in tardive dyskinesia.
15. Hauser RA, Factor SA, Marder SR, et al. KINECT3: a phase 3 rando-
mized, double-blind, placebo-controlled trial of valbenazine for
tardive dyskinesia. Am J Psychiatry. 2017;174:476–484.
•• The randomized, double-blind, placebo-controlled trial of val-
benazine in tardive dyskinesia.
16. Factor SA, Remington G, Comella CL, et al. The effects of valbena-
zine in participants with tardive dyskinesia: results of the 1-year
KINECT 3 extension study. J Clin Psychiatry. 2017;78:
1344–1350.
• Important long-term observations of valbenazine treatment.
17. Correll CU, Cutler AJ, Kane JM, et al. Characterizing treatment
effects of valbenazine for tardive dyskinesia: additional results
from the KINECT 3 study. J Clin Psychiatry. 2018;80:18m12278.
DOI:10.4088/JCP.18m12278.
18. Claassen DO, Carroll B, De Boer LM, et al. Indirect tolerability
comparison of deutetrabenazine and tetrabenazine for
Huntington disease. J Clin Mov Disord. 2017;4:3.
19. Rodrigues FB, Duarte GS, Costa J, et al. Meta-research metrics
matter: letter regarding article “indirect tolerability comparison
of deutetrabenazine and tetrabenazine for Huntington dis-
ease”. J Clin Mov Disord. 2017;4:19.
20. Niemann N, Jankovic J. Real-world experience with VMAT2
inhibitors. Clin Neuropharmacol. 2019;42:37–41.
21. Niemann N, Jankovic J. Treatment of tardive dyskinesia:
a general overview with focus on the vesicular monoamine
transporter 2 inhibitors. Drugs. 2018;78:525–541.
22. Aggarwal S, Serbin M, Yonan C. Indirect treatment comparison
of valbenazine and deutetrabenazine efficacy and safety in
tardive dyskinesia. J Comp Eff Res. 2019;8:1077–1088.