Treatment of Tardive Dyskinesia: A General Overview with Focus on the Vesicular Monoamine Transporter 2 Inhibitors

AbstractTardive dyskinesia (TD) encompasses the spectrum of iatrogenic hyperkinetic movement disorders following exposure to dopamine receptor-blocking agents (DRBAs). Despite the advent of atypical or second- and third-generation antipsychotics with a presumably lower risk of complications, TD remains a persistent and challenging problem. Prevention is the first step in mitigating the risk of TD, but early recognition, gradual withdrawal of offending medications, and appropriate treatment are also critical. As TD is often a persistent and troublesome disorder, specific antidyskinetic therapies are often needed for symptomatic relief. The vesicular monoamine transporter 2 (VMAT2) inhibitors, which include tetrabenazine, deutetrabenazine, and valbenazine, are considered the treatment of choice for most patients with TD. Deutetrabenazine —a deuterated version of tetrabenazine—and valbenazine, the purified parent product of one of the main tetrabenazine metabolites, are novel VMAT2 inhibitors and the only drugs to receive approval from the US FDA for the treatment of TD. VMAT2 inhibitors deplete presynaptic dopamine and reduce in voluntary movements in many hyperkinetic movement disorders, particularly TD, Huntington disease, and Tourette syndrome. The active metabolites of the VMAT2 inhibitors have high affinity for VMAT2 and minimal off-target binding. Compared with tetrabenazine, deutetrabenazine and valbenazine have phar macokinetic advantages that translate into...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research

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Authors: Dietrich DE, Bode L, Spannhuth CW, Hecker H, Ludwig H, Emrich HM Abstract BACKGROUND: Whether Borna disease virus (BDV-1) is a human pathogen remained controversial until recent encephalitis cases showed BDV-1 infection could even be deadly. This called to mind previous evidence for an infectious contribution of BDV-1 to mental disorders. Pilot open trials suggested that BDV-1 infected depressed patients benefitted from antiviral therapy with a licensed drug (amantadine) which also tested sensitive in vitro. Here, we designed a double-blind placebo-controlled randomized clinical trial (RCT) which cross-lin...
Source: BMC Pharmacology and Toxicology - Category: Drugs & Pharmacology Tags: BMC Pharmacol Toxicol Source Type: research
Publication date: Available online 18 February 2020Source: Pharmacology Biochemistry and BehaviorAuthor(s): Mei Huang, Wenqi He, Lakshmi Rajagopal, Andrea Kudwa, Dimitri E. Grigoriadis, Herbert Y. MeltzerAbstractValbenazine, a vesicular monoamine transporter 2 (VMAT2, SLC18A2) inhibitor, is a newly approved treatment for tardive dyskinesia. VMAT2 is present in the membrane of secretory vesicles and transports dopamine (DA), norepinephrine (NE), serotonin (5-HT), histamine, glutamate (Glu), and GABA into vesicles for presynaptic release. We utilized microdialysis in awake, freely moving mice to determine the effect of NBI-9...
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research
ConclusionWe have integrated machine learning (ML) with computational modeling and simulations and developed an accurate predictive model to determine MRI gradient-field induced voltage levels on implanted DBS systems.
Source: Frontiers in Human Neuroscience - Category: Neuroscience Source Type: research
Device titration is a major challenge when using deep brain stimulation (DBS) to treat behavioral disorders. Unlike in movement disorders, there is no reliable real-time clinical feedback for changes in complex behaviors resulting from DBS. Here, a female patient receiving DBS of the nucleus accumbens for the treatment of morbid obesity underwent cognitive testing via the flanker task alongside traditional methods of device titration. One set of stimulation parameters administered during titration resulted in acute cognitive improvement (p = 0.033) and increased frontal engagement as measured by electroencephalography (lef...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Condition:   Performance Enhancing Product Use Interventions:   Drug: Suvorexant 10 mg;   Drug: Zolpidem;   Drug: Placebos Sponsor:   Walter Reed Army Institute of Research (WRAIR) Enrolling by invitation
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Cerebral Palsy Intervention:   Drug: Amantadine Hydrochloride Sponsor:   Columbia University Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
This article reviews scales that have been developed for, validated in, and/or frequently used across multiple movement disorders with a focus on assessment of motor and nonmotor symptoms of Parkinson disease. Rating scales used in other disease states include those for essential tremor, dystonia (generalized dystonia, cervical dystonia, and blepharospasm), Tourette syndrome, Huntington disease, tardive dyskinesia, Wilson disease, ataxia, and functional movement disorders. Key features of each scale as well as cited criticisms and limitations of each scale are also discussed. Lastly, the article briefly discusses the emerg...
Source: Neurologic Clinics - Category: Neurology Authors: Source Type: research
ConclusionsInitial results of DBS studies for diverse neurological disorders are encouraging but larger, controlled, prospective, homogeneous clinical trials are necessary to establish long term safety and effectiveness. The field of neuromodulation continues to evolve and advances in DBS technology, stereotactic techniques, neuroimaging, and DBS programming capabilities are shaping the present and future of DBS research and use in practice.This article is protected by copyright. All rights reserved.
Source: European Journal of Neurology - Category: Neurology Authors: Tags: Reviews Source Type: research
Authors: Paton DM Abstract Deutetrabenazine is a derivative of tetrabenazine in which two trideuteromethoxy groups substitute two methoxy groups. The active metabolites of deutetrabenazine have a longer half-life than those of tetrabenazine, together with a greater overall absorption. However, the peak plasma concentrations are lower. Because of these pharmacokinetic differences, deutetrabenazine can be given twice daily, thus improving compliance. The lower peak concentrations may account for a lower incidence of some unwanted adverse effects. Unlike tetrabenazine, deutetrabenazine has no effect on the QT interval...
Source: Drugs of Today - Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research
Authors: Jankovic J Abstract INTRODUCTION: Abnormal involuntary movements often improve in response to anti-dopaminergic drugs. In contrast to classic neuroleptics that block dopamine receptors, drugs that deplete presynaptic dopamine by blocking vesicular monoamine transporter type 2 (VMAT2) seem to be safer and have little or no risk of tardive dyskinesia. This is one reason why there has been a recent emergence of novel VMAT2 inhibitors. Areas Covered: Since the approval of tetrabenazine, the classic VMAT2 inhibitor, in the treatment of chorea associated with Huntington disease (HD), other VMAT2 inhibitors (e.g....
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
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