Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review

Abstract

Up to 30% of patients taking antipsychotics may develop tardive dyskinesia (TD). Recent evidence-based recommendations demonstrate an unmet need for effective TD management. This systematic review was designed to update the evidence for TD treatment, comparing two vesicular monoamine transporter 2 (VMAT2) inhibitors, tetrabenazine and valbenazine. Of 487 PubMed/Embase search results, 11 studies met the review criteria. Valbenazine efficacy was demonstrated in rigorously designed clinical trials that meet the guidelines for AAN Class I evidence. Due to differences in study designs and a lack of standardized and controlled trials with tetrabenazine, a formal meta-analysis comparing the agents was not possible. However, valbenazine appears to have fewer side effects and a more favorable once-daily dosing regimen for the treatment of TD. Tardive dyskinesia (TD) is an involuntary movement disorder induced by prolonged exposure to dopamine receptor blocking agents (DRBAs), including antipsychotics and antiemetics [1,2]. Research shows that the prescription of antipsychotics alone increased more than threefold over 10 years; conservative estimates thus indicate that approximately 5 million patients have been exposed to antipsychotics in the United States (US) [3]. Given that the estimated global mean prevalence of TD is 30% in studies of patients currently treated with a first-generation antipsychotic and 21% in those currently treated with a second-generation antipsychotic, this disorder remains a significant problem for psychiatric patients who may experience stigma, embarrassment, and impairment in social functioning (and sometimes physical functioning) as a consequence of developing TD [4]. While the prevalence of TD has been extensively studied, the associated healthcare burden is the subject of continuing investigation [3][4][5]. Previous studies have shown that the presence of TD in patients with schizophrenia may correlate with impaired cognition, poor response to treatment, greater risk of relapse, longer hospital stays, lower quality of life and functioning, a progressive course, and increased mortality [6].Through the mechanism of blocking dopamine receptors, antipsychotics have proven to be highly effective and essential drugs for controlling psychotic symptoms in patients with conditions such as schizophrenia and bipolar disorder [7][8][9][10]. However, dopamine is also involved as a key neurotransmitter in other neural pathways, notably the motor circuit [7,11]. Blockade in the motor circuit may lead to upregulation and hypersensitivity of post-synaptic dopamine receptors, resulting in an increase of dopaminergic signaling and the emergence of abnormal movements associated with TD [10,12].Vesicular monoamine transporters (VMATs) are presynaptic intracellular transmembrane proteins that have a critical role in the packaging, storage and release of dopamine and other monoamines [13]. Inhibition of VMAT2, which is the predominant isoform in the brain, interferes with dopamine uptake and storage in presynapti...

Treatment of tardive dyskinesia with VMAT-2 inhibitors: a systematic review and meta-analysis of randomized controlled trials

“…One systematic review of the effects of tetrabenazine for TD 15 reported results from 12 studies overall, with partially overlapping studies populations, 51 with 2 DBRPCTs (n=10), 1 single-blind placebo-controlled study (n=12), and one haloperidol-controlled, randomized study (n=12). Each study had very small sample sizes, surprisingly with response rates up to 100% for tetrabenazine, and all used poor quality assessment tools and poor reporting of outcomes, precluding inclusion of any of these studies in our meta-analysis.…”

Drug-induced dyskinesias, can they be prevented?

“…Valbenzine and deutetrabenazine have a longer half-life, and are therefore metabolized more slowly in the body. Rigorous trials have confirmed that both drugs are more effective than placebo in reducing the severity of TD and are better tolerated than tetrabenazine [9]. Caroff in his study showed that the use of valbenazine reduces the symptoms of TD, even 4 weeks after its discontinuation [10].…”

“…Walbenzyna i deutetrabenazyna mają dłuższy okres półtrwania, przez co są wolniej metabolizowane w organizmie. Rygorystyczne próby potwierdziły, że oba leki są bardziej skuteczne niż placebo w zmniejszaniu nasilenia TD i są lepiej tolerowane niż tetrabenazyna [9]. Caroff w swoim badaniu wykazał, że stosowanie walbenazyny wpływa na zmniejszenie objawów TD, nawet 4 tygodnie po jej odstawieniu [10].…”

Prävention und Behandlung von Antipsychotika-induzierten tardiven Dyskinesien

“…Die Verwendung des GABA-A-Agonisten Clonazepam in der Therapie der TD wurde in den 1970er-und 1980er-Jahren untersucht, was schließlich in der Publikation einer sehr kleinen RCT im Jahr 1990 resultierte. [53,56,57,58]. Für Deutetrabenazin existieren zwei hochwertige RCT über 12 Wochen, die deutliche Effekte gemessen am AIMS zeigen konnten.…”

“…Tetrabenazin wurde in den Studien gut vertragen und zeigte positive Effekte. Die häufigsten unerwünschten Arzneimittelwirkungen (UAW) waren Parkinsonismus, Depressivität, erhöhte Erschöpfbarkeit und Schläfrigkeit[53]. Patienten mit Suizidgedanken oder einer ausgeprägten depressiven Symptomatik sollten nicht mit Tetrabenazin behandelt werden.…”