Tetrabenazine Augmentation in Treatment-Resistant Schizophrenia: A 12-Week, Double-Blind, Placebo-Controlled Trial

  title={Tetrabenazine Augmentation in Treatment-Resistant Schizophrenia: A 12-Week, Double-Blind, Placebo-Controlled Trial},
  author={Gary Remington and Shitij Kapur and George Foussias and Ofer Agid and Steve W. Mann and Carol Borlido and Sandra Richards and Naima Javaid},
  journal={Journal of Clinical Psychopharmacology},
Abstract Evidence linking schizophrenia to alterations in presynaptic dopamine (DA) grows, although treatments to date have largely focused on postsynaptic D2 receptor blockade. This study examined augmenting response in treatment-resistant schizophrenia through the addition of tetrabenazine (TBZ), a presynaptic vesicular monoamine transporter (VMAT2) inhibitor. Participants included 41 outpatients (mean age, 43.5 years) with treatment-refractory schizophrenia, stabilized on their present… 

Augmentation Strategies in Patients with Schizophrenia Who Show Partial Response to Clozapine Treatment: A Systematic Review 2

Relevant clinical investigations have determined that sufficient evidence does not yet exist regarding the success of various adjunctive treatments for clozapine resistant patients, and these studies have limitations consisting of small sample size, variable definitions of clozAPine resistance, heterogeneity of outcome measures, and methodological designs.

Augmentation strategies in partial responder and/or treatment-resistant schizophrenia patients treated with clozapine

More research is needed to better define outcomes in schizophrenia, the topic of treatment-resistance and more well-designed trials are required to establish true efficacy and safety of CLZ augmentation strategies.

[Augmentation strategies in patients with schizophrenia who show partial response to clozapine treatment].

Findings from relevant clinical studies point that sufficient evidence does not yet exist regarding the success of various adjunctive treatments for clozapine resistant patients and that theses studies have limitations of small sample size, variable definitions of clozAPine resistance, heterogenity of outcome measures and methodological designs.

Treatment-Resistant Schizophrenia Patients Show Elevated Anterior Cingulate Cortex Glutamate Compared to Treatment-Responsive.

It is suggested that glutamatergic treatments may be particularly effective in resistant patients and that 1H-MRS glutamate indices can potentially have clinical use.

Tetrabenazine for treatment of chorea associated with Huntington's disease and other potential indications

Tetrabenazine, the first FDA-approved therapy for HD, provides symptomatic relief of chorea but there is no evidence that it alters the natural course of HD through a disease-modifying effect, and a black box warning against depression and suicidality warrants careful patient selection, close monitoring and judicious use of antidepressants.

Dopamine depleters in the treatment of hyperkinetic movement disorders

  • J. Jankovic
  • Biology, Psychology
    Expert opinion on pharmacotherapy
  • 2016
This review, based largely on a detailed search of PubMed, will summarize the pharmacology and clinical experience with the various VMAT2 inhibitors and promise to be at least as effective as tetrabenazine but with a lower risk of adverse effects, such as sedation, insomnia, depression, parkinsonism, and akathisia.

Resistance is not futile: treatment-refractory schizophrenia – overview, evaluation and treatment

The authors discuss the pragmatic definitions of TRS and review treatments consisting of antipsychotic monotherapy and augmentation strategies, which support clozapine as having the most efficacy for TRS.

Valbenazine granted breakthrough drug status for treating tardive dyskinesia

  • T. Müller
  • Psychology, Medicine
    Expert opinion on investigational drugs
  • 2015
Valbenazine may also support the onset of symptoms, such as Parkinsonism and depression, with chronic administration, as it, to a certain extent, shares the mode of action of tetrabenazine.

Treatment of Resistant and Ultra Resistant Schizophrenia.

Attempts to augment clozapine effectiveness are being made by increasing the dose of monotherapy, using antipsychotic polipharmacy or adding other types of drugs to clozAPine, but these augmentation methods have not yet proven themselves to be effective enough to be added to standard therapy algorythms.



Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine.

In this relatively brief study, the apparently increased comparative risk of agranulocytosis requires that the use of clozapine be limited to selected treatment-resistant patients.

Augmenting Clozapine Response in Treatment-Resistant Schizophrenia

The present chapter focuses on controlled evidence available to guide clinical decision making in the face of clozapine partial response, and underscores the need for substantially more work along these lines.

Comparison of Weight Gain in Treatments for Tourette Syndrome: Tetrabenazine Versus Neuroleptic Drugs

Weight gain over time was compared in a group of pediatric tic patients taking only tetrabenazine with an age-matched group of tics taking only neuroleptic drugs.

Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials.

In certain clinical situations, antipsychotic cotreatment may be superior to monotherapy, however, the database is subject to possible publication bias and too heterogeneous to derive firm clinical recommendations, underscoring the need for future research.

Long‐term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders

Comparison of log‐likelihood ratios revealed that age was a reliable predictor of Parkinsonism (P < 0.0001) and TBZ is a safe and effective drug for the long‐term treatment of hyperkinetic movement disorders.

Long-term effects of tetrabenazine in hyperkinetic movement disorders

TBZ is an effective and safe drug for the treatment of a variety of hyperkinetic movement disorders and in contrast to typical neuroleptics, TBZ has not been demonstrated to cause tardive dyskinesia.

Tetrabenazine, an amine-depleting drug, also blocks dopamine receptors in rat brain.

It is concluded that, in addition to depleting monoamines, TBZ also blocks both presynaptic and postsynaptic DA receptors in rat brain.

Management of treatment resistance in schizophrenia

The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements.

An extensive literature review was conducted to determine whether the current psychopharmacological treatment recommendations required revision and whether there was sufficient evidence to warrant new treatment recommendations for prespecified outcomes of interest.

Antipsychotic drug doses and neuroleptic/dopamine receptors

It is reported here that all clinically effective antipsychotic drugs (tested so far) block the stereo-specific binding of 3H-haloperidol at concentrations which correlate directly with the clinical potencies.