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...

Any pre-existing medical condition, n (%) 0.0886 0.1799 Yes 436 (81.5%) 177 (86.8%) No 99 (18.5%) 27 (13.2%)

BackgroundPhase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI).MethodsParticipants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C).ResultsThe study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, −7.7 [6.1]; P < .001, 95 % CI: −8.4, −7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, −8.2 [−9.4, −7.0]) and numerically exceeds the improvement seen with placebo in that study (−5.7 [−6.8, −4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were “much” or ”very much” improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related.ConclusionsDM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q.Trial registrationClinicaltrials.gov, NCT01799941, registered on 25 February 2013Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0609-0) contains supplementary material, which is available to authorized users.