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The Journal of Clinical Psychiatry May 2020To examine the efficacy of pharmacologic treatments for tardive dyskinesia (TD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the efficacy of pharmacologic treatments for tardive dyskinesia (TD).
DATA SOURCES
PubMed was searched on December 12, 2017, for randomized, placebo-controlled trials examining the treatment of TD using the search terms (drug-induced dyskinesia OR tardive dyskinesia) AND (psychotic disorders OR schizophrenia).
STUDY SELECTION
Studies were included if they examined tardive dyskinesia treatment as the primary outcome and were randomized and placebo-controlled trials.
DATA EXTRACTION
The effect size (standard mean difference) of improvement (compared to placebo) stratified by medication class is reported for each of the trials included in this systematic review. A meta-analysis was conducted utilizing a fixed-effects model.
RESULTS
Vitamin E was associated with significantly greater reduction in TD symptoms compared to placebo (standardized mean difference [SMD] = 0.31 ± 0.08; 95% CI, 0.16 to 0.46; z = 4.1; P < .001). There was significant evidence of publication bias in vitamin E studies (Egger test: P = .02). Shorter duration of treatment and lower dose of vitamin E were significantly associated with greater measured treatment benefit. Vitamin B₆ was associated with significantly greater reduction in TD symptoms compared to placebo (SMD = 1.41 ± 0.22; 95% CI, 0.98 to 1.85; z = 6.4; P < .001) in 2 trials conducted by the same research group. Vesicular monoamine transporter 2 (VMAT2) inhibitors demonstrated significant benefit on tardive dyskinesia symptoms compared to placebo (SMD = 0.63 ± 0.11; 95% CI, 0.41 to 0.85; z = 5.58; P < .005). Amantadine was associated with significantly greater score reduction compared to placebo (SMD = 0.46 ± 0.21; 95% CI, 0.05 to 0.87; z = 2.20; P < .05). Calcium channel blockers were not associated with significantly greater score reduction compared to placebo (SMD = 0.31 ± 0.33; 95% CI, -0.34 to 0.96; z = 0.93; P = .35).
CONCLUSIONS
Data from multiple trials suggests that VMAT2 inhibitors, vitamin E, vitamin B₆, and amantadine may be effective for the treatment of TD. Evidence of publication bias and a significant negative association of dose and duration of treatment with measured efficacy suggest that the benefits of vitamin E in TD may be overstated. Head-to-head trials are needed to compare the efficacy and cost-effectiveness of pharmacologic agents for TD.
Topics: Humans; Psychotropic Drugs; Tardive Dyskinesia
PubMed: 32459404
DOI: 10.4088/JCP.19r12798 -
Current Opinion in Psychiatry Mar 2008To provide an update on tardive dyskinesia rates in patients treated with first-generation or second-generation antipsychotics in studies published since the last... (Review)
Review
PURPOSE OF REVIEW
To provide an update on tardive dyskinesia rates in patients treated with first-generation or second-generation antipsychotics in studies published since the last systematic review in 2004.
RECENT FINDINGS
Across 12 trials (n = 28 051, age 39.7 years, 59.7% male, 70.9% white, followed for 463 925 person-years), the annualized tardive dyskinesia incidence was 3.9% for second-generation antipsychotics and 5.5% for first-generation antipsychotics. Stratified by age, annual tardive dyskinesia incidence rates were 0.35% with second-generation antipsychotics in children, 2.98% with second-generation antipsychotics versus 7.7% with first-generation antipsychotics (P < 0.0001) in adults, and 5.2% with second-generation antipsychotics versus 5.2% with first-generation antipsychotics (P = 0.865) in the elderly (based almost exclusively on one retrospective cohort study). In four adult studies (n = 2088, age 41.2 years, 71.2% male, 62.0% white), tardive dyskinesia prevalence rates were 13.1% for second-generation antipsychotics, 15.6% for antipsychotic-free patients, and 32.4% for first-generation antipsychotics (P < 0.0001).
SUMMARY
Current evidence supports a lower tardive dyskinesia risk for second-generation antipsychotics than for first-generation antipsychotics. Tardive dyskinesia incidence was higher with second-generation antipsychotics than previously reported, possibly due to recent studies with relatively short mean durations and use of nonstandard tardive dyskinesia definitions.
Topics: Adult; Antipsychotic Agents; Cross-Sectional Studies; Dyskinesia, Drug-Induced; Female; Humans; Incidence; Male; Prevalence; Schizophrenia
PubMed: 18332662
DOI: 10.1097/YCO.0b013e3282f53132 -
Psychopharmacology Feb 2024Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce dopaminergic transmission but have limited activity at postsynaptic receptors and so may have antipsychotic activity with lower risk of tardive dyskinesia.
METHODS
We conducted a systematic database search from inception to September 2022 for articles describing the use of VMAT-2 inhibitors in psychosis. Inclusion criteria were as follows: Population: adults diagnosed with psychosis or schizophrenia; Intervention: treatment with tetrabenazine, deutetrabenazine or valbenazine; Comparison: comparison with placebo or/and antipsychotic drug; Outcomes: with efficacy outcomes (e.g. Brief Psychiatric Rating Scale (BPRS) change or clinician assessment) and adverse effects ratings (e.g. rating scale or clinician assessment or dropouts); and Studies: in randomised controlled trials and non-randomised studies.
RESULTS
We identified 4892 records relating to VMAT-2 inhibitor use of which 5 (173 participants) met our a priori meta-analysis inclusion criteria. VMAT-2 inhibitors were more effective than placebo for the outcome 'slight improvement' (risk ratio (RR) = 1.77 (95% CI 1.03, 3.04)) but not for 'moderate improvement' (RR 2.81 (95% CI 0.27, 29.17). VMAT-2 inhibitors were as effective as active comparators on both measures for-'slight improvement' (RR 1.05 (95% CI 0.6, 1.81)) and 'moderate improvement' (RR 1.11 (95% CI 0.51, 2.42). Antipsychotic efficacy was also suggested by a narrative review of 37 studies excluded from the meta-analysis.
CONCLUSIONS
VMAT-2 inhibitors may have antipsychotic activity and may offer promise for treatment of psychosis with the potential for a reduced risk of TD.
Topics: Adult; Humans; Antipsychotic Agents; Psychotic Disorders; Schizophrenia; Tardive Dyskinesia; Tetrabenazine; Vesicular Monoamine Transport Proteins
PubMed: 38238580
DOI: 10.1007/s00213-023-06488-3 -
Psychopharmacology Nov 2022Though clozapine is recommended for treatment of tardive dyskinesia (TD) relating to the use of antipsychotic medications, studies comprehensively investigating the... (Review)
Review
RATIONALE
Though clozapine is recommended for treatment of tardive dyskinesia (TD) relating to the use of antipsychotic medications, studies comprehensively investigating the treatment effect of clozapine on TD are still limited.
OBJECTIVES
This review examines the effectiveness of clozapine as an intervention for tardive dyskinesia and dystonia in patients with all psychiatric conditions. Effectiveness of clozapine, duration to exert the effect and dosage used were also analysed.
METHODS
A search in the PubMed, PsycINFO and clinicaltrials databases was performed, using the search terms "Clozapine" AND "dyskinesia" OR "dystonia". Full-text articles that reported the use of clozapine to treat abnormal involuntary movements and were written in English were included.
RESULTS
A total of 48 studies were identified, of which 13 were clinical trials and 35 were case reports. Significant improvement was seen in 86.7% of patients with schizophrenia spectrum disorders (average dose of clozapine = 355 mg/day) and 93% of patients with other psychiatric disorders (average dose of clozapine = 152.5 mg/day). Patients with other psychiatric diagnoses had faster improvement than the patients with schizophrenia spectrum disorders. Variation in improvements and dosage were also seen in the clinical trials.
CONCLUSION
Results suggested an overall effectiveness of clozapine in the treatment of TD for patients with a range of psychiatric conditions. Different response time and clozapine dosage were seen in patients with different psychiatric conditions, suggesting different treatment protocols are required for different conditions. Most of the studies identified are of inadequate qualities, highlighting the need for high quality studies to provide clearer evidence.
Topics: Humans; Clozapine; Tardive Dyskinesia; Antipsychotic Agents; Schizophrenia; Mental Disorders
PubMed: 36180741
DOI: 10.1007/s00213-022-06241-2 -
Neurological Sciences : Official... Feb 2023Several physical therapy modalities have been used to improve hand tremors in patients with Parkinson's disease (PD). However, little is known about the efficacy of... (Review)
Review
BACKGROUND
Several physical therapy modalities have been used to improve hand tremors in patients with Parkinson's disease (PD). However, little is known about the efficacy of these techniques. Therefore, we conducted this study to synthesize evidence from published studies on the efficacy of physical therapy techniques for hand tremors in PD patients.
METHODS
We followed the PRISMA statement and Cochrane handbook guidelines when conducting this study. We conducted an electronic literature search of PubMed, Cochrane Central Register of Clinical Trials, Web of Science, Ovid, and Embase, and then we selected clinical trials assessing the efficacy of any physical therapy intervention for hand tremors in patients with PD. Study outcomes were extracted, and evidence was synthesized narratively.
RESULTS
A total of six modalities described in six studies were included in this systematic review. Out of the six interventions, the tremor's glove and electrical stimulation showed significant improvements in root mean square angular velocity (59% and 43.8%, respectively) and UPDRS tremor score (P < 0.05 for both). Also, eccentric exercises were associated with significant reductions in the mean resting tremor amplitude (P < 0.05). These data were dependent on single studies; therefore, a meta-analysis was not feasible.
CONCLUSION
Several physical therapy interventions, such as electrical stimulation, exercises, transcranial low voltage pulsed electromagnetic fields, weights, and virtual reality showed promising results in reducing hand tremors. However, this evidence was based on a limited number of included studies, and more RCTs with larger sample sizes are required to confirm the efficacy of these interventions.
Topics: Humans; Parkinson Disease; Tremor; Physical Therapy Modalities; Exercise Therapy
PubMed: 36205810
DOI: 10.1007/s10072-022-06420-1 -
Drug Design, Development and Therapy 2018The aim of this study was to summarize the characteristics, efficacy, and safety of vesicular monoamine transporter-2 (VMAT-2) inhibitors for treating tardive dyskinesia... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this study was to summarize the characteristics, efficacy, and safety of vesicular monoamine transporter-2 (VMAT-2) inhibitors for treating tardive dyskinesia (TD).
MATERIALS AND METHODS
We conducted a literature search in PubMed, Cochrane Database, and ClinicalTrials.gov, screening for systematic reviews, meta-analyses or double-blind, randomized, placebo-controlled trials (DBRPCTs) reporting efficacy or safety data of VMAT-2 inhibitors (tetrabenazine, deutetrabenazine, and valbenazine) in patients with TD. A random effects meta-analysis of efficacy and safety data from DBRPCTs was performed.
RESULTS
Two acute, 12-week DBRPCTs with deutetrabenazine 12-48 mg/day (n=413) and 4 acute, 4-6-week double-blind trials with valbenazine 12.5-100 mg/day (n=488) were meta-analyzable, without meta-analyzable, high-quality data for tetrabenazine. Regarding reduction in total Abnormal Involuntary Movement Scale (AIMS) scores (primary outcome), both deutetrabenazine (k=2, n=413, standardized mean difference [SMD] =-0.40, 95% confidence interval [CI] =-0.19, -0.62, <0.001; weighted mean difference (WMD) =-1.44, 95% CI =-0.67, -2.19, <0.001) and valbenazine (k=4, n=421, SMD =-0.58, 95% CI =-0.26, -0.91, <0.001; WMD =-2.07, 95% CI =-1.08, -3.05, <0.001) significantly outperformed placebo. Results were confirmed regarding responder rates (≥50% AIMS total score reduction; deutetrabenazine: risk ratio [RR] =2.13, 95% CI =1.10, 4.12, =0.024, number-needed-to-treat [NNT] =7, 95% CI =3, 333, =0.046; valbenazine: RR =3.05, 95% CI =1.81, 5.11, <0.001, NNT =4, 95% CI =3, 6, <0.001). Less consistent results emerged from patient-rated global impression-based response (=0.15) and clinical global impression for deutetrabenazine (=0.088), and for clinical global impression change for valbenazine (=0.67). In an open-label extension (OLE) study of deutetrabenazine (≤54 weeks) and a dose-blinded valbenazine study (≤48 weeks), responder rates increased over time. With valbenazine, discontinuation effects were studied, showing TD symptom recurrence towards baseline severity levels within 4 weeks after valbenazine withdrawal. No increased cumulative or specific adverse (AEs) events versus placebo (acute trials) in extension versus acute trial data were observed.
CONCLUSION
The 2 VMAT-2 inhibitors, valbenazine and deutetrabenazine, are effective in treating TD, both acutely and long-term, without concerns about increased risk of depression or suicide in the TD population. No head-to-head comparison among VMAT-2 inhibitors and no high-quality, meta-analyzable data are available for tetrabenazine in patients with TD.
Topics: Antipsychotic Agents; Humans; Randomized Controlled Trials as Topic; Tardive Dyskinesia; Tetrabenazine; Valine; Vesicular Monoamine Transport Proteins
PubMed: 29795977
DOI: 10.2147/DDDT.S133205 -
Neuroscience and Biobehavioral Reviews Jun 2023Depression and apathy are associated with decreased functional capacity in Huntington's disease (HD) but frequency of depression and apathy in HD is largely unknown.... (Meta-Analysis)
Meta-Analysis Review
Depression and apathy are associated with decreased functional capacity in Huntington's disease (HD) but frequency of depression and apathy in HD is largely unknown. Systematic literature searching was conducted across 21 databases until 30 June 2021. Inclusion criteria was limited to clinician-rated assessments of depression and apathy and adult-onset HD. Inverse-variance heterogeneity meta-analyses were conducted exploring depression and apathy frequency within individuals from families affected by HD, and within individuals with confirmed HD gene-positive status. Screening identified 289 articles for full-text review; nine remained for meta-analysis. Depression frequency in the lifetime in adults affected by or at-risk for HD was 38%, I = 99%. Apathy frequency in the lifetime in adults affected by or at-risk for HD was 40%, I = 96%. The robustness of the findings improved when limiting the analysis to gene-positive individuals only where apathy was found to be slightly more common than depression, 48% and 43% respectively. Future studies may consider reporting results from juvenile-onset HD and adult-onset HD cohorts separately to further explore phenotypic profiles.
Topics: Adult; Humans; Apathy; Huntington Disease; Depression
PubMed: 37054804
DOI: 10.1016/j.neubiorev.2023.105166 -
Clinical Journal of Gastroenterology Oct 2021Biliary hyperkinesia is typically diagnosed in patients with biliary-like pain and no evidence of gall stones on imaging modalities but who have had biliary scintigraphy... (Meta-Analysis)
Meta-Analysis Review
Biliary hyperkinesia is typically diagnosed in patients with biliary-like pain and no evidence of gall stones on imaging modalities but who have had biliary scintigraphy scan (HIDA) that shows ejection fraction ≥ 80%. This study aims to identify whether the removal of the gall bladder can alleviate the symptoms associated with biliary hyperkinesia. Systematic search following PRISMA guidelines was done from inception to January 2020 using PubMed/Medline, OVID, Embase, Cochrane database of systemic reviews, Cochrane central register of controlled trials, The Database of Abstracts of Reviews of Effects (DARE) and Cochrane library databases. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardized MD (SMD) for continuous outcomes. A meta-analysis was done using random-effect model in RevMan 5.4 software. Thirteen studies met the inclusion criteria and were included in the review. A total of 332 patients diagnosed with biliary hyperkinesia underwent cholecystectomy, of whom 303 (91.3%) reported symptomatic improvement RR 8.67 (95% CI 4.95, 15.16) P = 0.01. Six studies described abnormal histological features in 163/181 (90.05%) with high GB EF. RR 7.88 (95% CI 3.94, 15.75) P = 0.08. Chronic cholecystitis n = 155 (95%), cholesterolosis n = 7 (4.3%), and one showed features of acute cholecystitis. Patients with typical biliary colic symptoms without gallstones and markedly high ejection fraction might benefit from having cholecystectomy to alleviate their symptoms.
Topics: Cholecystectomy; Cholecystitis, Acute; Gallbladder Diseases; Gallstones; Humans; Hyperkinesis
PubMed: 34115337
DOI: 10.1007/s12328-021-01463-x -
Brain and Behavior Jun 2023Sydenham's chorea (SC), prevalent in developing countries and occasionally affecting developed ones, poses a clinical challenge due to the lack of systematic guidelines... (Review)
Review
INTRODUCTION
Sydenham's chorea (SC), prevalent in developing countries and occasionally affecting developed ones, poses a clinical challenge due to the lack of systematic guidelines for diagnosis and treatment. Resulting from Group A Beta-Hemolytic Streptococcus infection, SC presents various symptoms. This review aims to collect and evaluate available data on SC management to propose a cohesive treatment plan.
METHODS
We searched PubMed, the Cochrane Library, Google Scholar, and ClinicalTrials.gov for literature on SC management from inception until 24th July 2022. Studies were screened by titles and abstracts. Cochrane Collaboration's Risk of Bias tool (RoB-1) assessed Randomized Controlled Trials, while the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool evaluated nonrandomized studies.
RESULTS
The review includes 11 articles assessing 579 patients. Excluding one study with 229 patients, of the remaining 550 patients, 338 (61.5%) were females. Treatments used were dopamine antagonists in 118 patients, antiepileptics in 198, corticosteroids in 134, IVIG in 7, and PE in 8 patients. Dopamine antagonists, particularly haloperidol, were the primary treatment choice, while valproic acid (VPA) was favored among antiepileptics. Prednisolone, a corticosteroid, showed promising results with weight gain as the only side-effect. Our review emphasizes the importance of immunomodulators in SC, contrasting previous literature.
CONCLUSION
Despite limitations, dopamine antagonists can serve as first-line agents in SC management, followed by antiepileptics. The role of immunomodulators warrants further investigation for conclusive recommendations.
Topics: Female; Humans; Male; Chorea; Anticonvulsants; Valproic Acid; Haloperidol; Dopamine Antagonists
PubMed: 37150977
DOI: 10.1002/brb3.3035 -
Tremor and Other Hyperkinetic Movements... 2024Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter... (Comparative Study)
Comparative Study Review
BACKGROUND
Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, have emerged as promising therapies for TD and several clinical trials have shown their efficacy. This study aims to compare the efficacy and safety profile of VMAT2 inhibitors, focusing on a recent trial conducted in the Asian population.
METHODS
We reviewed the PubMed, Cochrane Library, Embase database, and clinicaltrials.gov between January 2017 and October 2023, using the keywords "tardive dyskinesia" AND ("valbenazine" [all fields] OR " deutetrabenazine " [all fields]) AND "clinical trial". The reviewed articles were studied for efficacy and side effects.
RESULTS
An initial search yielded 230 articles, of which 104 were duplicates. Following the title and abstract screening, 25 additional articles were excluded. A full-text review resulted in the exclusion of 96 more articles. Ultimately, four double-blind clinical trials met the inclusion criteria. The deutetrabenazine studies demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared to placebo, with no difference in adverse events. The valbenazine studies showed favorable results in reducing TD symptoms and were well-tolerated.
DISCUSSION
The studies reviewed in this analysis underscore the potential of deutetrabenazine and valbenazine as valuable treatment options for TD in diverse populations. Both medications demonstrated significant improvements in AIMS scores, suggesting their effectiveness in managing TD symptoms. Additionally, they exhibited favorable safety profiles, with low rates of serious adverse events and no significant increase in QT prolongation, parkinsonism, suicidal ideation, or mortality.
CONCLUSION
The studies reviewed highlight the promising efficacy and tolerability of deutetrabenazine and valbenazine as treatments for Tardive Dyskinesia, providing new hope for individuals affected by this challenging condition.
Topics: Humans; Randomized Controlled Trials as Topic; Tardive Dyskinesia; Tetrabenazine; Valine; Vesicular Monoamine Transport Proteins
PubMed: 38497033
DOI: 10.5334/tohm.842