scholarly journals 132 Effects of Valbenazine on Depression and Suicidality in Adults With Tardive Dyskinesia: Pooled Results of 3 Double-Blind, Placebo-Controlled Trials

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 82-83
Author(s):  
Gary Remington ◽  
Dao Thai-Cuarto ◽  
Joshua Burke ◽  
Scott Siegert ◽  
Grace S. Liang
Keyword(s):  
Suicidal Ideation ◽  
Mood Disorder ◽  
Schizoaffective Disorder ◽  
Rating Scale ◽  
Depression Scale ◽  
Controlled Trials ◽  
Double Blind ◽  
Once Daily ◽  
Double Blind Placebo ◽  
Safety Population

AbstractStudy ObjectivesValbenazine (INGREZZA; VBZ) is a novel and highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor that is approved for the treatment of tardive dyskinesia (TD) in adults. The randomized, double-blind, placebo (PBO)-controlled trials of VBZ evaluated the treatment of TD in patients with a primary psychiatric diagnosis (schizophrenia/schizoaffective disorder or mood disorder) while on concomitant psychiatric medications to manage these disorders. Since treatment-emergent depression and suicidal ideation/behavior are important clinical concerns in psychiatric patient populations, data from these trials were analyzed to assess the effectsof once-daily VBZ on depression and suicidality.MethodsData were pooled from three 6-week trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), KINECT 3 (NCT02274558). Outcome data were analyzed in the safety population by pooled VBZ doses (40 mg, 80 mg) and PBO. Outcomes of interest included: treatment-emergent adverse events (TEAEs) related to depression or suicidality; mean score change from baseline to Week 6 in the Calgary Depression Scale for Schizophrenia (CDSS, for participants with schizophrenia/schizoaffective disorder) or the Montgomery-Åsberg Depression Rating Scale (MADRS, for participants with mood disorder); and, worsening from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation scores. All outcomes were analyzed descriptively.ResultsThere were 400 total participants in the pooled safety population; 286 participants had schizophrenia/schizoaffective disorder (40 mg, n=82; 80 mg, n=70; PBO, n=134) and 114 had a mood disorder (40 mg, n=28; 80 mg, n=42; PBO, n=44). Over one-third of participants had a lifetime history of suicidal ideation or behavior (40 mg, 45%; 80 mg, 39%; PBO, 37%). Few participants had a depression- or suicide-related TEAE, with no apparent differences between VBZ and PBO: suicidal ideation (40 mg, 3.6%; 80 mg, 0.9%; PBO, 2.2%); depression (40 mg, 0%; 80 mg, 1.8%; PBO, 1.1%); depressive symptom (40 mg, 0.9%; 80 mg, 0%; PBO, 0.6%); suicide attempt (40 mg, 0%; 80 mg, 0.9%; PBO, 0%). Mean changes from baseline to Week 6 in depression scale scores were generally small and similar across treatment groups: CDSS total score (40 mg, -0.5; 80 mg, -0.6; PBO, -0.3); MADRS total score (40 mg, -0.2; 80 mg, -1.7; PBO, 0.6). Few participants had a shift from no suicidal ideation at baseline (C-SSRS score=0) to any suicidal ideation during treatment (C-SSRS score=1-5): 40 mg, 3.9% (4/103); 80 mg, 0.9% (1/111); PBO, 2.9% (5/174).ConclusionData from 3 double-blind, placebo-controlled trials indicate that once-daily VBZ treatment was not associated with a worsening in depression-related symptoms or an increased risk of suicidal ideation or behavior.Funding AcknowledgementsThis study was funded by Neurocrine Biosciences, Inc.

ARIPIPRAZOLE IN THE TREATMENT OF SCHIZOAFFECTIVE DISORDER: POOLED ANALYSIS FROM TWO RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIALS

2008 ◽  
Vol 102 (1-3) ◽  
pp. 270
Author(s):  
Reza Moghadam ◽  
Ira D. Glick ◽  
Raymond Mankoski ◽  
James M Eudicone ◽  
Quyhn-Van Tran ◽  
...  
Keyword(s):  
Schizoaffective Disorder ◽  
Pooled Analysis ◽  
Controlled Trials ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals 77 Long-term Valbenazine Treatment in Patients with Schizophrenia/Schizoaffective Disorder or Mood Disorder and Tardive Dyskinesia

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 214-215 ◽  
Author(s):  
Jean-Pierre Lindenmayer ◽  
Stephen R. Marder ◽  
Carlos Singer ◽  
Cynthia Comella ◽  
Khody Farahmand ◽  
...  
Keyword(s):  
Adverse Events ◽  
Tardive Dyskinesia ◽  
Mood Disorder ◽  
Schizoaffective Disorder ◽  
Psychiatric Diagnosis ◽  
Rating Scale ◽  
Involuntary Movement ◽  
Depression Scale ◽  
Psychiatric Status

AbstractBackgroundPatients treated with antipsychotics, regardless of psychiatric diagnosis, are at risk for developing tardive dyskinesia (TD), a potentially debilitating drug-induced movement disorder. Valbenazine (INGREZZA; VBZ) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat TD in adults. Data from KINECT 4 (NCT02405091) were analyzed to evaluate the long-term effects of VBZ in adults with schizophrenia/schizoaffective disorder (SZD) or mood disorder (MD) and moderate or severe TD.MethodsKINECT 4 included open-label treatment (48weeks) followed by washout (4weeks). Entry requirements included: moderate or severe TD, qualitatively assessed at screening by a blinded, external reviewer; DSM diagnosis of SZD or MD; psychiatric stability (Brief Psychiatric Rating Scale score <50). Stable concomitant psychiatric medications were allowed. Dosing was initiated at 40mg, with escalation to 80mg at Wk4 if participants had a Clinical Global Impression of Change-TD score of ≥3 (minimally improved to very much worse) and tolerated 40mg. A reduction to 40mg was allowed if 80mg was not tolerated (80/40mg); participants unable to tolerate 40mg were discontinued. Safety was the primary focus, but the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7) was used to evaluate changes in TD. Mean changes from baseline (BL) in AIMS total score (rated by on-site investigators) were analyzed descriptively. Safety assessments included treatment-emergent adverse events (TEAEs) and psychiatric scales (Positive and Negative Syndrome Scale [PANSS], Calgary Depression Scale for Schizophrenia [CDSS], Montgomery-Åsberg Depression Rating Scale [MADRS], Young Mania Rating Scale [YMRS], and Columbia-Suicide Severity Rating Scale [C SSRS]).ResultsOf 163 participants in the analyses, 103 completed the study. Adverse events (n=26) was the most common reason for discontinuation. Analyses included 119 participants with SZD (40mg=37; 80mg=76; 80/40mg=6) and 44 with MD (40mg=8; 80mg=31; 80/40mg=5). At Wk48, mean improvements from BL in AIMS total score were: SZD (40mg, –10.1; 80mg,–10.7); MD (40mg, 10.2; 80mg: –11.6). AIMS total scores at Wk52 (end of washout) indicated a return toward BL levels. Compared to SZD, the MD subgroup had a higher incidence of any TEAE (84% vs 61% [all doses]) but fewer TEAEs leading to discontinuation (7% vs 18%). Urinary tract infection was the most common TEAE in the MD subgroup (18%); somnolence and headache were most common in the SZD subgroup (7% each). Psychiatric status remained stable from BL to Wk48: SZD (PANSS positive, –0.7, PANSS negative, –0.6; CDSS, –0.7); MD (MADRS, –0.3; YMRS, –0.3). Most participants (95%) had no change in C-SSRS score during the study.ConclusionSustained and clinically meaningful TD improvements were observed with VBZ, regardless of primary psychiatric diagnosis. VBZ was generally well tolerated and no notable changes in psychiatric status were observed.Funding Acknowledgements: Supported by Neurocrine Biosciences, Inc.

scholarly journals The Treatment of Anxiety in Patients with Somatoform Dysfunction, Reaction to Severe Stress and other Neurotic Disorders: A Multicenter Double-blind Placebo-controlled Randomized Trial

2021 ◽  
Author(s):  
Vladimir Parfenov ◽  
Pavel Kamchatnov ◽  
Aleksandr Amelin ◽  
Evgeny Barantsevich ◽  
Dina Khasanova ◽  
...  
Keyword(s):  
Rating Scale ◽  
Depression Scale ◽  
Severe Stress ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Neurotic Disorders ◽  
Group 3 ◽  
Anxiety Treatment ◽  
The Mean ◽  
Group 1

Abstract The existing treatment of somatoform dysfunction (SD), reaction to severe stress (RSS) and adjustment disorders (AjD) is insufficiently effective and safe. Anxiolytic drug Tenoten (Materia Medica Holding) is shown to be effective in clinical trials (CT). Objectives The aim of multicenter double-blind placebo-controlled randomized CT was to investigate the safety and efficacy of Tenoten in the anxiety treatment of adults with SD, RSS, AjD and other neurotic disorders (oNDs). Methods 390 adults with SD, RSS and AjD or oNDs with the Hospital Anxiety and Depression scale-anxiety (HADS-A) score≥11 were randomized into 4 groups (Tenoten group 14 tablets/day n=127; Tenoten group 3 8 tablets/day n=131, combined Placebo group 2+4 n= 132). The changes from baseline in the mean Hamilton Anxiety Rating Scale (HAM-A) score in groups 1 and 3 after 12 weeks was the primary outcome. Results The decrease in the HAM-A score from 18.81±5.81 to 7.26±4.63 (group 1) and from 18.38±4.3 to 6.40±4.02 (group 3) was observed post-treatment (p group 1/placebo =0.0055, p group 3/placebo <0.0001). The mean changes in the scores in the groups 1, 3 and the Placebo were 11.25, 11.91 and 9.71, respectively. In total, 46 AEs (28 AEs in the Tenoten groups, 18 in the Placebo) were registered in 37 patients (20 in the Tenoten groups, and 17 in the Placebo). No differences in frequency of AEs between groups were found. Conclusions Tenoten was shown to be significantly more effective than placebo in the anxiety treatment of adults with SD, RSS, AjD and oNDs (clinicaltrials.gov NCT03036293).

scholarly journals 67 Effects of Long-term Valbenazine on Psychiatric Status in Patients with Tardive Dyskinesia and a Primary Mood Disorder

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 210-211
Author(s):  
Roger S. McIntyre ◽  
Gary Remington ◽  
Christoph U. Correll ◽  
Rachel Weber ◽  
Khodayar Farahmand ◽  
...  
Keyword(s):  
Mood Disorder ◽  
Rating Scale ◽  
Major Depressive ◽  
Double Blind ◽  
Once Daily ◽  
Mood Symptom ◽  
Psychiatric Status ◽  
Symptom Stability ◽  
Drug Free

AbstractObjectiveValbenazine is approved for tardive dyskinesia (TD) in adults based on clinical trials that included patients with mood disorders (e.g., bipolar disorder, major depressive disorder). In two long-termphase 3 trials, KINECT 3 (NCT02274558) and KINECT 4 (NCT02405091), sustained TD improvements were found in participants who received once-daily treatment with valbenazine (40 or 80mg). Data from these studies were analyzed post hoc to evaluate changes in psychiatric status of patients with a primary mood disorder.MethodsData were pooled from participants with mood disorders in KINECT 3 (6-week double-blind, placebo-controlled period; 42-week double-blind extension period; 4-week drug-free washout) and KINECT 4 (48week open-label treatment; 4-week drug-free washout). At screening, patients must have had a Brief Psychiatric Rating Scale total score <50. Mood changes were evaluated after long-term treatment (Week 48) and washout (Week 52) using the Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS). For each scale, mean changes from baseline in the total score and individual item scores were analyzed descriptively.ResultsOf the 95 participants with a primary mood disorder (40mg , n=32; 80mg , n=63), 59 (62.1%) were diagnosed with bipolar disorder, 32 (33.7%) with major depressive disorder, and 4 (4.2%) with another mood disorder. A majority of all mood participants received concomitant antidepressants (84.2%) and/or antipsychotics (76.8%) during treatment; other common concomitant medications included antiepileptics (47.4%), anxiolytics (38.9%), and anticholinergics (22.1%). Mean YMRS and MADRS total scores in all mood participants indicated mood symptom stability at baseline (YMRS, 2.7; MADRS, 5.9). This stability was maintained during the studies, as indicated by minimal changes from baseline in mean total scores (YMRS: Week 48, 1.0; Week 52, –1.0; MADRS: Week 48, 0.3; Week52,0.9). Changes in individual items on both scales were also small (<±0.3), indicating no clinically significant changes or worsening in specific mood symptoms or domains.ConclusionsMood symptom stability was maintained in patients with TD and a primary mood disorder who received up to 48 weeks of treatment with once-daily valbenazine in addition to their psychiatric medication(s).Funding Acknowledgements: Neurocrine Biosciences, Inc.

scholarly journals 39 Long-term Safety and Tolerability of Once-Daily Valbenazine in Patients with Tardive Dyskinesia

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 196-196
Author(s):  
Stephen R. Marder ◽  
Martha Sajatovic ◽  
Dan Michel ◽  
Joshua Burke ◽  
Khody Farahmand ◽  
...  
Keyword(s):  
Suicidal Ideation ◽  
Rating Scale ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Lifetime History ◽  
Psychiatric Status ◽  
History Of ◽  
Drug Free

AbstractObjectiveTo evaluate the long-term safety and tolerability of once-dailyvalbenazine in adults with tardive dyskinesia(TD).MethodsData were pooled from KINECT 3 (NCT02274558: 6-week double-blind placebo-controlled period, followed by a 42-week double-blind extension and 4-week drug-free washout) and KINECT 4 (NCT02405091: 48-week open-label treatment period and 4-week drug-free washout). KINECT 3/4 study completers could enroll in a subsequent rollover study (NCT02736955: up to 72weeks of open-label treatment or until valbenazine became commercial available); data from this study were described separately for this analysis. Valbenazine dose groups (40 and 80mg) were pooled for analysis. Safety assessments included treatment-emergent adverse events (TEAEs) and the Columbia-Suicide Severity Rating Scale (C-SSRS). Psychiatric status was assessed in KINECT 3 and KINECT 4 using the following measures: Positive and Negative Syndrome Scale (PANSS) total score and Calgary Depression Scale for Schizophrenia (CDSS) in participants with schizophrenia/schizoaffective disorder; Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) in participants with a mood disorder.ResultsAnalyses included 304 KINECT 3/4 participants and 160 rollover participants. In KINECT 3/4, the summary of TEAEs was as follows: any TEAE (71.7%), serious TEAE (16.8%), and discontinuation due to TEAE (15.5%). TEAEs reported in ≥5% of all KINECT 3/4 participants were headache (8.9%), urinary tract infection (8.9%), somnolence (7.9%), fatigue (6.3%), dizziness (5.9%), and suicidal ideation (5.6%). The summary of TEAEs from the rollover study was as follows: any TEAE (53.1%), serious TEAE (10.0%), and discontinuation due to TEAE (5.6%). The most common TEAEs in the rollover study were back pain and urinary tract infection (4.4%, each); no TEAE was reported in ≥5% of participants. Minimal changes in psychiatric status were observed in KINECT 3/4, as indicated by mean score changes from baseline to Week 48 in participants with schizophrenia/schizoaffective disorder (PANSS total, –3.2; CDSS total, –0.5) or a mood disorder (MADRS total, 0.3; YMRS total, –1.0). Over one-third of study participants had a lifetime history of suicidal ideation or behavior (KINECT 3/4, 41%; rollover, 38%). Most participants had no C-SSRS suicidal ideation at study baseline; of these, >90% had no emergence of suicidal ideation at any time during the study (KINECT 3/4, 93% [276/296]; rollover, 98% [153/156]).ConclusionsValbenazine was well tolerated and no unexpected safety signals were found in adults who received >1 year of once-daily treatment. Psychiatric stability was maintained, and few participants experienced any emergence of suicidal ideation during the studies despite 35–40% having a lifetime history of suicidality. These results indicate that once-daily valbenazine may be an appropriate treatment for the long-term management of TD.Funding Acknowledgements: Neurocrine Biosciences, Inc.

The Effect of Desmopressin on Reducing Blood Loss in Cardiac Surgery – A Meta-Analysis of Double-Blind, Placebo-Controlled Trials

1995 ◽  
Vol 74 (04) ◽  
pp. 1064-1070 ◽  
Author(s):  
Marco Cattaneo ◽  
Alan S Harris ◽  
Ulf Strömberg ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Cardiac Surgery ◽  
Blood Loss ◽  
Meta Analysis ◽  
Postoperative Blood Loss ◽  
Controlled Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Transfusion Requirements ◽  
The Mean ◽  
Excessive Blood Loss

SummaryThe effect of desmopressin (DDAVP) on reducing postoperative blood loss after cardiac surgery has been studied in several randomized clinical trials, with conflicting outcomes. Since most trials had insufficient statistical power to detect true differences in blood loss, we performed a meta-analysis of data from relevant studies. Seventeen randomized, double-blind, placebo-controlled trials were analyzed, which included 1171 patients undergoing cardiac surgery for various indications; 579 of them were treated with desmopressin and 592 with placebo. Efficacy parameters were blood loss volumes and transfusion requirements. Desmopressin significantly reduced postoperative blood loss by 9%, but had no statistically significant effect on transfusion requirements. A subanalysis revealed that desmopressin had no protective effects in trials in which the mean blood loss in placebo-treated patients fell in the lower and middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in trials in which the mean blood loss in placebo-treated patients fell in the upper third of distribution (>1109 ml/24 h), desmopressin significantly decreased postoperative blood loss by 34%. Insufficient data were available to perform a sub-analysis on transfusion requirements. Therefore, desmopressin significantly reduces blood loss only in cardiac operations which induce excessive blood loss. Further studies are called to validate the results of this meta-analysis and to identify predictors of excessive blood loss after cardiac surgery.

Oral Azitromycin Prophylaxis, 250 Mg Once Daily Three-Times a Week, in Primary Antibody Deficiencies: A Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial

2018 ◽  
Author(s):  
Cinzia Milito ◽  
Federica Pulvirenti ◽  
Francesco Cinetto ◽  
Vassilios Lougaris ◽  
Annarosa Soresina ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Randomized Clinical Trial ◽  
Primary Antibody ◽  
Double Blind ◽  
Once Daily ◽  
Double Blind Placebo ◽  
Primary Antibody Deficiencies

scholarly journals Impact of maternal supplementation with probiotics during pregnancy on atopic eczema in childhood – a meta-analysis

2011 ◽  
Vol 107 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Katja Doege ◽  
Donata Grajecki ◽  
Birgit-Christiane Zyriax ◽  
Elena Detinkina ◽  
Christine zu Eulenburg ◽  
...  
Keyword(s):  
Atopic Eczema ◽  
Data Extraction ◽  
Meta Analysis ◽  
Significant Risk ◽  
Controlled Trials ◽  
Bacterial Strains ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Study Selection ◽  
The Impact

In the present study, we sought to conduct a literature review of randomised, double-blind, placebo-controlled trials, which assessed the impact of probiotics intake during pregnancy on the development of eczema in children. A meta-analysis was conducted for comparison of the development of atopic eczema in children whose mothers took probiotics during pregnancyv.placebo. Study selection, quality appraisal and data extraction were performed independently and in duplicate. The studies were rated according to their size in order to calculate the influence of individual studies on the meta-analysis. A total of seven randomised, double-blind, placebo-controlled trials, published between 2001 and 2009, were selected from the PubMed and Ovid databases for the meta-analysis. The meta-analysis was performed with statistical software Stata/SE11.0. The completed meta-analysis of the seven studies shows a significant risk reduction for atopic eczema in children aged 2–7 years by the administration of probiotics during pregnancy (reduction 5·7 %;P = 0·022). However, this effect was only significant for lactobacilli (reduction 10·6 %;P = 0·045), but not for a mixture of various bacterial strains as probiotics (difference 3·06 %,P = 0·204). In conclusion, the meta-analysis shows that the administration of lactobacilli during pregnancy prevents atopic eczema in children aged from 2 to 7 years. However, a mixture of various bacterial strains does not affect the development of atopic eczema, independent of whether they contain lactobacilli or not.

Efficacy and Safety of Lebrikizumab in Severe Uncontrolled Asthma: Results from the Lute and Verse Phase II Randomized, Double-Blind, Placebo-Controlled Trials

2014 ◽  
Vol 133 (2) ◽  
pp. AB402 ◽  
Author(s):  
Nicola A. Hanania ◽  
Michael J. Noonan ◽  
Jonathan Corren ◽  
Phillip Korenblat ◽  
Yanan Zheng ◽  
...  
Keyword(s):  
Phase Ii ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Uncontrolled Asthma ◽  
Double Blind ◽  
Double Blind Placebo
Sign in / Sign up

Export Citation Format

Share Document