scholarly journals Categorical improvement in functional impairment in depressed patients treated with desvenlafaxine

CNS Spectrums ◽  
2017 ◽  
Vol 24 (03) ◽  
pp. 322-332 ◽  
Author(s):  
Claudio N. Soares ◽  
Min Zhang ◽  
Matthieu Boucher
Keyword(s):  
Functional Outcome ◽  
Functional Impairment ◽  
Antidepressant Treatment ◽  
Pooled Analysis ◽  
Study Endpoint ◽  
Double Blind ◽  
Early Improvement ◽  
Outcome Monitoring ◽  
Treatment Comparisons ◽  
Post Hoc

ObjectiveThis post-hoc pooled analysis evaluated categorical change in functional impairment in patients with major depressive disorder (MDD) treated with desvenlafaxine versus placebo and examined whether early improvement in functioning predicted functional outcomes at study endpoint.MethodsData were pooled from eight randomized, double-blind, placebo-controlled studies of desvenlafaxine for the treatment of MDD, including adults who were randomly assigned to receive desvenlafaxine 50 or 100 mg/d or placebo (N=3,384). Shift tables were generated for categorical changes in functional impairment from baseline based on Sheehan Disability Scale (SDS) subscale scores. The categories were none/mild (0–3), moderate (4–6), and marked/extreme (7–10). Treatment comparisons for prespecified shifts of interest and predictive value of week 2 or 4 improvement in SDS subscale scores for functional outcome at week 8 were assessed using logistic regression.ResultsGreater proportions of patients receiving desvenlafaxine 50 and 100 mg achieved improvement from baseline to week 8 for each prespecified shift endpoint versus placebo (all p ≤ 0.02). Early improvement in SDS subscale scores was a statistically significant predictor of functional outcome at week 8, both overall and for each treatment group (all p<0.0001).ConclusionsTreatment with desvenlafaxine 50 or 100 mg/d led to significantly greater categorical improvement in functional impairment versus placebo, and improvement in SDS subscale scores significantly predicted functional outcome. Monitoring patient progress early in the course of antidepressant treatment using a functional assessment such as the SDS may help clinicians determine whether or not treatment adjustments are needed.

scholarly journals 139 Early Response with Valbenazine and Long-Term Symptom Reduction in Patients with Tardive Dyskinesia: Post Hoc Analysis of the KINECT 3 Study

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 288-289
Author(s):  
Stanley N. Caroff ◽  
Jean-Pierre Lindenmayer ◽  
Stephen R. Marder ◽  
Stewart A. Factor ◽  
Khodayar Farahmand ◽  
...  
Keyword(s):  
Tardive Dyskinesia ◽  
Early Response ◽  
Term Treatment ◽  
Score Change ◽  
Double Blind ◽  
Early Improvement ◽  
Long Term Treatment ◽  
Post Hoc ◽  
Improvement Score

Abstract:Study Objective:Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Valbenazine is a highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of TD in adults. Using data from a long-term study (KINECT 3; NCT02274558), the effects of once-daily valbenazine (40 mg, 80 mg) on TD were assessed using the Abnormal Involuntary Movement Scale (AIMS) in participants who were early responders based on subjective measures, including patient self-report (Patient Global Impression of Change [PGIC]) or clinician judgment (Clinical Impression of Change-Tardive Dyskinesia [CGI-TD]).Methods:Data from KINECT 3 (6-week double-blind, placebo-controlled [DBPC] period; 42-week double-blind extension) were analyzed post hoc. Long-term outcomes included mean change from baseline to Week 48 in AIMS total score (sum of items 1-7) and AIMS response (≥50% total score improvement from baseline) at Week 48. These AIMS outcomes were assessed in participants who achieved early improvement, defined as a PGIC or CGI-TD score of ≤3 (“minimally improved” or better) at Week 2 (first post-baseline visit of the DBPC period). Participants who initially received placebo were not included in the analyses.Results:In participants who received only valbenazine (40 or 80 mg) during KINECT 3 and had available Week 2 assessment, 50% (72/143) had early PGIC improvement (score ≤3) and 43% (61/142) had early CGI-TD improvement (score ≤3). Baseline characteristics were generally similar between participants who achieved early PGIC or CGI-TD improvement and those who did not. Based on available assessments at Week 48, mean AIMS total score change from baseline in participants with early PGIC improvement was similar to those who did not reach the early PGIC improvement threshold (-4.1 [n=35] vs -3.5 [n=41]). Mean AIMS total score change from baseline in participants with early CGI-TD improvement was similar to those who did not achieve early CGI-TD improvement (-4.2 [n=31] vs -3.5 [n=45]). AIMS response at Week 48 was also similar in those who achieved early PGIC and CGI-TD improvement (40% and 42%, respectively) compared to those who did not achieve early PGIC and CGI-TD improvement (39% and 38%, respectively).Conclusions:Results from this long-term valbenazine trial indicate that many participants achieved at least minimal patient- and clinician-reported improvement at Week 2. AIMS outcomes at Week 48 demonstrated long-term reductions in TD severity regardless of early response. More research is needed to understand the association between early improvement and long-term treatment effects, but early non-improvement based on subjective measures may not be predictive of long-term treatment failure.Presented:International Congress of Parkinson’s Disease and Movement Disorders; September 22-26, 2019; Nice, France.Funding Acknowledgements:This study was sponsored by Neurocrine Biosciences, Inc.

Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial

2020 ◽  
pp. 1-9 ◽  
Author(s):  
Le Xiao ◽  
Xuequan Zhu ◽  
Amy Gillespie ◽  
Yuan Feng ◽  
Jingjing Zhou ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Additional Treatment ◽  
Combination Group ◽  
Open Label ◽  
Major Depressive ◽  
Double Blind ◽  
Early Improvement

Abstract Background This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment. Methods This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization. Results A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects. Conclusions After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.

scholarly journals POST HOC EVIDENCE FOR AN ADDITIVE EFFECT OF MEMANTINE AND DONEPEZIL: CONSISTENT FINDINGS FROM DOMINO-AD STUDY AND MEMANTINE CLINICAL TRIAL PROGRAM

2015 ◽  
pp. 1-7
Author(s):  
S. Hendrix ◽  
N. Ellison ◽  
S. Stanworth ◽  
V. Otcheretko ◽  
P.N. Tariot
Keyword(s):  
Clinical Trial ◽  
Daily Living ◽  
Randomized Trials ◽  
Controlled Trial ◽  
Pooled Analysis ◽  
Neuropsychiatric Inventory ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Clinical Trial Program ◽  
Post Hoc

Background: Several randomized trials have demonstrated superiority of memantine-cholinesterase inhibitor combination therapy in patients with moderate to severe Alzheimer’s disease, yet a recent publication reported no additional benefit of add-on memantine therapy compared to donepezil alone. Objectives: In this post hoc analysis, we sought to re-evaluate the results from the DOMINO study using common statistical tools and to apply the statistical models used in the DOMINO study to a pooled data set of 24- to 28-week randomized trials of memantine in patients with moderate to severe AD in order to explore the robustness of the primary findings from the DOMINO study. Design: DOMINO study: Randomized, double-blind, placebo-controlled trial (Current Controlled Trial number, ISRCTN49545035); Memantine Clinical Trial Program: Pooled analysis from four randomized, double-blind, placebo-controlled trials. Setting: DOMINO study: United Kingdom; Memantine Clinical Trial Program: Multinational. Participants: DOMINO study: 295 participants enrolled during the period of February 2008 to March 2010; Memantine Clinical Trial Program: 1417 participants enrolled between August 1998 and January 2008. Measurements: In the DOMINO study, the co-primary outcome measures were scores on the Standardized Mini-Mental State Examination and the Bristol Activities of Daily Living Scale; Neuropsychiatric Inventory was a secondary measure. In the Memantine Clinical Trial Program, outcome measures included the Severe Impairment Battery, the 19-item Alzheimer’s Disease Cooperative Study – Activities of Daily Living scale, Neuropsychiatric Inventory, and a 4-Domain Composite Index (Z-score; a post hoc assessment). Results: Both the pooled analysis of the Memantine Clinical Trial Program and the re-assessment of the DOMINO study with common statistical tools showed that adding memantine to donepezil therapy is associated with benefits across multiple clinical domains. Conclusions: The current analyses suggest that the results of the DOMINO study do not contradict previous studies which investigated the combined effects of memantine-cholinesterase inhibitor treatment.

scholarly journals Lurasidone for the treatment of depressive symptoms in schizophrenia: analysis of 4 pooled, 6-week, placebo-controlled studies

CNS Spectrums ◽  
2014 ◽  
Vol 20 (2) ◽  
pp. 140-147 ◽  
Author(s):  
Henry A. Nasrallah ◽  
Josephine B. Cucchiaro ◽  
Yongcai Mao ◽  
Andrei A. Pikalov ◽  
Antony D. Loebel
Keyword(s):  
Depressive Symptoms ◽  
Rating Scale ◽  
Antipsychotic Agent ◽  
Pooled Analysis ◽  
Double Blind ◽  
Madrs Score ◽  
Level Data ◽  
Post Hoc ◽  
Major Depressive Episodes ◽  
Depressive Episodes

ObjectiveDepressive symptoms are common in schizophrenia and can worsen outcomes and increase suicide risk. Lurasidone is an atypical antipsychotic agent indicated for the treatment of schizophrenia and for the treatment of major depressive episodes associated with bipolar I disorder. This post hoc analysis evaluated the effect of lurasidone on depressive symptoms in patients with schizophrenia.MethodsPatient-level data were pooled from 4 similarly designed, double-blind, placebo-controlled, 6-week registration studies of lurasidone (40–160 mg/d) in adult patients with an acute exacerbation of schizophrenia. Changes in depressive symptoms, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), were analyzed for the overall sample and for subgroups of patients stratified by baseline MADRS scores.ResultsMADRS assessments at baseline and endpoint (day 42 or last observation carried forward [LOCF]) were available for 1330 patients. Patients receiving lurasidone experienced significantly greater decreases in MADRS score (–2.8, least-squares [LS] mean change, LOCF) compared with patients receiving placebo (–1.4, P < .001, effect size 0.24). Analysis of change in MADRS score (LOCF) by baseline symptom severity (MADRS score of ≥12, ≥14, ≥16, ≥18) showed significantly greater improvement for lurasidone-treated patients across all severity groups; effect sizes ranged from 0.25 to 0.34. Among patients with a baseline MADRS score of ≥12, depressive symptom remission (defined as MADRS score <10 at LOCF endpoint) was attained by 45.0% of lurasidone-treated patients and 36.3% of patients receiving placebo (P < .05).ConclusionsIn a pooled analysis of short-term, placebo-controlled studies, lurasidone significantly improved depressive symptoms in patients with schizophrenia.

Effects of once-daily adjunct quetiapine XR on sleep disturbance in patients with mdd: a pooled analysis from two acute studies

2011 ◽  
Vol 26 (S2) ◽  
pp. 608-608
Author(s):  
M. Bauer ◽  
R.S. McIntyre ◽  
J. Szamosi ◽  
H. Eriksson
Keyword(s):  
Sleep Quality ◽  
Sleep Disturbance ◽  
Pooled Analysis ◽  
Inadequate Response ◽  
Score Change ◽  
Madrs Total Score ◽  
Double Blind ◽  
Disturbance Factor ◽  
Secondary Endpoints ◽  
Post Hoc

IntroductionDisrupted sleep is common in depression.ObjectivesInvestigate effects of adjunct extended release quetiapine fumarate (QTP-XR) on sleep disturbance and quality in patients with MDD and inadequate response to antidepressant (AD) therapy.MethodsData were pooled from two (D1448C00006/D1448C00007) 6-week, double-blind, randomised, placebo (placebo+AD)-controlled studies of adjunct QTP-XR (15 0 mg/day and 300 mg/day). Primary endpoint: MADRS total score change versus placebo+AD. Secondary endpoints (post hoc): change from randomisation in MADRS item 4 (reduced sleep), HAM-D items 4, 5 and 6 (early-, middle- and late-insomnia), sleep disturbance factor (HAM-D items 4+5+6) and sleep quality (PSQI global score). MADRS total score change in patients with baseline HAM-D sleep disturbance factor score > = 4 or < 4 (high and low sleep disturbance, respectively) was evaluated.Results919 patients received adjunct QTP-XR: 150 mg/day (n = 309), 300 mg/day (n = 307), placebo+AD (n = 303). At Week 6, adjunct QTP-XR (both doses) reduced MADRS item 4, HAM-D sleep disturbance factor, HAM-D items 4, 5 and 6 and PSQI global scores from baseline versus placebo+AD (p < 0.001). In patients with baseline HAM-D>=4 (n = 226, 215 and 210, respectively) adjunct QTP-XR (both doses) improved (p< 0.01) MADRS total score versus placebo+AD from Week 1 onward. In patients with baseline HAM-D< 4 (n = 83, 92, 93, respectively) adjunct QTP-XR (both doses) improved (not statistically significantly) MADRS total score versus placebo+AD at Week 6.ConclusionsAdjunct QTP-XR significantly restored sleep and improved sleep quality in patients with MDD and inadequate response to AD. Significant improvement in depressive symptoms was demonstrated with adjunct QTP-XR in patients with MDD and high baseline sleep disturbance. AstraZeneca funded.

P.3.d.045 Early improvement predicts endpoint response to lurasidone in schizophrenia: pooled analysis of five double-blind trials

2013 ◽  
Vol 23 ◽  
pp. S485 ◽  
Author(s):  
C. Correll ◽  
P. Werner ◽  
A. Pikalov ◽  
J. Hsu ◽  
J. Cucchiaro ◽  
...  
Keyword(s):  
Pooled Analysis ◽  
Double Blind ◽  
Early Improvement ◽  
Blind Trials

130 Consistent Efficacy of DR/ER-MPH on Early Morning Functioning in Children With ADHD: Analysis of BSFQ Item Ratings From a Pivotal Phase 3 Trial

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 82-82
Author(s):  
Timothy E. Wilens ◽  
Steven R. Pliszka ◽  
Valerie K. Arnold ◽  
Andrea Marraffino ◽  
Norberto J. DeSousa ◽  
...  
Keyword(s):  
Early Morning ◽  
Analysis Of Covariance ◽  
Phase 3 ◽  
Pivotal Phase ◽  
Double Blind ◽  
Children With Adhd ◽  
Item Scores ◽  
Before School ◽  
Treatment Comparisons ◽  
Post Hoc

AbstractObjectiveIn a phase 3 trial of children with attention-deficit/hyperactivity disorder (ADHD), DR/ER-MPH (formerly HLD200), a delayed-release and extended-release methylphenidate, improved ADHD symptoms and reduced at-home early morning and late afternoon/evening functional impairment versus placebo. The validated Before School Functioning Questionnaire (BSFQ), a key secondary endpoint, was used to measure early morning functional (EMF) impairment. This post hoc analysis evaluated the effect of DR/ER-MPH versus placebo on individual BSFQ item scores from baseline.MethodData were analyzed from a pivotal, randomized, double-blind, multicenter, placebo-controlled, parallel-group, phase 3 trial of DR/ER-MPH in children (6-12 years) withADHD (NCT02520388). Using the 20-item BSFQ, investigators evaluated EMF impairment by scoring each item on a severity scale of 0 to 3, with 0 denoting “no impairment” and 3 denoting “severe impairment”. For post hoc analyses, treatment comparisons between DR/ER-MPH and placebo at endpoint were determined by using least squares mean changes from baseline on individual BSFQ items score derived from an analysis of covariance (ANCOVA) model with treatment as the main effect, and study center and baseline score as covariates.ResultsOf 163 children enrolled across 22 sites, 161 were included in the intent-to-treat population (DR/ER-MPH, n=81; placebo, n=80) and 138 completed the study. The mean DR/ER-MPH dose achieved after 3 weeks of treatment was 68.1 mg. Following 3 weeks of treatment, DR/ER-MPH significantly reduced mean BSFQ item scores frombaseline on 18 out of 20 items versus placebo (P<0.001 in 8 items [listening, following directions, attention, forgetfulness, talkativeness, silliness, time awareness, getting to school]; P<0.01 in 7 items [overall organization, being quiet, distraction, interrupt/blurt out, breakfast, hygiene, independence]; P<0.05 in 3 items [procrastination, hyperactivity, awaiting turn]). Only “dressing” and “misplacing/losing items” showed no significant between-group differences (P=0.171 and P=0.175, respectively). Distributions of the severity ratings for each item will be presented. No serious TEAEs were reported; TEAEs were consistent with methylphenidate.ConclusionsPost hoc analyses revealed that DR/ER-MPH significantly reduced 18 out of 20 individual BSFQ item scores versus placebo in children with ADHD. These findings are worth further exploration.Funding AcknowledgementsIronshore Pharmaceuticals & Development, Inc.

scholarly journals Outcome for headache and pain-free nonresponders to treatment of the first attack: A pooled post-hoc analysis of four randomized trials of eletriptan 40 mg

Cephalalgia ◽  
2013 ◽  
Vol 34 (5) ◽  
pp. 376-381 ◽  
Author(s):  
Steve H Landy ◽  
Stewart J Tepper ◽  
Edward Schweizer ◽  
Mary Almas ◽  
Elodie Ramos
Keyword(s):  
Logistic Regression ◽  
Initial Dose ◽  
Logistic Regression Model ◽  
Randomized Trials ◽  
Pooled Analysis ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
Multiple Attack

Objective The objective of this article is to evaluate, in first attack eletriptan headache and pain-free nonresponders, the efficacy of treating a second and third attack with the same dose of eletriptan 40 mg (ELE-40). Methods Data were pooled from four randomized, double-blind, placebo-controlled, multiple attack studies of eletriptan in the treatment of migraine. The first-attack eletriptan headache (HNR) and pain-free (PFNR) nonresponder samples consisted of patients who did not achieve headache or pain-free responses at two hours, or sustained headache or pain-free responses at 24 hours. The efficacy of the same dose of eletriptan (vs placebo; PBO) in treating the second and third attacks was evaluated using a logistic regression model. Results Among Attack 1 eletriptan HNRs, treatment with ELE-40 (vs PBO) was associated with significantly higher two-hour headache response and pain-free rates, respectively, on both Attack 2 (48.8% vs 20.2%; 17.0% vs 3.9%; p < 0.0001 for both comparisons) and Attack 3 (37.4% vs 15.5%; 18.8% vs 3.2%; p < 0.0001 for both comparisons). Significantly higher sustained headache response and pain-free rates at 24 hours were also observed on both Attack 2 and Attack 3. Conclusions The results of this pooled analysis suggest that patients who have HNR or PFNR to an initial dose of eletriptan may respond when a second and third attack is treated with the same dose.

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