Predictors of functional response and remission with desvenlafaxine 50 mg/d in patients with major depressive disorder

CNS Spectrums ◽  
2014 ◽  
Vol 19 (6) ◽  
pp. 519-527 ◽  
Author(s):  
Claudio N. Soares ◽  
Jean Endicott ◽  
Matthieu Boucher ◽  
Rana S. Fayyad ◽  
Christine J. Guico-Pabia
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Functional Response ◽  
Rating Scale ◽  
Treatment Success ◽  
Functional Improvement ◽  
Characteristic Analysis ◽  
Major Depressive ◽  
Double Blind ◽  
Four Levels

BackgroundThe predictive value of early functional improvement for treatment success at week 8 was assessed in a pooled analysis in patients with major depressive disorder (MDD).MethodsData were pooled from 7 double-blind studies in adult patients with MDD randomly assigned to desvenlafaxine 50 mg/d or placebo. Four levels of treatment success were determined at week 8 for patients with baseline Sheehan Disability Scale (SDS) score > 12 (N = 2156): functional response (SDS ≤12 and ≥50% improvement in SDS), functional/depression response (SDS ≤12 and ≥50% improvement in both SDS and 17-item Hamilton Rating Scale for Depression [HAM-D17] score), functional remission (SDS < 7), and functional/depression remission (SDS < 7 and HAM-D17 ≤7). Week 2 improvement in SDS was evaluated as a predictor of later functional response/remission using receiver operating characteristic analysis. Odds ratios (ORs) of the predictability of improvement thresholds were computed from a logistic regression model.ResultsThe proportion of patients achieving each level of treatment success was significantly greater for patients treated with desvenlafaxine (40%, 32%, 23%, 15%, respectively) vs placebo (31%, 22%, 17%, 10%; all P ≤ 0.002). Early change in SDS was a highly significant predictor of functional response/remission (ORs, 0.958–0.970; all P < 0.0001).DiscussionPatients’ early functional response to desvenlafaxine 50 mg/d is predictive of treatment success.

Predictors of functional response and remission with desvenlafaxine 50 mg and 100 mg: a pooled analysis of randomized, placebo-controlled studies in patients with major depressive disorder

CNS Spectrums ◽  
2019 ◽  
Vol 25 (3) ◽  
pp. 363-371
Author(s):  
Claudio N. Soares ◽  
Dalia B. Wajsbrot ◽  
Matthieu Boucher
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Functional Response ◽  
Functional Outcomes ◽  
Roc Analysis ◽  
Treatment Success ◽  
Pooled Analysis ◽  
Functional Improvement ◽  
Major Depressive ◽  
Early Improvement

Objective.The value of early functional improvement at week 2 for predicting subsequent functional outcomes at week 8 was assessed in a pooled analysis of patients with major depressive disorder (MDD) treated with desvenlafaxine (50 or 100 mg/d) or placebo.Methods.Data were pooled from eight double-blind, placebo-controlled studies of desvenlafaxine 50 mg/d or 100 mg/d for the treatment of MDD. Optimal week-2 improvement thresholds in Sheehan Disability Scale (SDS) score, which best predicted week-8 treatment success, were determined using receiver operating characteristic (ROC) analysis. Four definitions of treatment success were established: (1) functional response, (2) functional/depression response, (3) functional remission, and (4) functional/depression remission. Odds ratios (ORs) of early improvement for prediction (based on thresholds determined in the ROC analysis) of week-8 treatment success were computed using logistic regression models.Results.Functional early improvement thresholds of 17%–32% were predictive of week-8 treatment success across treatment groups and definitions of treatment success. Optimal thresholds were higher for more stringent definitions. Negative predictive value exceeded positive predictive value, indicating that failure to achieve early functional improvement was more informative about later treatment success than was the achievement of early functional improvement. Early change in SDS was a highly significant predictor of functional response/remission (ORs, 4.981–8.737; all p < 0.0001); the interaction between treatment and early functional improvement was not significant.Conclusion.Early improvement in SDS total score was predictive of functional outcomes for patients treated with desvenlafaxine 50 mg, desvenlafaxine 100 mg, or placebo.

Propofol Anaesthesia in Electroconvulsive Therapy

1994 ◽  
Vol 165 (4) ◽  
pp. 506-509 ◽  
Author(s):  
Christopher F. Fear ◽  
Carl S. Littlejohns ◽  
Eryl Rouse ◽  
Paul McQuail
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Induction Agent ◽  
Double Blind Study ◽  
Major Depressive ◽  
Seizure Duration ◽  
Double Blind ◽  
Induction Agents

BackgroundThe induction agent propofol is known to reduce electroconvulsive therapy (ECT) seizure duration. It is assumed that outcome from depression is adversely affected by this agent. This study compares propofol and methohexitone as induction agents for ECT.MethodIn a prospective, randomised, double-blind study 20 subjects with major depressive disorder (DSM-III-R criteria) received propofol or methohexitone anaesthesia. The Hamilton Depression Rating Scale and Beck Depression Inventory were used to assess depression before therapy, at every third treatment, and at the end of therapy. Seizure duration was measured using the cuff technique.ResultsMean seizure durations (P < 0.01) and mean total seizure duration (P < 0.01) were shorter in the propofol group. There was no difference in outcome.ConclusionsUse of propofol may not adversely affect outcome from depression and it is not necessarily contraindicated as an induction agent for ECT. Our results should be interpreted cautiously, and larger studies are needed.

EEG Synchronized TMS for Individualized Therapy in Major Depressive Disorder

2011 ◽  
Vol 26 (S2) ◽  
pp. 1144-1144
Author(s):  
Y. Jin ◽  
J. Phillips ◽  
Yueqin Huang ◽  
Steven Heurta
Keyword(s):  
Major Depressive Disorder ◽  
Side Effects ◽  
Depressive Disorder ◽  
Active Treatment ◽  
Rating Scale ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Stimulus Frequency ◽  
List Type ◽  
Major Depressive ◽  
Double Blind

IntroductionEfficacy of conventional repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder (MDD) is limited. The authors report here on an alternative treatment using low energy synchronized TMS (sTMS) at the intrinsic frequency of subjects’ alpha electroencephalogram (EEG).ObjectivesEstablish efficacy and safety profile of sTMS in MDD.Aim(1)Examine the clinical effectiveness of sTMS.(2)Identify adverse effects associated with sTMS.MethodsFifty-two MDD subjects with 17-item Hamilton Depression Rating Scale (HAMD17) scores >17 were enrolled into a randomized, sham controlled, double-blind trial. Current medication remained unchanged during the trial. Depressive symptoms were evaluated by HAMD17 administered weekly.EEGs were recorded at baseline to determine the stimulus frequency and at week 4 to evaluate the physiological effect. sTMS was delivered through three 6000-G cylindrical neodymium magnets synchronously rotating at a rate equal to the subject's intrinsic alpha frequency.ResultsForty-five subjects completed at least 1 week of treatment and were evaluable. Those who received active treatment had superior clinical response to sham (t = 2.54, P = 0.01), where 55.2% in the active treatment group were clinical responders versus 12.5% in sham (X2 = 7.82, P = 0.005). No significant side effects were reported. The clinical improvement was correlated with the degree of EEG improvement (r = .46, P = 0.009).ConclusionsA therapeutic effect in MDD subjects can be achieved through administration of sTMS at the subject's alpha EEG frequency. Because of minimal side effects, this appears to be a safe and effective treatment option.

scholarly journals Efficacy of levomilnacipran extended-release in major depressive disorder: pooled analysis of 5 double-blind, placebo-controlled trials

CNS Spectrums ◽  
2014 ◽  
Vol 20 (2) ◽  
pp. 148-156 ◽  
Author(s):  
Stuart A. Montgomery ◽  
Carl P. Gommoll ◽  
Changzheng Chen ◽  
William M. Greenberg
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Extended Release ◽  
Rating Scale ◽  
Pooled Analysis ◽  
Major Depressive ◽  
Double Blind ◽  
Madrs Score ◽  
Wide Range ◽  
Remission Rates

Introduction/ObjectivePost hoc analyses were conducted to evaluate the efficacy of levomilnacipran extended-release (ER) in subgroups of patients with major depressive disorder (MDD).MethodsData were pooled from 5 completed Phase II/III studies. Patients were categorized by sex, age, MDD duration, recurrence of MDD, current episode duration, number of prior episodes, and baseline Montgomery–Åsberg Depression Rating Scale (MADRS) score. Efficacy was evaluated by MADRS least squares (LS) mean change from baseline, response (MADRS improvement ≥50%), and remission (MADRS ≤10).ResultsIn the pooled population, treatment with levomilnacipran ER versus placebo resulted in greater improvement in MADRS score (−15.8 versus −12.9; LS mean difference, −2.9; P < .001) and higher response rates (44.7% versus 34.5%; P < .001). Comparable treatment effects were found in most subgroups. Remission rates in the overall population were higher for levomilnacipran ER versus placebo (27.7% versus 21.5%; P < .05); notably high remission rates were seen in patients with baseline MADRS score < 30 (48.8% versus 28.9%; P < .001).DiscussionClinically meaningful improvements in depressive symptoms were found across subgroups, including statistically significant outcomes for both response and remission.ConclusionLevomilnacipran ER was efficacious across a wide range of MDD patients, including men and women, ages 18–78, with varying histories and symptom severity.

Escitalopram Versus SNRI Antidepressants in the Acute Treatment of Major Depressive Disorder: Integrative Analysis of Four Double-Blind, Randomized Clinical Trials

CNS Spectrums ◽  
2009 ◽  
Vol 14 (6) ◽  
pp. 326-333 ◽  
Author(s):  
Susan G. Kornstein ◽  
Dayong Li ◽  
Yongcai Mao ◽  
Sara Larsson ◽  
Henning F. Andersen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Randomized Clinical Trials ◽  
Rating Scale ◽  
Severe Depression ◽  
Major Depressive ◽  
Double Blind ◽  
Madrs Score ◽  
Treatment Difference

AbstractIntroduction: Recent data suggest that escitalopram may be more effective in severe depression than other selective serotonin reuptake inhibitors.Methods: Individual patient data from four randomized, double-blind comparative trials of escitalopram versus a serotonin/norepinephrine reuptake inhibitor (SNRI) (two trials with duloxetine and two with venlafaxine extended release) in outpatients (18–85 years of age) with moderate-to-severe major depressive disorder were pooled. The primary efficacy parameter in all four trials was mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) score.Results: Significantly fewer escitalopram (82/524) than SNRI (114/527) patients prematurely withdrew from treatment due to all causes (15.6% vs. 21.6%, Fisher Exact: P=.014) and adverse events (5.3% vs. 12.0%, Fisher Exact: P <.0001). Mean reduction in MADRS score from baseline to Week 8 was significantly greater for the escitalopram group versus the SNRI group using the last observation carried forward (LOCF) approach [mean treatment difference at Week 8 of 1.7 points (P <.01)]. Similar results were observed in the severely depressed (baseline MADRS score ≥30) patient subset (mean treatment difference at Week 8 of 2.9 points [P <.001, LOCF]). Observed cases analyses yielded no significant differences in efficacy parameters.Conclusion: This pooled analysis indicates that escitalopram is at least as effective as the SNRIs (venlafaxine XR and duloxetine), even in severe depression, and escitalopram treatment was better tolerated.

scholarly journals Sexual Function during Bupropion or Paroxetine Treatment of Major Depressive Disorder

2006 ◽  
Vol 51 (4) ◽  
pp. 234-242 ◽  
Author(s):  
Sidney H Kennedy ◽  
Kari A Fulton ◽  
R Michael Bagby ◽  
Andrea L Greene ◽  
Nicole L Cohen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Sexual Function ◽  
Rating Scale ◽  
Primary Objective ◽  
Major Depressive ◽  
Double Blind ◽  
Significant Difference ◽  
To Receive ◽  
Over Time

Objective: The primary objective was to evaluate sexual function (SF) separately in men and women with major depressive disorder (MDD) before and during treatment with bupropion sustained release (SR) or paroxetine. The secondary objectives involved a comparative evaluation of the Sex Effects Scale (Sex FX) and the Investigator-Rated Sexual Desire and Functioning Scale (IRSD-F), as well as a comparison of antidepressant outcomes and an examination of the relation between level of depression and SF over time. Method: There were 141 patients (68 women and 73 men) who met DSM-IV criteria for a current major depressive episode. They were randomly assigned to receive bupropion SR (150 to 300 mg daily) or paroxetine (20 to 40 mg daily) under double-blind trial conditions. Patients were assessed at baseline and at 2, 4, 6, and 8 weeks with the 17-item Hamilton Depression Rating Scale (HDRS17), Sex FX, and IRSD-F. Results: Prior to treatment, women reported significantly lower SF on both the Sex FX and IRSD-F scales, compared with men. During treatment, there were no significant drug differences on measures of SF over time for women; however, men who were treated with paroxetine reported a worsening of SF, whereas bupropion SR did not significantly alter SF. Both bupropion SR and paroxetine produced clinically and statistically significant reductions in HDRS17 scores as well as comparable rates of response and remission. There was a statistically significant correlation between the 2 measures of SF at all visits. There was also a significant inverse relation between depression and SF in women, but not in men, irrespective of drug. Conclusion: According to the Sex FX scale, a significant difference in antidepressant-related sexual dysfunction was detected in men, but not women, during treatment with bupropion SR or paroxetine.

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 A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and tolerability of 5 mg vortioxetine in adults with major depressive disorder*

2012 ◽  
Vol 16 (2) ◽  
pp. 313-321 ◽  
Author(s):  
Rakesh Jain ◽  
Atul R. Mahableshwarkar ◽  
Paula L. Jacobsen ◽  
Yinzhong Chen ◽  
Michael E. Thase
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
P Value ◽  
Depression Symptoms ◽  
Major Depressive ◽  
Double Blind ◽  
Efficacy Measure ◽  
Efficacy Measures ◽  
Hamilton Anxiety Scale

Abstract Vortioxetine (Lu AA21004) is a multi-modal antidepressant in clinical development for the treatment of major depressive disorder (MDD). The current study evaluated the efficacy and tolerability of 5 mg vortioxetine compared to placebo after 6 wk of treatment in adults with MDD in an out-patient setting. Adults aged 18–75 yr, with a diagnosis of MDD and a baseline Montgomery–Asberg Depression Rating Scale (MADRS) total score ⩾30, were randomized to receive either 5 mg vortioxetine or placebo over 6 wk, followed by a 2-wk medication-free discontinuation period. The primary efficacy measure was change from baseline in Hamilton Rating Scale for Depression (HAMD)-24 total score at week 6 compared to placebo. Additional measures included response and remission rates, Clinical Global Impression Scale – Improvement scores, HAMD-24 total score in subjects with baseline Hamilton Anxiety Scale (HAMA) >19 and MADRS-S total score. Adverse events (AEs) were assessed throughout the study. A total of 600 adults were randomized. There were no significant differences in efficacy measures between subjects in the 5 mg vortioxetine and placebo groups at week 6. HAMD-24 total score in subjects with baseline HAMA >19 in the 5 mg vortioxetine group was improved at weeks 3–6 compared to the placebo group (nominal p value <0.05). The most common AEs for the vortioxetine and placebo groups were nausea (19.1 and 9.4%), headache (17.1 and 15.1%) and diarrhoea (11.4 and 7.0%), respectively. In this study of adults with MDD, 5 mg vortioxetine did not differ significantly from placebo in reducing depression symptoms after 6 wk of treatment.

scholarly journals Measures of suicidality in phase 3 clinical trials of levomilnacipran ER in adults with major depressive disorder

CNS Spectrums ◽  
2017 ◽  
Vol 22 (6) ◽  
pp. 475-483 ◽  
Author(s):  
Michael E. Thase ◽  
Carl Gommoll ◽  
Changzheng Chen ◽  
Kenneth Kramer ◽  
Arif Khan ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Suicidal Ideation ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Short Term ◽  
Open Label ◽  
Major Depressive ◽  
Double Blind ◽  
And Behavior

ObjectiveTo evaluate the effects of levomilnacipran extended-release (ER) on suicidal ideation and behavior in adults with major depressive disorder (MDD).MethodsPost hoc analyses were conducted in patients from 4 randomized, double-blind, placebo-controlled trials and a long-term, open-label extension study of levomilnacipran ER (40-120 mg/d) in adults with MDD. Analyses included incidence of suicide-related treatment-emergent adverse events (TEAEs); incidence of Columbia–Suicide Severity Rating Scale (C-SSRS) suicidal ideation (score=1–5) and behavior (score=6-10); percent of patients who shifted from no C-SSRS suicidal ideation/behavior at baseline to suicidal ideation during treatment (worsened from score=0 to score=1–5), or vice-versa (improved from score=1-5 to score=0).ResultsSuicide-related TEAEs occurred in<1% of patients in the levomilnacipran ER studies. The incidence of C-SSRS suicidal ideation was 22.2%, 23.9%, and 21.7% for placebo, short-term levomilnacipran ER, and long-term levomilnacipran ER, respectively; C-SSRS suicidal behavior was<1% in all of these groups. In the short-term studies, the percentage of patients with C-SSRS shifts were as follows: worsening from score=0 to score=1–5 (placebo, 8.6%; levomilnacipran ER, 11.0%); improvement from score=1–5 to score=0 (placebo, 24.0%; levomilnacipran ER, 27.7%).ConclusionIn adult MDD patients, the incidence of suicidal ideation and behavior was similar between placebo and short-term levomilnacipran ER as indicated by TEAE reports and C-SSRS scores. Worsening in C-SSRS scores was also similar between placebo and levomilnacipran ER. There was no indication of increased suicidality during longer courses of continued therapy. Together, these findings suggest that this medication is not associated with increased risks of suicidal ideation or behavior.

An Integrated Analysis of the Efficacy of Desvenlafaxine Compared with Placebo in Patients with Major Depressive Disorder

CNS Spectrums ◽  
2009 ◽  
Vol 14 (3) ◽  
pp. 144-154 ◽  
Author(s):  
Michael E. Thase ◽  
Susan G. Kornstein ◽  
Jean-Michel Germain ◽  
Qin Jiang ◽  
Christine Guico-Pabia ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Dose Group ◽  
Rating Scale ◽  
Fixed Dose ◽  
Integrated Analysis ◽  
Full Data ◽  
Major Depressive ◽  
Double Blind ◽  
Data Set

ABSTRACTIntroduction: To assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) in outpatients with major depressive disorder.Methods: A meta-analysis of individual patient data was performed on the complete set of registration trials (nine randomized, double-blind, placebo-controlled 8-week studies) of desvenlafaxine. Patients received fixed (50, 100, 200, or 400 mg/day; n = 1,342) or flexible doses (100–400 mg/day; n = 463) of desvenlafaxine or placebo (n = 1,108). The primary efficacy variable was the 17-item Hamilton Rating Scale for Depression (HAM-D17); the primary intent to treat analyses used the last-observation-carried-forward method.Results: Significantly greater improvement with desvenlafaxine versus placebo on the HAM-D17 total score was observed for the full data set (difference in adjusted means: −1.9; P<.001), each fixed-dose group (all P<.001), and the flexible-dose group (P=.024). Overall rates of HAM-D17 response (≥50% decrease from baseline score: 53% vs 41%) and remission (HAM-D17 ≤7: 32% vs 23%) were significantly greater for desvenlafaxine versus placebo (all P<.001). Discontinuation rates due to adverse events increased with dose (4% to 18%; placebo: 3%).Conclusion: Desvenlafaxine demonstrated short-term efficacy for treating major depressive disorder across the range of doses studied. No evidence of greater efficacy was observed with doses >50 mg/day; a strong dose-response effect on tolerability was observed.

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