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.

scholarly journals Suicidal ideation and behavior in adults with major depressive disorder treated with vortioxetine: post hoc pooled analyses of randomized, placebo-controlled, short-term and open-label, long-term extension trials

CNS Spectrums ◽  
2019 ◽  
Vol 25 (3) ◽  
pp. 352-362 ◽  
Author(s):  
Atul R. Mahableshwarkar ◽  
John Affinito ◽  
Elin Heldbo Reines ◽  
Judith Xu ◽  
George Nomikos ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Suicidal Ideation ◽  
Depressive Disorder ◽  
Short Term ◽  
Open Label ◽  
Major Depressive ◽  
Increased Risk ◽  
And Behavior ◽  
Post Hoc

ObjectivesThis study aimed to evaluate the risk of suicidal ideation and behavior associated with vortioxetine treatment in adults with major depressive disorder (MDD).MethodsSuicide-related events were evaluated post hoc using 2 study pools: one short-term pool of 10 randomized, placebo-controlled studies (6–8 weeks) and another long-term pool that included 3 open-label extension studies (52 weeks). Evaluation of suicide-related events was performed using Columbia-Suicide Severity Rating Scale (C-SSRS) scores and treatment-emergent adverse events (TEAEs) data.ResultsAt baseline, the percentage of patients reporting any C-SSRS ideation or behavior events in short-term studies was similar between placebo (14.7%), vortioxetine (19.8%, 13.0%, 11.2%, and 13.7% for 5-, 10-, 15-, and 20-mg groups, respectively), and duloxetine active reference (13.2%) and did not change throughout the 6- to 8-week treatment period for placebo (17.0%), vortioxetine (19.3%, 13.5%, 12.6%, and 15% for 5-, 10-, 15-, and 20-mg groups, respectively), or duloxetine (11.3%). The incidence of suicide-related events for TEAEs in the short-term pool was 0.4% for placebo, 0.2% or 1.0% for vortioxetine 5 mg or 10 mg, and 0.7% each for vortioxetine 15 mg and 20 mg, as well as duloxetine. After 52-week treatment with vortioxetine, suicidal ideation based on C-SSRS was 9.8%, C-SSRS suicidal behavior was 0.2%, and the incidence of suicide-related events based on TEAEs was <1%. There were no completed suicides in any study.ConclusionsVortioxetine is not associated with increased risk of suicidal ideation or behavior in MDD patients.

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 Predictors of Suicidal Ideation and Attempt among Patients with Major Depressive Disorder at a Tertiary Care Hospital, Puducherry

2021 ◽  
Vol 12 (01) ◽  
pp. 122-128
Author(s):  
Ralte Lalthankimi ◽  
Padmavathi Nagarajan ◽  
Vikas Menon ◽  
Jeby Jose Olickal
Keyword(s):  
Major Depressive Disorder ◽  
Suicidal Ideation ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Tertiary Care ◽  
Severe Depression ◽  
Care Hospital ◽  
Suicidal Behaviors ◽  
Major Depressive ◽  
Severity Of Depression

Abstract Objectives Mental disorders have a large impact on death by suicide. Hence, this study aims to determine the prevalence of suicidal behaviors among major depressive disorder (MDD) patients and the associated factors. Materials and Methods This cross-sectional analytical study was conducted among individuals aged 18 to 65 years, diagnosed with MDD in the Psychiatry Outpatient Department of a Tertiary Care Center, Puducherry during March to October 2019. Severity of depression was assessed using Hamilton Depression Rating Scale and Columbia-Suicide Severity Rating Scale was used to find the suicidal behaviors. Results For 166 participants in the study, mean (standard deviation) age was 40 (11) years and majority were females (76%). More than one-third (37%) had severe or very severe depression, and the prevalence of suicidal ideation, plan, and attempts were 83, 24, and 35%, respectively. After adjusting the covariates, the severity of depression and unemployment were significantly associated with suicidal attempts (adjusted prevalence ratios [aPR] = 11.4 and 1.9), and very severe depression was associated with suicidal ideation (aPR = 1.6). Among 140 individuals with suicidal ideation, 45 (32%) had an ideation frequency of 2 to 3 times/week, 69 (50%) had ideation for 1 hour, 36 (26%) could control ideation with little difficulty, and 12% had suicidal ideation mostly to end or stop their pain. Conclusion Suicidal ideation and attempts were significantly high in MDD patients, and the severity of depression was significantly associated with it. Early identification of high-risk suicidal behavior and implementation of effective preventive interventions are necessary to reduce death by suicide in these groups.

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.

Short-term and long-term effects of major depressive disorder subtypes on obesity markers and impact of sex on these associations

2021 ◽  
Author(s):  
Clémentine Ottino ◽  
Marie-Pierre F Strippoli ◽  
Mehdi Gholam ◽  
Aurélie M Lasserre ◽  
Caroline L Vandeleur ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Long Term Effects ◽  
Short Term ◽  
Major Depressive

Safety, Tolerability, and Efficacy of Desvenlafaxine in Children and Adolescents with Major Depressive Disorder: Results from Two Open-Label Extension Trials

CNS Spectrums ◽  
2018 ◽  
Vol 24 (5) ◽  
pp. 496-506 ◽  
Author(s):  
Sarah Atkinson ◽  
Louise Thurman ◽  
Sara Ramaker ◽  
Gina Buckley ◽  
Sarah Ruta Jones ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Children And Adolescents ◽  
Rating Scale ◽  
Transition Period ◽  
Extension Study ◽  
Open Label ◽  
Major Depressive ◽  
Children’S Depression ◽  
Flexible Dose

ObjectiveTwo similarly designed extension studies evaluated the long-term safety and tolerability of desvenlafaxine for the treatment of children and adolescents with major depressive disorder (MDD). Efficacy was evaluated as a secondary objective.MethodsBoth 6-month, open-label, flexible-dose extension studies enrolled children and adolescents who had completed one of two double-blind, placebo-controlled, lead-in studies. One lead-in study included a 1-week transition period prior to the extension study. Patients received 26-week treatment with flexible-dose desvenlafaxine (20–50 mg/d). Safety assessments included comprehensive psychiatric evaluations, vital sign assessments, laboratory evaluations, 12-lead electrocardiogram, physical examination with Tanner assessment, and Columbia-Suicide Severity Rating Scale. Adverse events (AEs) were collected throughout the studies. Efficacy was assessed using the Children’s Depression Rating Scale–Revised (CDRS-R).ResultsA total of 552 patients enrolled (completion rates: 66.4 and 69.1%). AEs were reported by 79.4 and 79.1% of patients in the two studies; 8.9 and 5.2% discontinued due to AEs. Treatment-emergent suicidal ideation or behavior was reported for 16.6 and 14.1% of patients in the two studies. Mean (SD) CDRS-R total score decreased from 33.83 (11.93) and 30.92 (10.20) at the extension study baseline to 24.31 (7.48) and 24.92 (8.45), respectively, at week 26.ConclusionDesvenlafaxine 20 to 50 mg/d was generally safe and well tolerated with no new safety signals identified in children and adolescents with MDD who received up to 6 months of treatment in these studies. Patients maintained the reduction in severity of depressive symptoms observed in all treatment groups at the end of the lead-in study.

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.

scholarly journals 50 Adjunctive Buprenorphine/Samidorphan Combination in Patients with Major Depressive Disorder: Phase 3 Long-term Extension Study Results

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 203-204 ◽  
Author(s):  
Michael Thase ◽  
Arielle D. Stanford ◽  
Asli Memisoglu ◽  
William Martin ◽  
Amy Claxton ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Safety Profile ◽  
Rating Scale ◽  
Remission Rate ◽  
Term Treatment ◽  
Adjunctive Treatment ◽  
Major Depressive ◽  
Long Term Treatment

AbstractIntroductionBuprenorphine/samidorphan (BUP/SAM), a combination of BUP (a µ-opioid receptor partial agonist and κ-antagonist) and SAM (a sublingually bioavailable µ-opioid antagonist), is an investigational opioid system modulator for depression. BUP/SAM has shown efficacy versus placebo as an adjunctive treatment for major depressive disorder (MDD) and a consistent safety profile in previously reported, placebo-controlled clinical studies.1,2Study Objective(s)1. To characterize the safety profile following long-term treatment with BUP/SAM2. To explore depression symptoms and remission rates in patients with MDD following long-term treatment with BUP/SAMMethodsFORWARD-2 (Clinicaltrials.gov ID: NCT02141399) enrolled patients who had participated in 1 of 4 controlled studies as well as de novo patients. All patients had a confirmed diagnosis of MDD, had a history of inadequate response to standard antidepressant therapies (ADTs), and had been treated with an adequate dose of an established ADT for ≥8weeks before BUP/SAM initiation. ADT dosage could be titrated, but the ADT could not be changed. During the study, patients received open-label, sublingual BUP/SAM 2mg/2mg as adjunctive treatment for up to 52weeks. Safety (primary objective) was assessed via adverse events (AEs), vital signs, laboratory analytes, and electrocardiography. Suicidal ideation or behavior (SIB) was evaluated by the Columbia Suicide Severity Rating Scale. Abuse potential, dependence, and withdrawal were assessed by AEs and the Clinical Opiate Withdrawal Scale. Exploratory efficacy endpoints included mean Montgomery–Åsberg Depression Rating Scale (MADRS) scores and remission rate (MADRS ≤10).ResultsOf 1454 total patients, 49% completed the 52-week study, 11% discontinued due to an AE, and 40% discontinued because of other reasons as of the interim data cutoff date (April 30, 2017). Most AEs were of mild/moderate severity. Serious AEs were reported in 3.2% of patients. AEs occurring in ≥10% of patients were nausea, headache, constipation, dizziness, and somnolence. There was no evidence of increased risk of SIB with BUP/SAM. Incidence of euphoria-related events was low (1.2%). After abrupt discontinuation of BUP/SAM, there was little evidence of withdrawal. BUP/SAM was not associated with meaningful changes in laboratory or metabolic parameters or in bodyweight. The mean MADRS score decreased from 22.9 (±9.7) at baseline to 9.8 (±8.8) after 52weeks. The remission rate at 52weeks was 52.5%.ConclusionsLong-term treatment with BUP/SAM did not reveal any new safety findings and confirmed that the risk of abuse and dependence with BUP/SAM was low. BUP/SAM maintained an antidepressant effect for up to 52weeks of treatment in patients with MDD.Funding Acknowledgements: Alkermes, Inc.

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