scholarly journals Efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients aged 55 years or older

CNS Spectrums ◽  
2016 ◽  
Vol 22 (4) ◽  
pp. 348-362 ◽  
Author(s):  
George G. Nomikos ◽  
Dapo Tomori ◽  
Wei Zhong ◽  
John Affinito ◽  
William Palo

ObjectiveThese post hoc analyses evaluate the efficacy, safety, and tolerability of vortioxetine versus placebo in patients aged ≥55 years with major depressive disorder (MDD).MethodsStudy-level efficacy data from 12 short-term, fixed-dose, randomized, placebo-controlled trials of vortioxetine 5–20 mg/day were assessed using a random-effects meta-analysis. Adverse events (AEs), vital signs, ECG values, liver enzymes, and body weight were pooled from the same studies. Patients had baseline Montgomery–Åsberg Depression Rating Scale (MADRS) total scores ranging from 22–30.Results1508 patients (mean age=62.4 years; range, 55–88 years) were included. Mean differences from placebo in change from baseline to study end (6/8 weeks) in MADRS were –2.56 (5 mg, n=324, P=0.035), –2.87 (10 mg, n=222, P=0.007), –1.32 (15 mg, n=90, P=NS), and –4.65 (20 mg, n=165, P=0.012). Odds ratios for response versus placebo were 1.6 (5 mg, P=NS), 1.8 (10 mg, P=0.002), 1.2 (15 mg, P=NS), and 2.5 (20 mg, P<0.001), and for remission versus placebo were 1.5 (5 mg, P=NS), 1.5 (10 mg, P=NS), 1.4 (15 mg, P=NS), and 2.7 (20 mg, P=0.001). The proportion of patients with AEs for placebo and vortioxetine 5–20 mg was 61.5% and 62.3%, respectively, with no increase at increased doses. Vortioxetine demonstrated a placebo-level incidence of serious AEs (1.2%). AEs occurring in ≥5% of any treatment group were nausea, headache, diarrhea, dizziness, dry mouth, constipation, fatigue, vomiting, and anxiety. No clinically significant mean changes in vital signs, ECG values, liver enzymes, or body weight emerged during treatment.ConclusionVortioxetine 5–20 mg/day is efficacious and well tolerated in MDD patients aged ≥55 years, a group that is often comorbid with other conditions and treated with other medications.

2021 ◽  
Vol 12 ◽  
Author(s):  
Yudan Ding ◽  
Zirou Wei ◽  
Haohao Yan ◽  
Wenbin Guo

Abnormal hypothalamic-pituitary-adrenal (HPA) axis has been implicated in major depressive disorder (MDD). A number of studies have attempted to use HPA-modulating medications to treat depression. However, their results are inconsistent. The efficacy of these drugs for MDD remains uncertain. The aims of this meta-analysis were to determine the effect and safety profile of HPA-targeting medications for MDD. World of Science and PubMed databases were comprehensively searched up to March 2021. All randomized controlled trials (RCTs) and open-label trials exploring antiglucocorticoid and related medications in patients with depression were included. Standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for continuous or dichotomous outcomes, respectively. In the meta-analysis, we identified 16 RCTs and seven open-label studies that included 2972 subjects. Pooling the change data that assessed the efficacy across all included HPA-targeting medications for depression showed a significant difference between interventions and controls with very small heterogeneity after influence analysis (SMD = 0.138, 95%CI = 0.052, 0.224, p = 0.002; I2 = 20.7%, p = 0.212). No obvious publication bias was observed (p = 0.127). Effectiveness remained significant in patients with MDD (SMD = 0.136, 95%CI = 0.049, 0.223, p = 0.002). Subgroup analysis showed a significant difference favoring mifepristone and vasopressin 1B (V1B) receptor antagonist treatment. Adverse events were reported by 14 studies and our analysis of high-quality studies showed a significant difference in favor of controls (RR = 1.283, 95%CI = 1.134, 1.452, p = 0). Our study suggested that patients with MDD may benefit from mifepristone and V1B receptor antagonist treatments that have tolerable side effects. HPA-based medications are promising for depression treatment. However, additional high-quality RCTs, including head-to-head trials, are needed.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier registration number: CRD42021247279


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 ◽  
...  

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.


CNS Spectrums ◽  
2010 ◽  
Vol 15 (3) ◽  
pp. 187-193 ◽  
Author(s):  
Karen A. Tourian ◽  
Qin Jiang ◽  
Philip T. Ninan

ABSTRACTBackground: This analysis evaluated the effects of the serotonin-norepinephrine reuptake inhibitor, desvenlafaxine (administered as desvenlafaxine succinate), on anxiety symptoms associated with depression.Methods: Data were pooled from 9 randomized, placebo-controlled, double-blind, 8 week studies of desvenlafaxine (50-400 mg/day, fixed or flexible dose) in patients with major depressive disorder (MDD), without a primary anxiety diagnosis. Changes from baseline in scores on the anxiety/somatization factor of the 17-item Hamilton Rating Scale for Depression (HAM-D17) and on the Covi Anxiety Scale at the final evaluation (last observation carried forward) were compared between desvenlafaxine and placebo groups using analysis of covariance.Results: In the overall data set (intent to treat n=2,913 [desvenlafaxine, n=1,805; placebo, n=1,108]), desvenlafaxine was associated with significantly greater reductions compared with placebo in scores on the HAM-D17 anxiety/somatization factor (-3.41 vs -2.92, P<.001) and Covi Anxiety Scale (-1.35 vs -1.04, P<.001). In the subset of fixed-dose studies, significant differences were observed for all dose groups on the HAM-D17 anxiety/somatization factor (P≤.OH), and for the 50, 100, and 200 mg/day dose groups on the Covi Anxiety Scale (all P≤.015 vs placebo).Conclusions: Desvenlafaxine was associated with significantly greater improvement in anxiety symptoms compared with placebo in patients with MDD.


2021 ◽  
Author(s):  
Akira Nishi ◽  
Kyosuke Sawada ◽  
Hiroyuki Uchida ◽  
Masaru Mimura ◽  
Hiroyoshi Takeuchi

Abstract No clinical guidelines currently recommend antipsychotic monotherapy (APM) for major depressive disorder (MDD). Although several randomized controlled trials (RCTs) have compared the effectiveness, efficacy, and safety of APM versus placebo in patients with MDD, no meta-analysis has examined this topic. We conducted a systematic literature search using MEDLINE and Embase to identify relevant RCTs and performed a meta-analysis to compare the following outcomes between APM and placebo: study discontinuation due to all causes, lack of efficacy, and adverse events, changes in total scores on depression severity scales (e.g., Hamilton Depression Rating Scale and Montgomery Åsberg Depression Rating Scale) and in the Clinical Global Impression - Severity scale (CGI-S) score, and individual adverse event rates. A total of 13 identified studies with 14 comparisons involving 3,197 participants that met the eligibility criteria were included in the meta-analysis. No significant difference was found in study discontinuation due to all causes between the APM and placebo groups. However, there were significant differences in study discontinuation due to lack of efficacy in favor of the APM group and study discontinuation due to adverse events in favor of the placebo group. Compared with the placebo group, the APM group was significantly superior in relation to score reduction on the depression severity scales and CGI-S and inferior in relation to 8 of 23 individual adverse events. APM could be a useful treatment option for the acute phase of MDD, although clinicians should be aware of an increased risk of some adverse events.


2021 ◽  
Vol 4 ◽  
pp. 42
Author(s):  
Diana Grunberg ◽  
Jason A. Martin ◽  
John F. Cryan ◽  
Ken D. O’Halloran ◽  
Eric Kelleher ◽  
...  

Background: Depression currently affects 4.4% of the global population, and 93.7% of this population suffer from major depressive disorder (MDD) according to 2017 statistics. MDD patients are more likely to suffer from co-morbidities such as cardiovascular disease and high body mass index (BMI), thus contributing to its large cost to society. Throughout the literature, there are known links between inflammation and MDD. Interestingly, while exercise is considered a promising intervention for MDD, the mechanism(s) of action remain unclear, thereby preventing the creation of optimal, cost-saving, exercise “prescriptions” for those with MDD. Thus, the aim of this review and meta-analysis is to summarize and analyse the current literature exploring how quantified exercise interventions modulate inflammatory molecules in MDD patients. Methods: Electronic databases (APA PsycINFO, and PubMed/MEDLINE (EBSCO interface), EMBASE) will be searched using a detailed search strategy comprised of three search term themes: exercise, depression/MDD, and inflammation/inflammatory molecules. Only quantified exercise interventions performed in adult humans with MDD validated via a recognized diagnostic criterion will be included. Studies should also include a MDD control group and explore changes in inflammatory molecules. Examples of these molecules include: C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-1 beta (IL-1b), tumour necrosis factor-alpha (TNF-a), homocysteine, d-dimer and myeloperoxidase (MPO). After eligible studies are identified, standardized data extraction will be employed and the risk of bias in each study will be appraised using the Cochrane handbook checklists. In the event of two or more homogenous studies exploring exercise effects over a similar period of time, raw mean differences or standardized mean differences will be pooled using random effects analysis. This systematic review and meta-analysis will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Dissemination: This systematic review and meta-analysis will be disseminated in peer-reviewed journals. PROSPERO registration: CRD42020186006 (31/08/2020)


2017 ◽  
Vol 30 (suppl 1) ◽  
pp. 335-349
Author(s):  
Rafaela Liberali

Abstract Introduction: MBCT practices increases the ability of concentration and attention, as well is particularly effective for people with current and treatment-resistant depression. Objective: To analyze the effects of the application of MBCT in symptoms of MDD. Methods: systematic review and meta-analysis. To find suitable studies, we searched PubMed/MEDLINE's database using the keywords mindfulness and major depressive disorder. Studies in English published between 2003 and 2015 were selected. The studies were evaluated according to their methodological quality by PEDro scale (score greater than 3), studies that showed empirical evidence, had an experimental study design (randomized and non-randomized), and whose full text was available. For the meta-analysis, we used a random-effects model with standardized mean differences and 95% confidence intervals. Results: Fourteen es were included, of which three were non-randomized, with only one group with intervention of MBCT, and 11 were randomized studies, divided into two-group samples and three-group samples. The non-randomized studies showed a PEDro score of 5, while the two-group and three-group randomized studies showed PEDro scores of 5-10 and 6-9, respectively. In the meta-analysis, the four randomized studies selected revealed a moderate effect of MBCT on the outcome of depression symptoms, with a mean difference of -0.52 (95% CI: -1.050 to -0.002; p = 0.04). Conclusion: The MBCT presented as a promising alternative for the treatment of this disorder.


2021 ◽  
Vol 12 (01) ◽  
pp. 122-128
Author(s):  
Ralte Lalthankimi ◽  
Padmavathi Nagarajan ◽  
Vikas Menon ◽  
Jeby Jose Olickal

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.


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