Dataset Information

Acceptability of escitalopram versus duloxetine in outpatients with depression who did not respond to initial second-generation antidepressants: Study protocol for a randomized, parallel-group, non-inferiority trial.

ABSTRACT: Aim: The purpose of this study is to compare acceptability of two second generation antidepressants for major depressive disorder patients who have not responded to the first antidepressant for current episode. We will investigate the treatment discontinuation rate and treatment adherence as well as incidence of adverse events in order to evaluate safety.

Methods: This is a two-arm, three-phased randomized controlled trial in which independent assessors will be blinded while treating psychiatrists and patients remain unblinded to treatment allocation. Patients will be randomized to escitalopram or duloxetine in Step 1 (8 weeks), and when entering Step 2 (8 weeks), the drug will be switched to the other if the first one is not effective at the end of Step 1. The acceptability of the allocated drugs, improvements in depression from baseline, adverse events, and attrition rates will be recorded and assessed for up to 52 weeks, including the follow-up step.

Results: It is going to be disseminated via our following reports or presentations.

Conclusions: This study will provide valuable information for clinicians who encounter patients who failed to respond to their first treatment.

SUBMITTER: Yokoi Y

PROVIDER: S-EPMC7292285 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Acceptability of escitalopram versus duloxetine in outpatients with depression who did not respond to initial second-generation antidepressants: Study protocol for a randomized, parallel-group, non-inferiority trial.

Yokoi Yuma Y Nakagawa Atsuo A Yoshimura Naoki N Furukawa Toshiaki A TA Mimura Masaru M Iwanami Akira A Abe Takayuki T Nakagome Kazuyuki K

Neuropsychopharmacology reports 20190918 4

<h4>Aim</h4>The purpose of this study is to compare acceptability of two second generation antidepressants for major depressive disorder patients who have not responded to the first antidepressant for current episode. We will investigate the treatment discontinuation rate and treatment adherence as well as incidence of adverse events in order to evaluate safety.<h4>Methods</h4>This is a two-arm, three-phased randomized controlled trial in which independent assessors will be blinded while treatin ...[more]

PMID: 31531962

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Project description:Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of action of escitalopram/citalopram focusing on a set of 31 metabolites from neurotransmitter-related pathways. Overall, 290 unipolar patients with major depressive disorder were profiled at baseline, after 4 and 8 weeks of drug treatment. The 17-item Hamilton Depression Rating Scale (HRSD17) scores gauged depressive symptom severity. More significant metabolic changes were found after 8 weeks than 4 weeks post baseline. Within the tryptophan pathway, we noted significant reductions in serotonin (5HT) and increases in indoles that are known to be influenced by human gut microbial cometabolism. 5HT, 5-hydroxyindoleacetate (5HIAA), and the ratio of 5HIAA/5HT showed significant correlations to temporal changes in HRSD17 scores. In the tyrosine pathway, changes were observed in the end products of the catecholamines, 3-methoxy-4-hydroxyphenylethyleneglycol and vinylmandelic acid. Furthermore, two phenolic acids, 4-hydroxyphenylacetic acid and 4-hydroxybenzoic acid, produced through noncanconical pathways, were increased with drug exposure. In the purine pathway, significant reductions in hypoxanthine and xanthine levels were observed. Examination of metabolite interactions through differential partial correlation networks revealed changes in guanosine-homogentisic acid and methionine-tyrosine interactions associated with HRSD17. Genetic association studies using the ratios of these interacting pairs of metabolites highlighted two genetic loci harboring genes previously linked to depression, neurotransmission, or neurodegeneration. Overall, exposure to escitalopram/citalopram results in shifts in metabolism through noncanonical pathways, which suggest possible roles for the gut microbiome, oxidative stress, and inflammation-related mechanisms.

Project description:PurposeTo compare treatment outcomes in patients with major depressive disorder treated with duloxetine, escitalopram, fluoxetine, paroxetine, or sertraline for up to 6 months.Patients and methodsData were taken from a 6-month prospective, observational study that included 1,549 major depressive disorder patients without sexual dysfunction in 12 countries. We report the overall results and those from Asian countries. Depression severity was measured using the Clinical Global Impression and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Clinical and functional remissions were defined as having a QIDS-SR16 <6, and as having a rating of <3 on all three Sheehan Disability Scale items and no reduced productivity, respectively. Mixed effects modeling with repeated measures analysis and generalized estimating equation models were used. Propensity scores were included in the models.ResultsThe mixed effects modeling with repeated measures regression models showed that the Clinical Global Impression rating during follow-up was significantly lower in those patients treated with duloxetine compared with escitalopram (0.40, 95% CI 0.25 to 0.56); fluoxetine (0.22, 95% CI 0.05 to 0.38); paroxetine (0.38, 95% CI 0.23 to 0.54); and sertraline (0.32, 95% CI 0.16 to 0.49). The QIDS-SR16 of duloxetine-treated patients was significantly lower than those treated with escitalopram (1.58, 95% CI 1.03 to 2.12); fluoxetine (1.48, 95% CI 0.90 to 2.06); paroxetine (1.53, 95% CI 1.00 to 2.07); and sertraline (1.19, 95% CI 0.61 to 1.78). The probability of clinical remission of the patients treated with escitalopram, fluoxetine, paroxetine, and sertraline was lower than those treated with duloxetine (OR 0.46, 95% CI 0.33 to 0.64; OR 0.42, 95% CI 0.29 to 0.61; OR 0.40, 95% CI 0.29 to 0.56; OR 0.50, 95% CI 0.35 to 0.71; respectively). The regression analysis of functional remission also showed more favorable results for duloxetine, with OR ranging from 0.43, 95% CI 0.31 to 0.60 for paroxetine to 0.49, 95% CI 0.35 to 0.70 for sertraline. The results for the Asian countries were generally consistent.ConclusionDuloxetine-treated patients had better 6-month outcomes in terms of depression severity and clinical and functional remission, compared with selective serotonin reuptake inhibitor-treated patients.

Project description:Study questionWhat are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults?MethodsThis was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January 1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT. Ten trials compared antidepressant monotherapy with CBT alone; three compared antidepressant monotherapy with antidepressant plus CBT.Summary answer and limitationsMeta-analyses found no statistically significant difference in effectiveness between second generation antidepressants and CBT for response (risk ratio 0.91, 0.77 to 1.07), remission (0.98, 0.73 to 1.32), or change in 17 item Hamilton Rating Scale for Depression score (weighted mean difference, -0.38, -2.87 to 2.10). Similarly, no significant differences were found in rates of overall study discontinuation (risk ratio 0.90, 0.49 to 1.65) or discontinuation attributable to lack of efficacy (0.40, 0.05 to 2.91). Although more patients treated with a second generation antidepressant than receiving CBT withdrew from studies because of adverse events, the difference was not statistically significant (risk ratio 3.29, 0.42 to 25.72). No conclusions could be drawn about other outcomes because of lack of evidence. Results should be interpreted cautiously given the low strength of evidence for most outcomes. The scope of this review was limited to trials that enrolled adult patients with major depressive disorder and compared a second generation antidepressant with CBT, and many of the included trials had methodological shortcomings that may limit confidence in some of the findings.What this study addsSecond generation antidepressants and CBT have evidence bases of benefits and harms in major depressive disorder. Available evidence suggests no difference in treatment effects of second generation antidepressants and CBT, either alone or in combination, although small numbers may preclude detection of small but clinically meaningful differences. Funding, competing interests, data sharing This project was funded under contract from the Agency for Healthcare Research and Quality by the RTI-UNC Evidence-based Practice Center. Detailed methods and additional information are available in the full report, available at http://effectivehealthcare.ahrq.gov/.

Project description:Background"Evergreening" refers to the numerous strategies whereby owners of pharmaceutical products use patent laws and minor drug modifications to extend their monopoly privileges on the drug. We aimed to evaluate the impact of evergreening through the case study of the antidepressant citalopram and its chiral switch form escitalopram by evaluating treatment efficacy and acceptability for patients, as well as health insurance costs for society.MethodsTo assess efficacy and acceptability, we performed meta-analyses for efficacy and acceptability. We compared direct evidence (meta-analysis of results of head-to-head trials) and indirect evidence (adjusted indirect comparison of results of placebo-controlled trials). To assess health insurance costs, we analyzed individual reimbursement data from a representative sample of the French National Health Insurance Inter-regime Information System (SNIIR-AM) from 2003 to 2010, which allowed for projecting these results to the whole SNIIR-AM population (53 million people).ResultsIn the meta-analysis of seven head-to-head trials (2,174 patients), efficacy was significantly better for escitalopram than citalopram (combined odds ratio (OR) 1.60 (95% confidence interval 1.05 to 2.46)). However, for the adjusted indirect comparison of 10 citalopram and 12 escitalopram placebo-controlled trials, 2,984 and 3,777 patients respectively, efficacy was similar for the two drug forms (combined indirect OR 1.03 (0.82 to 1.30)). Because of the discrepancy, we could not combine direct and indirect data (test of inconsistency, P = 0.07). A similar discrepancy was found for treatment acceptability. The overall reimbursement cost burden for the citalopram, escitalopram and its generic forms was 120.6 million Euros in 2010, with 96.8 million Euros for escitalopram.ConclusionsThe clinical benefit of escitalopram versus citalopram remains uncertain. In our case of evergreening, escitalopram represented a substantially high proportion of the overall reimbursement cost burden as compared with citalopram and the generic forms.

Project description:Background: Most guidelines for major depressive disorder recommend initial treatment with either a second-generation antidepressant (SGA) or cognitive behavioral therapy (CBT). Although most trials suggest that these treatments have similar efficacy, their health economic implications are uncertain.Objective: To quantify the cost-effectiveness of CBT versus SGA for initial treatment of depression.Design: Decision analytic model.Data sources: Relative effectiveness data from a meta-analysis of randomized controlled trials; additional clinical and economic data from other publications.Target population: Adults with newly diagnosed major depressive disorder in the United States.Time horizon: 1 to 5 years.Perspectives: Health care sector and societal.Intervention: Initial treatment with either an SGA or group and individual CBT.Outcome measures: Costs in 2014 U.S. dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.Results of base-case analysis: In model projections, CBT produced higher QALYs (3 days more at 1 year and 20 days more at 5 years) with higher costs at 1 year (health care sector, $900; societal, $1500) but lower costs at 5 years (health care sector, -$1800; societal, -$2500).Results of sensitivity analysis: In probabilistic sensitivity analyses, SGA had a 64% to 77% likelihood of having an incremental cost-effectiveness ratio of $100 000 or less per QALY at 1 year; CBT had a 73% to 77% likelihood at 5 years. Uncertainty in the relative risk for relapse of depression contributed the most to overall uncertainty in the optimal treatment.Limitation: Long-term trials comparing CBT and SGA are lacking.Conclusion: Neither SGAs nor CBT provides consistently superior cost-effectiveness relative to the other. Given many patients' preference for psychotherapy over pharmacotherapy, increasing patient access to CBT may be warranted.Primary funding source: Department of Veterans Affairs, National Institute of Mental Health.

Dataset Information

Acceptability of escitalopram versus duloxetine in outpatients with depression who did not respond to initial second-generation antidepressants: Study protocol for a randomized, parallel-group, non-inferiority trial.

Publications

Acceptability of escitalopram versus duloxetine in outpatients with depression who did not respond to initial second-generation antidepressants: Study protocol for a randomized, parallel-group, non-inferiority trial.

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