Comparative efficacy of selective serotonin reuptake inhibitors (SSRI) in treating major depressive disorder: a protocol for network meta-analysis of randomised controlled trials

Abstract

IntroductionThere have been inconsistent findings from randomised controlled trials (RCTs) and systematic reviews on the efficacies of selective serotonin reuptake inhibitors (SSRIs) as the first-line treatment of major depressive disorder (MDD). Besides inconsistencies among randomised controlled trials (RCTs), their risks of bias and evidence grading have seldom been evaluated in meta-analysis. This study aims to compare the efficacy of SSRIs by conducting a Bayesian network meta-analysis, which will be the most comprehensive evaluation of evidence to resolve the inconsistency among previous studies.Methods and analysesSSRIs including citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and vilazodone have been selected. Systematic database searching and screening will be conducted for the RCTs on drug treatment of patients with MDD according to pre-specified search strategies and selection criteria. PubMed, the Cochrane Library, EMBASE, ScienceDirect, the US Food and Drug Administration Website, ClinicalTrial.gov and WHO Clinical Trials will be searched. Outcome data including Hamilton Depression Rating Scale (HDRS), Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) from eligible RCTs will be extracted. The outcomes will be analysed as ORs and mean differences under a random-effects model. A Bayesian network meta-analysis will be conducted with WinBUGS software, to compare the efficacies of SSRIs. Subgroup and sensitivity analysis will be performed to explain the study heterogeneity and evaluate the robustness of the results. Meta-regression analysis will be conducted to determine the possible factors affecting the efficacy outcomes. The Cochrane risk of bias assessment tool will be used to assess the RCT quality, and the Grading of Recommendation, Assessment, Development and Evaluation will be used to assess the strength of evidence from the meta-analysis.Ethics and disseminationNo ethical approval is required because this study includes neither confidential personal patient data nor interventions with patients.Protocol registration numberCRD42015024879.

Systems Biology of Phenotypic Robustness and Plasticity

“…A given drug is only effective in a fraction of the patients and its efficacy is variable (Jia et al 2016). We can use a system population model of 5HT signaling to study how a population of virtual individuals with a broad range of variation in all parameters responds to an SSRI treatment.…”

Puerarin ameliorated the behavioral deficits induced by chronic stress in rats

“…In view of the pathways, a number of drugs are considered beneficial to combat depressive-like behavior. For instance, selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Ser) and paroxetine, are the usual treatment options 4 . Nonetheless, long-term use of these drugs induces multiple inevitable side effects, including cognitive dysfunction, sexual dysfunction, dependence, weight gain, sedation and withdrawal 5 , 6 .…”

“…In addition, evidences also suggested that abnormal monoaminergic neurotransmission is one of most important mechanisms underlying depressive-like behavior. Numerous studies demonstrated that monoamines were important neurotransmitters involved in the etiology of depressive-like behavior 3 , 4 . Actually, most of the antidepressants act on more than one mechanisms, such as inhibition of the reuptake of serotonin (5-HT) and its metabolites.…”

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“…6. Hence the oxidant and antioxidant defence systems are getting deranged in depression 38 and diabetes 39 .…”