Dose-response relationship of selective serotonin reuptake inhibitor (SSRI) in the treatment of depression: Protocol for a systematic review of reviews and meta-synthesis

Background: Antidepressant prescribing continues to grow (1,2). In part this is due to the use and availability of SSRIs (3), increased long-term prescribing (4), and the use of higher doses (5-7). In Scotland, SSRI accounted for 51% of antidepressant prescriptions and 66% of defined daily doses dispensed in 2014/15 (2). There is ambiguity in guidelines regarding SSRI dose related efficacy (8,9) Review question: Is there a dose-response relationship for SSRI in the treatment of depression? Aim: To review previous published reviews to assess and clarify the relationship between SSRI dose efficacy, acceptability (early treatment discontinuation – drop outs) and tolerability (reported ADEs), and critically evaluate the methods previously used to examine SSRI dose-response effects for the treatment of depression in adults. Method Search strategy, and criteria of eligibility and inclusion: Recommendations from the Cochrane Handbook for Systematic Reviews of Interventions informed the design of this systematic review (10). The predefined inclusion criteria for this systematic review and synthesis are presented according to PICOS (Population, Intervention, Comparator, Outcomes, Study design) criteria, Table 1. Article titles and abstracts will be screened for inclusion. Subsequently, potentially relevant full-text articles from the literature search will then be screened for inclusion, using a structured process and standard terms supporting inclusion and exclusion. Studies that do not meet the criteria outlined above were excluded. Reviews were excluded that involved children and adolescents age