ObjectiveThe objective of this study was to assess the quality of clinical practice guidelines (CPGs) for the pharmacological treatment of depression along with their recommendations and factors associated with higher quality.DesignWe conducted a systematic review that included CPGs for the pharmacological treatment of depression in adults.Data sourcesWe searched for publications from 1 January 2011 to 31 December 2021, in MEDLINE, Cochrane Library, Embase, PsycINFO, BVS and 12 other databases and guideline repositories.Eligibility criteria for selecting studiesWe included CPGs containing recommendations for the pharmacological treatment of depression in adults at outpatient care setting, regardless of whether it met the U.S. National Academy of Medicine criteria, or not. If a CPG included recommendations for both children and adults, they were considered. No language restriction was applied.Data extraction and synthesisData extraction was also conducted independently and in duplicate, a process that was validated in a previous project. The quality of the CPGs and their recommendations were assessed by three independent reviewers using Appraisal of Guidelines for Research and Evaluation (AGREE II) and Appraisal of Guidelines for Research and Evaluation-Recommendations Excellence (AGREE-REX). A CPG was considered to be of high quality if AGREE II Domain 3 was ≥60%; while their recommendations were considered high if AGREE-REX Domain 1 was ≥60%.ResultsSeventeen out of 63 (27%) CPGs were classified as high quality, while 7 (11.1%) had high-quality recommendations. The factors associated with higher-scoring CPGs and recommendations in the multiple linear regression analyses were ‘Handling of conflicts of interest’, ‘Multiprofessional team’ and ‘Type of institution’. ‘Inclusion of patient representative in the team’ was also associated with higher-quality recommendations.ConclusionsThe involvement of professionals from diverse backgrounds, the handling of conflicts of interest, and the inclusion of patients’ perspectives should be prioritised by developers aiming for high-quality CPGs for the treatment of depression.