Objective We have developed a protocol for the systematic review and meta-analysis of the factors associated with nonadherence to antidepressants in depressive patients more than 18 years of age. Methods We will search articles with the databases PubMed- Medline, Scopus, Embase and PsychINFO. All the published literature reporting factors associated with nonadherence to antidepressants in depressive disorders in patients more than 18 years of age and fulfilling all the eligibility criteria till October 2022 will be included. The data will then be extracted and examined to be included in the systematic review. Finally, we will conduct meta-analysis for factors associated with non-adherence. Conclusion We will do extensive search on the proposed topic within the available literature and come up with a robust review of factors associated with nonadherence to antidepressants in patients age more than 18 years globally. The evidence generated would assist in designing interventions to address non-adherence in this group of patients leading to better productivity and quality of life.