OBJECTIVE: To explore patient and health professional views and experiences of antidepressant treatment with particular focus on barriers and facilitators to discontinuing use. DESIGN: Systematic review with thematic synthesis DATA SOURCES: MEDLINE, PubMed, Embase, PsycINFO, CINAHL, AMED, Health Management Information Consortium, OpenGrey, and the Networked Digital Library of Theses and Dissertations from inception until February 2017. Updated searches were carried out in July 2018. ELIGIBILITY CRITERIA: Primary studies, published in English, that used qualitative data collection and analysis, and had data on attitudes, beliefs, feelings, perceptions on continuing or discontinuing antidepressant use, of patients (aged 18 or above, who received treatment with antidepressants for at least 6 months) or any health professionals. DATA EXTRACTION: One reviewer extracted data and assessed study quality, which was checked by a second reviewer. FINDINGS: Twenty two papers were included in the review. A thematic synthesis was performed for patient perspectives only, due to insufficient data from a health professional perspective. The thematic synthesis yielded nine themes: (1) psychological and physical capabilities; (2) perception of antidepressants; (3) fears; (4) intrinsic motivators and goals; (5) the Doctor as a navigator to maintenance or discontinuation; (6) perceived cause of depression; (7) aspects of information that support decision-making; (8) significant others - a help or a hindrance; and (9) support from other health professionals. LIMITATIONS: Coding and development of subthemes and themes was performed by one researcher and further developed through discussion between two researchers. CONCLUSIONS: Barriers and facilitators to discontinuing antidepressant use are numerous and complex, and likely to require detailed conversations between patients and their general practitioners (GPs). These conversations are more likely to happen if GPs raise the issue of discontinuation. Further research from a health professional perspective including, but not limited to GPs, is needed.