Long-term antidepressant use and outcomes in adults: A systematic review

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Aims: This is the first study to systematically review the evidence for the outcomes (adverse or beneficial) associated with long-term (>12 months) antidepressant use in adults (18 years or over). Millions of people are taking antidepressants long-term, yet without evidence for the associated outcomes are unable to make an informed choice about whether to continue or attempt stopping. Methods: We searched MEDLINE, Embase, PsycINFO, CINAHL, Scopus and Cochrane Library databases from inception to January 5, 2026, and conducted backward citation search. Eligible studies were randomised controlled trials and observational studies involving adults taking an antidepressant long-term (>12 months) for any indication and a comparator, excluding discontinuation studies (because of the problem of confounding by withdrawal effects). Two reviewers independently extracted data and assessed quality using the Quality Assessment Tool for Quantitative Studies developed by the Effective Public Health Practice Project. Results were reported using a narrative synthesis approach. Results: Forty-eight studies, mostly of weak- or moderate-quality, met inclusion criteria. Four weak-quality studies investigated mental health symptoms, including three RCT-extension studies investigating depressive symptoms with inconsistent findings. Forty-four observational studies examined eight other outcome domains: diabetes, weight and glucose homeostasis; dementia and cognitive performance; cancer; eye conditions; self-reported emotional, interpersonal and biological effects; functional limitation, falls and fracture in older people; Parkinson’s disease and levodopa-induced dyskinesia in people with Parkinson’s disease; and all-cause mortality and suicide. There is evidence that long-term antidepressant use is associated with diabetes onset and weight gain. Evidence across the remaining outcome domains was sparse, inconsistent and generally insufficient to support firm conclusions. There were no studies investigating long-term antidepressant use and broader outcomes such as quality of life, occupational functioning, cost-effectiveness or healthcare utilisation. Conclusions: This review exposes the lack of high-quality evidence for long-term antidepressant use, calling into question justification for the high and rising prevalence of long-term use internationally and highlighting the challenge of informed decision-making. Importantly the evidence for mental health symptoms, the primary clinical indication for these medicines, is sparse and inconsistent. Review findings suggest the need for regular antidepressant monitoring which includes assessment of weight and diabetes risk. High-quality research is needed to clarify the benefits and harms of both continuing antidepressants long-term and stopping long-term antidepressants to inform clinical care and enable people to make informed choices. Systematic review registration: PROSPERO: CRD42023446361

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