The Possibility of Open-Label Use of Placebo in Healthcare Practice: A Systematic Review of Recent Clinical Trials

The use of placebos in primary treatment causes ethical concerns, as some may argue that the practice of prescribing placebos is deceptive. As a result, patients must be well-informed about their treatment plan and medications for physicians to maintain a positive patient-care relationship. This literature review evaluates the data from clinical open-label placebos (OLPs) and proposes preliminary suggestions regarding why the practice of prescribing placebos without deception may be effective. This systematic review aimed to address the research question: With patients receiving healthcare, if introduced, do OLPs improve patient-related or objective functional outcomes compared with the methods of usual care (UC) or treatment as usual (TAU)?  A systematic review was conducted following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines. The keywords "open-label placebos (OLPs), patient-related outcomes, functional outcomes, UC, TAU, and clinical trials" were used to search for studies from PubMed, Cochrane Library, and Scopus. The search was limited to articles written in English and published between the 1st of January 2020, and before the 31st of August 2025. The risk of bias (RoB) was assessed using Cochrane RoB 2.0. A narrative approach was used to synthesize evidence due to the heterogeneity of the studies. The review retrieved 120 articles initially. As not all studies are relevant, only 15 randomized controlled trials (RCTs) (nine of them with some concerns and six with low RoB) were included to synthesize evidence. OLPs are a potentially ethically viable intervention, as they effectively impact subjective symptom perception without changing the pathological discourse of the underlying disease. It works effectively, especially when it comes to symptom management of chronic conditions with a dominating subjective factor (e.g., patient- and psychosomatic-related symptoms or complications). OLPs do not meaningfully change the pathological course of the disease. Its effectiveness is seemingly due to a complex interaction between clear communication with patients and the ability for patients to regulate the perception of the symptoms. Therefore, OLPs should not be used as a standalone treatment to replace evidence-based primary treatment of clinical, chronic conditions, but OLPs can very possibly be considered as an add-on treatment if current primary treatments have failed, were ineffective, or were limited or have side effects that are intolerable. OLPs can be prescribed to patients who do not wish to proceed with primary treatment. The methodological challenges need to be addressed by future researchers.