Nocebo effects in long-term health conditions: a systematic review of experimental studies

The nocebo effect refers to adverse symptoms triggered by negative expectations rather than active treatment mechanisms. These responses can undermine treatment adherence, increase symptom burden, and reduce clinical effectiveness. Patients with long-term conditions (LTCs) may be particularly vulnerable because they frequently interact with healthcare systems, monitor symptoms closely, and often have prior negative treatment experiences. Despite these important clinical implications, experimental evidence on nocebo responses in LTC populations has not been systematically synthesised. This review evaluated induction methods, symptom domains, and potential moderators to inform strategies for reducing avoidable nocebo-related harm in clinical practice.

The review followed PRISMA 2020 guidelines and was preregistered on OSF. MEDLINE, Web of Science, PsycINFO, and CINAHL were searched to 21 August 2025. Eligible studies experimentally induced nocebo effects in adults with physical or neurological LTCs using verbal suggestion, conditioning, or negatively framed communication. Quality was assessed using the Mixed Methods Appraisal Tool (MMAT). Due to substantial heterogeneity in induction procedures and outcome measures, findings were synthesised narratively.

Thirteen studies met the inclusion criteria, covering chronic pain, asthma, Parkinson's disease, cancer, and dermatology. Nocebo effects were commonly induced through negative verbal suggestion or negatively framed clinical information. Several studies demonstrated increased subjective symptom intensity, alterations in physiological markers, and brain activation patterns associated with expectancy. Evidence was mixed for neurological symptoms. Anxiety and other psychological moderators were measured inconsistently, and outcome definitions varied considerably across studies.

Individuals with long-term conditions can show strong nocebo responses across a range of symptoms. These findings highlight the importance of how treatment information is communicated in clinical encounters. More consistent induction and measurement approaches, routine assessment of psychological moderators, and evidence-based communication strategies are needed to reduce unnecessary symptom burden and improve treatment engagement in long-term condition management.

Open Science Framework, https://osf.io/nj7yt/.