Systematic review on nocebo effect induction in chronic conditions and clinical communication

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Frontiers in Medicine Published May 12, 2026 Medically reviewed May 12, 2026 DOI ↗ By Dr. Ji-eun Park, MD · Brain, Mind & Pain

Key Takeaway

Consider how clinical communication may influence nocebo effects in long-term conditions, given the mixed and heterogeneous evidence.

This is a systematic review of experimental studies on nocebo effect induction in adults with physical or neurological long-term conditions, including chronic pain, asthma, Parkinson's disease, cancer, and dermatology. The review synthesizes evidence that nocebo effects are commonly induced through negative verbal suggestion or negatively framed clinical information, leading to increased subjective symptom intensity, alterations in physiological markers, and brain activation patterns associated with expectancy.

The authors note that evidence was mixed for neurological symptoms and that findings are narrative due to heterogeneity. They highlight substantial heterogeneity in induction procedures and outcome measures, inconsistent measurement of anxiety and other psychological moderators, and considerable variation in outcome definitions across studies.

The review does not report pooled effect sizes, p-values, or confidence intervals, as these were not provided in the abstract. No specific study populations, interventions, comparators, or adverse events are described, as these details were not reported.

Practice relevance is restrained: findings highlight the importance of how treatment information is communicated in clinical encounters to reduce unnecessary symptom burden and improve treatment engagement. The authors caution that this is a systematic review of experimental studies and does not establish causation in clinical settings.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

BackgroundThe 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.MethodsThe 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.ResultsThirteen 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.ConclusionIndividuals 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.Systematic review registrationOpen Science Framework, https://osf.io/nj7yt/.