Quantitative language features identify placebo responders in chronic back pain

Sara E. Berger, Paulo Branco, Etienne Vachon-Presseau, Taha B. Abdullah, Guillermo Cecchi, A. Vania Apkarian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Although placebo effect sizes in clinical trials of chronic pain treatments have been increasing, it remains unknown if characteristics of individuals' thoughts or previous experiences can reliably infer placebo pill responses. Research using language to investigate emotional and cognitive processes has recently gained momentum. Here, we quantified placebo responses in chronic back pain using more than 300 semantic and psycholinguistic features derived from patients' language. This speech content was collected in an exit interview as part of a clinical trial investigating placebo analgesia (62 patients, 42 treated; 20 not treated). Using a nested leave-one-out cross-validated approach, we distinguished placebo responders from nonresponders with 79% accuracy using language features alone; a subset of these features-semantic distances to identity and stigma and the number of achievement-related words-also explained 46% of the variance in placebo analgesia. Importantly, these language features were not due to generic treatment effects and were associated with patients' specific baseline psychological traits previously shown to be predictive of placebo including awareness and personality characteristics, explaining an additional 31% of the variance in placebo analgesia beyond that of personality. Initial interpretation of the features suggests that placebo responders differed in how they talked about negative emotions and the extent that they expressed awareness to various aspects of their experiences; differences were also seen in time spent talking about leisure activities. These results indicate that patients' language is sufficient to identify a placebo response and implie that specific speech features may be predictive of responders' previous treatment.

Original languageEnglish (US)
Pages (from-to)1692-1704
Number of pages13
Issue number6
StatePublished - Jun 1 2021


  • Chronic back pain
  • Interview
  • Machine learning
  • Natural language processing
  • Placebo response
  • Psycholinguistics
  • Semantic proximity

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Anesthesiology and Pain Medicine


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