Medicine:Lessebo effect

From HandWiki

The lessebo effect is a phenomenon in psychology and medicine in which a person in a blinded clinical trial knows that they might receive placebo due to the existence of a placebo control group in the trial and this results in the person experiencing diminished placebo effects (positive expectations) and therapeutic improvement.[1][2] It has been described in several contexts including clinical trials of treatment for depression,[3][4][5] schizophrenia,[6] Parkinson's disease,[7][8][9] and rheumatoid arthritis.[10][1] The phenomenon was first named the "lessebo effect" by Mark Sinyor and colleagues in 2010.[1][2] They showed in a meta-analysis that antidepressant and placebo response rates are influenced by the presence of a placebo arm and by the number of treatment arms (and thus likelihood of receiving placebo) in trials.[2] A closely related but slightly distinct concept is the inverse placebo effect,[11][12][13] which the lessebo effect has sometimes been inappropriately confused and conflated with.[14][15]

See also

  • Inverse placebo effect
  • Amplified placebo effect

References

  1. ↑ 1.0 1.1 1.2 "Nocebo and lessebo effects". Int Rev Neurobiol 153: 121–146. 2020. doi:10.1016/bs.irn.2020.04.005. PMID 32563285. 
  2. ↑ 2.0 2.1 2.2 "Does inclusion of a placebo arm influence response to active antidepressant treatment in randomized controlled trials? Results from pooled and meta-analyses". J Clin Psychiatry 71 (3): 270–279. March 2010. doi:10.4088/JCP.08r04516blu. PMID 20122371. 
  3. ↑ "Study design features affecting outcome in antidepressant trials". J Affect Disord 141 (2-3): 160–167. December 2012. doi:10.1016/j.jad.2012.03.021. PMID 22658811. 
  4. ↑ "Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD". Eur Neuropsychopharmacol 19 (1): 34–40. January 2009. doi:10.1016/j.euroneuro.2008.08.009. PMID 18823760. 
  5. ↑ "Does study design influence outcome?. The effects of placebo control and treatment duration in antidepressant trials". Psychother Psychosom 78 (3): 172–181. 2009. doi:10.1159/000209348. PMID 19321970. 
  6. ↑ "Control group bias in randomized atypical antipsychotic medication trials for schizophrenia". Arch Gen Psychiatry 62 (9): 961–970. September 2005. doi:10.1001/archpsyc.62.9.961. PMID 16143728. 
  7. ↑ "Another face of placebo: the lessebo effect in Parkinson disease: meta-analyses". Neurology 82 (16): 1402–1409. April 2014. doi:10.1212/WNL.0000000000000340. PMID 24658930. 
  8. ↑ "Factors influencing the outcome of deep brain stimulation: Placebo, nocebo, lessebo, and lesion effects". Mov Disord 31 (3): 290–296. March 2016. doi:10.1002/mds.26500. PMID 26952118. 
  9. ↑ "The Lessebo Effect in Disease Modification Trials in Parkinson's Disease". Mov Disord 38 (7): 1346–1350. July 2023. doi:10.1002/mds.29414. PMID 37093589. 
  10. ↑ "The lessebo effect in randomized controlled trials of rituximab in patients with rheumatoid arthritis: a meta-analysis". Z Rheumatol 82 (Suppl 1): 44–50. January 2023. doi:10.1007/s00393-021-01126-9. PMID 34761312. 
  11. ↑ "Placebo Effects in the Treatment of Depression-Implications for the Psychedelic Renaissance". Neurol Clin 44 (1): 63–75. February 2026. doi:10.1016/j.ncl.2025.08.009. PMID 41232997. 
  12. ↑ "Psychedelic Therapy vs Antidepressants for the Treatment of Depression Under Equal Unblinding Conditions: A Systematic Review and Meta-Analysis". JAMA Psychiatry. March 2026. doi:10.1001/jamapsychiatry.2025.4809. PMID 41848744. 
  13. ↑ Hamzelou, Jessica (20 March 2026). "Mind-altering substances are (still) falling short in clinical trials". https://www.technologyreview.com/2026/03/20/1134419/psychedelics-overhyped-psilocybin-depression-placebo/. 
  14. ↑ "Expectancy Effects, Failure of Blinding Integrity, and Placebo Response in Trials of Treatments for Psychiatric Disorders: A Narrative Review". JAMA Psychiatry 82 (5): 531–538. May 2025. doi:10.1001/jamapsychiatry.2025.0085. PMID 40072447. 
  15. ↑ "Magnitude of Response in Treatment and Control Groups within Psychedelic Trials for Psychiatric Disorders: A Meta-Analysis". Eur Psychiatry: 1–35. February 2026. doi:10.1192/j.eurpsy.2026.10168. PMID 41705428. "A further methodological consideration is that psychedelic trials may be especially susceptible to lessebo effects attenuated improvement when participants infer assignment to placebo or a sub-therapeutic condition, particularly in settings characterized by strong prior expectations and imperfect masking [48,49].". 



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