Placebo effects in adult and adolescent patients with schizophrenia: combined analysis of nine RCTs

Acta Psychiatr Scand. 2019 Feb;139(2):108-116. doi: 10.1111/acps.12960. Epub 2018 Sep 9.


Objective: To examine characteristics of placebo responders and seek optimal criteria of early improvement with placebo for predicting subsequent placebo response in patients with schizophrenia.

Method: Data of 672 patients with schizophrenia randomized to placebo in nine double-blind antipsychotic trials were analyzed. Multiple logistic regression analyses were conducted to examine associations between placebo response at week 6 (i.e., a ≥ 25% reduction in the Positive and Negative Syndrome Scale [PANSS] score) and gender, age, study locations, baseline PANSS total or Marder 5-Factor scores, and per cent PANSS score reduction at week 1. Predictive power of improvement at week 1 for subsequent response was investigated; sensitivity and specificity of incremental 5% cutoff points between 5% and 25% reduction in the PANSS total score at week 1 were calculated.

Results: Per cent PANSS total score reduction at week 1 and lower PANSS Marder disorganized thought scores at baseline were significantly associated with subsequent placebo response. A 10% reduction in a per-protocol analysis or a 15% reduction in last-observation-carried-forward analysis in the PANSS total score at week 1 showed the highest predictive power.

Conclusion: These findings are informative to identify potential placebo responders at the earliest opportunity for optimal trial design for schizophrenia.

Keywords: antipsychotic agents; placebo effect; placebos; schizophrenia.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Child
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Placebo Effect
  • Placebos / administration & dosage
  • Placebos / pharmacology*
  • Predictive Value of Tests
  • Psychiatric Status Rating Scales
  • Schizophrenia / drug therapy*
  • Schizophrenia / epidemiology
  • Sensitivity and Specificity
  • Young Adult


  • Antipsychotic Agents
  • Placebos