Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: Identifying potential placebo responders among apparent drug responders is critical to dissect drug-specific and nonspecific effects in depression. OBJECTIVE: This project aimed to develop and test a prediction model for the probability of responding to placebo in antidepressant trials. Such a model will allow us to estimate the probability of placebo response among drug responders in antidepressants trials. METHODS: We identified all placebo-controlled, double-blind randomised controlled trials (RCTs) of second generation antidepressants for major depressive disorder conducted in Japan and requested their individual patient data (IPD) to pharmaceutical companies. We obtained IPD (n=1493) from four phase II/III RCTs comparing mirtazapine, escitalopram, duloxetine, paroxetine and placebo. Out of 1493 participants in the four clinical trials, 440 participants allocated to placebo were included in the analyses. Our primary outcome was response, defined as 50% or greater reduction on Hamilton Rating Scale for Depression at study endpoint. We used multivariable logistic regression to develop a prediction model. All available candidate of predictor variables were tested through a backward variable selection and covariates were selected for the prediction model. The performance of the model was assessed by using Hosmer-Lemeshow test for calibration and the area under the ROC curve for discrimination. FINDINGS: Placebo response rates differed between 31% and 59% (grand average: 43%) among four trials. Four variables were selected from all candidate variables and included in the final model: age at onset, age at baseline, bodily symptoms, and study-level difference. The final model performed satisfactorily in terms of calibration (Hosmer-Lemeshow p=0.92) and discrimination (the area under the ROC curve (AUC): 0.70). CONCLUSIONS: Our model is expected to help researchers discriminate individuals who are more likely to respond to placebo from those who are less likely so. CLINICAL IMPLICATIONS: A larger sample and more precise individual participant information should be collected for better performance. Examination of external validity in independent datasets is warranted. TRIAL REGISTRATION NUMBER: CRD42017055912.

Original publication




Journal article


Evid Based Ment Health

Publication Date





10 - 16


Adult, Antidepressive Agents, Second-Generation, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Depressive Disorder, Major, Female, Humans, Japan, Male, Middle Aged, Models, Statistical, Outcome Assessment, Health Care, Placebo Effect, Placebos, Prognosis, Randomized Controlled Trials as Topic