Few Randomized Controlled Trials of Antidepressants Conduct a Blinding Assessment

Investigators searched publication databases through December 2020 for randomized controlled trials of antidepressants.

A systematic review and meta-analysis found that fewer than 10% of randomized controlled trials (RCTs) of antidepressants reported blinding assessments. These findings were published in eClinicalMedicine.

Investigators with Kyoto University Graduate School of Medicine and School of Public Health in Japan searched publication databases from 2010 to 2020 for RCTs of antidepressants. The primary outcome for this analysis was the degree of success in blinding. Successful blinding was defined as a κ range of -0.20 to 0.20, slightly broken blinding as κ 0.21 to 0.40, moderately broken blinding as κ 0.41 to 0.60, and severely broken blinding as κ 0.61 to 1.

A total of 154 studies were eligible for this analysis. Only 16 studies reported blinding assessments. There were no temporal trends in blinding reporting during the study period. Patients were assessed for blinding in 75% and assessors in 56.3% of studies.

Only 2 studies evaluated old generation antidepressants, neither or which reported a blinding assessment.

In new generation antidepressants, 1177 patients were included in studies (n=9) with patient blinding and 269 patients were included in studies (n=4) with assessor blinding. The study drugs were fluoxetine (n=3), sertraline (n=3), escitalopram (n=1), venlafaxine (n=1), and venlafaxine and paroxetine (n=1).

The correct guess about blinding ranged from 45% to 71% in studies (κ range, -0.14 to 0.38). The summary of blinding among patents was a κ of 0.21 (95% CI, 0.14-0.28) and for assessors was a κ of 0.17 (95% CI,

Similar results were observed in sensitivity analyses.

There was insufficient evidence to indicate a relationship between blinding successfulness and effect sizes in either studies with patient blinding (r, 0.37; P =.032) or assessor blinding (r, 0.28; P =.72) assessments.

This study was unable to compare older generation with newer generation antidepressant trials due to lack of information.

The study authors concluded, “Blinding assessment was reported in less than 10% of recent antidepressant trials, and the results of blinding assessments in new generation antidepressant trials indicated that patients or assessors were unlikely to judge which treatment the patients were on. Currently, the available evidence suggests that efficacy of new antidepressants is probably not overestimated due to broken blinding. However, there are only a very limited number of studies that report blinding success and so more accountability and transparency is needed among clinical trials.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Lin YH, Sahker E, Shinohara K, et al. Assessment of blinding in randomized controlled trials of antidepressants for depressive disorders 2000−2020: A systematic review and meta-analysis. EClinicalMedicine. 2022;50:101505. doi:10.1016/j.eclinm.2022.101505