JMIR Publications

ABSTRACT

Background:

Depressive disorders are one of the most prevalent psychiatric disorders globally and impose considerable individual and societal burdens. Psychotherapy, including cognitive behavioral therapy, is recommended as a first-line treatment especially for mild to moderate depressive disorders. However, face-to-face psychotherapy is often limited by issues of accessibility and cost. Digital therapeutics (DTx) have gained increasing attention as alternatives for overcoming these hurdles. With advances in digital technology, digital placebos have been increasingly adopted as comparators in the clinical trials for DTx. However, the characteristics of the clinical trials, the magnitude of digital placebos and their moderators remain poorly understood.

Objective:

The objectives of this study were to investigate the characteristics of clinical trials using digital placebos as comparators, and to assess the magnitude of the digital placebo effects and their moderators on depressive symptoms measured by Patient Health Questionnaire-9 (PHQ-9).

Methods:

The blind randomized clinical trials (RCTs) evaluating PHQ-9 by setting digital placebos as comparators were identified by searching MEDLINE, Scopus, Web of Science, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, ISRCTN in November 2025. The characteristics of the RCTs and of the digital placebos were reviewed systematically. The meta-analysis including sub-group analyses and meta-regressions were conducted to investigate the magnitude and the moderators of the digital placebos.

Results:

29 articles and 30 studies with 5680 participants were included in this systematic review and meta-analysis. The most common trial design was 2-arm, parallel-group study conducted in a single country, adopting “Replaced” and “Mobile” as the placebo approach and delivery type, respectively. The pooled effect size for all the included studies was Hedges’ g = 0.44 (95% CI 0.29 to 0.59) with an overall I2 = 93.2 %. Subgroup analyses showed moderate-to-large and statistically significant placebo effect in the group of primary psychiatric disorders (Hedges’ g = 0.69; 95% CI 0.40 to 0.99). Meta-regressions indicated that the group of primary psychiatric disorders and baseline PHQ-9 score were the independent moderators of the digital placebo effects and the major contributing factors of the high heterogeneity (R2 = 51.5%).

Conclusions:

Statistically significant digital placebo effects were observed on depressive symptoms, and target population and baseline PHQ-9 score were identified as the independent moderators. These findings would have implications for the planning of future DTx clinical trials using digital placebos for depressive symptoms.