Magnitude and Moderators of Depressive Symptom Improvement in Digital Placebo Arms: Systematic Review and Meta-Analysis

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)-defined as health software intended to treat or alleviate a disease, disorder, condition, or injury by generating and delivering a medical intervention that has a demonstrable positive therapeutic impact on a patient by the International Organization for Standardization-have gained increasing attention as alternatives for overcoming these hurdles. With advances in digital technology, digital placebos have begun to be used as comparators in the clinical trials of DTx to assess the effects of active interventions accurately. However, the characteristics of clinical trials, the magnitude of digital placebos effects, and their moderators remain poorly understood.