JMIR Publications

ABSTRACT

Background:

Major depressive disorder (MDD) is common worldwide and can be highly disabling. People with MDD face many barriers to treatment and may not experience full symptom relief even when treated. Therefore, new treatment modalities are needed for MDD. Digital therapeutics (DTx) may provide people with MDD an additional treatment option.

Objective:

To describe a phase 3 virtual, multicenter, randomized, masked, sham-controlled trial evaluating the efficacy of a smartphone appbased DTx in adult participants diagnosed with MDD, used as an adjunct to antidepressant therapy (ADT).

Methods:

Methods:

Participants aged 22–64 years with a current primary diagnosis of MDD and an inadequate response to ADT were included. Participants were randomized 1:1 to the treatment DTx or a sham DTx. The treatment is a smartphone, appbased DTx that delivers a cognitive-emotional and behavioral therapeutic intervention. The core components of the DTx are the Emotional Faces Memory Task exercises; brief lessons to learn and apply key therapeutic skills; and SMS text messaging to reinforce lessons and encourage engagement with the app. The sham DTx is a digital working memory exercise with emotionally neutral stimuli designed to match the treatment DTx for time and attention. Participants took part in the trial for up to 13 weeks. The trial included a screening period of up to 3 weeks, a treatment period of 6 weeks, and an extension period for 4 weeks to assess durability of effect. Sites and participants had the option of an in-person or virtual screening visit; the remaining trial visits were virtual. Efficacy was evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Generalized Anxiety Disorder-7 (GAD-7), Clinical Global Impression–Severity scale, the Patient Health Questionnaire-9, and World Health Organization Disability Assessment Schedule 2.0. Durability of effect was evaluated with the MADRS and GAD-7. Adverse events were also assessed. Satisfaction, measured by the Participant and Healthcare Professional Satisfaction Scales, and health status, measured by the EuroQol 5-Dimension, 5-Level, were summarized using descriptive statistics.

Results:

The study was completed in October 2022.

Conclusions:

This represents the methodological design for the first evaluation of this DTx as an adjunct to ADT. This study protocol is methodologically robust and incorporates many aspects of conventional pivotal pharmaceutical phase 3 trial design, such as randomization and safety endpoints. Novel considerations included the use of an active comparator, masking considerations for visible app content, and outcome measures relevant to DTx. The rigor of this methodology will provide a more comprehensive understanding of the effectiveness of the DTx. Clinical Trial: ClinicalTrials.gov NCT04770285