Smartphone Cognitive Behavioral Therapy as an Adjunct to Pharmacotherapy for Refractory Depression: Randomized Controlled Trial.

Background: In the treatment of major depression, antidepressants are effective but not curative. Cognitive behavioral therapy (CBT) is also effective, alone or in combination with pharmacotherapy, but accessibility is a problem.

Objective: The aim is to evaluate the effectiveness of a smartphone CBT app as adjunctive therapy among patients with antidepressant-resistant major depression.

Methods: A multisite, assessor-masked, parallel-group randomized controlled trial was conducted in 20 psychiatric clinics and hospitals in Japan. Participants were eligible if they had a primary diagnosis of major depression and were antidepressant-refractory after taking one or more antidepressants at an adequate dosage for four or more weeks. After a 1-week run-in in which participants started the medication switch and had access to the welcome session of the app, patients were randomized to medication switch alone or to medication switch plus smartphone CBT app via the centralized Web system. The smartphone app, called Kokoro-app ("kokoro" means "mind" in Japanese), included sessions on self-monitoring, behavioral activation, and cognitive restructuring presented by cartoon characters. The primary outcome was depression severity as assessed by masked telephone assessors with the Patient Health Questionnaire-9 (PHQ-9) at week 9. The secondary outcomes included the Beck Depression Inventory-II (BDI-II) and Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER).

Results: In the total sample (N=164), 81 participants were allocated to the smartphone CBT in addition to medication change and 83 to medication change alone. In the former group, all but one participant (80/81, 99%) completed at least half, and 71 (88%) completed at least six of eight sessions. In the intention-to-treat analysis, patients allocated the CBT app scored 2.48 points (95% CI 1.23-3.72, P<.001; standardized mean difference 0.40) lower on PHQ-9 than the control at week 9. The former group also scored 4.1 points (95% CI 1.5-6.6, P=.002) lower on BDI-II and 0.76 points (95% CI -0.05 to 1.58, P=.07) lower on FIBSER. In the per-protocol sample (comfortable with the smartphone app, still symptomatic, and adherent to medication with mild or less side effects after run-in), the intervention group (n=60) scored 1.72 points (95% CI 0.25-3.18, P=.02) lower on PHQ-9, 3.2 points (95% CI -0.01 to 6.3, P=.05) lower on BDI-II, and 0.75 points (95% CI 0.03-1.47, P=.04) lower on FIBSER than the control (n=57). The treatment benefits were maintained up to week 17.

Conclusions: This is the first study to demonstrate the effectiveness of a smartphone CBT in the treatment of clinically diagnosed depression. Given the merits of the mobile mental health intervention, including accessibility, affordability, quality control, and effectiveness, it is clinically worthwhile to consider adjunctive use of a smartphone CBT app when treating patients with antidepressant-resistant depression. Research into its effectiveness in wider clinical contexts is warranted.

Trial Registration: Japanese Clinical Trials Registry UMIN CTR 000013693; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000015984 (Archived by WebCite at http://www.webcitation.org/6u6pxVwik).