Optimizing smartphone psychotherapy for depressive symptoms in patients with cancer: Multiphase optimization strategy using a decentralized multicenter randomized clinical trial (J-SUPPORT 2001 Study).

AIM: Patients with cancer experience various forms of psychological distress, including depressive symptoms, which can impact quality of life, elevate morbidity risk, and increase medical costs. Psychotherapy and pharmacotherapy are effective for reducing depressive symptoms among patients with cancer, but most patients prefer psychotherapy. This study aimed to develop an efficient and effective smartphone psychotherapy component to address depressive symptom. METHODS: This was a decentralized, parallel-group, multicenter, open, individually randomized, fully factorial trial. Patients aged ≥20 years with cancer were randomized by the presence/absence of three cognitive-behavioral therapy (CBT) skills (behavioral activation [BA], assertiveness training [AT], and problem-solving [PS]) on a smartphone app. All participants received psychoeducation (PE). The primary outcome was change in the patient health questionnaire-9 (PHQ-9) total score between baseline and week 8. Secondary outcomes included anxiety. RESULTS: In total, 359 participants were randomized. Primary outcome data at week 8 were obtained for 355 participants (99%). The week 8 PHQ-9 total score was significantly reduced from baseline for all participants by -1.41 points (95% confidence interval [CI] -1.89, -0.92), but between-group differences in change scores were not significant (BA: -0.04, 95% CI -0.75, 0.67; AT: -0.16, 95% CI -0.87, 0.55; PS: -0.19, 95% CI -0.90, 0.52). CONCLUSION: As the presence of any of the three intervention components did not contribute to a significant additive reduction of depressive symptoms, we cannot make evidence-based recommendations regarding the use of specific smartphone psychotherapy.

Three types of university students with subthreshold depression characterized by distinctive cognitive behavioral skills.

Subthreshold depression impairs young people's quality of life and places them at greater risk of developing major depression. Cognitive behavioral therapy (CBT) is an evidence-based approach for addressing such depressive states. This study identified subtypes of university students with subthreshold depression and revealed discrete profiles of five CBT skills: self-monitoring, cognitive restructuring, behavioral activation, assertive communication, and problem solving. Using data from the Healthy Campus Trial (registration number: UMINCTR-000031307), a hierarchical clustering analysis categorized 1,080 students into three clusters: Reflective Low-skilled, Non-reflective High-skilled, and Non-reflective Low-skilled students. Non-reflective Low-skilled students were significantly more depressed than other students (p < .001). The severity of depression seemed to be related to the combination of self-monitoring skills and other CBT skills. Considering the high prevalence of poor self-monitoring skills in persons with autism, the most severe depression was observed in the significant association between Non-reflective Low-skilled students and autistic traits (p = .008). These findings suggest that subthreshold depression can be categorized into three subtypes based on CBT skill profiles. The assessment of autistic traits is also suggested when we provide CBT interventions for Non-reflective Low-skilled students.

Efficacy of the unified protocol for transdiagnostic cognitive-behavioral treatment for depressive and anxiety disorders: a randomized controlled trial.

BACKGROUND: The efficacy of the unified protocol of the transdiagnostic treatment for emotional disorders (UP) has been poorly studied in patients with depressive disorders. This study aimed to examine the efficacy of UP for improving depressive symptoms in patients with depressive and/or anxiety-related disorders. METHODS: This assessor-blinded, randomized, 20-week, parallel-group, superiority study compared the efficacy of the UP with treatment-as-usual (UP-TAU) v. wait-list with treatment-as-usual (WL-TAU). Patients diagnosed with depressive and/or anxiety disorders and with depressive symptoms participated. The primary outcome was depressive symptoms assessed by GRID-Hamilton depression rating scale (GRID-HAMD) at 21 weeks. The secondary outcomes included assessor-rated anxiety symptoms, severity and improvement of clinical global impression, responder and remission status, and loss of principal diagnosis. RESULTS: In total, 104 patients participated and were subjected to intention-to-treat analysis [mean age = 37.4, s.d. = 11.5, 63 female (61%), 54 (51.9%) with a principal diagnosis of depressive disorders]. The mean GRID-HAMD scores in the UP-TAU and WL-TAU groups were 16.15 (s.d. = 4.90) and 17.06 (s.d. = 6.46) at baseline and 12.14 (s.d. = 5.47) and 17.34 (s.d. = 5.78) at 21 weeks, with a significant adjusted mean change difference of -3.99 (95% CI -6.10 to -1.87). Patients in the UP-TAU group showed significant superiority in anxiety and clinical global impressions. The improvement in the UP-TAU group was maintained in all outcomes at 43 weeks. No serious adverse events were observed in the UP-TAU group. CONCLUSIONS: The UP is an effective approach for patients with depressive and/or anxiety disorders.

Feasibility, acceptability, and preliminary efficacy of cognitive processing therapy in Japanese patients with posttraumatic stress disorder.

Cognitive processing therapy (CPT) is one of the most widely tested evidence-based treatments for posttraumatic stress disorder (PTSD). However, most studies on CPT have been conducted in Western cultural settings. This open-label, single-arm trial investigated the feasibility, acceptability, and preliminary efficacy of CPT for treating Japanese patients with PTSD. A total of 25 outpatients underwent 12 CPT sessions. The primary outcome was the assessment of PTSD symptoms using the Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV); secondary outcomes included the assessment of subjective PTSD severity, depressive and anxiety symptoms, trauma-related cognitions, and subjective quality of life. All outcomes were evaluated at pretreatment (i.e., baseline), posttreatment, and 6- and 12-month follow-ups. On average, participants attended 13 sessions of CPT (SD = 1.38), with a completion rate of 96.0%. One serious adverse event (hospitalization) occurred. Significant within-subjects standardized mean differences in CAPS-IV scores were found from baseline to treatment completion, g = -2.28, 95% CI [-3.00, -1.56]; 6-month follow-up, g = -2.95, 95% CI [-3.79, -2.12]; and 12-month follow-up, g = -2.15, 95% CI [-2.89, -1.41]. Moderate-to-large effects, gs = -0.77 to -2.45, were found on secondary outcomes. These findings support the feasibility, acceptability, and preliminary efficacy of CPT in a Japanese clinical setting.

Group Cognitive-Behavioral Therapy With Interoceptive Exposure for Drug-Refractory Irritable Bowel Syndrome: A Randomized Controlled Trial.

INTRODUCTION: Few people can access psychotherapy for irritable bowel syndrome (IBS). Group cognitive-behavioral therapy (GCBT) may be efficient, but the evidence for its efficacy is weak and limited. We aimed to assess the efficacy and safety of GCBT with interoceptive exposure (GCBT-IE), a novel form of GCBT for drug-refractory IBS. METHODS: A single-center, open-label, randomized, controlled trial was conducted in Japan among people aged 18-75 years with moderate-to-severe drug-refractory IBS. Participants were stratified by IBS severity and allocated 1:1 to 10-week GCBT-IE or waiting list (WL) in a blockwise randomization by independent staff. Both arms practiced self-monitoring and received treatment as usual. Multiple primary outcomes were changes from baseline to week 13 in the IBS Symptom Severity Score and the IBS Quality of Life Measure (IBS-QOL), assessed in the intention-to-treat sample. RESULTS: A total of 114 people with drug-refractory IBS were randomized to GCBT-IE (n = 54) or WL (n = 60). Forty-nine participants (90.7%) in the GCBT-IE arm and 58 (96.7%) in the WL arm completed the week 13 assessment. Participants in the GCBT-IE arm reported greater improvements in both IBS symptom severity and quality of life compared with the WL arm, with -115.8 vs -29.7 on the IBS Symptom Severity Score (a difference of -86.1, 95% confidence interval -117.3 to -55.0), and 20.1 vs -0.2 on the IBS-QOL (a difference of 20.3, 95% confidence interval 15.2-25.3), respectively. Six unexpected serious adverse events were reported but were judged as unrelated to the interventions. DISCUSSION: GCBT-IE is an efficacious, safe, and efficient treatment option for people with drug-refractory IBS.

Affective styles and their association with anxiety and depression in a Japanese clinical sample.

Affective styles are assumed to play an important role in maintaining negative affect, including anxiety and depression. However, little is known about the longitudinal relationship between affective styles and symptoms. Therefore, we conducted a longitudinal study to examine the influence of affective styles, assessed using the Affective Style Questionnaire, on anxiety and depression among clinical populations in Japan. Using an online survey, 1521 participants (406 with major depressive disorder; 479 with one or more anxiety disorders; and 636 with both) answered the Affective Style Questionnaire and measures of emotion regulation, anxiety and depression symptoms. Data were collected twice over 2 months. Confirmatory factor analyses replicated the same four-factor structure found in a previous sample of Japanese university students. Hierarchical regression analyses revealed that the affective styles had a slightly greater effect on anxiety symptoms but not on depression compared to other common emotion regulation strategies, such as suppression and reappraisal measured by the Emotion Regulation Questionnaire (ERQ). Limitations of this study were that it used online surveys, in which, participants' diagnostic statuses were based on unverifiable self-reports. In conclusion, the association of affective styles with anxiety and depression among the clinical populations was prospectively confirmed. Further study is needed to examine the association considering the combination or profiles of affective styles among different emotional disorders.

Efficacy and Acceptability of Remote Cognitive Behavioral Therapy for Patients With Major Depressive Disorder in Japanese Clinical Settings: A Case Series.

Remote cognitive and behavioral therapy (CBT) via videoconference has been garnering attention as a means of improving access to CBT for depression, in particular during the coronavirus disease 2019 pandemic. However, there is a lack of evidence supporting its implementation in Japanese clinical settings. This case series aimed to establish preliminary evidence of whether remote CBT can be an effective therapy for major depression in Japanese clinical settings. Five patients who met the diagnostic criteria for major depressive disorder were enrolled and underwent remote CBT via videoconference and face-to-face assessment interviews. The results showed that remote CBT via videoconference improved depressive symptoms, enabling a relatively high level of patient satisfaction and working alliance. Moreover, detailed feedback from our patients showed that continuous monitoring was preferable for increasing treatment engagement. Further research is warranted to test the efficacy and acceptability of remote CBT via videoconference for treating major depression.

Group cognitive behavioural therapy (GCBT) versus treatment as usual (TAU) in the treatment of irritable bowel syndrome (IBS): a study protocol for a randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a common disease that affects the quality of life (QOL) and social functioning of sufferers. Visceral anxiety is currently considered a key factor in the onset and exacerbation of IBS, and cognitive-behavioural therapy (CBT) targeting visceral anxiety is thought to be effective. However, access to CBT is limited due to the lack of trained therapists, the substantial time required for therapy and the associated costs. Group CBT (GCBT) may solve some of these problems. We have therefore planned this trial to examine the efficacy of GCBT for IBS. METHODS: The trial is a two-armed, parallel group, open label, stratified block randomized superiority trial. The study group will consist of 112 participants (aged 18-75 years) with IBS (Rome-III or IV criteria). Participants will be randomly allocated 1:1 to (i) the intervention group: ten-week GCBT plus treatment as usual (TAU) or (ii) the control group: waiting list (WL) plus TAU. The co-primary outcomes are the change in IBS severity or disease-specific quality of life from baseline to week 13 which is 1 month after the end of treatment. The efficacy of GCBT for IBS will be examined through mixed-effects repeated-measures analysis. DISCUSSION: GCBT, if found effective, can address the issues of the shortage of therapists as well as the time required and the costs associated with individual CBT. Clinically, the findings will help make effective CBT programmes accessible to a large number of distressed IBS patients at lower costs. Theoretically, the results will clarify the relationship between IBS and psychological stress and will help elucidate the underlying mechanisms of IBS. TRIAL REGISTRATION: UMIN, CTR-UMIN000031710. Registered on March 13, 2018.

Smartphone problem-solving therapy to reduce fear of cancer recurrence among breast cancer survivors: an open single-arm pilot study.

OBJECTIVES: The purpose of this study was to investigate a newly developed smartphone problem-solving therapy (PST) application's feasibility and preliminary effectiveness for reducing fear of cancer recurrence (FCR) among breast cancer survivors. METHODS: Female disease-free breast cancer survivors aged 20-49 years who were more than 6 months post-breast surgery participated in the study. The patients received the smartphone PST using an iPhone or iPad for 8 weeks. The feasibility of the intervention program was evaluated using the overall participation rate, the percentage of survivors who expressed interest in the intervention, and the percentage of completion of the study. Patients were also asked to complete the Concern About Recurrence Scale (CARS) as a primary outcome at baseline, 4 weeks and 8 weeks. RESULTS: A total of 38 patients participated in this study. The overall participation and completion rates in the study were 47.1% and 97.4%, respectively. The overall fear assessed by CARS was significantly reduced at 8 weeks compared with baseline. A pairwise comparison showed a significant decrease from 4 weeks to 8 weeks and from baseline to 8 weeks. CONCLUSIONS: Smartphone PST, a novel brief intervention to reduce FCR, was well accepted by breast cancer survivors and yielded a favorable effect on FCR. The efficacy of this newly developed smartphone PST needs to be confirmed in a future well-designed randomized controlled trial.

Predicting recurrence of depression using lifelog data: an explanatory feasibility study with a panel VAR approach.

BACKGROUND: Although depression has a high rate of recurrence, no prior studies have established a method that could identify the warning signs of its recurrence. METHODS: We collected digital data consisting of individual activity records such as location or mobility information (lifelog data) from 89 patients who were on maintenance therapy for depression for a year, using a smartphone application and a wearable device. We assessed depression and its recurrence using both the Kessler Psychological Distress Scale (K6) and the Patient Health Questionnaire-9. RESULTS: A panel vector autoregressive analysis indicated that long sleep time was a important risk factor for the recurrence of depression. Long sleep predicted the recurrence of depression after 3 weeks. CONCLUSIONS: The panel vector autoregressive approach can identify the warning signs of depression recurrence; however, the convenient sampling of the present cohort may limit the scope towards drawing a generalised conclusion.

A new device-aided cognitive function test, User eXperience-Trail Making Test (UX-TMT), sensitively detects neuropsychological performance in patients with dementia and Parkinson's disease.

BACKGROUND: A newer generation neuropsychological tests can take advantage of touch screen and mobile technology. We have developed a new Android application termed "User eXperience-Trail Making Test (UX-TMT)" for neurocognitive assessment and training. This study investigated the utility, including the reliability and the validity, of the UX-TMT as a screening test for cognitive decline in adults. METHODS: A total of 84 individuals aged 27-86 years were divided into three groups; healthy controls ([HC] n = 29), people with Parkinson's disease (PD; n = 28), and people with mild cognitive impairment (MCI) and dementia (MCI&D; n = 27). We examined the distributions of the scores and the time required, and the effects of age and group on these distributions. We analyzed internal consistency and convergent validity in all samples and applied receiver operator characteristic (ROC) analysis to determine a cutoff score that could differentiate the MCI & D group from the HC group. RESULTS: 97.6% of the participants completed all of the tasks, and the average total test time required for UX-TMT was 428.8 (± 109.1) s in the HC, 542.0 (± 168.7) s in the PD, and 777.5 (± 256.1) s in the MCI&D groups, respectively. The MCI&D group showed significantly lower UX-TMT scores and longer total time in completing the task than the HC group. In an ROC analysis, a score of 21 showed high sensitivity (.83) and specificity (.92), and the UX-TMT score plus age improved sensitivity to .96. Additionally, the UX-TMT scores showed significant correlation with the Mini-Mental State Examination (Japanese version) scores (r = .77, p = .001), and Cronbach's alpha (.71-.83) indicated acceptable internal consistency. CONCLUSION: The UX-TMT demonstrated high reliability and validity to detect cognitive decline in Japanese adults, highlighting its utility as a screening tool for epidemiological and clinical research.

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

[This corrects the article DOI: 10.2196/jmir.8602.].

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).

Japan Unified Protocol Clinical Trial for Depressive and Anxiety Disorders (JUNP study): study protocol for a randomized controlled trial.

BACKGROUND: The unified protocol for the transdiagnostic treatment of emotional disorders is a promising treatment approach that could be applicable to a broad range of mental disorders, including depressive, anxiety, trauma-related, and obsessive-compulsive disorders. However, no randomized controlled trial has been conducted to verify the efficacy of the unified protocol on the heterogeneous clinical population with depressive and anxiety disorders. METHODS/DESIGN: The trial was designed as a single-center, assessor-blinded, randomized, 20-week, parallel-group superiority study in order to compare the efficacy of the combination of unified protocol and treatment-as-usual versus waiting-list with treatment-as-usual for patients with depressive and/or anxiety disorders. The primary outcome was depression at 21 weeks, assessed by the 17-item version of the GRID-Hamilton Rating Scale for Depression. Estimated minimum sample size was 27 participants in each group. We will also examine the treatment mechanisms, treatment processes, and neuropsychological correlates. DISCUSSION: The results of this study will clarify the efficacy of the unified protocol for depressive and anxiety disorders, and the treatment mechanism, process, and neurological correlates for the effectiveness of the unified protocol. If its efficacy can be confirmed, the unified protocol may be of high clinical value for Japan, a country in which cognitive behavioral treatment has not yet been widely adopted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02003261 (registered on December 2, 2013).

[Supervision in Psychiatric Training].

Psychotherapy is an essential component of psychiatric treatment. Although appropriate training including supervision is essential to become able to conduct psychotherapy skillfully, supervision has not been performed in the training of Japanese psychiatrists. In this article, we explain how to utilize supervision in psychiatric training.

Effectiveness of group cognitive behavioral therapy for somatoform pain disorder patients in Japan: A preliminary non-case-control study.

AIMS: Somatoform pain disorder is associated with psychosocial dysfunction, and psychotherapies, such as cognitive behavioral therapy (CBT), are thought to provide useful interventions to address such dysfunction as well as the pain itself. However, little is known about whether CBT for somatoform pain disorder is effective, including the long-term course of the illness, in non-Western populations. We therefore tailored such a program based on an existing CBT protocol and examined its effectiveness in Japan. METHODS: Thirty-four Japanese participants (22 women; mean age = 52.5 years) enrolled in a weekly 12-session group treatment, with 32 completing both wait-list and treatment conditions. The primary outcome measure was pain intensity. Secondary outcome measures included pain characteristics, as measured by pain catastrophizing and psychometric evaluations, including depression, anxiety, and quality of life. The patients were followed up for 12 months after treatment. RESULTS: We found that pain intensity, anxiety, depressive symptoms, and social functioning all significantly improved after treatment compared with the wait-list period, and the improvements in pain intensity, depressive symptoms, and social functioning were sustained at 12 months following the completion of CBT. There were strong positive correlations (P < 0.01) among pre- and post-treatment changes in the affective dimension of pain, depression, anxiety, and pain catastrophizing. CONCLUSIONS: These results show that the present CBT program was effective for Japanese patients with somatoform pain disorder and that gains were maintained over the long term. More work is needed to further clarify the effects of CBT interventions on somatoform symptoms, particularly in Japan.

[Adverse Events and Precautions Regarding Cognitive Behavioral Therapy].

Adverse events of cognitive behavioral therapy (CBT) can be used to identify two types depending on whether or not CBT is practiced appropriately. The results of a randomized control trial (RCT) when CBT is performed effectively show that the rate of adverse events is as low as, or lower than, that on using a pill placebo. Many adverse events are associated with a low quality of CBT caused by inappropriate practice due to therapists' lack of knowledge, skills, and experience. In order to achieve effective CBT for RCT, it is considered important to frequently assess the status of patients before and during CBT sessions, utilize the Cognitive Therapy Rating Scale after the session, and conduct supervision based on audio recordings of the session.

Long-Term Effects of Internet-Based Cognitive Behavioral Therapy on Depression Prevention Among University Students: Randomized Controlled Factorial Trial.

Background: Internet-based cognitive behavioral therapy (iCBT) shows promise in the prevention of depression. However, the specific iCBT components that contribute to its effectiveness remain unclear. Objective: We aim to evaluate the effects of iCBT components in preventing depression among university students. Methods: Using a smartphone cognitive behavioral therapy (CBT) app, we randomly allocated university students to the presence or absence of 5 different iCBT components: self-monitoring, behavioral activation, cognitive restructuring, assertiveness training, and problem-solving. The active intervention lasted 8 weeks but the app remained accessible through the follow-up. The primary outcome was the onset of a major depressive episode (MDE) between baseline and the follow-up after 52 weeks, as assessed with the computerized World Health Organization Composite International Diagnostic Interview. Secondary outcomes included changes in the 9-item Patient Health Questionnaire, 7-item General Anxiety Disorder, and CBT Skills Scale. Results: During the 12-month follow-up, 133 of 1301 (10.22%) participants reported the onset of an MDE. There were no significant differences in the incidence of MDEs between the groups with or without each component (hazard ratios ranged from 0.85, 95% CI 0.60-1.20, for assertiveness training to 1.26, 95% CI 0.88-1.79, for self-monitoring). Furthermore, there were no significant differences in the changes on the 9-item Patient Health Questionnaire, 7-item General Anxiety Disorder, or for CBT Skills Scale between component allocation groups. However, significant reductions in depression and anxiety symptoms were observed among all participants at the 52-week follow-up. Conclusions: In this study, we could not identify any specific iCBT components that were effective in preventing depression or the acquisition of CBT skills over the 12-month follow-up period, but all participants with and without intervention of each iCBT component demonstrated significant improvements in depressive and anxiety symptoms. Further research is needed to explore the potential impact of frequency of psychological assessments, nonspecific intervention effects, natural change in the mental state, and the baseline depression level.

Four 2×2 factorial trials of smartphone CBT to reduce subthreshold depression and to prevent new depressive episodes among adults in the community-RESiLIENT trial (Resilience Enhancement with Smartphone in LIving ENvironmenTs): a master protocol.

INTRODUCTION: The health burden due to depression is ever increasing in the world. Prevention is a key to reducing this burden. Guided internet cognitive-behavioural therapies (iCBT) appear promising but there is room for improvement because we do not yet know which of various iCBT skills are more efficacious than others, and for whom. In addition, there has been no platform for iCBT that can accommodate ongoing evolution of internet technologies. METHODS AND ANALYSIS: Based on our decade-long experiences in developing smartphone CBT apps and examining them in randomised controlled trials, we have developed the Resilience Training App Version 2. This app now covers five CBT skills: cognitive restructuring, behavioural activation, problem-solving, assertion training and behaviour therapy for insomnia. The current study is designed as a master protocol including four 2×2 factorial trials using this app (1) to elucidate specific efficacies of each CBT skill, (2) to identify participants' characteristics that enable matching between skills and individuals, and (3) to allow future inclusion of new skills. We will recruit 3520 participants with subthreshold depression and ca 1700 participants without subthreshold depression, to examine the short-term efficacies of CBT skills to reduce depressive symptoms in the former and to explore the long-term efficacies in preventing depression in the total sample. The primary outcome for the short-term efficacies is the change in depressive symptoms as measured with the Patient Health Questionnaire-9 at week 6, and that for the long-term efficacies is the incidence of major depressive episodes as assessed by the computerised Composite International Diagnostic Interview by week 50. ETHICS AND DISSEMINATION: The trial has been approved by the Ethics Committee of Kyoto University Graduate School of Medicine (C1556). TRIAL REGISTRATION NUMBER: UMIN000047124.

Optimization of smartphone psychotherapy for depression and anxiety among patients with cancer using the multiphase optimization strategy (MOST) framework and decentralized clinical trial system (SMartphone Intervention to LEssen depression/Anxiety and GAIN resilience: SMILE AGAIN project): a protocol for a randomized controlled trial.

BACKGROUND: Cancer patients experience various forms of psychological distress. Their distress, mainly in the form of depression and anxiety, leads to poor quality of life, increased medical spending due to frequent visits, and decrease in treatment adherence. It is estimated that 30-50% among them would require support from mental health professionals: in reality, much less actually receive such support partly due to a shortage of qualified professionals and also due to psychological barriers in seeking such help. The purpose of the present study is to develop the easily accessible and the most efficient and effective smartphone psychotherapy package to alleviate depression and anxiety in cancer patients. METHODS: Based on the multiphase optimization strategy (MOST) framework, the SMartphone Intervention to LEssen depression/Anxiety and GAIN resilience project (SMILE-AGAIN project) is a parallel-group, multicenter, open, stratified block randomized, fully factorial trial with four experimental components: psychosocial education (PE), behavioral activation (BA), assertion training (AT), and problem-solving therapy (PS). The allocation sequences are maintained centrally. All participants receive PE and then are randomized to the presence/absence of the remaining three components. The primary outcome of this study is the Patient Health Questionnaire-9 (PHQ-9) total score, which will be administered as an electronic patient-reported outcome on the patients' smartphones after 8 weeks. The protocol was approved by the Institutional Review Board of Nagoya City University on July 15, 2020 (ID: 46-20-0005). The randomized trial, which commenced in March 2021, is currently enrolling participants. The estimated end date for this study is March 2023. DISCUSSION: The highly efficient experimental design will allow for the identification of the most effective components and the most efficient combinations among the four components of the smartphone psychotherapy package for cancer patients. Given that many cancer patients face significant psychological hurdles in seeing mental health professionals, easily accessible therapeutic interventions without hospital visits may offer benefits. If an effective combination of psychotherapy is determined in this study, it can be provided using smartphones to patients who cannot easily access hospitals or clinics. TRIAL REGISTRATION: UMIN000041536, CTR. Registered on 1 November 2020  https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000047301 .