Prediction of remission in pharmacotherapy of untreated major depression: development and validation of multivariable prediction models.

BACKGROUND: Depression is increasingly recognized as a chronic and relapsing disorder. However, an important minority of patients who start treatment for their major depressive episode recover to euthymia. It is clinically important to be able to predict such individuals. METHODS: The study is a secondary analysis of a recently completed pragmatic megatrial examining first- and second-line treatments for hitherto untreated episodes of non-psychotic unipolar major depression (n = 2011). Using the first half of the cohort as the derivation set, we applied multiply-imputed stepwise logistic regression with backward selection to build a prediction model to predict remission, defined as scoring 4 or less on the Patient Health Quetionnaire-9 at week 9. We used three successively richer sets of predictors at baseline only, up to week 1, and up to week 3. We examined the external validity of the derived prediction models with the second half of the cohort. RESULTS: In total, 37.0% (95% confidence interval 34.8-39.1%) were in remission at week 9. Only the models using data up to week 1 or 3 showed reasonable performance. Age, education, length of episode and depression severity remained in the multivariable prediction models. In the validation set, the discrimination of the prediction model was satisfactory with the area under the curve of 0.73 (0.70-0.77) and 0.82 (0.79-0.85), while the calibration was excellent with non-significant goodness-of-fit χ2 values (p = 0.41 and p = 0.29), respectively. CONCLUSIONS: Patients and clinicians can use these prediction models to estimate their predicted probability of achieving remission after acute antidepressant therapy.

Optimising first- and second-line treatment strategies for untreated major depressive disorder - the SUN☺D study: a pragmatic, multi-centre, assessor-blinded randomised controlled trial.

BACKGROUND: For patients starting treatment for depression, current guidelines recommend titrating the antidepressant dosage to the maximum of the licenced range if tolerated. When patients do not achieve remission within several weeks, recommendations include adding or switching to another antidepressant. However, the relative merits of these guideline strategies remain unestablished. METHODS: This multi-centre, open-label, assessor-blinded, pragmatic trial involved two steps. Step 1 used open-cluster randomisation, allocating clinics into those titrating sertraline up to 50 mg/day or 100 mg/day by week 3. Step 2 used central randomisation to allocate patients who did not remit after 3 weeks of treatment to continue sertraline, to add mirtazapine or to switch to mirtazapine. The primary outcome was depression severity measured with the Patient Health Questionnaire-9 (PHQ-9) (scores between 0 and 27; higher scores, greater depression) at week 9. We applied mixed-model repeated-measures analysis adjusted for key baseline covariates. RESULTS: Between December 2010 and March 2015, we recruited 2011 participants with hitherto untreated major depression at 48 clinics in Japan. In step 1, 970 participants were allocated to the 50 mg/day and 1041 to the 100 mg/day arms; 1927 (95.8%) provided primary outcomes. There was no statistically significant difference in the adjusted PHQ-9 score at week 9 between the 50 mg/day arm and the 100 mg/day arm (0.25 point, 95% confidence interval (CI), - 0.58 to 1.07, P = 0.55). Other outcomes proved similar in the two groups. In step 2, 1646 participants not remitted by week 3 were randomised to continue sertraline (n = 551), to add mirtazapine (n = 537) or to switch to mirtazapine (n = 558): 1613 (98.0%) provided primary outcomes. At week 9, adding mirtazapine achieved a reduction in PHQ-9 scores of 0.99 point (0.43 to 1.55, P = 0.0012); switching achieved a reduction of 1.01 points (0.46 to 1.56, P = 0.0012), both relative to continuing sertraline. Combination increased the percentage of remission by 12.4% (6.1 to 19.0%) and switching by 8.4% (2.5 to 14.8%). There were no differences in adverse effects. CONCLUSIONS: In patients with new onset depression, we found no advantage of titrating sertraline to 100 mg vs 50 mg. Patients unremitted by week 3 gained a small benefit in reduction of depressive symptoms at week 9 by switching sertraline to mirtazapine or by adding mirtazapine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01109693 . Registered on 23 April 2010.

Association study of polymorphism in the serotonin transporter gene promoter, methylation profiles, and expression in patients with major depressive disorder.

The serotonin transporter (5HTT) may be associated with the pathogenesis of major depressive disorder (MDD). The 5HTT-linked polymorphic region (5HTTLPR) genotype may determine how levels of 5HTT mRNA are influenced by promoter methylation. We examined the association of 5HTT gene methylation, which influences gene expression, and the 5HTTLPR genotype before antidepressant treatment and expression before and after treatment. The aims of this study were (1) to investigate the association between 5HTT methylation or expression in leukocytes and depression and (2) to investigate a possible effect of 5HTT methylation, expression, and genotype on clinical symptoms in MDD. The 5HTTLPR genotype was significantly associated with mean methylation levels in patients only (patients: r = 0.40, p = 0.035, controls: p = 0.96). The mean methylation level was significantly increased in patients compared with controls (patients: 5.30 ± 0.24, controls: 4.70 ± 0.19, unpaired t-test, p = 0.04). 5HTT expression using real-time PCR and Taqman probes was increased in unmedicated patients compared with controls and then decreased 8 weeks after antidepressant treatment. The mean 5HTT expression level was not associated with the 5HTTLPR genotype in patients or controls. Increased depressive symptoms were related to decreased levels of methylation. Copyright © 2016 John Wiley & Sons, Ltd.

Cost-effectiveness of cognitive behavioral therapy for insomnia comorbid with depression: Analysis of a randomized controlled trial.

AIM: Although the efficacy of cognitive behavioral therapy for insomnia has been confirmed, dissemination depends on the balance of benefits and costs. This study aimed to examine the cost-effectiveness of cognitive behavioral therapy for insomnia consisting of four weekly individual sessions. METHODS: We conducted a 4-week randomized controlled trial with a 4-week follow up in outpatient clinics in Japan. Thirty-seven patients diagnosed as having major depressive disorder according to DSM-IV and suffering from chronic insomnia were randomized to receive either treatment as usual (TAU) alone or TAU plus cognitive behavioral therapy for insomnia. Effectiveness was evaluated as quality-adjusted life years (QALY) over 8 weeks' time, estimated by bootstrapping of the observed total scores of the Hamilton Depression Rating Scale. Direct medical costs for cognitive behavioral therapy for insomnia and TAU were also evaluated. We calculated the incremental cost-effectiveness ratio. RESULTS: Over the 8 weeks of the study, the group receiving cognitive behavioral therapy for insomnia plus TAU had significantly higher QALY (P = 0.002) than the TAU-alone group with an incremental value of 0.019 (SD 0.006), and had non-significantly higher costs with an incremental value of 254 (SD 203) USD in direct costs. The incremental cost-effectiveness ratio was 13 678 USD (95% confidence interval: -5691 to 71 316). Adding cognitive behavioral therapy for insomnia demonstrated an approximately 95% chance of gaining one more QALY if a decision-maker was willing to pay 60 000 USD, and approximately 90% for 40 000 USD. CONCLUSION: Adding cognitive behavioral therapy for insomnia is highly likely to be cost-effective for patients with residual insomnia and concomitant depression.

[Early intervention in an early psychosis outpatient clinic].

The importance of early detection and intervention for psychiatric disorders, such as schizophrenia, is beginning to attract attention based on the results of imaging and psychosocial studies. Unfortunately, Japan still lags markedly behind Western countries and Australia in respect of early detection and intervention. We conducted a collaborative questionnaire survey of mental health among junior and senior high school students, and found that education on psychiatric disorders is not provided in schools and that the detection of these disorders is delayed due to the lack of awareness and accurate information. Early detection and treatment of psychiatric disorders takes more time than regular outpatient care, and an early psychosis outpatient clinic was established at our institution as a special outpatient clinic. The early psychosis outpatient clinic managed by me cannot be involved in visiting schools to carry out educational activities due to manpower problems and other reasons. However, through individual cases, I am aware that cooperation with schools is as important as cooperation with patients' families, not only to treat psychiatric symptoms, but also to check whether students are viewed with discomfort by classmates due to adverse effects of treatment, such as extrapyramidal symptoms. My aim is to improve the mental health of as many children as possible through future activities.

Family psychoeducation for major depression: randomised controlled trial.

BACKGROUND: The value of family psychoeducation for schizophrenia has been well established, and indications for its use have recently expanded to include bipolar affective disorder. However, no study to date has adequately examined its use in depression. AIMS: To examine family psychoeducation in the maintenance treatment of depression and to investigate the influence of the family's expressed emotion (EE) on its effectiveness. METHOD: Of 103 patients diagnosed with major depression and their primary family members, 57 pairs provided written informed consent. The pairs were randomly allocated to the intervention (n = 25) or control (n = 32). One family in the intervention group and two in the control group withdrew their consent after randomisation. The intervention group underwent four psychoeducation sessions consisting of didactic lectures about depression and group problem-solving focusing on how to cope in high-EE situations. Patients did not attend these sessions. Patients in both the intervention and control groups received treatment as usual. The families' EE levels were evaluated through Five-Minute Speech Samples. The primary outcome was relapse. RESULTS: Time to relapse was statistically significantly longer in the psychoeducation group than in the control group (Kaplan-Meier survival analysis, P = 0.002). The relapse rates up to the 9-month follow-up were 8% and 50% respectively (risk ratio 0.17, 95% CI 0.04-0.66; number needed to treat 2.4, 95% CI 1.6-4.9). In Cox proportional hazard analysis, baseline EE did not moderate the effectiveness of the intervention. CONCLUSIONS: Family psychoeducation is effective in the prevention of relapse in adult patients with major depression.

Innovative approach to adolescent mental health in Japan: School-based education about mental health literacy.

AIMS: Improving mental health literacy through school-based education may encourage mental health promotion, prevention and care and reduce stigma in adolescents. In Japan, instruction about mental illness has been formulated in a Course of Study that reflects governmental curriculum guidelines, which will be enforced from 2022 to promote an understanding of current issues of adolescent health. Educational resources available to schoolteachers have been developed. This article describes the development processes and contents of these resources. METHODS: Our collaborating team, consisting of mental health professionals and schoolteachers, developed educational resources, based on feedback from high school students in general and young people who had experienced mental health problems. RESULTS: The new Course of Study covers: (1) mechanisms of mental illness, prevalence, age at onset, risk factors and treatability; (2) typical symptoms of mental health problems and illnesses; (3) self-help strategies for prevention of and recovery from mental illness; (4) enhancing help-seeking and helping behaviour and (5) decreasing stigma associated with people with mental health problems. The educational strategy is targeted at high school students (grades 10-12) and is conducted by teachers of health and physical education. The educational resources include short story animated films, filmed social contact and educators' manuals, which are freely available through the internet and open to all concerned including schoolteachers in Japan. CONCLUSIONS: Our efforts are expected to help implement mental health education of the public throughout Japan and other countries and promote the practice of early intervention and prevention of mental illnesses in adolescents.

Assessing recurrence of depression using a zero-inflated negative binomial model: A secondary analysis of lifelog data.

When studying recurrence of depression, researchers should pay attention to cases where physicians' assessment corresponds to the patients' perception. However, they should also focus on potential signs of recurrence when the recurrence is suspected by the physicians but not the patients (false-negative zeros). Because false negatives can delay diagnosis and treatment, we aimed to investigate "sitting idly" as a predictor influencing no alert sign of recurrence and estimated the counts of recurrence of depression. A smartphone application and a wearable device were used to collect lifelog data from 89 remitted depressive patients over one year. Recurrent depression was defined using the Japanese version of the Kessler Psychological Distress Scale and Patient Health Questionnaire-9 scores. Estimates of the population-averaged parameters indicated that daily hours of sitting idly increased the chances of recurrent depression occurring two to four weeks later. Exposure to daily ultraviolet light reduced depression relapse. Although long sleep was a determinant of zero outcome of the recurrence of depression after two to four weeks, daily hours of sitting idly can negate it. Thus, daily hours of sitting idly could reduce overdispersion of the recurrence of depression, and we could measure recurrent depression accurately by considering changes in sitting idly.

Effect of a family psychoeducational program on relatives of schizophrenia patients.

AIMS: Family psychoeducational programs have been shown to be effective in terms of knowledge acquirement and relapse prevention, but few studies have looked at whether one mode of educational method is more effective than another. The aim of the present study was to compare several modes of educational approaches and to elucidate which mode of education is more effective. METHODS: A total of 110 relatives of 95 patients with schizophrenia received three types of family psychoeducational programs between January 1995 and September 2003: a small group with two sessions (P1), a large group with nine sessions (P2), and a large group with five sessions (P3). In addition to the demographic data, acquired knowledge was measured using the modified Knowledge About Schizophrenia Interview (KASI), family expressed emotion (EE), and relapse episodes. RESULTS: Overall there were significant increases in many KASI subcategory scores after the three programs, in mothers in particular. The change in KASI scores indicated that the low EE group was able to be highly educated and that the relatives of non-relapsers were more effectively educated. As for the mode of the family psychoeducational program, the P1 and P2 groups surpassed the P3 in terms of knowledge acquired. CONCLUSIONS: Effects of family psychoeducation may depend not on the number of members or sessions but on the time spent on the program per member.

Cognitive and Behavioral Skills Exercises Completed by Patients with Major Depression During Smartphone Cognitive Behavioral Therapy: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: A strong and growing body of evidence has demonstrated the effectiveness of cognitive behavioral therapy (CBT), either face-to-face, in person, or as self-help via the Internet, for depression. However, CBT is a complex intervention consisting of several putatively effective components, and how each component may or may not contribute to the overall effectiveness of CBT is poorly understood. OBJECTIVE: The aim of this study was to investigate how the users of smartphone CBT use and benefit from various components of the program. METHODS: This is a secondary analysis from a 9-week, single-blind, randomized controlled trial that has demonstrated the effectiveness of adjunctive use of smartphone CBT (Kokoro-App) over antidepressant pharmacotherapy alone among patients with drug-resistant major depressive disorder (total n=164, standardized mean difference in depression severity at week 9=0.40, J Med Internet Res). Kokoro-App consists of three cognitive behavioral skills of self-monitoring, behavioral activation, and cognitive restructuring, with corresponding worksheets to fill in. All activities of the participants learning each session of the program and completing each worksheet were uploaded onto Kokoro-Web, which each patient could use for self-check. We examined what use characteristics differentiated the more successful users of the CBT app from the less successful ones, split at the median of change in depression severity. RESULTS: A total of 81 patients with major depression were allocated to the smartphone CBT. On average, they completed 7.0 (standard deviation [SD] 1.4) out of 8 sessions of the program; it took them 10.8 (SD 4.2) days to complete one session, during which they spent 62 min (SD 96) on the app. There were no statistically significant differences in the number of sessions completed, time spent for the program, or the number of completed self-monitoring worksheets between the beneficiaries and the nonbeneficiaries. However, the former completed more behavioral activation tasks, engaged in different types of activities, and also filled in more cognitive restructuring worksheets than the latter. Activities such as "test-drive a new car," "go to a coffee shop after lunch," or "call up an old friend" were found to be particularly rewarding. All cognitive restructuring strategies were found to significantly decrease the distress level, with "What would be your advice to a friend who has a similar problem?" found more helpful than some other strategies. CONCLUSIONS: The CBT program offered via smartphone and connected to the remote server is not only effective in alleviating depression but also opens a new avenue in gathering information of what and how each participant may utilize the program. The activities and strategies found useful in this analysis will provide valuable information in brush-ups of the program itself and of mobile health (mHealth) in general. 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).

Biological tests for major depressive disorder that involve leukocyte gene expression assays.

BACKGROUND: Development of easy-to-use biological diagnostic tests for major depressive disorder (MDD) may facilitate MDD diagnosis and delivery of optimal treatment. Here, we examined leukocyte gene expression to develop a biological diagnostic test for MDD. METHODS: 25 drug-naive MDD patients (MDDs) and 25 age- and sex-matched healthy subjects (Controls) participated in a pilot study. A subsequent replication study involved 20 MDDs and 18 Controls. We used custom-made PCR array plates to examine mRNA levels of 40 candidate genes in leukocyte samples to assess whether any combination of these genes could be used to differentiate MDDs from Controls based on expression profiles. RESULTS: Among 40 candidate genes, we identified a set of seven genes (PDGFC, SLC6A4, PDLIM5, ARHGAP24, PRNP, HDAC5, and IL1R2), each of which had expression levels that differed significantly between MDD and Control samples in the pilot study. To identify genes whose expression best differentiated between MDDs and Controls, a linear discriminant function was developed to discriminate between MDDs and Controls based on the standardized values of gene expression after Z-score transformation. Ultimately, five genes (PDGFC, SLC6A4, ARHGAP24, PRNP, and HDAC5) were selected for a multi-assay diagnostic test. In the pilot study, this diagnostic test demonstrated sensitivity and specificity of 80% and 92%, respectively. The replication study yielded nearly identical results, sensitivity of 85% and specificity of 89%. CONCLUSIONS: Using leukocyte gene expression profiles, we could differentiate MDDs from Controls with adequate sensitivity and specificity. Additional markers not yet identified might further improve the performance of this test.

Validity of a five-minute speech sample for the measurement of expressed emotion in the families of Japanese patients with mood disorders.

Both the Camberwell Family Interview (CFI) and the Five-Minute Speech Sample (FMSS) have been used to define expressed emotion (EE), but the validity of the FMSS relative to the CFI in mood disorders has not been evaluated. In our study, the FMSS and the CFI were performed on the same day in close family members of inpatients with mood disorders within 2 weeks after their admission. The ratings obtained from the CFI were then used to estimate the validity of the FMSS, which was defined by sensitivity and specificity on the basis of the overall evaluation of EE. Validity was also assessed by including borderline ratings of 'low EE' in the category of 'high EE.' Based on the overall evaluation, sensitivity and specificity were 66.7 and 96.8%, respectively. When borderline low EE was included in high EE, the sensitivity and specificity were 100 and 90.3%, respectively. The validity of definitions of EE by the FMSS relative to the CFI was high in mood disorders. Evaluation of EE by the FMSS, which is clinically applicable to patients with mood disorders, is feasible. The validity of this approach is enhanced when families defined as 'borderline low EE' are included in the high-EE category.

Family attitude scale: measurement of criticism in the relatives of patients with schizophrenia in Japan.

Expressed emotion (EE) is traditionally measured with the Camberwell Family Interview (CFI), but the CFI requires considerable time for both execution and evaluation. As an alternative, we investigated the validity of the Family Attitude Scale (FAS), a questionnaire developed for the measurement of EE. The CFI, the FAS, the General Health Questionnaire (GHQ), and the Five-Minute Speech Sample (FMSS) were administered in 57 members of the families of 41 patients with acute episodes of schizophrenia. The relative sensitivity and specificity of EE assessment with the FAS compared with the criticism component of the CFI were 100% and 88.5%, respectively. EE assessment based on criticism as assessed with the FMSS compared with the CFI had a sensitivity of 40.0% and a specificity of 90.4%. The GHQ score tended to be higher in the high-scoring FAS group than in the low-scoring FAS group. The FAS showed excellent validity for the measurement of critical aspects of family attitudes, and the FAS score reflected the state of psychological health of the families.

Change in quality of life after brief behavioral therapy for insomnia in concurrent depression: analysis of the effects of a randomized controlled trial.

STUDY OBJECTIVES: The efficacy of cognitive behavioral therapy for insomnia (CBT-I) has been suggested for insomnia concomitant with depression, but its impact on quality of life (QoL) has not been adequately evaluated. The study aimed to determine which aspects of QoL could be affected by CBT-I and how any changes in QoL were mediated by changes in insomnia and depression. METHODS: We conducted a 4-week randomized controlled trial with 4-week follow-up in outpatient clinics in Japan. Thirty-seven patients with DSM-IV diagnosis of major depressive disorder concomitant with chronic insomnia were randomly assigned to the treatment-as-usual (TAU) alone arm or the TAU with brief behavioral therapy for insomnia (TAU plus psychotherapy) arm using modified CBT-I consisting of 4 weekly individual sessions. We evaluated QoL using norm-based scoring of the Short Form-36 at baseline and at 8 weeks. We also examined associations between QoL subscales and remission in insomnia or depression while controlling for baseline scores of the entire sample. RESULTS: We tested group effects while controlling for baseline scores. TAU plus psychotherapy resulted in significantly better scores on physical functioning (p = 0.006), social functioning (p = 0.002), and mental health (p = 0.041) subscales than TAU alone at 8 weeks. Patients with either remitted insomnia or depression showed higher QoL scores than non-remitted patients; scores approximated those within the normal range. CONCLUSIONS: For patients with insomnia in depression, adding CBT-I to TAU can produce substantive benefits in some aspects of QoL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00610259, http://www.clinicaltrials.gov/.

Psychoeducation for major depressive disorders: a randomised controlled trial.

Various psychological therapies have been shown to be effective for the treatment of mood disorders. Among them, family psychoeducation has demonstrated efficacy in reducing symptom severity and extending the time to relapse. We tested the efficacy of adding psychoeducation focussed on how to deal with the family's expressed emotion to treatment as usual (TAU) to prevent relapse among patients with remitted major depression. A total of 34 patients with major depressive disorders in full or partial remission were randomised to receive either group psychoeducation over six sessions, each consisting of a didactic lecture and group problem-solving (n=19), plus TAU or TAU alone (n=15). The primary outcome was relapse by Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) criteria. Masked raters administered the Hamilton Rating Scale for Depression-17 (HRSD-17). As many as 18 patients in the intervention group and 14 patients in the control group completed the study. Time to relapse was significantly longer in the intervention group than in the control group, with a risk ratio (RR) of relapse by 9 months of 0.12. At 9 months, there was a significantly greater decrease in the HRSD-17 score in the intervention group than in the control group. We demonstrated the effectiveness of patient psychoeducation on the course and outcome of major depressive disorders.

Duration of untreated psychosis in a rural/suburban region of Japan.

AIMS: We examined the duration of untreated psychosis (DUP) and its social and clinical correlates in patients with schizophrenia in a rural/suburban region of Japan. METHODS: We conducted a retrospective cohort study of patients with first-episode psychosis from 11 hospitals in Kochi Prefecture. There were 108 patients who met the eligibility criteria, and data regarding their DUP and social/clinical variables were collected. RESULTS: The median (mean) DUP of our cohort was 10.5 (34.6) months. Longer DUP was associated with younger age at onset, older age at first consultation, less educational attainment, insidious mode of onset and not being accompanied by another person at first consultation. After adjusting for confounding factors, age at onset, age at first consultation and mode of onset remained significantly and independently associated with DUP. In terms of treatment and response, longer DUP was associated with less antipsychotics prescribed upon first visit, and worse Clinical Global Impression Severity and Improvement scores after 1 year. CONCLUSION: The patients treated in a rural/suburban region of Japan had a long DUP, and shortening their DUP through promoting family involvement could improve their outcomes.

Mapping hypofrontality during letter fluency task in schizophrenia: a multi-channel near-infrared spectroscopy study.

Cognitive impairment and associated frontal lobe dysfunction characterize schizophrenia. The letter fluency test (LFT) has been used as one of the most sensitive measures of the cognitive dysfunction, but the nature and topography of the hypofrontality have yet to be fully elucidated. In this study we used multi-channel near-infrared spectroscopy (NIRS), a recently developed noninvasive functional imaging technique, to measure changes in the concentration of oxygenated hemoglobin in the prefrontal cortices of 31 schizophrenia patients and 26 age- and sex-matched healthy controls during performance of the LFT. The results demonstrated reduced prefrontal cortex activation during the LFT among the schizophrenia patients in comparison with the healthy controls, even after controlling for medication. The hypofrontality was most salient in the prefrontal ventrolateral subregion bilaterally. The reduced activity appeared to be due not only to the lesser magnitude but also to the lesser fluctuation of the changes in oxygenated hemoglobin concentration. The hypofrontality appeared to be independent of the patients' symptomatological manifestations. We concluded that measuring NIRS during performance of the LFT can detect prefrontal lobe dysfunction of schizophrenia patients and may provide a new tool to monitor their treatment and course.

The first 100 patients in the SUN(

BACKGROUND: Initial glitches and unexpected inconsistencies are unavoidable in the early stage of a large, multi-centre trial. Adaptive modifications of the trial's protocol and operational procedures to ensure its smooth running are therefore imperative. We started a large pragmatic, multi-centre, assessor-blinded, 25-week trial to investigate the optimal first- and second-line treatments for untreated episodes of nonpsychotic major depression in 2010 [Strategic Use of New generation antidepressants for Depression, abbreviated SUN(^_^)D] and would like to herein report an examination of the trial's feasibility and adherence among the first 100 participants. METHODS: We examined the participants' characteristics, the treatments that were allocated and received during each step of the trial, and the quality of the outcome assessments among the first 100 patients enrolled in the SUN(^_^)D trial. RESULTS: Of the 2,743 first-visit patients who visited the two collaborating centres between December 2010 and July 2011, 382 were judged as potentially eligible, and 100 of these patients provided written informed consent. These patients represented the whole spectrum of mild to very severe depression. Of the 93 patients who had reached Week 3 of the study by the end of July 2011, one withdrew consent for both the treatment and the assessment, and eight withdrew consent for the treatment only. Altogether, the primary outcomes were successfully assessed in 90 (96.8%) of the patients at Week 3. Of the 72 patients who had reached Week 9, three withdrew consent for the treatment, but 70 were successfully interviewed (97.2%). Of the 32 patients who had reached Week 25, 29 (90.5%) were successfully followed up. The inter-rater reliability of the assessments of the primary outcomes was nearly perfect and their successful blinding was confirmed. Minor modifications and clarifications to the protocol were deemed necessary. DISCUSSION: Given the satisfactory feasibility and adherence to the study protocol and the minor modifications that were necessary, we conclude that the data obtained from the first 100 patients can be safely included in the main study. We now intend to accelerate the study by recruiting more collaborating centres and clinics/hospitals. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01109693.