The aim of this study is to determine whether there is difference in the change in each symptom of depression and in symptomatic improvement pattern between placebo and antidepressant responses.Methods: Using data from a randomized, double-blind (DB), placebo-controlled trial of esketamine (ESK) in patients with treatment-resistant depression (TRD), we conducted exploratory analyses. To determine differences in the change in each depressive symptom on the MADRS subscale between placebo and antidepressant responses, a two-way factorial analysis was conducted using the amount of change on Day 2 and 28 of treatment. In addition, exploratory and confirmatory factor analyses were conducted on the MADRS subtotal variables on Day 2 and 28 of treatment to determine symptomatic improvement pattern between placebo response and antidepressant responses.Results: We found that as well as MADRS total score, each subscale of MADRS score did not significantly differ between esketamine and placebo at Day 2 and 28. On the other hand, factor analysis revealed that the factor structure of the response was different between esketamine and placebo at the 2nd day. There was no difference in the factor structure between esketamine and placebo in response on Day 28 of treatment. Conclusion:Factor analysis revealed different patterns of symptom improvement in the early phase of the intervention between esketamine and placebo. This finding suggests that a data driven approach may provide detailed efficacy information in clinical trials for antidepressants.

BACKGROUND Many countries have taken measures to ensure physical distance as a countermeasure against the COVID-19 pandemic, such as lockdowns and encouraging telecommuting, but these measures have also resulted in social isolation and loneliness for large populations. OBJECTIVE The aim of this study was to determine the impact of the COVID-19 epidemic on mental health, the relationship between loneliness and worsening mental health, and risk factors for mental health problems among telecommuting. METHODS Data were collected via an online anonymous survey from October 5~9, 2021. Participants were recruited from survey panel consisted with 1,344,877 people, with random sampling. and 2904 responses were valid. The questionnaire included categorical questions which asked demographics, lifestyle changes and mental status such as loneliness, anxiety and depression. Path analysis was used to determine the association between loneliness and anxiety and depression. Logistic regression, analysis of variance and Fisher's exact tests were used to understand factors associated with mental health problems. RESULTS The COVID-19 pandemic had a major impact on the lifestyle and financial situation in also office workers of relatively high socioeconomic status. Regarding mental health, 83.9% felt lonely, 34.9% had more than mild anxiety, and 38.5% had more than mild depression. Importantly, 16.5% of participants indicated a suicide risk. Path analysis revealed that emotional loneliness contributed to anxiety (r=0.55) and depression (r=0.58). We found that deteriorating relationships with close people (for depression; odds ratio (95%CI) 2.77(1.81~4.25), p<0.001, for suicide risk; odds ratio (95%CI)3.03 (2.09−4.39), p<.001), financial uncertainty (for depression; 2.53(2.12~3.02), p<.001, for suicide risk; 1.99 (1.57−2.53), p<.001) and work-related problems (for depression; 2.35(1.75~3.15), p<.001, for suicide risk; 1.93 (1.39−2.70), p<.001) were important predictors for both depression and suicide risk. Decreased online communication (for depression; 1.39(1.15-1.68), p<.001, for suicide risk; 1.76 (1.31−2.35), p<.001) younger age (for depression; 1.28(1.05~1.55), p=.012, for suicide risk; 1.74 (1.33−2.27), P<.001) and weight changes >5Kg (for depression: 1.72(1.41~2.10), p<.001, for suicide risk; 1.43 (1.13−1.82), p=.003), were also predictors for both depression and suicide risk. CONCLUSIONS The results indicate that public health needs to consider mental health issues even for those who are relatively socioeconomically advantaged and considered low risk. We believe that the risk factors presented in this study can be used to guide public health measures. CLINICALTRIAL Not registered, Because of anonymous nature of the methods and noninvasive nature, this survey was as exempt research activity defined by Ethical Guidelines for Medical and Health Research Involving Human Subjects (Ministry of Health, Laboure and Welfare, Japan). COVID-19; social isolation; loneliness; telecommuting; mental health; depression; suicide risk