Discussion
anxiety disorder, anxiety, depressive, schizophrenia and affective disorders, depressive symptoms
ADVERSE EVENTS, SECONDARY, REMISSION, DISORDERS
This is the first randomized controlled trial to test the efficacy of the UP that includes either a principal diagnosis of depressive or anxiety disorder. As hypothesized, the addition of the UP to TAU was more effective than waiting for the UP while receiving TAU with regards to improving the severity of depressive symptoms between baseline and post-treatment assessments. The UP-TAU group showed significant improvements compared with the WL-TAU group in the blinded assessor evaluation of anxiety, severity, and improvement of clinical global impression. In the UP-TAU group, improvements from the baseline to 21 weeks were maintained in all continuous outcomes at 43 weeks. The sensitivity analyses controlling the types of principal diagnosis and per-protocol sample analyses showed the robustness of these results. There was no significant difference regarding the treatment response, the remission status, and the loss of primary diagnosis at 21 weeks between the UP-TAU and WL-TAU groups. The proportion of dropout was low in the UP-TAU group (3/52, 5.8%). No serious adverse events and few non-serious adverse events occurred in the UP-TAU group during the intervention period.The UP was effective for improving primary and most of the secondary outcomes. Compared to the largest clinical trial of the UP, our participants seemed to exhibit more severe depressive and anxiety symptoms (our trial: mean baseline GRID-HAMD = 16.15, Despite the efficacy evidence, our results suggest that the UP-TAU is not sufficient for most of our patients to fully recover from clinical conditions. The mean reduction in GRID-HAMD was 4.01, which is within the range of 1 Our results provide additional evidence regarding the feasibility of the UP with TAU in a Japanese clinical setting. No serious and only a few (This study must be interpreted while considering the following limitations. First, although we intentionally included heterogeneous clinical populations to test the efficacy of UP for depressive and anxiety disorders, such broad inclusion of participants might hinder the interpretation of the results in comparison with previous clinical trials conducted under traditional diagnostic systems. Second, the statistical test did not indicate blinding success. The proportion of the evaluators' correct guesses was 69.8% at the primary time point. This is relatively higher than that of randomized controlled trials regarding schizophrenia and affective disorders (62.0%) (Baethge, Assall, & Baldessarini, 