A web-based survey on the occurrence of emotional blunting in patients with major depressive disorder in Japan: Patient perceptions and attitudes.

AIMS: To determine the prevalence and impact of emotional blunting (EB) in patients with major depressive disorder (MDD) in Japan, and identify treatment needs for EB using patients' perceptions and attitudes. METHODS: Eligible patients in Japan (aged 18-59 years) who reported a diagnosis of MDD and antidepressant medication use for >3 months were eligible to complete an online survey. The primary outcome was the prevalence of EB, self-reported using a validated screening question. Secondary outcomes included the correlation between EB symptoms (measured by the Oxford Depression Questionnaire [ODQ]) and scores on the Patient Health Questionnaire 9-item (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Work and Social Adjustment Scale (WSAS), and the EuroQol 5-Dimension 5-Levels questionnaire (EQ-5D-5L). Descriptive questions were used to explore patients' perceptions and attitudes toward EB. RESULTS: In total, 3376 patients were included in the analysis (56% male; 48% aged 50-59 years). Overall, 67.1% of patients self-reported symptoms of EB, with 10% rating these as severe. The mean (SD) ODQ total score was 78.2 (21.5), which increased with worsening EB symptoms. There were correlations between ODQ total scores and the PHQ-9, GAD-7, WSAS, and EQ-5D-5L scores (correlation coefficients: 0.67, 0.55, 0.56, -0.51, respectively; all p < 0.0001). Descriptive analyses showed that one-third of patients reporting EB symptoms did not tell their physician, with two-thirds finding these symptoms distressing and likely to affect recovery. CONCLUSION: EB is an important clinical issue in Japan that needs to be considered alongside functional recovery when managing treatment of patients with MDD.

Validation and Functional Relevance of the Short Form of the Perceived Deficits Questionnaire for Depression for Japanese Patients with Major Depressive Disorder.

Purpose: To validate the five-item version of the Perceived Deficits Questionnaire for Depression (PDQ-D-5) for assessing subjective cognitive function in Japanese patients with major depressive disorder (MDD) using data from the PERFORM-J study. Patients and Methods: A total of 518 Japanese outpatients diagnosed with MDD were assessed on severity of depressive symptoms, cognitive function, social and work function, and quality of life (QoL) over 6 months following initiation of antidepressant therapy. This post hoc analysis evaluated the internal consistency and convergent validity of the PDQ-D-5 in relation to the original PDQ-D-20. Correlations of scores on these measures were examined at each time point and over time. The same set of analyses was explored between PDQ-D-5 and the Patient Health Questionnaire-nine-item (PHQ-9), Montgomery-Asberg Depression Rating Scale (MADRS), Digit Symbol Substitution Test (DSST), five-level version of EQ-5D (EQ-5D-5L), Sheehan Disability Scale (SDS), and Work Productivity and Activity Impairment (WPAI) questionnaire. Results: PDQ-D-5 scores showed good internal consistency. Strong positive correlations were observed between PDQ-D-5 and PDQ-D-20 at each time point (correlation coefficient: baseline, 0.94; month 1, 0.94; month 2, 0.96; month 6, 0.96) and over time (0.92) (all p < 0.0001). Longitudinally, there were positive correlations between PDQ-D-5 scores versus those on the PHQ-9, MADRS, and SDS. Similarly, negative correlations were noted between PDQ-D-5 scores and EQ-5D-5L and DSST scores to a variable degree. There were moderate positive correlations over time between PDQ-D-5 and all WPAI subscale scores except those on absenteeism. Conclusion: PDQ-D-5 scores rated in Japanese patients with MDD were found to adequately represent scores on the PDQ-D-20. The short version also showed associations with several measures of functional outcome, depression severity and QoL. This validates the PDQ-D-5 as a feasible and clinically reliable tool to assess subjective experience on cognition, which is applicable to time-limited consultations. UMIN Clinical Trials Registry for Primary Study: UMIN000024320.

Discovery of 6-[5-(4-fluorophenyl)-3-methyl-pyrazol-4-yl]-benzoxazin-3-one derivatives as novel selective nonsteroidal mineralocorticoid receptor antagonists.

In the course of our study on selective nonsteroidal mineralocorticoid receptor (MR) antagonists, a series of novel benzoxazine derivatives possessing an azole ring as the core scaffold was designed for the purpose of attenuating the partial agonistic activity of the previously reported dihydropyrrol-2-one derivatives. Screening of alternative azole rings identified 1,3-dimethyl pyrazole 6a as a lead compound with reduced partial agonistic activity. Subsequent replacement of the 1-methyl group of the pyrazole ring with larger lipophilic side chains or polar side chains targeting Arg817 and Gln776 increased MR binding activity while maintaining the agonistic response at the lower level. Among these compounds, 6-[1-(2,2-difluoro-3-hydroxypropyl)-5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one (37a) showed highly potent in vitro activity, high selectivity versus other steroid hormone receptors, and good pharmacokinetic profiles. Oral administration of 37a in deoxycorticosterone acetate-salt hypertensive rats showed a significant blood pressure-lowering effect with no signs of antiandrogenic effects.