Search

Objective: To evaluate the efficacy and safety of escitalopram (ESC) in a 48-week relapse prevention study in Japanese adolescents with major depressive disorder (MDD). Methods: This was a 48-week multicenter randomized double-blind placebo-controlled parallel-group study of patients aged 12-17 years with MDD. Patients received ESC for 12 weeks as an open-label treatment period (open-label period). Patients who achieved criteria for remission or response in the open-label period received either ESC or placebo for 36 weeks as a double-blind treatment period (double-blind period). The primary endpoint was the time to relapse during the double-blind period. Safety was evaluated in terms of type, incidence, and severity of adverse events. Results: Of the 128 patients who entered the open-label period, 80 patients entered the double-blind period, all of whom were in the primary analysis population. The primary endpoint, time to relapse, was marginally less than statistically significant between the ESC and placebo groups ( p  = 0.051, log-rank test). In the Cox proportional hazards model, the estimated hazard ratio [two-sided 95% confidence interval] for relapse in the placebo group versus the ESC group was 2.96 [0.94, 9.30]. There were statistically significant differences between the ESC and placebo groups in several secondary endpoints (change in Children's Depression Rating Scale-Revised, change in Clinical Global Impressions-Severity Scale, etc.). No notable safety/tolerability issues were observed in this study compared with the results of studies in Japanese adults with MDD. Conclusions: Superiority of ESC over placebo for relapse prevention in Japanese adolescents aged 12-17 years with MDD could not be verified with time to relapse evaluated by log-rank test. However, secondary endpoint results and a post hoc analysis of time to relapse suggest that ESC may be effective in preventing MDD relapse. No notable safety/tolerability issues were observed compared with the results of studies in Japanese adults with MDD. Study Registry Number: jRCT2080224520.

Background: Patients with remitted major depressive disorder (rMDD) generally rely on maladaptive coping strategies for stressful situations. These maladaptive copings are associated with an elevated relapse risk of rMDD; however, their neural basis remains poorly understood., Methods: We enrolled (1) 45 patients with rMDD (17-item Hamilton Depression Rating Scale [HRSD 17 ] total score ≤ 3) and (2) 56 healthy controls (HCs). Coping styles were measured using the Coping Inventory for Stressful Situations (CISS) according to three coping dimensions: avoidance-, emotion-, and task-oriented copings. The cognitive strategic processes of the prefrontal cortex were measured using a verbal fluency task (VFT). Furthermore, regional frontotemporal hemodynamic responses were monitored by near-infrared spectroscopy (NIRS)., Results: Patients with rMDD had significantly lower task-oriented coping scores and significantly higher avoidance- and emotion-oriented coping scores than HCs. Predominantly in the left frontotemporal region, patients with rMDD had lower frontotemporal hemodynamic responses during a VFT than HCs. Hemodynamic responses in the right inferior frontal gyrus of patients with rMDD were significantly and negatively associated with avoidance-oriented coping scores, but not of HCs. Conversely, those responses of HCs were significantly and positively associated with task-oriented coping scores, but not of patients with rMDD., Discussion: Alteration in the right inferior frontal cortex plays an important role in dysfunction to stress response in patients with rMDD. Differential functioning patterns of the right inferior frontal cortex associated with coping strategies may link to MDD recurrence vulnerability., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Previous neuroimaging studies have revealed frontal and temporal functional abnormalities in patients with major depressive disorder (MDD) and a history of suicidal behavior. However, it is unknown whether multi-channel near-infrared spectroscopy (NIRS) signal changes among individuals with MDD are associated with a history of suicide attempts and a diathesis for suicidal behavior (impulsivity, hopelessness, and aggression). Therefore, we aimed to explore frontotemporal hemodynamic responses in depressed patients with a history of suicide attempts using 52-channel NIRS. We recruited 30 patients with MDD and a history of suicidal behavior (suicide attempters; SAs), 38 patient controls without suicidal behavior (non-attempters; NAs), and 40 healthy controls (HCs) matched by age, gender ratio, and estimated IQ. Regional hemodynamic responses during a verbal fluency task (VFT) were monitored using NIRS. Our results showed that severities of depression, impulsivity, aggression, and hopelessness were similar between SAs and NAs. Both patient groups had significantly reduced activation compared with HCs in the bilateral frontotemporal regions. Post hoc analyses revealed that SAs exhibited a smaller hemodynamic response in the left precentral gyrus than NAs and HCs. Furthermore, the reduced response in the left inferior frontal gyrus was negatively correlated with impulsivity level and hemodynamic responses in the right middle frontal gyrus were negatively associated with hopelessness and aggression in SAs but not in NAs and HCs. Our findings suggest that MDD patients with a history of suicide attempts demonstrate patterns of VFT-induced NIRS signal changes different from those demonstrated by individuals without a history of suicidal behaviors, even in cases where clinical symptoms are similar. NIRS has a relatively high time resolution, which may help visually differentiate SAs from NAs.

This study aimed to determine whether quality of life (QOL) reflects specific functional abnormalities of frontotemporal hemodynamic responses in melancholia. We recruited 30 patients with major depressive disorder (MDD) with melancholic features (MDD-MF), 52 with non-melancholic features (MDD-NMF), and 68 healthy control subjects who were matched for age, sex ratio, and years of education. QOL was assessed using the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), and regional hemodynamic responses during a verbal fluency task were monitored with near-infrared spectroscopy (NIRS). Patients with MDD-MF scored significantly lower than those with MDD-NMF on the role emotional domain of SF-36. Both MDD patient groups exhibited lower hemodynamic responses in the frontotemporal regions than the control group. Hemodynamic responses in the frontotemporal regions were significantly smaller in patients with MDD-MF than in those with MDD-NMF. The role emotional domain of patients with MDD-MF was significantly and positively correlated with hemodynamic responses in the prefrontal region, whereas that of patients with MDD-NMF revealed no significant correlation. In conclusion, our results indicate that patients with MDD-MF exhibit qualitatively distinct prefrontal dysfunction patterns associated with emotional role functioning compared with patients with MDD-NMF., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Studies on major depressive disorder (MDD) show that the degree of correlation between the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) varies widely. We aimed to determine whether this discrepancy reflects specific functional abnormalities in the frontotemporal cortex., Methods: Mildly depressed or euthymic patients with MDD (n=52), including 21 patients with MDD with the discrepancy, i.e., those with low HAMD17 scores (≤13) but high BDI-II scores (>28), and 31 patients without the discrepancy, i.e., those with low HAMD17 scores and low BDI-II scores (≤28), participated in the study along with 48 control subjects. Regional changes of oxygenated hemoglobin (oxy-Hb) levels during a verbal fluency task (VFT) were monitored using a 52-channel near-infrared spectroscopy (NIRS) device., Results: In the frontotemporal regions, mean oxy-Hb changes induced by the VFT were significantly smaller in patients with MDD than in control subjects. In 5 channels within frontal regions, the increase in mean oxy-Hb levels was significantly greater in MDD patients with the BDI-HAMD discrepancy than in those without the discrepancy. In 6 channels within the frontal region of the patients with MDD, significant positive correlations were observed between mean oxy-Hb changes and BDI total scores (ρ=0.38-0.59; P<0.05, false discovery rate corrected)., Limitations: Our findings required replication in severely depressed patients, particularly those with melancholia., Conclusions: The distinct pattern of activation of the prefrontal cortex suggests that MDD with the BDI-HAMD discrepancy is pathophysiologically different from MDD without the discrepancy., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The aim of this study was to determine whether melancholia differs from nonmelancholic depression in frontotemporal functioning by means of multichannel near-infrared spectroscopy. We recruited 32 major depressive disorder (MDD) patients with melancholic features (MDD-MF), 28 MDD patients with nonmelancholic features (MDD-NMF), and 24 healthy controls. Regional hemodynamic changes induced by a verbal fluency task (VFT) were monitored, and their correlations with depressive symptoms were examined. In comparison with the controls, significant differences were observed in mean oxygenated hemoglobin (oxy-Hb) changes induced by VFT in patients with MDD-MF in 25 channels (p = 0.000-0.047) and in those with MDD-NMF in 12 channels (p = 0.000-0.023). Moreover, patients with MDD-MF had significantly smaller mean oxy-Hb changes than those with MDD-NMF in 8 channels of the right temporal region (p = 0.001-0.048). No significant correlations were observed between mean oxy-Hb changes and the Hamilton rating scale for depression (HAMD) 17 total score in both groups of patients with MDD. On examining each item of HAMD17, psychomotor retardation in patients with MDD-MF showed a significant positive correlation with mean oxy-Hb changes in the right temporal region (ch43; ρ = 0.55; p = 0.001), whereas that in patients with MDD-NMF showed a significant negative correlation with mean oxy-Hb changes in the frontal and left temporal regions in 3 channels (ρ = -0.60 to -0.53; p = 0.000-0.004). In conclusion, our results indicate that melancholia is qualitatively distinct from nonmelancholic depression both clinically and biologically., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Alzheimer's disease and major depression are representative diseases that present forgetfulness and a depressive mood. It is often difficult to make a differential diagnosis between the two in the initial phase., Aim: To evaluate the differential diagnosis method using regional cerebral blood flow patterns with a three-dimensional stereotactic surface projection technique., Methods: Twenty early-elderly patients with mild and moderate forgetfulness were studied. Among them, 10 were diagnosed as having major depression (the MD group) and the other 10 as having Alzheimer's disease (the AD group). All patients underwent cerebral perfusion single photon emission computed tomography (SPECT) with [(123)I]iodoamphetamine. A z-score was calculated for each pixel of the cerebral surface. Twenty-one circular regions of interest (ROIs) were placed on the z-score map. The significance of the statistical difference in ROI values between the two groups was determined by using the two-sided Mann-Whitney U-test., Results: The z-scores for the lateral parietal, lateral temporal, bilateral precuneus and bilateral posterior cingulate gyrus were significantly reduced in the AD group compared with those in the MD group. The z-scores for the lateral frontal, left thalamus and bilateral medial frontal regions were significantly lower in the MD group than in the AD group., Conclusion: Our study demonstrated a difference in regional cerebral blood flow patterns between the early elderly with Alzheimer's disease and those with major depression. All patients were classified into the appropriate categories using discriminant analysis and z-scores of frontal and parietal regions. Brain perfusion SPECT was a useful tool for the differential diagnosis between Alzheimer's disease and major depression.