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Background: The critical issue of treating Treatment-Resistant Depression (TRD) is to improve antidepressant effect rapid onset and the recovery rates. Significant antidepressant effects of ketamine onset rapidly, but decay rapidly and repeated dosing increases the risks. This study aimed to explore the efficacy and safety of single intravenous ketamine, combined with venlafaxines hydrochloride for TRD.Methods: 32 patients with treatment-resistant depression will be randomly selected to undergo a four weeks double-blind treatment with single-dose ketamine (0.5 mg/kg over 40 min) and venlafaxine hydrochloride (4 weeks) or midazolam maleate (0.045 mg/kg over 40 min) and venlafaxine hydrochloride (4 weeks). Depressive symptoms will be measured by the Montgomery–Asberg Depression Rating Scale (MADRS) and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Adverse effects will be measured by the Brief Psychiatric Rating Scale-4 (BPRS-4), Young Manic Rating Scale (YMRS), the Clinician-Administered Dissociative States Scale (CADSS), Frequency and Intensity of Side Effects Rating/Global Rating of Side Effects Burden (FISER/GRSEB）and Patient Rated Inventory of Side Effects (PRISE). Patients will be assessed at baseline, after intervention 1, 2, 4, 24, 48, 72 hours and 7, 14, 21 and 28 days.Discussion: This study will provide important information on whether this new combined intervention can rapidly relieve the symptoms of depression and improve the remission rates of treatment-resistant depression.

Si Zu,1 Dong Wang,1 Jiexin Fang,1 Le Xiao,2 Xuequan Zhu,2 Wenyuan Wu,3 Gang Wang,2,4 Yongdong Hu1 1Department of Psychiatry, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Psychiatry, Tongji Hospital of Tongji University, Shanghai, People’s Republic of China; 4Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Gang WangThe National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Xicheng District, Beijing Anding Hospital, Beijing, 100088, People’s Republic of ChinaEmail gangwangdoc@ccmu.edu.cnYongdong HuDepartment of Psychiatry, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongtinanlu, Chaoyang District, Beijing Chaoyang Hospital, Beijing, 100020, People’s Republic of ChinaTel +86-10-85231754Email haiyong.xie@ustc.eduObjective: This prospective study aimed to investigate the prognosis and rehabilitation of patients with recurrent depression and first episode depression after acute treatment in China.Methods: A total of 434 patients with first-episode or recurrent depression who received acute treatment respectively from sixteen hospitals in thirteen cities in China were enrolled in this prospective study. All patients were followed up for 6 months after acute treatment. The following data were collected at baseline period and 1, 3, and 6 months after acute treatment: general information of patients, medication information and patient’s condition changes, brief 16-item quick inventory of depressive symptomatology self-report (QIDS-SR16), patient health questionnaire-15 (PHQ-15), quality of life enjoyment and satisfaction questionnaire-short form (Q-LES-Q-SF), Sheehan disability scale (SDS) and digit symbol substitution test (DSST).Results: During the baseline period, there was a significant difference in QIDS-SR16 between recurrent patients and first-episode patients (p < 0.05), and there was no significant difference in other indicators (p > 0.05). At one month after acute treatment, there were significant differences in the total QIDS-SR16 score, the total Q-LES-SF score, the social life score, and the family life/home responsibilities score of SDS in patients with recurrent depression and first-episode depression (p < 0.05). At three months after acute treatment, there were significant differences in the total Q-LES-SF score and social life score of SDS in patients with recurrent depression and first-episode depression (p < 0.05). At six months after acute treatment, there were significant differences in the total QIDS-SR16 score, the social life score, and the total Q-LES-SF score in patients with recurrent depression and first-episode depression (p < 0.05). Compared with that data during the baseline period, the QIDS-SR16 scores and the SDS scores of all patients decreased, and the Q-LES-SF scores of all patients gradually increased as time went on during the consolidation period.Conclusion: The recurrent patients have more severe social function impairment, depressive symptoms, and lower life quality than that of the first-episode depressed patients. Given the negative impact of depressed symptom on recurrent patient, more attention should be paid to the treatment of recurrent patient and recurrence prevention of first episode patient.Keywords: depression, first-episode, recurrent patient, prognosis

Background Depression is common among chronic heart failure (CHF) patients, and it is associated with significant re-hospitalization and mortality as well as lower quality of life. While psychotherapy is efficacious treatment for depression, the effect for depression among CHF is uncertain. And barriers preclude widely utility of psychotherapy among the elderly. Telephone-delivered psycho-behavioural intervention specifically focuses on depression among the elderly with CHF, and could be a promising alternative to conventional treatment. The present study was designed to prospectively investigate the effect of a telephone-delivered psycho-behavioural intervention on depression in the elderly with chronic heart failure (CHF). Method/design In this prospective, multicentre, parallel, randomized, and controlled trial, 236 participants with depression associated with CHF (New York Heart Association classes II and III) will be enrolled. The study will consist of a 12-week intensive intervention and a 24-week maintenance intervention. Eligible participants will be randomized to either the intervention arm or the control arm. During the intensive phase, participants will receive either a guided telephone psycho-behavioural intervention or regular telephone contacts from the counsellors weekly. During the maintenance phase, participants will receive either psychological behavioural support or regular telephone contacts monthly from counsellors. Depressive symptoms, cardiac outcome and quality of life will be assessed at baseline and weeks 1, 2, 4, 8, 12, 24 and 36. Participants will undergo echocardiography and the plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) tested at baseline, weeks 12 and 36. The primary outcome is the response rate of depression, from baseline to week 12. The second outcomes include the change in cardiac function, quality of life and severity of depressive symptoms during the trial. Discussion To our knowledge, this study is the first prospective randomized trial to test the effective of the telephone-delivered psycho-behavioural intervention on depression in the elderly with CHF. The findings are expected to provide a new and evidence-based approach for depression among the elderly with CHF. Trial registration The trial was registered at www.clinicaltrials.gov (identification number: NCT03233451) on 28 July 2017 and updated on 18 August 2017.

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Background In the population of postmenopausal patients with major depressive disorder (MDD), the superiority of serotonin-norepinephrine reuptake inhibitors (SNRIs) over selective serotonin reuptake inhibitors (SSRIs) has not yet been definitively proven. Consequently, a direct comparison of the efficacy of SSRIs and SNRIs in the treatment of postmenopausal depression could provide relevant data. The aim of this study was to compare the efficacy and safety of venlafaxine vs. fluoxetine in the treatment of postmenopausal MDD. Methods This was an 8-week, multicenter, randomized, single-blind, active-controlled trial conducted at a psychiatric hospital (Beijing Anding Hospital) and a general hospital (Beijing Chaoyang Hospital) between April 2013 and September 2017. The primary outcome measure was improving depressive symptoms (Hamilton Depression Rating Scale (HAMD-24) score). The secondary outcomes included the change of HAMD-24 anxiety/somatization factor score and Clinical Global Impressions-Improvement (CGI-I) response rate. Safety was assessed by treatment-emergent adverse events (TEAEs) and laboratory tests. Efficacy was analyzed by using the full analysis set (FAS) following the modified intention-to-treat (mITT) principle. The primary endpoint measurements were analyzed using a mixed-effect model for repeated measures (MMRM) model with patients as a random-effect factor, treatment group as the independent variable, time as a repeated measure, and baseline covariates, using a first-order ante dependence covariance matrix. Results A total of 184 women were randomized. The full analysis set (FAS) included 172 patients (venlafaxine, n = 82; fluoxetine, n = 90). Over the 8-week study period, the reduction in HAMD-24 scores was significant (P P = 0.001). The baseline-to-week-8 least-squares mean change of the anxiety/somatization factor scores, CGI-I response rate were greater in the venlafaxine group than in the fluoxetine group (all P Conclusion Venlafaxine was well tolerated and compared to fluoxetine, it led to a greater improvement in the treatment of postmenopausal MDD. Trial registration Clinical Trials. gov #NCT01824433. The trial was registered on April 4, 2013.

Background Major depressive disorder (MDD) is a common mental illness characterized by persistent sadness and a loss of interest in activities. Using smartphones and wearable devices to monitor the mental condition of patients with MDD has been examined in several studies. However, few studies have used passively collected data to monitor mood changes over time. Objective The aim of this study is to examine the feasibility of monitoring mood status and stability of patients with MDD using machine learning models trained by passively collected data, including phone use data, sleep data, and step count data. Methods We constructed 950 data samples representing time spans during three consecutive Patient Health Questionnaire-9 assessments. Each data sample was labeled as Steady or Mood Swing, with subgroups Steady-remission, Steady-depressed, Mood Swing-drastic, and Mood Swing-moderate based on patients’ Patient Health Questionnaire-9 scores from three visits. A total of 252 features were extracted, and 4 feature selection models were applied; 6 different combinations of types of data were experimented with using 6 different machine learning models. Results A total of 334 participants with MDD were enrolled in this study. The highest average accuracy of classification between Steady and Mood Swing was 76.67% (SD 8.47%) and that of recall was 90.44% (SD 6.93%), with features from all types of data being used. Among the 6 combinations of types of data we experimented with, the overall best combination was using call logs, sleep data, step count data, and heart rate data. The accuracies of predicting between Steady-remission and Mood Swing-drastic, Steady-remission and Mood Swing-moderate, and Steady-depressed and Mood Swing-drastic were over 80%, and the accuracy of predicting between Steady-depressed and Mood Swing-moderate and the overall Steady to Mood Swing classification accuracy were over 75%. Comparing all 6 aforementioned combinations, we found that the overall prediction accuracies between Steady-remission and Mood Swing (drastic and moderate) are better than those between Steady-depressed and Mood Swing (drastic and moderate). Conclusions Our proposed method could be used to monitor mood changes in patients with MDD with promising accuracy by using passively collected data, which can be used as a reference by doctors for adjusting treatment plans or for warning patients and their guardians of a relapse. Trial Registration Chinese Clinical Trial Registry ChiCTR1900021461; http://www.chictr.org.cn/showprojen.aspx?proj=36173

Age differences exist in many aspects in patients with major depressive disorder (MDD). The present study aims to examine the effect of age on treatment outcomes in first-episode MDD.A total of 982 first-episode major depressive patients, who were above 18 years old and admitted in both psychiatric hospitals and units of general hospitals were recruited for the present study. These patients were newly treated and responded to 8-12 weeks of antidepressant treatment. Depressive symptoms, psychosocial functioning and quality of life were measured using standardized instruments. The study population was divided into three age groups: early adult (18-44 years old), middle adult (45-59 years old), and late adult (60-85 years old).Earlier age was associated with greater symptom severity, severer depressive symptoms in hypersomnia, concentration/decision making, negative view of the self, suicide ideation and restlessness, more impaired function, poorer satisfaction in social relationship and economic status, when compared to late adults with MDD (all P 0.05). In the multivariable analyses, among the other variables, early age remained as an independent correlation of residual depressive severity (middle age vs. early age: OR = 0.631, 95%CI[0.462, 0.862]; old age vs. early age: OR = 0.521, 95%CI[0.348, 0.780]) and functional impairment. Comorbidity of physical illness had a negative contribution to all treatment outcomes.In first major depressive episode, early age was strongly associated with depressive severity and functional impairment after responding to antidepressant treatment. Early-life depression may be an indicator of MDD for poor clinical outcomes and high clinical burden.

Modelling WiMAX network traffic based on the self-similarity character is better than the traditional model based on the Poisson process, because the former can provide more accurate calculation for effective bandwidth. In this paper we propose a WiMAX network traffic model based on M/Pareto model to describe its self-similarity character. Then we deduce the average transmission rate and the variance coefficient for the FBM traffic model by the M/Pareto model, and get the Hurst parameter of the FBM traffic model by statistical analysis method. By the FBM traffic model we get a formula for calculating the effective bandwidth. Accordingly, we propose a modified self-similar call admission control algorithm (SS-CAC). SS-CAC can avoid measuring the parameter values of FBM traffic flow to do call admission control. Simulation results show that SS-CAC greatly reduces the call blocking rate and improves the bandwidth utilization.

Background Adjunctive ketamine with electroconvulsive therapy (ECT) has been investigated for treating major depressive disorder (MDD), but the findings have been inconsistent. Aim This is an updated meta-analysis of the efficacy and safety of ketamine augmentation of ECT in the treatment of MDD. Methods Randomized controlled trials (RCTs) reporting on the efficacy and safety of ketamine and ECT were identified and analyzed. Results Seventeen RCTs (n = 1,035) compared ketamine alone or ketamine plus other anesthetic drugs (n = 557) with other anesthetic agents (n = 478) in MDD patients who received ECT. Ketamine+other anesthetic drugs was superior in improving depressive symptoms over other anesthetic medications at early study time point, but not at post-ECT or end of study time points. Ketamine alone was not more efficacious in treating depressive symptoms than other anesthetic drugs at early study, post-ECT and end of study time points. Sensitivity analysis and 19 of the 20 subgroup analyses also confirmed the lack of significance of these findings. Eleven RCTs testing the effects of ketamine on neurocognitive functions with various test batteries found mixed results. Ketamine alone significantly increased blood pressure more than other anesthetic drugs in MDD treated with ECT. Conclusion Compared to other anesthetic agents, ketamine alone does not appear to improve the efficacy of ECT. However, ketamine+other anesthetic combinations may confer a short-term advantage in improving depressive symptom at the early stages of ECT.

Background:Depression among older adults is under-recognized either in the community or in general hospitals in Chinese culture. This study aimed to develop a culturally appropriate screening instrument for late-life depression in the non-psychiatric settings and to test its reliability and validity for a diagnosis of depression.Methods:Using a Delphi method, we developed a geriatric depression inventory (GDI), consisting of 12 core symptoms of depressive disorder in old age. We investigated its reliability and validity on 89 patients with late-life depression and 249 non-depression controls. Both self-report (GDI-SR) and physician-interview (GDI-RI) versions were assessed.Results:Cronbach's α coefficient was 0.843 for GDI-SR and 0.880 for GDI-RI. Both GDI-SR and GDI-RI showed good concurrent validity with the 15-item Geriatric Depression Scale (GDS-15) (GDI-SR: r = 0.750, p < 0.001; GDI-RI: r = 0.733, p < 0.001). The area under the curve of the receiver operating characteristic (ROC) was 0.938 for GDI-SR and 0.961 for GDI-RI, suggesting good to excellent discrimination of depression versus non-depression. Using a cut-off of three items endorsed, sensitivity and specificity were 92.1% and 81.9% for GDI-SR, and 93.3% and 87.1% for GDI-RI.Conclusions:The GDI, either based on self-report or rater interview, is a reliable and valid instrument for the detection of depression among older adults in non-psychiatric medical settings in Chinese culture.

Background This study aimed to investigate the endothelial function by reactive hyperemia index (RHI) in patients with depression, subjects recovering from depression, and subjects without a history of depression. Material/Methods Outpatients were recruited from a general hospital in China; 62 patients diagnosed with depression and the 17-item Hamilton Rating Scale for Depression (HAMD17) total scores ≥17 were enrolled as the depression group, 62 patients with a history of depression, discontinuation of antidepressants therapy at least 3 months ago, and HAMD17 ≤7 were recruited as remission group, and 62 subjects without a history of depression served as the control group (HAMD17 ≤7). Results The mean RHI was 1.93, 2.34, and 2.19 in depression, control, and remission groups, respectively, showing a significant difference among the 3 groups (P=0.0004). In addition, a marked difference in RHI was found between depression and control groups (P=0.0003) and between depression and remission groups (P=0.0270). However, there was no significant difference between remission and control groups (P=0.3363). Conclusions There is a relationship between depression and endothelial dysfunction in outpatients from a general hospital in China. The improvement of depression is synchronous with the improvement of endothelial function.

Background Depression is associated with substantial personal suffering and reduced quality of life and functioning. The aim of this study was to investigate gender differences on quality of life and functional impairment of outpatients with depression after acute phase treatment. Methods 1503 depression outpatients were recruited from eleven hospitals in China. Subjects were evaluated with sociodemographic characteristics, history and self-report instruments, related to severity of symptoms, function and quality of life. All data were analyzed to determine the gender differences. Results Men had a younger age at onset and the first onset age, higher education compared to women in total patients and with or without residual symptoms group. Using regression analysis, it was found that gender was significantly statistically related to severity scores of SDS and had no correlation with Q-LES-Q-SF total scores. In the residual symptoms group, greater functional impairment was noted by men in the area of work and social life. Significant gender differences of mood, work and sexual life in quality of life were observed. Limitations This is a cross-sectional study of depressed outpatients and duration of acute phase treatment may not an adequate time to measure changes. Conclusions Depression appears to affect men more seriously than women after acute phase treatment. Men had a younger age at onset and the first onset age, higher education, more functional impairment and lower satisfaction of quality of life in mood, work and sexual life. Gender differences affect acute treatment, remission and recovery.

The wireless channel is user dependent and time-varying, so that the scheduling algorithm and its stability are the key technical issue in M-WiMAX. We propose a modified M-LWDF scheduling algorithm, and then the M-WiMAX with PMP mode is modeled as a M/G/1 queueing system to analyze system performance. Accordingly, the system capacity region is derived, and the system stability region is calculated. Furthermore, the packet level stability of the Pre-LWDF scheduling algorithm is proved with Lyapunov drift stability theory. Finally, a M-WiMAX network simulation is built in NS2 platform to verify the packet level stability of the Pre-LWDF scheduling algorithm. The simulation results show that the Pre-LWDF algorithm has the packet level stability in M-WiMAX.

To investigate the association between the level of serum brain-derived neurotrophic factor (sBDNF) and the therapeutic efficacy of modified electroconvulsive therapy (MECT) in Chinese patients with depressive disorder.Twenty-eight patients with depressive episode and 28 healthy subjects were recruited in the current study. The sBDNF level was examined in all subjects before treatment and after a 2-week treatment with MECT in patients with depression. The severity of depression was measured according to the 17-item Hamilton Rating Scale for Depression in patients with depression.The severity of depression reduced significantly in patients with depression after a 2-week treatment with MECT (31.39 [SD, 4.65] vs 8.14 [5.52], P0.001). Serum BDNF level in patients with depression was significantly lower than that of the control group before treatment (5.66 [SD, 2.07] vs 9.17 [SD, 1.26] ng/mL, P0.001), then increased remarkably to the level of control subjects 2 weeks after MECT (7.90 [SD, 3.42] ng/mL). The increasing rate of sBDNF in patients with depression was significantly correlated with the decreasing rate of the total 17-item Hamilton Rating Scale for Depression score (r = 0.532, P = 0.004) and cluster scores of cognitive dysfunction (P = 0.018) and retardation (P = 0.048).The change in sBDNF is associated with the therapeutic efficacy of MECT in Chinese patients with depression.

BackgroundWhile oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD).MethodThirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology – Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾50% MADRS score reduction) was the primary outcome.ResultsBy 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response [hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01–0.22, p < 0.001] and remission (HR 0.11, 95% CI 0.02–0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks [(peak = 3 days–2 weeks; effect size (ES) = 1.08–1.18)], QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation.ConclusionsSingle-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy.