Efficacy and safety of prolonged-release trazodone in major depressive disorder: a multicenter, randomized, double-blind, flexible-dose trial.

OBJECTIVE: To investigate the efficacy, safety, and clinical benefit of prolonged-release trazodone (Trittico) in the treatment of major depressive disorder (MDD). METHODS: In this study, 363 Chinese patients with MDD were randomized 1:1 to receive either prolonged-release trazodone (150-450 mg) or placebo treatment for 6 weeks. The primary efficacy measurement was the change of the 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of the study. The secondary efficacy measurements were the response and remission rates, the Clinical Global Impression - Improvement of Illness (CGI-I) score at the end of the study, and the change of the HAMD-14 total score and quality of sleep [evaluated by the Pittsburgh Sleep Quality Index (PSQI) scale] during the study period. RESULTS: The mean maximum daily dose was 273.11 mg for the trazodone group and 290.92 mg for the placebo group. At the end of the study, there was a significant difference between the two groups in the HAMD-17 change score (trazodone vs. placebo: -11.07 vs. -8.29, p < 0.001). Trazodone showed advantages at 1 week of treatment, and the effect lasted until the end of the study (week 6). The response and remission rates of the trazodone group were significantly higher than those in the placebo group (response rate: 59.6 vs. 37.2%, p < 0.001; remission rate: 35.5 vs. 22.2%, p = 0.005). The majority of the adverse reactions of trazodone were mild to moderate, and the most frequent adverse reactions (≥5%) were dizziness, dry mouth, somnolence, and nausea. CONCLUSIONS: Prolonged-release trazodone was more effective than placebo in MDD and was well tolerated.

Simultaneous extracting area and quantity of agricultural greenhouses in large scale with deep learning method and high-resolution remote sensing images.

Greenhouses are an important part of modern facility-based agriculture. While creating well-being for human society, greenhouses also bring negative impacts such as air pollution, soil pollution, and water pollution. Therefore, it is of great significance to obtain information such as the area and quantity of greenhouses. It is still a challenging task to find a low-cost, high-efficiency, and easy-to-use method for the dual extraction of greenhouse area and quantity on a large scale. In this study, relatively easy-to-obtain high-resolution Google Earth remote sensing images are used as the experimental data source, and an area and quantity simultaneous extraction framework (AQSEF) is constructed to extract both the area and quantity of greenhouses. The AQSEF uses UNet and YOLO v5 series networks as core operators to complete model training and prediction, and main components such as SWP, OSW&NMS and GCA complete data postprocessing. To evaluate the feasibility of our method, we take Beijing, China, as the research area and select multiple accuracy evaluation indicators in the two branches for accuracy verification. The results show that the mIoU, OA, Kappa, Recall and Precision with the best performance model in the area extraction branch can reach 0.931, 0.987, 0.867, 0.91 and 0.914, respectively. Additionally, the Recall, Precision, AP@0.5 and mAP@0.5: 0.95 values of the best performance model are 0.781, 0.891, 0.812 and 0.509, respectively, in the extraction of the quantity of greenhouses. Finally, in Beijing, the area covered by greenhouses is approximately 85.443 km2, and the quantity of greenhouses is approximately 155,464. With the proposed method, the time consumed for area extraction and quantity extraction is 6.73 h and 12.97 h, respectively. The experimental results show that AQSEF helps to overcome the spatiotemporal diversity of greenhouses and quickly and accurately map a high-spatial-resolution greenhouse distribution product within the research area.

A randomised, double-blind, placebo-controlled study to evaluate the safety and efficacy of lamotrigine in the maintenance treatment of Chinese adult patients with bipolar I disorder.

BACKGROUND: Lamotrigine is approved as a maintenance therapy for bipolar I disorder in many countries, including China in 2021. This study evaluated the efficacy and safety of lamotrigine in controlling relapse and/or recurrence of mood episodes in Chinese patients with bipolar I disorder. METHODS: Patients aged ≥ 18 years with bipolar I disorder who met response criteria (Clinical Global Impression-Severity [CGI-S] score of ≤ 3 for ≥ 4 consecutive weeks) during treatment with lamotrigine in a 6-16 week open-label (OL) phase, and who were maintained for ≥ 1 week on lamotrigine 200 mg/day monotherapy, were randomised (1:1) to continue receiving lamotrigine 200 mg/day or switch to placebo in a 36-week randomised double-blind (RD) phase. The primary efficacy outcome measure was time from entry into the RD phase to intervention for relapse and/or recurrence of a mood episode (TIME). Post hoc analyses assessed the impact of OL baseline mood severity on TIME. Safety assessments were conducted throughout the study. RESULTS: Of 420 patients treated in the OL phase, 264 were randomised to receive lamotrigine (n = 131) or placebo (n = 133). Overall, 112 patients had an intervention for relapse and/or recurrence of a mood episode (lamotrigine, n = 50/130 [38.5%]; placebo, n = 62/133 [46.6%]), with no significant difference in TIME between groups (adjusted hazard ratio [95% confidence interval (CI)] 0.93 [0.64, 1.35]; p = 0.701). Post hoc analyses indicated a significant difference in TIME, favouring lamotrigine over placebo, for patients with baseline CGI-S score ≥ 4 (hazard ratio [95% CI] 0.52 [0.30, 0.89]; p = 0.018) and with baseline Hamilton Depression Rating Scale ≥ 18 or Young Mania Rating Scale ≥ 10 (0.44 [hazard ratio [95% CI] 0.25, 0.78]; p = 0.005). Lamotrigine was well tolerated with no new safety signals. CONCLUSIONS: Lamotrigine was not significantly superior to placebo in preventing relapse and/or recurrence of mood episodes in this study of Chinese patients with bipolar I disorder but post hoc analyses suggested a therapeutic benefit in patients with moderate/severe mood symptoms at baseline. The discrepancy between these findings and the positive findings of the pivotal studies may be attributable to the symptom severity of the bipolar patients recruited, a high dropout rate, and the comparatively short duration of the RD phase rather than race/ethnicity differences. Clinical trial registration ClinicalTrial.gov Identifier NCT01602510; 21st May 2012; https://clinicaltrials.gov/ct2/show/NCT01602510 .

Efficacy and safety of aripiprazole once-monthly versus oral aripiprazole in Chinese patients with acute schizophrenia: a multicenter, randomized, double-blind, non-inferiority study.

OBJECTIVE: The present study aimed to evaluate the efficacy and safety of aripiprazole once-monthly (AOM) compared to oral aripiprazole in treating acute schizophrenia. METHODS: This randomized, double-blind, non-inferiority study recruited patients from 15 trial sites across China from May 2017 to April 2019. Patients with an acute psychotic episode received AOM at 400 mg or oral aripiprazole at 10-20 mg for 12 weeks. The primary and secondary efficacy endpoints were the difference in scores from baseline to week 10, as assessed on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions-Severity (CGI-S) scores, respectively. RESULTS: A total of 436 patients were randomized. Among them, 159/218 (72.9%) and 165/218 (75.7%) in the AOM and oral aripiprazole groups completed 10 weeks of treatment, respectively. The least-squares (LS) mean changes from baseline to endpoint (week 10) in PANSS were - 33.6 for the AOM group and - 34.8 in the oral aripiprazole group, respectively, with a difference of - 1.2 (95% CI: - 4.1, 1.7). The non-inferiority margin of AOM to oral aripiprazole was - 4.1, which was above the lower limit of the pre-defined margin. The altered CGI-S score was - 2.2 and - 2.3 in the AOM and oral aripiprazole groups, respectively. The incidence of treatment-emergent adverse events (TEAEs) was similar in both groups. The rate of discontinuation due to TEAEs was 2.3% and 3.2% in the AOM and oral aripiprazole groups, respectively. CONCLUSIONS: This study confirmed the efficacy and safety of AOM for the treatment of Chinese patients with acute schizophrenia. The non-inferiority of AOM to oral aripiprazole was established, with comparable efficacy and tolerability. These findings suggested that AOM could be used as a treatment option for patients experiencing an acute episode of schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03172871.

Efficacy and safety of bupropion hydrochloride extended-release versus escitalopram oxalate in Chinese patients with major depressive disorder: Results from a randomized, double-blind, non-inferiority trial.

BACKGROUND: This study evaluated the non-inferiority of bupropion extended-release (XL) compared to escitalopram for acute-phase treatment of Chinese patients with major depressive disorder (MDD). METHODS: This randomized (1:1), double-blind, active-control study conducted between February 2015 and October 2016 included patients with MDD (DSM-IV) (N = 538). The treatment phase had three dose levels (level 1 [Week 1], level 2 [Week 2-4], and level 3 [Week 5-8]), which included either bupropion XL 150 mg, 300 mg, 300 mg or escitalopram 10 mg, 10 mg, 10-20 mg (once-daily), respectively. Primary outcome was mean change from baseline in Hamilton Depression Rating Scale-17 (HAMD-17) total score at Week 8. RESULTS: Overall, 534 patients (bupropion XL, n = 266; escitalopram, n = 268) received at least one dose of study medication. The least square mean (standard error) change from baseline in HAMD-17 total score at Week 8 was -14.5 (0.41) in bupropion XL group and -15.4 (0.39) in escitalopram group (mean difference: 0.8 [-0.27, 1.94]). The response rate was 69.6% versus 72.9%, remission rate was 39.7% versus 47.2%, sustained response rate was 51.6% versus 56.3%, and sustained remission rate was 25.5% versus 28.6%, respectively, for bupropion XL versus escitalopram group. Adverse events were reported by 313 patients (bupropion XL, n = 157; escitalopram, n = 156); the most common on-treatment adverse event in both groups was nausea (10.5% versus 18.7%, respectively). LIMITATIONS: A non-inferiority short-term (8 weeks) study without a placebo arm. CONCLUSION: Results from this study demonstrated that the efficacy of bupropion XL was non-inferior to that of escitalopram in Chinese patients with MDD.

A 6-week, multicenter, double-blind, double-dummy, chlorpromazine-controlled non-inferiorityrandomized phase iiitrial to evaluate the efficacy and safety of quetiapine fumarate (SEROQUEL) extended-release (XR) in the treatment of patients with schizophrenia and acute episodes.

This study aimed to evaluate the efficacy and safety of quetiapine fumarate extended-release (XR) in the treatment of Chinese patients with acute schizophrenia. Multicenter, double-blind, double-dummy, active-controlled non-inferiority randomized study in Chinese patients (n = 388) with schizophrenia randomly assigned to quetiapine XR or chlorpromazine for 6 weeks. Primary outcome was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at the end of treatment. Safety objectives included adverse event (AE) monitoring, laboratory test results, and electrocardiograms. Changes in PANSS total score were -33.4 for quetiapine XR and -35.9 for chlorpromazine (P > 0.05). Least squares mean changes were: positive subscale, -9.9 ± 0.53 and -11.1 ± 0.51; negative subscale, -5.9 ± 0.50 and -6.7 ± 0.48; general psychopathology subscale, -12.9 ± 0.74 and -13.9 ± 0.71; aggression and hostility cluster scores, -4.8 ± 0.33 and -5.4 ± 0.32; and depression cluster scores, -1.8 ± 0.18 and -1.7 ± 0.18, for quetiapine XR and chlorpromazine, respectively. For quetiapine XR, AEs were constipation, dizziness, insomnia, and agitation, and nine patients (4.6%) discontinued due to AEs. For chlorpromazine, AEs were extrapyramidal symptoms, constipation, insomnia, dizziness, and agitation, and 17 patients (8.9%) discontinued due to AEs; two patients reported serious AEs. Quetiapine XR monotherapy was not inferior to chlorpromazine for treating acute schizophrenia in Chinese patients and was well tolerated.

CARDIOPROTECTIVE ROLES OF THE CHINESE MEDICINAL FORMULA BAO-XIN-TANG ON ACUTE MYOCARDIAL INFARCTION IN RATS.

BACKGROUND: Bao-Xin-Tang (BXT) is a traditional Chinese medicinal formula used for the treatment of coronary heart disease and known to have favorable therapeutic benefits. The current study was designed to determine whether BXT has a cardioprotective role for acute myocardial infarction. The underlying mechanisms were also explored. MATERIALS AND METHODS: The Sprague-Dawley rat model of acute myocardial infarction was established by occluding the left anterior descending branch of the coronary artery. After a 3-h ischemic period, we determined the myocardial infarction size, inflammatory components, and antioxidant activities. RESULTS: The data showed that BXT could reduce the infarction size and lower the levels of C-reactive protein, interleukin-6, and myeloperoxidase, and increase the activities of superoxide dismutase and the anti-inflammatory cytokine, interleukin-10. These results indicate that administration of BXT, following acute myocardial infarction, could reduce infarct size. CONCLUSION: The effects of BXT may be related to its anti-inflammatory and anti-oxidative properties.

Efficacy and safety of quetiapine extended release monotherapy in bipolar depression: a multi-center, randomized, double-blind, placebo-controlled trial.

RATIONALE: Quetiapine extended release (XR) has been used to treat various psychiatric disorders, including depressive episodes associated with bipolar I and II disorders. Quetiapine XR is the first approved drug in China for the treatment of bipolar disorder. OBJECTIVES: The study evaluated the efficacy and safety of short-term quetiapine XR monotherapy in the treatment of depressive episodes of bipolar I and II disorders. METHODS: This was an 8-week multi-center, randomized, double-blind, placebo-controlled, fixed-dose phase 3 study. The primary endpoint was the mean change of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary endpoints included Clinical Global Impressions-Bipolar (CGI-BP) and remission rates. RESULTS: The study recruited 279 adult bipolar I or II patients currently experiencing depression from 11 Chinese provinces. Of these, 139 received quetiapine XR (300 mg/day) and 140 received placebo for 8 weeks. The mean change in the MADRS total score was significantly greater in the quetiapine XR group than in the placebo group (-19.00 ± 7.88 vs. -16.20 ± 9.32; p = 0.004). Adverse events occurred in 96 patients (65.3 %) in the quetiapine XR group and 72 (49.0 %) in the placebo group. The incidence of serious adverse events did not differ significantly between the groups (p = 0.247). CONCLUSIONS: This study, which is the first to evaluate 300 mg/day quetiapine XR monotherapy for depression in Chinese patients with bipolar disorders, found that this drug was superior to the placebo. Quetiapine XR was generally safe and well tolerated (ClinicalTrials.gov number, NCT01256177).

Comparative study of the efficacy and safety between blonanserin and risperidone for the treatment of schizophrenia in Chinese patients: A double-blind, parallel-group multicenter randomized trial.

This randomized, double-blind study compared the efficacy and safety of blonanserin and risperidone to treat Chinese schizophrenia patients aged ≥18 and < 65 years. Patients with Positive and Negative Syndrome Scale (PANSS) total scores ≥70 and ≤ 120 were randomized to receive blonanserin or risperidone using a gradual dose-titration method (blonanserin tablets: 8-24 mg/day; risperidone tablets: 2-6 mg/day), twice daily. Treatment populations consisted of 128 blonanserin-treated patients and 133 risperidone-treated patients. Intention-to-treat analysis was performed using the last observation carried forward method. Reductions of PANSS total scores by blonanserin and risperidone treatment were -30.59 and -33.56, respectively. Risperidone treatment was associated with elevated levels of serum prolactin (67.16% risperidone versus 52.31% blonanserin) and cardiac-related abnormalities (22.39% risperidone versus 12.31% blonanserin), and blonanserin patients were more prone to extrapyramidal side effects (48.46% blonanserin versus 29.10% risperidone). In conclusion, blonanserin was as effective as risperidone for the treatment of Chinese patients with schizophrenia. The overall safety profiles of these drugs are comparable, although blonanserin was associated with a higher incidence of EPS and risperidone was associated with a higher incidence of prolactin elevation and weight gain. Thus, blonanserin is useful for the treatment of Chinese schizophrenia patients.

Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study.

RATIONALE: S-citalopram (escitalopram) is the very active moiety of citalopram. It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder (MDD). OBJECTIVE: The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients. METHODS: In the double-blind study, 240 MDD patients were randomly assigned to treatment for 6 weeks either with escitalopram (10-20 mg/d) or citalopram (20-40 mg/d). The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of study. The secondary efficacy measurements were response and remission rates. The adverse events (AEs) were recorded by the investigator. RESULTS: Two hundred and three (85%) patients completed the trial. The average dose was 13.9 mg/d in the escitalopram group and 27.6 mg/d in the citalopram group. No significant differences were found between the two groups in the change in HAMD-17 total score, response, and remission rate. These results were similar in severe MDD patients. No significant differences were found between the two groups in AEs. No serious AEs were observed in this study. CONCLUSIONS: The study suggests that escitalopram 10-20 mg/d are as effective and safe as citalopram 20-40 mg/d in the short-term treatment for Chinese MDD patients.

Association between painful physical symptoms and clinical outcomes in Chinese patients with major depressive disorder: a three-month observational study.

BACKGROUND: Painful physical symptoms (PPS) may present as a component of major depressive disorder (MDD). Their effect in Chinese patients has not been investigated. This analysis reports the changes in disease severity, treatment patterns, quality of life and outcomes in a Chinese cohort according to the presence (PPS+) or absence (PPS-) of painful physical symptoms. METHODS: A subgroup of Chinese patients from a large observational 3-month study of patients from Asian countries and regions of China were classified using the modified Somatic Symptom Inventory (SSI) as PPS+ (mean score >or= 2) or PPS- (mean score < 2). Depression severity was assessed with the Clinical Global Impression of Severity (CGI-S) scale and 17-item Hamilton depression rating scale (HAMD(17)). Pain severity was measured using a visual analogue scale (VAS), while the EuroQoL (EQ-5D) assessed patient well-being. Antidepressants were compared with regard to their efficacy. RESULTS: Of the 299 Chinese patients enrolled in the study, 105 were classified as PPS+ (73/105, 70% women). At baseline, PPS+ patients reported greater pain severity (VAS, mean (SD): 49.56 (26.49) vs. 16.60 (20.99) for PPS-, P < 0.01), were more depressed (HAMD(17), mean (SD): 25.32 (5.47) vs. 23.33 (5.24) for PPS-, P = 0.002) and had poorer quality of life (EQ-5D Health State, mean (SD): 38.48 (22.38) vs. 49.57 (18.54) for PPS-, P < 0.001). PPS+ patients showed less overall improvement in depressive symptom severity (HAMD(17), change from baseline (95%CI): -17.38 (-18.65, -16.12) vs. -19.20 (-20.05, -18.35) for PPS-, P = 0.032; CGI-S, change from baseline (95%CI): -2.85 (-3.11, -2.58) vs. -3.20 (-3.38, -3.02) for PPS-, P = 0.044). CONCLUSIONS: PPS were less frequent than expected compared with previous studies of Asian populations. PPS+ were associated with greater MDD severity and less improvement than PPS- when antidepressants were given.