BACKGROUND: The optimal antidepressant dosages remain controversial. This study aimed to analyze the efficacy of antidepressants and characterize their dose-response relationships in the treatments of major depressive disorders (MDD). METHODS: We searched multiple databases, including the Embase, Cochrane Central Register of Controlled Trials, PubMed, and Web of Science, for the studies that were conducted between January 8, 2016, and April 30, 2023. The studies are double-blinded, randomized controlled trials (RCTs) involving the adults (≥18 years) with MDD. The primary outcomes were efficacy of antidepressant and the dose-response relationships. A frequentist network meta-analysis was conducted, treating participants with various dosages of the same antidepressant as a single therapy. We also implemented the model-based meta-analysis (MBMA) using a Bayesian method to explore the dose-response relationships. RESULTS: The network meta-analysis comprised 135,180 participants from 602 studies. All the antidepressants were more effective than the placebo; toludesvenlafaxine had the highest odds ratio (OR) of 4.52 (95% confidence interval [CI]: 2.65-7.72), and reboxetine had the lowest OR of 1.34 (95%CI: 1.14-1.57). Moreover, amitriptyline, clomipramine, and reboxetine showed a linear increase in effect size from low to high doses. The effect size of toludesvenlafaxine increased significantly up to 80 mg/day and subsequently maintained the maximal dose up to 160 mg/day while the predictive curves of nefazodone were fairly flat in different dosages. CONCLUSIONS: Although most antidepressants were more efficacious than placebo in treating MDD, no consistent dose-response relationship between any antidepressants was observed. For most antidepressants, the maximum efficacy was achieved at lower or middle prescribed doses, rather than at the upper limit. REGISTRATION No. CRD42023427480; https://www.crd.york.ac.uk/prospero/display_record.php?
Humans ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Dose-Response Relationship, Drug ; Randomized Controlled Trials as Topic

Objective:To investigate the association of risky drinking and decision-making ability among off-spring of fathers with alcohol dependence(OFAD).Methods:A case-control study was conducted according to the cutoff of the Alcohol Use Disorder Identification Test(AUDIT)(delimited as 7).OFAD were divided into"risky drinking group"(n=29)and"non-risky drinking group"(n=43).The Iowa Gambling Task(IGT)was used to e-valuate the decision-making ability.Covariance analysis was used to compare differences of IGT between the two groups,and multivariate logistic regression was used to explore the association between risky drinking and decision making ability.Results:There was no significant difference in total scores of IGT between the risky drinking group and the non-risky drinking group(P＞0.05).Risky drinking group had less Selection 2 in block 5 of IGT[(3.8± 2.5)v.s.(5.7±3.1),P＜0.05]than non-risky drinking group.Selection 2 in block 5 was still associated with risky drinking after controlling the covariates(OR=0.72,95％CI:0.57～0.90,P＜0.05).Conclusion:This study indicates that risky drinking group in offspring of parents with alcohol dependence may have better decision-making ability.

Objective:To evaluate the clinical efficacy and failure patterns of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) on the basis of modern chemoradiotherapy and diagnostic techniques.Methods:In this retrospective study, clinical data of 201 LS-SCLC patients treated with chemotherapy (EP/CE regimens, ≥4 cycles) and intensity-modulated radiotherapy (IMRT) in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were reviewed. All patients were primarily managed with concurrent or sequential chemoradiotherapy and achieved complete response (CR) or partial response (PR). Ninety percent of patients were revaluated for brain metastasis (BM) by MRI and 10% by CT scan. Long-term survival and failure patterns were compared between the PCI ( n=91) and non-PCI groups ( n=110). Results:The median follow-up time was 77.3 months (95% CI 73.0-81.5 months). The median overall survival (OS), 2-and 5-year OS rates were 58.5 months, 72.5% and 47.7% in the PCI group, and 34.5 months, 61.7% and 35.8% in the non-PCI group ( P=0.075). The median progression-free survival (PFS), 2-and 5-year PFS rate were 22.0 months, 48.0% and 43.4% in the PCI group, significantly higher than 13.9 months, 34.4% and 26.7% in the non-PCI group ( P=0.002). The 2- and 5-year cumulative incidence of BM were 6.6% and 12.2% in the PCI group, and 30.0% , 31.0% in the non-PCI group ( P=0.001). The median time and rate of BM as an isolated first site of relapse were 11.9 months and 4.4% in the PCI group, and 8.7 months and 25.5% in the non-PCI group ( P<0.001). Multivariate analysis showed that response after chemoradiotherapy ( P<0.001) and PCI ( P=0.033) were the independent prognostic factors for PFS. Stratified analysis demonstrated that PCI significantly improved the 5-year PFS in patients who achieved CR (72.7% vs. 48.0%, P=0.013), while it did not improve the 5-year PFS in patients who obtained PR (26.1% vs. 20.2%, P=0.213). Conclusion:In the new era of standard chemoradiotherapy and more accurate diagnostic methods for BM, PCI was associated with improved PFS and lower incidence of BM in LS-SCLC patients.

Objective: To evaluate the tolerability and short-term efficacy of chemo-radiotherapy in 125 patients with stage ⅡB-ⅣA esophageal carcinoma after radical resection. Methods: We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo-radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results: 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo-radiotherapy (41.6%), while 73 patients underwent only 1-4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up (6.4%). The 1-year and 3-year overall survival rate were 91.6% and 57.0%, respectively, with a median survival time of 64.4 months. The 1-year and 3-year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo-radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1-2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P=0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P=0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor (P=0.010). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB-ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

Objective: To evaluate the incidence and risk factors of symptomatic radiation-induced lung toxicity (SRILT) in non-small cell lung cancer (NSCLC) patients treated with modern radiotherapy after surgery. Methods: Clinical data of consecutive NSCLC patients treated with postoperative three-dimensional conformal or intensity-modulated radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences between November 2002 and December 2011 were retrospectively analyzed. According to the Common Terminology Criteria for Adverse Events (CTCAE, version 3.0), SRILT was defined as ≥grade 2 radiation-induced lung toxicity. Potential clinical risk factors and dosimetric parameters for SRILT were evaluated using logistic regression model. Results: Among 227 enrolled patients, 190 cases underwent lobectomy and 37 patients received pneumonectomy. Twenty-three patients (10.1%) developed SRILT after lobectomy. Seventeen patients experienced grade 2 SRILT, 5 cases of grade 3 SRILT and 1 case of grade 4 SRILT. Univariate analysis showed that postoperative concurrent chemoradiotherapy, relatively large PTV, mean lung dose and V₂₀- V₄₀ were significantly correlated with the incidence of SRILT (P=0.015, 0.048 and<0.001). Multivariate analysis demonstrated that postoperative concurrent chemoradiotherapy and V₂₀ were significantly associated with the incidence of SRILT (P=0.017 and P=0.009). Conclusions The incidence of SRILT is relatively low in NSCLC patients after postoperative radiotherapy. Concurrent chemoradiotherapy and V₂₀ are risk factors of SRILT.

Objective To evaluate the tolerability and short?term efficacy of chemo?radiotherapy in 125 patients with stageⅡB?ⅣA esophageal carcinoma after radical resection. Methods We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo?radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan?Meier method and analyzed using the log?rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo? radiotherapy (41.6%), while 73 patients underwent only 1?4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up ( 6.4%). The 1?year and 3?year overall survival rate were 91.6%and 57.0%, respectively, with a median survival time of 64.4 months. The 1?year and 3?year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo?radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1?2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P＝0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P＝0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor ( P ＝ 0.010 ). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB?ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

Objective To evaluate the tolerability and short?term efficacy of chemo?radiotherapy in 125 patients with stageⅡB?ⅣA esophageal carcinoma after radical resection. Methods We retrospectively evaluated the rate of completion, toxicity and survival of patients undergoing adjuvant concurrent chemo?radiotherapy after radical resection of esophageal carcinoma from January 2004 to December 2014 in our institution. The survival rate was determined by the Kaplan?Meier method and analyzed using the log?rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results 122 patients received more than 50 Gy dose (97.6%). A total of 52 patients received more than 5 weeks chemo? radiotherapy (41.6%), while 73 patients underwent only 1?4 weeks (58.4%). The median following up was 48.4 months. 8 patients lost follow up ( 6.4%). The 1?year and 3?year overall survival rate were 91.6%and 57.0%, respectively, with a median survival time of 64.4 months. The 1?year and 3?year disease free survival rate were 73.2% and 54.3%, respectively, with a median disease free survival time of 59.1 months. The most common acute complications associated with chemo?radiotherapy were myelosuppression, radiation esophagitis and radiation dermatitis, the majority of which were Grade 1?2. Of the 125 patients, there were 59 cases of recurrence, including 23 cases with local regional recurrence, 26 cases with hematogenous metastasis, and 8 cases with mixed recurrence. Univariate analysis showed that the numbers of concurrent chemotherapy was associated with the overall survival (P＝0.006). But receiving more than 5 weeks was not the prognostic factor compared to 1 to 4 weeks chemotherapy (P＝0.231). Multivariate analysis showed that only the numbers of concurrent chemotherapy was an independent prognostic factor ( P ＝ 0.010 ). Conclusions Postoperative radiotherapy concurrent with weekly chemotherapy could improve the overall survival and decrease the recurrence for stage ⅡB?ⅣA esophageal carcinoma after radical resection. However, the completion rate of chemotherapy was low, so it was necessary to explore reasonable regimens to improve the completion rate and carry out prospective randomized controlled trial.

Objective To investigate the clinical efficacy and prognosis of intensity-modulated radiotherapy(IMRT)combined with chemotherapy for limited-stage small cell lung cancer(LS-SCLC). Methods A retrospective analysis was performed on the clinical data of 484 LS-SCLC patients treated with chemoradiotherapy in our center from 2006 to 2014. The patients with partial or complete response to IMRT received prophylactic cranial irradiation(PCI). The Kaplan?Meier method was used to calculate survival rates, and the log-rank test and Cox regression were used for univariate and multivariate analyses, respectively. Results In all the patients, the follow-up rate was 93%;the median overall survival(OS) time was 23.8 months;the 2-,3-,and 5-year OS rates were 48.7%,39.8%,and 28.6%,respectively;the median progression-free survival(PFS)time was 14.1 months;the 2-, 3-, and 5-year PFS rates were 34.4%,30.5%, and 28.3%, respectively. The incidence rates of grade ≥3 bone marrow suppression, grade ≥2 radiation esophagitis, and grade ≥2 radiation pneumonitis were 26.9%, 24.8%, and 18.4%, respectively, in SCLC patients after IMRT. The objective response rate was 84.5%. The univariate analysis showed that age, smoking history, TNM stage, PCI, and the number of chemotherapy cycles before radiotherapy were prognostic factors for OS(P= 0.006, 0.001, 0.047, 0.000, and 0.046). The multivariate analysis showed that smoking history and PCI were independent prognostic factors(P=0.001 and 0.000).Conclusions IMRT combined with chemotherapy achieves satisfactory clinical outcomes in the treatment of LS-SCLC. Smoking history and PCI are independent prognostic factors for OS of LS-SCLC patients.

Objective: The aim of this retrospective study was to evaluate the prognostic significance of pretreatment Neutrophil-to-Lymphocyte Ratio(NLR) in locally advanced non-small cell lung cancer(NSCLC) patients treated with thoracic radiotherapy. Methods: We retrospectively analyze 420 patients who received thoracic radiotherapy alone, sequential chemoraiotherapy or concurrent chemoradiotherapy for locally advanced stage NSCLC from January 2007 to December 2010 of our hospital. The patients were divided into two groups (high NLR group and low NLR group) with appropriate cutoff point using the receiver operating characteristic (ROC) curve method. The survival curve was established by Kaplan-Meier method. The Log-rank test was used to compare the survival of the two NLR groups and the multivariate analysis was carried out by Cox regression model. Results: Among the 420 patients, 99 received radiotherapy alone, 139 received sequential chemoradiotherapy and 182 received concurrent chemoradiotherapy. 345 patients died and 75 were still alive. The median follow-up time was 5.2 years and the median overall survival was 22 months. The cut-off value of pretreatment NLR was 2.1. The 5-year PFS and OS rates in high NLR group and low NLR group were 10.6% vs 15.7% (P=0.033) and 15.5% vs 22.7% (P=0.012). Multivariate analysis confirmed that pretreatment NLR (hazard ratio 1.06, P=0.041) was independent prognostic factor of OS. Conclusions Our study revealed that the pretreatment NLR is the independent prognostic factor of OS in patients with locally advanced stage NSCLC treated with thoracic radiotherapy. However, NLR is still greatly influenced by patient′s condition and treatment which needs further research.

Objective: To evaluate the short-term clinical efficacy and adverse events of volumetric modulated arc therapy (VMAT) in the treatment of locally advanced non-small cell lung cancer (NSCLC). Methods: From January to December 2016, 58 patients (47 male and 11 female) with unresectable locally advanced NSCLC received concurrent or sequential chemoradiotherapy. The radiation dose was ranged from 38 Gy to 66 Gy. The radiation dose was equal or higher than 56 Gy in 53 patients (92%). The median radiotherapy fraction was 30, 1.8 Gy to 3.0 Gy for each fraction. Twenty-eight patients (48%) received concurrent chemoradiotherapy. Results: The median follow-up time was 9 months. The 1-year overall survival (OS) rate was 84% and the 1-year progression-free survival (PFS) rate was 48%.Eleven patients (19%) suffered from symptomatic radiation pneumonitis and one of them died of radiation pneumonitis. Within 6 months after radiotherapy, 31 patients (53%) developed asymptomatic local pulmonary fibrosis on CT images. Seventeen patients (29%) suffered from grade Ⅱ esophagitis. Ten cases (17%) had ≥ grade Ⅲ adverse events and 9 of them presented with leucopenia. Conclusions VMAT yields high short-term clinical efficacy and tolerable adverse events in the treatment of locally advanced NSCLC, which does not increase the risk of pneumonitis.