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:The purpose of this study is to investigate the interactive effects of chronic physical diseases and leisure activities on depression in the elderly.Methods:Through a cross-sectional study design, 3 007 adults aged 60 and over were recruited for eligibility psychological status screening between June 20, 2014 and August 20, 2014 in communities of China. Geriatric Depression Inventory (GDI) was used to assess depressive symptoms. Leisure Activity Questionnaire was used to assess the participation of leisure activities. Logistic regression was used to analyze the relationship between chronic physical disease and leisure activity and depression, and the interaction between was also analyzed.Results:In the community cross-sectional survey, the incidence of depression among the elderly in community was 35.78% (1 076/3 007). Logistic regression analysis showed that Diabetes ( OR=1.42, 95 %CI: 1.14-1.76), hyperlipidemia ( OR=1.27, 95 %CI: 1.09-1.56), coronary heart disease ( OR=1.31, 95 %CI: 1.04-1.63), and transient ischemic attack ( OR=1.31, 95 %CI: 1.04-1.63) were significantly associated with increased risk of geriatric depression (all P<0.05), while stretching and flexibility exercises ( OR=0.79, 95 %CI: 0.68-0.92) was associated with a decrease in the risk of depression ( P<0.05). Diabetes and non-participation in stretching exercises had an interactive effect as a risk factor for depression [attributable proportion due to interaction (AP)=41.75%]. Conclusions:Depression is common in the elderly in the community. Chronic physical diseases may increase the risk of geriatric depression, especially diabetes, hyperlipidemia, coronary heart disease, and transient ischemic attack. Active participation in stretching exercises may be beneficial to reduce the occurrence of depression.

Objective:The purpose of this study is to investigate the interactive effects of chronic physical diseases and leisure activities on depression in the elderly.Methods:Through a cross-sectional study design, 3 007 adults aged 60 and over were recruited for eligibility psychological status screening between June 20, 2014 and August 20, 2014 in communities of China. Geriatric Depression Inventory (GDI) was used to assess depressive symptoms. Leisure Activity Questionnaire was used to assess the participation of leisure activities. Logistic regression was used to analyze the relationship between chronic physical disease and leisure activity and depression, and the interaction between was also analyzed.Results:In the community cross-sectional survey, the incidence of depression among the elderly in community was 35.78% (1 076/3 007). Logistic regression analysis showed that Diabetes ( OR=1.42, 95 %CI: 1.14-1.76), hyperlipidemia ( OR=1.27, 95 %CI: 1.09-1.56), coronary heart disease ( OR=1.31, 95 %CI: 1.04-1.63), and transient ischemic attack ( OR=1.31, 95 %CI: 1.04-1.63) were significantly associated with increased risk of geriatric depression (all P<0.05), while stretching and flexibility exercises ( OR=0.79, 95 %CI: 0.68-0.92) was associated with a decrease in the risk of depression ( P<0.05). Diabetes and non-participation in stretching exercises had an interactive effect as a risk factor for depression [attributable proportion due to interaction (AP)=41.75%]. Conclusions:Depression is common in the elderly in the community. Chronic physical diseases may increase the risk of geriatric depression, especially diabetes, hyperlipidemia, coronary heart disease, and transient ischemic attack. Active participation in stretching exercises may be beneficial to reduce the occurrence of depression.

Objective:This study aimed to examine the prevalence of comorbid generalized anxiety disorder (GAD) among adult patients with major depressive disorder (MDD) in China and explore its potential risk factors.Methods:This is a multicenter, cross-sectional study, involving 1 086 patients in 9 clinical settings. The diagnosis of MDD and GAD were confirmed by the MINI. Life events were evaluated by the Life Events Scale (LES), and early life stress was assessed by the Childhood Trauma Questionnaire (CTQ). The severity of depression, social support, coping style and personality traits were assessed by Hamilton Depression Rating Scale-17 item (HAMD 17), Simplified Coping Style Questionnaire (SCSQ), and Eysenck Personality Questionnaire, short scale for China (EPQ-RSC), respectively. Pearson correlation analysis, univariate regression analysis and Logistic regression analysis were used to explore the association of clinical characteristics, life stress, social factors and comorbidity of MDD and GAD. Results:Among 1 086 MDD patients, 276 of them (25.4%) were diagnosed with comorbid GAD. Patients with comorbid GAD were more likely to report adulthood adversity then those without (60.2% （165/276） vs. 39.9%（321/810）, χ2=33.993， P<0.01). However, there was no difference in social support and coping styles between the two groups. Furthermore, patients with comorbid GAD had higher levels of neuroticism, and lower levels of extraversion. After controlling for confounders, logistic regression results showed that adulthood adversity ( OR=1.720, 95% CI 1.262-2.343, P<0.01) and higher neuroticism levels (O R=1.211, 95% CI 1.141-1.286, P<0.01) were significantly associated with comorbid GAD in patients with MDD. Conclusion:Adulthood adversity and high levels of neuroticism were potential risk factors of comorbidity of MDD and GAD. This finding provides empirical evidence for developing targeted interventions for this subgroup population with MDD.

Objective:This study aimed to examine the prevalence of comorbid generalized anxiety disorder (GAD) among adult patients with major depressive disorder (MDD) in China and explore its potential risk factors.Methods:This is a multicenter, cross-sectional study, involving 1 086 patients in 9 clinical settings. The diagnosis of MDD and GAD were confirmed by the MINI. Life events were evaluated by the Life Events Scale (LES), and early life stress was assessed by the Childhood Trauma Questionnaire (CTQ). The severity of depression, social support, coping style and personality traits were assessed by Hamilton Depression Rating Scale-17 item (HAMD 17), Simplified Coping Style Questionnaire (SCSQ), and Eysenck Personality Questionnaire, short scale for China (EPQ-RSC), respectively. Pearson correlation analysis, univariate regression analysis and Logistic regression analysis were used to explore the association of clinical characteristics, life stress, social factors and comorbidity of MDD and GAD. Results:Among 1 086 MDD patients, 276 of them (25.4%) were diagnosed with comorbid GAD. Patients with comorbid GAD were more likely to report adulthood adversity then those without (60.2% （165/276） vs. 39.9%（321/810）, χ2=33.993， P<0.01). However, there was no difference in social support and coping styles between the two groups. Furthermore, patients with comorbid GAD had higher levels of neuroticism, and lower levels of extraversion. After controlling for confounders, logistic regression results showed that adulthood adversity ( OR=1.720, 95% CI 1.262-2.343, P<0.01) and higher neuroticism levels (O R=1.211, 95% CI 1.141-1.286, P<0.01) were significantly associated with comorbid GAD in patients with MDD. Conclusion:Adulthood adversity and high levels of neuroticism were potential risk factors of comorbidity of MDD and GAD. This finding provides empirical evidence for developing targeted interventions for this subgroup population with MDD.

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.