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 assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.

Objective:To assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.

Objective:To assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.

Objective:To assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.

Objective:To assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.

Objective:To assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.

Objective:To assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.

Objective:To assess the effects of nutritional interventions combined with Traditional Chinese Med-icine(TCM)physical dialectics on the development of gestational diabetes mellitus(GDM),dietary status during pregnancy,and maternal and infant outcomes in high-risk pregnant women in early pregnancy.Methods:298 high-risk pregnant women with GDM in early pregnancy(gestational week≤14 weeks)registered in the Obstet-rics Department of Urumqi Maternal and Child Health Hospital from 1st December 2022 to 30th March 2023 were selected as the study subjects and randomly divided into the intervention group(149 cases)and the control group(149 cases).During 14 to 23+6 weeks of pregnancy,TCM constitution nutritional intervention was carried out for pregnant women in the intervention group,and routine guidance and healthy dietary education was carried out in the control group.The incidence of GDM in the two groups was compared at 24-28 weeks of pregnancy,and the relationship between early pregnancy nutritional intervention combined with TCM constitution and the risk of GDM was analysed in subgroups using logistic regression and likelihood ratio test.The dietary situation,biochemical in-dexes and delivery outcomes after the intervention were compared at 32-36 weeks of pregnancy.Results:①The incidence of GDM in the intervention group was significantly lower than that in the control group(14.09％vs.23.49％,P＜0.05).The effect of the TCM constitution based nutritional intervention on the risk probability of GDM was statistically significant only among pregnant women with different ranges of gestational weight gain(GWG)(P=0.018).Among them,pregnant women with GWG lower than the recommended range had a reduced risk of GDM after intervention(OR 0.27,95％Cl 0.10-0.68,P=0.008).② After intervention,the evaluation index of di-etary balance index of pregnant women in the intervention group was better than that of the control group(P＜0.05),and the intake of cereals and potatoes,vegetables,and water of pregnant women in late pregnancy in the intervention group was higher than that of the control group(P＜0.05).③The levels of triglycerides,total choles-terol,low-density lipoprotein,glycated haemoglobin,uric acid and creatinine of pregnant women in the intervention group were lower than those of the control group in late pregnancy(P＜0.05).GWG,gestational age at delivery,the rate of low-birth-weight,and the neonatal 1-minute Apgar scores were all better than those of the control group(P＜0.05.Conclusions:Nutritional interventions in early pregnancy combined with TCM constitution can sig-nificantly reduce the incidence of GDM in high-risk pregnant women and the chances of low-birth-weight babies.Obstetrics outpatient clinics can actively develop extensive collaboration with TCM and clinical nutrition depart-ments to reduce adverse pregnancy outcomes for both mother and fetus.

Objective To observe the effects of Shengxue Tongbian Granules on colonic myoelectricity and Ca2+/CaM/MLCK signaling pathway in rats with slow transit constipation(STC)of blood deficiency and intestinal dryness syndrome;To explore its mechanism for the treatment of STC.Methods The STC model of blood deficiency and intestinal dryness syndrome was established by intragastric administration of loperamide combined with tail bloodletting.The rats were divided into control group,model group,mosapride citrate group and Shengxue Tongbian Granules group,with 8 rats in each group.The administration group was given corresponding drugs by gavage for 14 days.The general condition of rats before and after treatment was observed,the fecal water content was detected,the slow wave frequency,amplitude,and coefficient of variation of colonic electromyography were detected using a biological function experimental system,and intestinal propulsion rate was detected.HE staining was used to observe the pathological changes of colon tissue,the concentration of Ca2+ in colonic smooth muscle cells was detected by colorimetry,the expression of Cx43,calmodulin(CaM),myosin light chain kinase(MLCK)and p-MLC20 in smooth muscle tissue were detected by Western blot.Results Compared with the control group,the body mass,fecal water content and intestinal propulsion rate of rats in the model group decreased(P<0.01),the slow wave frequency of colonic electromyography slowed down,the coefficient of variation of frequency increased(P<0.01),and the amplitude and coefficient of variation of slow wave increased(P<0.01);colonic mucosal structure was damaged,with visible inflammatory changes and significant erosion,and the concentration of Ca2+ and the expressions of Cx43,CaM,MLCK,p-MLC20 proteins in colonic smooth muscle cells were significantly decreased(P<0.01).Compared with the model group,the body mass,fecal water content and intestinal propulsion rate of the rats in the mosapride citrate group and the Shengxue Tongbian Granules group significantly increased(P<0.05,P<0.01),the slow wave frequency of colonic electromyography increased and the coefficient of variation of frequency decreased(P<0.01),and the slow wave amplitude and amplitude variation coefficient decreased(P<0.05,P<0.01);the colonic mucosal structure was relatively intact,the erosion situation was improved,and the Ca2+ concentration,Cx43,CaM,MLCK and p-MLC20 protein expressions in colonic smooth muscle cells significantly increased(P<0.01).Conclusion Shengxue Tongbian Granules can improve defecation symptoms and promote colonic motility in STC rats with blood deficiency and intestinal dryness syndrome,which may be related to regulating colonic myoelectric rhythm and activating Ca2+/CaM/MLCK signaling pathway.