The Clinical Study Of Venlafaxine Initial Combined With Tandospirone In The Treatment Of Major Depressive Disorder

Backgrounds:Major depressive disorder is a multifactorial disorder with unknown etiology and pathogenesis.The current etiology and pathogenesis of major depressive disorder are unknown,with a lag in the onset of first-line antidepressant therapy,low treatment efficiency and recovery rates,high incidence of sexual dysfunction,impairment of cognitive function,poor patient compliance with treatment,impairment of patient social functioning,and economic and social burden.Tandospirone has been shown to have potential antidepressant effects,but there are few studies on the initial combination treatment of major depressive disorder,few reports on the potentiation of 5-HT1 AR partial agonists for other subtypes of major depressive disorder,and few comprehensive studies on whether venlafaxine combined with tandospirone can provide early onset of effect,enhance efficacy,and improve sexual and cognitive function in major depressive disorder,which still need further longitudinal investigation is needed.Objective:To explore the efficacy and side effects of venlafaxine initially combined with tandospirone in the treatment of patients with major depressive disorder,effects on patients’ sexual and cognitive functions,as well as effects on BMI,fasting blood glucose,lipids,liver function and serum prolactin levels.Methods: A total of 124 depression patients who were treated at the No.904 Hospital of The PLA Joint Logistic Support Force from March 2021 to November 2022 and met the enrollment criteria were selected and randomly divided into a monotherapy group(venlafaxine combined with placebo,61 cases)and a combination group(venlafaxine combined with tandospirone,63 cases)according to the random number table method.Patients in both groups were treated for 6 weeks.They are performed to assess efficacy,sexual and cognitive function by Hamilton Rating Scale for Depression(HAMD-17),Hamilton Anxiety Scale(HAMA),Arizona Sexual Experience Scale(ASEX),Digit Symbol Substitution Test(DSST),Perceived Deficit Questionnaire for Depression(PDQ-D)at baseline,1-week,2-week,4-week,and 6-week treatment.The Treatment Emergent Symptom Scale(TESS)were performed to assess safety and tolerability of 6-week treatment.At baseline and 4-week,BMI,blood glucose,lipids,liver function,serum prolactin levels were recorded and assessed.Results:(1)The HAMD-17 and HAMA scores of the combination group were statistically lower than the monotherapy group at 1-week,2-week,4-week,6-week(P<0.05).After 6 weeks of treatment in both groups,the treatment efficiency was higher in the combination group than in the monotherapy group(71.4% VS.60.7%),but the overall distribution of efficiency was not significantly different between the two groups(χ~2=1.983,P=0.389),and there was no statistical difference in the invalidation rate,improvement rate,and cure rate in both groups(P>0.05).Repeated ANOVA showed that time and group factors had significant effects in HAMD-17 and HAMA(P<0.05),and there was interaction between time and group factors in HAMD-17 and HAMA(P<0.05).(2)The ASEX scores decreased at 4-week,and 6-week in the combination group compared with baseline(P<0.05),and there was no significant difference in the ASEX scores before and after treatment in the monotherapy group(P>0.05).(3)The DSST and PDQ-D scores at 4-week and 6-week in the combination group were significantly different from baseline(P<0.05),and there was no significant difference in the DSST and PDQ-D scores before and after treatment in the monotherapy group(P>0.05).(4)There was no evident difference in the incidence of adverse reactions between the two groups(χ~2=6.690,P=0.713).(5)Repeated ANOVA showed that BMI,total cholesterol levels,and triglyceride levels increased significantly over time in both groups(F=5.153～7.387,P>0.05).Time,group factors and interaction between time and group factors had no significant effects in both groups(P>0.05),and there was interaction between time and group factors in HAMD-17 and HAMA(P<0.05).There were no significant effect on BMI,fasting blood glucose,lipids,liver function levels and serum prolactin levels in the combination group compared with the single drug group before and after treatment(F=0.002 ～1.849,P>0.05).There were no significant differences in BMI,fasting blood glucose,lipids,liver function levels,the serum prolactin levels and the difference in serum prolactin levels at baseline and 4-week between the combination group and the monotherapy group(P > 0.05).Conclusions: Compared with venlafaxine,the initial combination of venlafaxine with tandospirone in the treatment of patients with major depressive disorder can improve the efficacy,shorten the onset of action,have a good safety profile,improve sexual and cognitive function.BMI,total cholesterol,and triglyceride levels increased over time in the combination group,but were not significantly different from the monotherapy group.There was no significant effect on BMI,fasting blood glucose,liver function,or serum prolactin levels in both groups.