The Clinical Research And Advantages Of Acupuncture And SSRIs In The Treatment Of Depression

ObjectivesAs a common mental illness,depression lead to heavy burden on human society.At present,the effectiveness and acceptability of first-line antidepressants are not satisfactory.Clinical trials have revealed that acupuncture has a safe and effective antidepressant effect,but the methodological quality of previous clinical studies in acupuncture for depression was considered to be generally low.In this study,a multicenter,prospective,large sample size,practical randomized controlled trial and a brain magnetic resonance imaging study were conducted to explore:(1)the overall effectiveness,early onset profile,and safety of manual acupuncture(MA)/electroacupuncture(EA)added on SSRIs antidepressants in patients with moderate to severe depression;(2)the improvement on clinical symptom clusters and quality of life in depressed patients by add-on MA/EA;(3)the treatment outcomes of add-on MA/EA in depressed patients with or without anxiety characteristics;(4)the different manifestations on brain structural imaging in depressed patients with or without anxiety characteristics.The purpose of this study is to reveal the clinical advantages of add-on acupuncture in the treatment of depression.Methods1.Randomized controlled trial477 first episode,moderate to severe depressive outpatients were allocated into MA+Selective serotonin reuptake inhibitors(SSRIs)group(N=161),EA+SSRIs group(N=160),and SSRIs alone group(N=156)with a ratio of 1:1:1.Usual dosage of oral SSRIs was used as basic treatment in all the three groups.In addition to SSRIs,MA and EA treatments were given to MA+SSRIs group and EA+SSRIs group respectively,30minutes per session,three sessions per week.The treatment period was six weeks.Patients were followed for another four weeks.Outcome measures were 17-item Hamilton Depression Scale(HAMD-17,included retardation,cognitive impairment,anxiety/somatization,sleep disturbance,and weight factors),Self-Rating Depression Scale(SDS),Clinical Global Impression(CGI);Rating Scale for Side Effects(SERS),and WHO Quality of Life-BREF(WHOQOL-BREF).The drug usage and adverse events during treatment were also recorded.In the secondary analysis,the anxious depression(AD,N=374)subgroup and nonanxious depression(NAD,N=91)subgroup were divided by the anxiety/somatization factor score(?7:AD;<7:NAD)of HAMD-17.2.Brain magnetic resonance imaging study40 first diagnosis depressive outpatients and 22 healthy controls(HC)were enrolled.All subjects underwent brain MRI scan and were assessed with HAMD-24 scale.According to the anxiety/somatization factor score(?7:AD;<7:NAD)of HAMD-24,patients were allocated to AD group(N=19)and NAD group(N=21).Voxel-based morphology(VBM)analysis was used to compare the gray matter volume among the three groups,and the correlation between the HAMD-24 anxiety/somatization factor score and the gray matter volume of all subjects was analyzed.Results1.Randomized controlled trial(1)Overall effectiveness:At the end of the 6th week,the HAMD-17 response rate of MA+SSRIs group and EA+SSRIs group were significantly higher than SSRIs alone group(P=0.013,P=0.0014).There was no significant difference between the two acupuncture groups(P>0.05).(2)Early onset profile:At the end of the 1st week,the HAMD-17 early onset rate of MA+SSRIs group and EA+SSRIs group were significantly higher than SSRIs alone group(P<0.0001,P<0.0001).There was no significant difference between the two acupuncture groups(P>0.05).(3)Safety:At the end of the 6th week,physical tiredness,tremor,dry mouth,constipation,and somnolence of SERS scale were less severe in the two acupuncture groups than in the group taking SSRIs alone(P<0.05).In addition,there were significantly fewer sexual problems in the MA+SSRIs group than in SSRIs alone group(P<0.01).There were significantly fewer headaches,sleep disorders,and episodes of dizziness in EA+SSRIs group than in SSRIs alone group(P<0.05).There were 28 cases of adverse events in total,9,10,and 9 each in MA+SSRIs,EA+SSRIs and SSRIs alone groups.(4)Clinical symptom clusters:? Retardation factor:The improvement in MA+SSRIs group was significantly better than that of SSRIs alone group in general,except for the 2nd week(P<0.05).The improvement in EA+SSRIs group was also significantly better than SSRIs alone group at the 4th and 10th week(P<0.05).? Cognitive impairment factor:There was no significant difference among the three groups(P>0.05).?Anxiety/somatization factor:The improvement in EA+SSRIs group was all the way significantly better than that of SSRIs alone group(P<0.05).? Sleep disturbance factor:The improvement in EA+SSRIs group was all the way significantly better than that in SSRIs alone group(P<0.01),and it was also significantly better than that in MA+SSRIs group at the 10th week(P=0.024).The improvement in MA+SSRIs group was also significantly better than that in SSRIs alone group at the 1st and 2nd week(P<0.05).? Weight factor:There was no significant difference among the three groups(P>0.05).(5)Quality of life:At the end of the 6th week,EA+SSRIs group produced a significantly improvement in overall quality of life,general health,physical health,and psychological health compared with SSRIs alone group(P<0.05).In MA+SSRIs group,only improvement in psychological health was superior to SSRIs alone group(P=0.023).No significant differences was observed in the fields of social relationships and environment domains among these three groups(P>0.05).(6)Secondary analysis:At baseline,80.4%patients met the criterion of AD subgroup.AD subgroup reported a lower history of self-injury than NAD subgroup(P=0.013).Most variables of AD subgroup reflected more severe depressive severity and lower quality of life(P<0.05).After treatment,there was no significant difference in terms of HAMD response rate between AD subgroup and NAD subgroup(P>0.05).Compared to NAD.subgroup,patients from AD subgroup had lower HAMD-17 remission rate(P<0.001)and early onset rate(P=0.045),and a higher incidence of adverse events(RR=3.16).In AD subgroup,both MA+SSRIs and EA+SSRIs groups were significantly better than SSRIs alone in HAMD scores(response rate,remission rate,early onset rate,and total scores),SDS total scores(except for the 1st week in EA+SSRIs group),CGI scores,SERS total scores and psychological health of WHOQOL-BREF(P<0.05),while no significant difference was observed between the two acupuncture groups(P>0.05).In addition,the overall quality of life,physical health,and environment in EA+SSRIs group were significantly better than SSRIs alone group(P<0.05).There was no significant difference among the three groups in other indexes(P>0.05).In the NAD subgroup,the two acupuncture groups were significantly better than SSRIs alone group in HAMD-17early onset rate and total score at the 1st week(P<0.05),while the two acupuncture groups did not significantly differ(P>0.05).In addition,the SDS total scores at all time points and SERS total score at the 4th week were significantly better than SSRIs alone group(P<0.05).There was no significant difference among the three groups in other indexes(P>0.05).2.Brain magnetic resonance imaging study(1)Brain gray matter volume comparisons:? Compared with HC group,there was no brain region with increased gray matter volume in AD group,while the gray matter volume of right inferior temporal gyrus,right fusiform gyrus,right caudate nucleus,and left middle occipital gyrus was decreased in AD group.? Compared with HC group,the gray matter volume of right temporal pole and right middle temporal gyrus was increased in NAD group;while the gray matter volume of left inferior orbitofrontal gyrus,right middle frontal gyrus,right triangular inferior frontal gyrus,right precuneus,and right paracentral lobule was decreased.? Compared with NAD group,the gray matter volume of left upper cerebellum,left lingual gyrus,and right inferior orbitofrontal gyrus was increased in AD group;while the gray matter volume of bilateral inferior temporal gyrus and bilateral fusiform was decreased.(2)Correlation analysis:There were significantly negatively correlation between HAMD-24 anxiety/somatization factor scores and the gray matter volume of bilateral caudate nucleus in all subjects(r=0.49,P=15.8×10-5).Conclusions1.In a large sample randomized controlled trial,our study firstly provided scientific and rigorous evidence-based medical evidence for the further application of add-on acupuncture therapies,confirmed that MA/EA added on SSRIs antidepressants could significantly enhance the effectiveness of SSRIs in patients with moderate to severe primary depression,had a rapid onset,and was safe and acceptable.2.Our study found the characteristics and clinical advantages of add-on MA/EA,which could be used as clear suggestions for clinicians to accurately select personalized treatment protocols before treatment begin.Add-on MA demonstrated more effectiveness in impro-ving retardation cluster,while add-on EA manifested more improvement in anxiety,somatization,and sleep disturbance clusters.Both the two add-on acupuncture treatments could improve psychological health,while add-on EA could also improve the overall quality of life,general health,and physical health.3.Our study firstly put forward the feasible treatment suggestions with clinical significance and practical value of add-on MA/EA for the treatment of AD/NAD by the dimensional approach.For patients with AD,which accouncted for a high proportion and was difficult to treat,add-on MA/EA could accelerate treatment response,enhanced therapeutic effects,improved quality of life,and effectively reduced adverse effects of antidepressants.The two add-on acupuncture treatments provided new treatment strategies to solve the great clinical challenge of AD.Meanwhile,for patients with NAD,both add-on acupuncture treatments had a faster onset.EA could also continuously improve subjective experience in NAD patients.4.In this study,the specific characteristics of brain regions in patients with AD/NAD were explored by a brain magnetic resonance imaging study and a dimendional approach,and found that there were different brain structural imaging manifestations in first diagnosis,drug naive depressed patients with or without high level of anxiety symptoms.Our study provided imaging exploring direction for further identification of AD in clinical diagnosis and precise treatment.