Acupunture Based On Soothing Liver Qi And Regulating Spirit Theory In Treating Depression Related Insomnia

Objective1. Through the modern literature study, to explore the law of acupoints selection in the treatment of depression related insomnia with acupuncture.2.To evaluate the efficacy and safety of acupuncture based on Soothing Liver Qi and Regulating Spirit Theory in depression related insomnia.Methods1. Literature researchElectronic databases were searched in English and Chinese, which were CNKI, CBM, VIP, Wanfang, PubMed, Web of science, and Cochrane Library. Articles relating to depression related insomnia about acupuncture treatment were collected. After bibliometric analysis, the law of the acupoints selection was explored by using data mining technology.2. Clinical study(1) PatientsPatients were recruited from the clinic of Guangdong Province Hospital TCM during May 2015 to March 2016.(2) Randomizing, grouping and blinding methodTotal 120 cases of depression related insomnia patients were randomly assigned to one of the four groups:acupuncture group based on Soothing Liver Qi (group A), Regulating Spirit Theory (group B), Soothing Liver Qi and Regulating Spirit Theory (Group C), and minimal acupuncture (Group D) in a ratio of 1:1:1:1. Neither the valuator nor the data analyst knew the grouping.(3) intervention measuresGroup AAcupoints:DU20(Baihui), EX-HN03(Yintang), LI4(Hegu), LR3(Taichong), BL18(Ganshu).Manipulation:after sterilizing, acupuncture was applied at acupoints DU20, EX-HN03, LI4, LR3, and BL18 using tube needles. Manipulations were done to achieve de-qi sensation. The needles were maintained in the acupoints for 30 minutes. The size of the needles was 0.30X25mm. After removing the needles, the embedded needles were inserted into the BL18 acupoints and fixed with medical proof fabric.Group BAcupoints:HT7 (Shenmen), SP6 (Sanyingjiao), N-HN-54 (Anmian), BL15 (Xinshu)Manipulation:after sterilizing, after sterilizing, acupuncture was applied at acupoints HT7, SP6, and N-HN-54 using tube needles. Manipulations were done to achieve de-qi sensation. The needles were maintained in the acupoints for 30 minutes. The size of the needles was 0.30X25mm. After removing the needles, the embedded needles were inserted into the BL15 acupoints and fixed with medical proof fabric.Group CAcupoints:DU20(Baihui), EX-HN03(Yintang), LI4(Hegu), LR3(Taichong), HT7(Shenmen), SP6 (Sanyingjiao), N-HN-54 (Anmian), BL18 (Ganshu), BL15 (Xinshu)Manipulation:Combining the manipulations in Group A and Group B.Group DAcupoints:acupoints one inch lateral to these point- DU20(Baihui), EX-HN03(Yintang), LI4(Hegu), LR3(Taichong), BL18(Ganshu).Manipulation:after sterilizing, acupuncture was applied at the sham acupoints DU20, EX-HN03, LI4, LR3, and BL18 using tube needles. The needle inserted into the skin for only 2 to 3 mm. The needles were maintained in the acupoints for 30 minutes. The size of the needles was 0.30X25mm. After removing the needles, the sham embedded needles were fixed with medical proof fabric.(3) Sessions and follow-upThe patients received the treatments 2 times a week for 5 weeks a course, and the treatment interval was more than 48 hours. There were total 2 courses and the follow-up last for 4 weeks.(4) The outcomes and the observation timePittsburgh sleep quality index scale (PSQI), Hamilton depression rating table (HAMD) and Self Rating Depression Scale (SDS) were completed by all the patients in baseline, week 5, week 10 and week 14. And the daily dose of the hypnotics was recorded, also the adverse reaction.(5) Statistical analysisData analysis was done by intention to treat(ITT) using SPSS 17.0. And the primary outcomes also applied per-protocol analysis(PP). Regarding clinical-demographic features, continuous data were expressed as mean ±SD and significant differences among groups was assessed using the One-Way ANOVA test or Kruskal-Wallis H test according to the results of Gaussian distribution test and homogeneity test of variances. Non-continuous data were expressed as percentages and the comparison among groups was performed using Chi-square Test or Fisher’s Exact Test. The differences on HAMD, PSQI, SDS, and the average daily dose of the hypnotics among groups and different times were done by Repeated ANOVA Test. And the significant differences among groups at different times were assessed using the One-Way ANOVA test or Kruskal-Wallis H test. The significant differences among groups on efficacy was assessed using Rank-sum Test.Results1.literature researchOf the 2164 articles retrieved,76 articles were included in the study. Bibliometric statistics found that the number of the articles on this field was increasing. And the present researches mainly focused on clinical observation, mainly comparing the effects of acupuncture with Western medicine. The most frequently used therapies were acupuncture, electro-acupuncture and auricular therapy. The most widely applied assessment for insomnia was PSQI scale, and HAMD, SDS for depression.The study found that the most commonly used acupoints were DU20 (Baihui), HT7 (Shenmen), EX-HN01(Sishencong), EX-HN3(Yintang), SP6(Sanyinjiao), PC6(Neiguan), ST36(Zusanli), LR3(Taichong), and N-HN-54(Anmian). And there were some pairs of acupoints appearing together in the treatments, which were DU20-EX-HN03, HT7-SP6, HT7-PC6, HT7-N-HN-54, and LI4-LR3. The main points could be sorted into three groups by cluster analysis. And the first group consisted of Baihui and Yintang, which impling the principle of regulating the mind, the second group consisted of HT7, SP6 and PC6, which impling the principle of nourishing heart, and the third group consisted of ST36, KI6, BL62, LR3, LI4, DU24, N-HN-54 and EX-HN1, which impling the principle of modifying the prescription according to the syndrome differentiation.2. clinical researchA total of 105 cases finished the whole treatments and follow-up, and 15 cases fell off or were eliminated. There were 8 cases in group D,3 cases in group B,4 in group C, and 0 in group A. The comparison showed no significantly differences among the groups.(1) baselineAt baseline, there were no significantly differences among the groups on age, gender, marital status, occupation, history of chronic disease, insomnia history, depression history, course of disease, previous treatment, drug use, PSQI score, HAMD and SDS score, indicating that the groups could be compared.(2) PSQI scale①Total scoreThe ITT anlysis suggested:Four groups could all reduce the total score of PSQI scale. The comparison did show a significantly trend toward improvement in PSQI in all the four groups (P<0.05).The PSQI score showed significantly differences between group A and group D, and also group C and group D at week 10 and week 14(P<0.05).The PP anlysis also suggested the same results in all the four groups. And the differences between groups were the same at week 5 and week 10. While The PSQI score showed significantly differences between group A and group D, group B and D, and also group C and group D at week 10 and week 14 (P<0.05).②PSQI-sleep quality (SQ)Group A, group B and group C could all reduce the score of sleep quality dimension of PSQI scale. The comparison did show a significantly trend toward improvement in all the three groups, but no significantly differences in group D.The comparison showed significantly differences between group A and group D at week 10 and week 14(P<0.05).③PSQI-sleep latency (SL)Group A, group B and group C could all reduce the score of sleep latency dimension of PSQI scale. The comparison did show a trend toward improvement in group A and C at every evaluation(P<0.05). While in group B, the comparison showed no significantly difference between baseline evaluation and 5-week evaluation(P>0.05). But there were significantly differences when 10-week evaluation and 14-week evaluation comparing with baseline evaluation(P< 0.05).The comparison showed no differences among the groups in every evaluation.④PSQI-sleep duration (SD)Four groups could all reduce the score of sleep duration dimension of PSQI scale. The comparison did show a trend toward improvement in group A and B at every evaluation(P<0.05). While in group C and group D, the comparison only showed significantly difference between baseline evaluation and 10-week evaluation(/<0.05).The comparison showed no differences among the groups in every evaluation.⑤PSQI-habitual sleep efficiency(HSE)Group B and group C could both reduce the score of habitual sleep efficiency dimension of PSQI scale. In group B, the comparison showed significantly differences when 10-week evaluation and 14-week evaluation comparing with baseline evaluation(P<0.05). In group C, the comparison showed significantly differences between baseline evaluation and 10-week evaluation(P<0.05).The comparison showed no differences among the groups in every evaluation(P>0.05).⑥PSQI-sleep disturbances (SDI)Group A, group B and group C could all reduce the score of sleep disturbances dimension of PSQI scale. The comparison did show a trend toward improvement in group A and C at every evaluation(P<0.05). While in group B, there were only significantly differences when 10-week evaluation and 14-week evaluation comparing with baseline evaluation (P<0.05).The PSQI score showed significantly differences between group A and group D, and also group C and group D at week 10 and week 14(P<0.05).⑦PSQI-use of sleep medications (SM)Group A could all reduce the score of sleep medications dimension of PSQI scale. In group A, the comparison showed significantly differences when 10-week evaluation and 14-week evaluation comparing with baseline evaluation (P<0.05).The comparison showed no differences among the groups in every evaluation.⑧PSQI-daytime dysfunction (DD)Group A, group B and group C could all reduce the score of daytime dysfunction dimension of PSQI scale. The comparison did show a significantly trend toward improvement in group A and C at every evaluation(P<0.05). While in group B, there were only significantly differences when 10-week evaluation and 14-week evaluation comparing with baseline evaluation(P<0.05).At 5th week, there was significantly differences between the group B and D (P<0.05). While at week 10 and week 14, there were significantly differences between group A and D(P<0.05).(2) HAMD scaleFour groups could all reduce the score of HAMD scale. The comparison did show a trend toward improvement in all the three groups.The ITT anlysis suggested:The comparison showed no differences among the groups in the 5-week evaluation. After 10-weeks treatment and 4-weeks follow-up, there were significantly differences between group A and D, group B and C, and group C and D. But there was also significantly differences between group B and D at week 14(P<0.05).The PP anlysis also suggested the same results in all the four groups. And the differences between groups were the same at week 10 and week 14. While The PSQI score showed no significantly differences between groups.(3) SDS scaleFour groups could all reduce the score of SDS scale. The comparison did show a trend toward improvement in group A, group B and group C. While in group D show a signigucant trend toward going back at week 14.The comparison showed no differences among the groups in the 5-week evaluation. After 10-weeks treatment and 4-weeks follow-up, the total score of HAMD scale in the group C was significantly lower than that in the group B, and also lower in group C than in group D.(4) the average daily dose of hypnoticsGroup B and group C could both reduce the average daily dose of hypnotics. The comparisons did show a trend toward improvement in group B at week 5 and week 10, and a trend toward improvement in group C in every evaluation.The comparison showed difference between group C and D in the 5-week evaluation. After 10-weeks treatment and 4-weeks follow-up, the score of HAMD scale in the group A was significantly lower than that in the group D, and also lower in group C than in group B and lower in group C than in group D.(5) effective rate①Effective rate based on PSQI scale:The ITT anlysis showed that effective rates in group A, B, C and D were 66.7%,50.0%,56.7%, and 16.7%, relatively at week 10, and 60.0%,40.0%,56.7% and 6.7%, relatively at week 14. The comparisons showed differences between group A and D, and also group C and D at week 10 and week 14. And there was also difference between group group B and D and week 14. The PP anlysis showed that effective rates in group A, B, C and D were 66.7%,55.5%,65.4% and 22.7% relatively, at week 10, and60.0%, 40.8%,61.6% and 9.1%, relatively, at week 14. The comparisons showed same differences between groups as the ITT anlysis at week 10, while did not show difference between group group B and D and week 14.②Effective rate based on HAMD scale:The ITT anlysis showed that effective rates in group A, B, C and D were 90.0%,70.0%,83.3%, and 50.0%, relatively at week 10, and 86.7%,73.3%,90.0% and 23.3%, relatively at week 14. The comparisons showed differences between group A and D, group B and C, and also group C and D at week 10 and week 14. The PP anlysis showed that effective rates in group A, B, C and D were 90%,70.4%,84.6% and 59% relatively, at week 10, and 86.7%,74.1%,96.2% and 14.6%, relatively, at week 14. The comparisons showed same differences between groups as the ITT anlysis.(6) safetyThe total incidence of adverse events was 10.83%. The adverse events were hematoma, Needle-sickness, headache and local pain. There was no significant difference in the incidence of adverse reactions among the groups.Conclusion1. Literature study found that the most commonly used acupoint-pairs are Baihui-Yintang, Shenmen-Sanyingjiao, Shenmen-Anmian, and Hegu-Taichong. And there maybe three principles while treating insomnia relating to depression, which are regulating liver qi, nourishing heart and modifying the prescription according to the syndrome differentiation.2. Clinical trials found that all the groups maybe effective in improving reported sleep quality and reducing depressive symptoms in depression related insomnia, and maybe more effective than minimal acupuncture. While Group A and Group C maybe more effective than group B on sleep quality, and Group C maybe the most effective group on depressive symptoms, and then is Group A, followed by Group B.