柴胡桂枝汤治疗以疼痛为主诉的广泛性焦虑症的临床研究
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摘要
目的：
本研究通过调查广州市中医医院就诊的以疼痛躯体症状(Painful Physical Symptoms, PPS)为主诉的广泛性焦虑症(Generalized Anxiety Disorder, GAD)患者的现状,了解患者的一般资料特点：通过随机平行对照临床研究,评价柴胡桂枝汤对以PPS为主诉的GAD患者的临床疗效和安全性。
方法：
从2010年9月至2012年2月,我们对广州市中医医院就诊的215例无PPS的GAD患者以及153例以PPS为主诉的GAD患者进行了调查,使用自制的一般情况问卷采集患者的一般信息(性别、血型、年龄、婚姻状况、职业、文化程度、收入水平、病程),通过汉密顿焦虑量表(Hamilton Anxiety Scale, HAMA)、简化McGill疼痛询问量表(Short-form of McGill Pain Questionnaire, SF-MPQ)、社会功能缺陷筛选量表(Social Disability Screening Schedule, SDSS)分别了解患者的焦虑状况、疼痛特点、社会功能缺陷情况。
接下来,将广州市中医医院就诊的80例以PPS为主诉的肝气郁结型GAD患者按照1：1的比例随机分为两组,试验组使用柴胡桂枝汤进行治疗(n=40),对照组使用氟哌噻吨美利曲辛进行治疗(n=40),疗程为6周,分别在治疗前、治疗2周后、4周后、6周后及停药2周后使用HAMA、SF-MPQ、SDSS、中医证候量表评价临床疗效,治疗前和治疗6周后使用治疗副反应量表(Treatment Emergent Symptom Scale, TESS)评价药物安全性。
使用SPSS13.0统计软件对结果进行统计描述和统计分析。研究中使用了配对资料与独立资料t检验、配对资料与独立资料秩和检验,以及x2检验等统计分析方法。
结果：
1.一般资料特点：
(1)GAD患者男女比例约为1：2,两类GAD患者的性别比例经χ2检验无显著统计学差异(P>0.05)；
(2)GAD患者以已婚者居多,二者的婚姻状况经x2检验(Fisher确切概率法)无显著统计学差异(P>0.05)；
(3)GAD患者血型以0型血居多,二者的血型分布经x2检验无显著统计学差异(P>0.05)：
(4)GAD患者年龄以36-55岁居多,二者的年龄构成经秩和检验无显著统计学差异(P>0.05)；
(5)以PPS为主诉的GAD患者的教育水平以本科以下居多,文化水平低于无PPS的GAD患者,结果经秩和检验有显著统计学差异(P<0.05)；
(6)以PPS为主诉的GAD患者中无业、退休人员、个体户、农民所占比例高于无PPS的GAD患者,结果经χ2检验有显著统计学差异(P<0.05)；
(7)以PPS为主诉的GAD患者低收入人群所占比例明显高于无PPS的GAD患者,结果经秩和检验有显著统计学差异(P<0.05)；
(8)以PPS为主诉的GAD患者病程明显长于不合并PPS的GAD患者,结果经秩和检验有显著统计学差异(P<0.05)；
(9)两类患者中气郁化火型所占比例基本相同,结果经x2检验无显著统计学差异(P>0.05),以PPS为主诉的GAD患者中肝气郁结型所占比例明显高于无PPS的GAD患者(P<0.01),而后者中心脾两虚型、忧郁伤神型、和阴虚火旺型所占比例均高于前者,结果经x2检验有显著统计学差异(P<0.01,P<0.05,P<0.05)。
(10)以PPS为主诉的GAD患者的HAMA评分、HAMA精神焦虑因子评分高、HAMA躯体焦虑因子评分、SDSS评分均高于无PPS的GAD患者,经t检验有显著统计学差异(P<0.01,P<0.05,P<0.01,P<0.01)。
(11)不同中医证型的疼痛程度分布结果经x2检验有高度显著统计学差异(P<0.01)。
2.在降低HAMA评分方面,全分析集(Full Analysis Set, FAS)显示,柴胡桂枝汤与氟哌噻吨美利曲辛治疗2周后均可取得明显的临床疗效,结果经秩和检验均有高度显著统计学差异(P<0.01)；
柴胡桂枝汤治疗4周后的临床疗效明显优于治疗2周后,结果经秩和检验有高度显著统计学差异(P<0.01),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效则与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
氟哌噻吨美利曲辛治疗4周后的临床疗效与治疗2周后基本相等,结果经秩和检验无显著统计学差异(P>0.05),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
柴胡桂枝汤治疗2周后、4周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无显著统计学差异(P>0.05),治疗6周后、回访时的临床疗效则优于氟哌噻吨美利曲辛,结果经秩和检验有显著统计学差异(P<0.05)；
符合方案数据分析集(Per-Protocol PoPulation Set, PPS)略有不同,柴胡桂枝汤治疗2周后、4周后、6周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效则优于氟哌噻吨美利曲辛,结果经秩和检验有显著统计学差异(P<0.05)。
3.在降低SF-MPQ评分方面,FAS显示,柴胡桂枝汤与氟哌噻吨美利曲辛治疗2周后即可取得明显的临床疗效,结果经秩和检验有高度显著统计学差异(P<0.01)；
柴胡桂枝汤治疗4周后的临床疗效明显优于治疗2周后,结果经秩和检验有高度显著统计学差异(P<0.01),治疗6周后的临床疗效明显优于治疗4周后,结果经秩和检验有高度显著统计学差异(P<0.01),回访时的临床疗效则与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
氟哌噻吨美利曲辛治疗4周后的临床疗效优于治疗2周后,结果经秩和检验有显著统计学差异(P<0.05),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
柴胡桂枝汤治疗2周后、4周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无显著统计学差异(P>0.05),柴胡桂枝汤治疗6周后、回访时的临床疗效则明显优于氟哌噻吨美利曲辛。结果经秩和检验有高度显著统计学差异(P<0.01)。
PPS所得结论与FAS分析集基本相同。
4.在降低SDSS评分方面,FAS显示,柴胡桂枝汤与氟哌噻吨美利曲辛治疗2周后即可取得明显的临床疗效,结果经秩和检验有高度显著统计学差异(P<0.01)；
柴胡桂枝汤治疗4周后的临床疗效明显优于治疗2周后,结果经秩和检验有高度显著统计学差异(P<0.01),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效则与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
氟哌噻吨美利曲辛治疗4周后的临床疗效与治疗2周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
柴胡桂枝汤治疗2周后、4周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无业显著统计学差异(P>0.05),治疗6周后、回访时的临床疗效则优于氟哌噻吨美利曲辛,结果经秩和检验有显著统计学差异(P<0.05)。PPS所得结论与FAS分析集基本相同。
5.在降低中医证候评分方面,FAS显示,柴胡桂枝汤与氟哌噻吨美利曲辛治疗2周后即可取得明显的临床疗效,结果经秩和检验有高度显著统计学差异(P<0.01)；
柴胡桂枝汤治疗4周后的临床疗效明显优于治疗2周后,结果经秩和检验有高度显著统计学差异(P<0.01),治疗6周后的临床疗效优于治疗4周后,结果经秩和检验有显著统计学差异(P<0.05),回访时的临床疗效则与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
氟哌噻吨美利曲辛治疗4周后的临床疗效与治疗2周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
柴胡桂枝汤治疗2周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无业显著统计学差异(P>0.05),治疗4周后、6周后、回访时的临床疗效则优于氟哌噻吨美利曲辛,结果经秩和检验有显著统计学差异(P<0.05,P<0.01,P<0.01)。
PPS略有不同,柴胡桂枝汤治疗2周后、4周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无显著统计学差异(P>0.05),柴胡桂枝汤治疗6周后、回访时的临床疗效则优于氟哌噻吨美利曲辛,结果经秩和检验有高度显著统计学差异(P<0.01)。
6.两组患者无严重不良反应。治疗组的常见不良反应为口干、厌食,对照组的常见不良反应为失眠、口干、震颤、焦虑、头晕、厌食以及疲乏,两组不良反应经x2检验(Fisher确切概率法)无显著统计学差异(P>0.05)。
结论：
1.教育程度低,收入水平低,职业为无业、退休人员、个体户、农民,肝气郁结型的GAD患者更易出现PPS,以PPS为主诉的GAD患者病程明显长于无PPS的GAD患者,且焦虑情况和社会功能缺陷更为严重。PPS的主要病机是气机不畅。
2.柴胡桂枝汤在改善以PPS为主诉的肝气郁结型GAD患者的焦虑症状、疼痛症状、社会功能以及中医证候方面疗效可靠,尤其是疼痛症状和中医证候可获得持续性的改善。
3.柴胡桂枝汤与氟哌噻吨美利曲辛治疗以PPS为主诉的肝气郁结型GAD起效较快,短期疗效基本相当,而柴胡桂枝汤的远期疗效明显优于氟哌噻吨美利曲辛。
4.柴胡桂枝汤与氟哌噻吨美利曲辛治疗以PPS为主诉的肝气郁结型GAD均无明显不良反应。
Objective
The present study is to explore the profile of generalized anxiety disorder patients with painful physical symptoms in a TCM hospital, and to investigate the efficacy and safety of Chaihu Guizhi Decoction on the syndrome of Stagnation of liver Qi in GAD with PPS.
Methods
First, we investigated215GAD patients with PPS and153without PPS from September2010to February2012in Guangzhou Hospital of Traditional Chinese Medicine. A self-designed questionnaire was used which covers the information of age, gender, blood type, marital status, occupation, educational background, economic conditions and duration of GAD. GAD was assessed by Hamilton Anxiety Scale (HAMA), PPS was assessed by Short-form of McGill Pain Questionnaire (SF-MPQ) Social Disability was assessed by Social Disability Screening Schedule (SDSS).
Next,80cases with the syndrome of stagnation of liver qi in GAD Patients with PPS were randomly assigned into study group (n=40), treated by Chaihu Guizhi Decoction and control group (n=40), treated by Flupentixol and Melitracen Tablets for6weeks. HAMA, SF-MPQ, SDSS and self-designed TCM Syndromes Scale were used to evaluate the efficacy of Chaihu Guizhi Decoction. Treatment Emergent Symptom Scale (TESS) was used to assess side effects. Assessments began at baseline, and the2nd,4th and6th weekend as well as2week later after a withdrawal.
All statistical analyses were performed by SPSS13.0software, including t-tests, Wilcoxon singed-rank tests, Wilcoxon rank sum tests, x2tests and tests of Fisher's exact probability.
Results
1. There are no difference on Age, gender, blood type, marital status between GAD patients with PPS and the group without PPS (P>0.05), but occupation, educational background, economic conditions, course of the disease, TCM syndromes, HAMA scores, SDSS scores were found some difference (P<0.05).
2. In the Full Analysis Set (FAS), we found that HAMA score of both2groups decreased significantly after treatment (P<0.01).
In the4th weekend after treatment, the effect of study group was better than in the2nd weekend (P<0.01). The effect in study group had no significant difference in the4th and6th weekend after treatment (P>0.05), as well as in the6th weekend after treatment and2nd weekend after withdrawal (P>0.05).
The effect of control group had no significant difference in the2nd,4thweekend after treatment (P>0.05), as well as in the4th,6thweekend after treatment (P>0.05), and had no significant difference between the6th weekend after treatment and2nd weekend after withdrawal (P>0.05).
In the2nd,4thweekend after treatment, the effect between2groups had no significant difference (P>0.05). At the6th weekend after treatment and2nd weekend after withdrawal, the effect of study group was better than that in control group (P<0.05).
But Per-Protocol Population Set (PPS), revealed a different result. In the2nd,4th,6th weekend after treatment, the effect between2groups had no significant difference (P>0.05). In the2nd weekend after withdrawal, the effect of study group was better than control group (P<0.05).
3. Full Analysis Set (FAS) showed that SF-MPQ score of both groups decreased significantly after treatments (P<0.01).
The effect of study group in the4th weekend was better than that in the2nd weekend after treatment (P<0.01), and that in the6th weekend was better than that in the4th weekend (P<0.01), and there was no significant difference between the6th weekend and2nd weekend after withdrawal (P>0.05).
In the4th weekend after treatment, the effect of control group was better than that in the2nd weekend (P<0.05), but has no significant difference compared with that in6thweekend (P>0.05), and no difference between that in the6th weekend and that in2nd weekend after withdrawal (P>0.05).
In the2nd,4thweekend, the effect between2groups had no significant difference (P>0.05). In the6th weekend after treatment and2nd weekend after withdrawal, the effect of study group was better than control group (P<0.01).
This study gained the same results from the Per-Protocol Population Set (PPS).
4. In the Full Analysis Set (FAS), we found that SDSS score of both2groups after therapy decreased significantly (P<0.01).
In the4th weekend after treatment, the effect of study group was better than in the2nd weekend after treatment (P<0.01). In the6th weekend after treatment, the effect of study group was same as in the4th weekend after treatment (P>0.05). The effect of study group had no significant difference in the6th weekend after treatment and2nd weekend after withdrawal (P>0.05). The effect of control group had no significant difference in the2nd,4thweekend after treatment (P>0.05).
The effect of control group had no significant difference in the4th6thweekend after treatment (P>0.05). The effect of control group had no significant difference in the6th weekend after treatment and2nd weekend after withdrawal (P>0.05).
In the2nd,4thweekend after treatment, the effect between2groups had no significant difference (P>0.05). In the6th weekend after treatment and2nd weekend after withdrawal, the effect of study group was better than comparative group (P<0.05).
There were same results in the Per-Protocol PoPulation Set (PPS).
5. In the Full Analysis Set (FAS), we found that TCM syndromes score of both2groups decreased significantly after treatment (P<0.01).
In the4th weekend, the effect of study group was better than that in the2nd weekend (P<0.01), and that in the6th weekend was better than that in the4th weekend (P<0.05). Study group had no different results in the6th weekend and in the2nd weekend after withdrawal (P>0.05).
The effect of control group had no significant difference in the2nd and the4thweekend after treatment (P>0.05), and no significant difference in the4th and the6thweekend (P>0.05), and no significant difference in the6th weekend and in the2nd weekend after withdrawal (P>0.05).
In the2nd weekend, the effect between2groups had no significant difference (P>0.05). But in the4th,6th weekend after treatment and2nd weekend after withdrawal, study group was better than control group (P<0.01).
Otherwise, Per-Protocol Population Set (PPS), revealed some difference. In the2nd and the4th weekend after treatment, the effect between2groups had no significant difference (P>0.05), but study group was better than control group in the6th weekend and the2nd weekend after withdrawal (P<0.05, P<0.01, P<0.01).
6. There were no serious side effects in both groups. The side effects found in study group were dry mouth, anorexia, and found in control group were insomnia, dry mouth, tremor, anxiety, dizzy, anorexia, fatigue. TESS evaluation revealed that the side effect between two groups had no significant difference(P>0.05).
Conclusion
1. The poorly educated, low income level, jobless, retiree, farmer, self-employed, Stagnation of liver Qi are risk factors for PPS. The patients of GAD with PPS are more anxious and have a longer history and worse social disability than ones without PPS. The main TCM pathogenesis for PPS is stagnation of qi activity.
2. Chaihu Guizhi Decoction has certain effect in the treatment of Liver Qi Stagnation GAD with PPS. This therapy is more effective in releasing symptoms such as anxiety and pain, and has less side-effect compared with Deaxit after6weeks of treatment.
3. Chaihuguizhitang Recipe is an effective therapy in improving anxiety, pain, social disability and chinese symptoms.
4. Chaihuguizhitang Recipe and Deaxit has the same short-time efficacy, but Chaihuguizhitang Recipe are better in long-time.
5. There is minor side-effect in treatment with Chaihuguizhitang Recipe.
本研究通过调查广州市中医医院就诊的以疼痛躯体症状(Painful Physical Symptoms, PPS)为主诉的广泛性焦虑症(Generalized Anxiety Disorder, GAD)患者的现状,了解患者的一般资料特点：通过随机平行对照临床研究,评价柴胡桂枝汤对以PPS为主诉的GAD患者的临床疗效和安全性。
方法：
从2010年9月至2012年2月,我们对广州市中医医院就诊的215例无PPS的GAD患者以及153例以PPS为主诉的GAD患者进行了调查,使用自制的一般情况问卷采集患者的一般信息(性别、血型、年龄、婚姻状况、职业、文化程度、收入水平、病程),通过汉密顿焦虑量表(Hamilton Anxiety Scale, HAMA)、简化McGill疼痛询问量表(Short-form of McGill Pain Questionnaire, SF-MPQ)、社会功能缺陷筛选量表(Social Disability Screening Schedule, SDSS)分别了解患者的焦虑状况、疼痛特点、社会功能缺陷情况。
接下来,将广州市中医医院就诊的80例以PPS为主诉的肝气郁结型GAD患者按照1：1的比例随机分为两组,试验组使用柴胡桂枝汤进行治疗(n=40),对照组使用氟哌噻吨美利曲辛进行治疗(n=40),疗程为6周,分别在治疗前、治疗2周后、4周后、6周后及停药2周后使用HAMA、SF-MPQ、SDSS、中医证候量表评价临床疗效,治疗前和治疗6周后使用治疗副反应量表(Treatment Emergent Symptom Scale, TESS)评价药物安全性。
使用SPSS13.0统计软件对结果进行统计描述和统计分析。研究中使用了配对资料与独立资料t检验、配对资料与独立资料秩和检验,以及x2检验等统计分析方法。
结果：
1.一般资料特点：
(1)GAD患者男女比例约为1：2,两类GAD患者的性别比例经χ2检验无显著统计学差异(P>0.05)；
(2)GAD患者以已婚者居多,二者的婚姻状况经x2检验(Fisher确切概率法)无显著统计学差异(P>0.05)；
(3)GAD患者血型以0型血居多,二者的血型分布经x2检验无显著统计学差异(P>0.05)：
(4)GAD患者年龄以36-55岁居多,二者的年龄构成经秩和检验无显著统计学差异(P>0.05)；
(5)以PPS为主诉的GAD患者的教育水平以本科以下居多,文化水平低于无PPS的GAD患者,结果经秩和检验有显著统计学差异(P<0.05)；
(6)以PPS为主诉的GAD患者中无业、退休人员、个体户、农民所占比例高于无PPS的GAD患者,结果经χ2检验有显著统计学差异(P<0.05)；
(7)以PPS为主诉的GAD患者低收入人群所占比例明显高于无PPS的GAD患者,结果经秩和检验有显著统计学差异(P<0.05)；
(8)以PPS为主诉的GAD患者病程明显长于不合并PPS的GAD患者,结果经秩和检验有显著统计学差异(P<0.05)；
(9)两类患者中气郁化火型所占比例基本相同,结果经x2检验无显著统计学差异(P>0.05),以PPS为主诉的GAD患者中肝气郁结型所占比例明显高于无PPS的GAD患者(P<0.01),而后者中心脾两虚型、忧郁伤神型、和阴虚火旺型所占比例均高于前者,结果经x2检验有显著统计学差异(P<0.01,P<0.05,P<0.05)。
(10)以PPS为主诉的GAD患者的HAMA评分、HAMA精神焦虑因子评分高、HAMA躯体焦虑因子评分、SDSS评分均高于无PPS的GAD患者,经t检验有显著统计学差异(P<0.01,P<0.05,P<0.01,P<0.01)。
(11)不同中医证型的疼痛程度分布结果经x2检验有高度显著统计学差异(P<0.01)。
2.在降低HAMA评分方面,全分析集(Full Analysis Set, FAS)显示,柴胡桂枝汤与氟哌噻吨美利曲辛治疗2周后均可取得明显的临床疗效,结果经秩和检验均有高度显著统计学差异(P<0.01)；
柴胡桂枝汤治疗4周后的临床疗效明显优于治疗2周后,结果经秩和检验有高度显著统计学差异(P<0.01),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效则与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
氟哌噻吨美利曲辛治疗4周后的临床疗效与治疗2周后基本相等,结果经秩和检验无显著统计学差异(P>0.05),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
柴胡桂枝汤治疗2周后、4周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无显著统计学差异(P>0.05),治疗6周后、回访时的临床疗效则优于氟哌噻吨美利曲辛,结果经秩和检验有显著统计学差异(P<0.05)；
符合方案数据分析集(Per-Protocol PoPulation Set, PPS)略有不同,柴胡桂枝汤治疗2周后、4周后、6周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效则优于氟哌噻吨美利曲辛,结果经秩和检验有显著统计学差异(P<0.05)。
3.在降低SF-MPQ评分方面,FAS显示,柴胡桂枝汤与氟哌噻吨美利曲辛治疗2周后即可取得明显的临床疗效,结果经秩和检验有高度显著统计学差异(P<0.01)；
柴胡桂枝汤治疗4周后的临床疗效明显优于治疗2周后,结果经秩和检验有高度显著统计学差异(P<0.01),治疗6周后的临床疗效明显优于治疗4周后,结果经秩和检验有高度显著统计学差异(P<0.01),回访时的临床疗效则与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
氟哌噻吨美利曲辛治疗4周后的临床疗效优于治疗2周后,结果经秩和检验有显著统计学差异(P<0.05),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
柴胡桂枝汤治疗2周后、4周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无显著统计学差异(P>0.05),柴胡桂枝汤治疗6周后、回访时的临床疗效则明显优于氟哌噻吨美利曲辛。结果经秩和检验有高度显著统计学差异(P<0.01)。
PPS所得结论与FAS分析集基本相同。
4.在降低SDSS评分方面,FAS显示,柴胡桂枝汤与氟哌噻吨美利曲辛治疗2周后即可取得明显的临床疗效,结果经秩和检验有高度显著统计学差异(P<0.01)；
柴胡桂枝汤治疗4周后的临床疗效明显优于治疗2周后,结果经秩和检验有高度显著统计学差异(P<0.01),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效则与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
氟哌噻吨美利曲辛治疗4周后的临床疗效与治疗2周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
柴胡桂枝汤治疗2周后、4周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无业显著统计学差异(P>0.05),治疗6周后、回访时的临床疗效则优于氟哌噻吨美利曲辛,结果经秩和检验有显著统计学差异(P<0.05)。PPS所得结论与FAS分析集基本相同。
5.在降低中医证候评分方面,FAS显示,柴胡桂枝汤与氟哌噻吨美利曲辛治疗2周后即可取得明显的临床疗效,结果经秩和检验有高度显著统计学差异(P<0.01)；
柴胡桂枝汤治疗4周后的临床疗效明显优于治疗2周后,结果经秩和检验有高度显著统计学差异(P<0.01),治疗6周后的临床疗效优于治疗4周后,结果经秩和检验有显著统计学差异(P<0.05),回访时的临床疗效则与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
氟哌噻吨美利曲辛治疗4周后的临床疗效与治疗2周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),治疗6周后的临床疗效与治疗4周后基本相当,结果经秩和检验无显著统计学差异(P>0.05),回访时的临床疗效与治疗6周后基本相当,结果经秩和检验无显著统计学差异(P>0.05)；
柴胡桂枝汤治疗2周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无业显著统计学差异(P>0.05),治疗4周后、6周后、回访时的临床疗效则优于氟哌噻吨美利曲辛,结果经秩和检验有显著统计学差异(P<0.05,P<0.01,P<0.01)。
PPS略有不同,柴胡桂枝汤治疗2周后、4周后的临床疗效与氟哌噻吨美利曲辛基本相当,结果经秩和检验无显著统计学差异(P>0.05),柴胡桂枝汤治疗6周后、回访时的临床疗效则优于氟哌噻吨美利曲辛,结果经秩和检验有高度显著统计学差异(P<0.01)。
6.两组患者无严重不良反应。治疗组的常见不良反应为口干、厌食,对照组的常见不良反应为失眠、口干、震颤、焦虑、头晕、厌食以及疲乏,两组不良反应经x2检验(Fisher确切概率法)无显著统计学差异(P>0.05)。
结论：
1.教育程度低,收入水平低,职业为无业、退休人员、个体户、农民,肝气郁结型的GAD患者更易出现PPS,以PPS为主诉的GAD患者病程明显长于无PPS的GAD患者,且焦虑情况和社会功能缺陷更为严重。PPS的主要病机是气机不畅。
2.柴胡桂枝汤在改善以PPS为主诉的肝气郁结型GAD患者的焦虑症状、疼痛症状、社会功能以及中医证候方面疗效可靠,尤其是疼痛症状和中医证候可获得持续性的改善。
3.柴胡桂枝汤与氟哌噻吨美利曲辛治疗以PPS为主诉的肝气郁结型GAD起效较快,短期疗效基本相当,而柴胡桂枝汤的远期疗效明显优于氟哌噻吨美利曲辛。
4.柴胡桂枝汤与氟哌噻吨美利曲辛治疗以PPS为主诉的肝气郁结型GAD均无明显不良反应。
Objective
The present study is to explore the profile of generalized anxiety disorder patients with painful physical symptoms in a TCM hospital, and to investigate the efficacy and safety of Chaihu Guizhi Decoction on the syndrome of Stagnation of liver Qi in GAD with PPS.
Methods
First, we investigated215GAD patients with PPS and153without PPS from September2010to February2012in Guangzhou Hospital of Traditional Chinese Medicine. A self-designed questionnaire was used which covers the information of age, gender, blood type, marital status, occupation, educational background, economic conditions and duration of GAD. GAD was assessed by Hamilton Anxiety Scale (HAMA), PPS was assessed by Short-form of McGill Pain Questionnaire (SF-MPQ) Social Disability was assessed by Social Disability Screening Schedule (SDSS).
Next,80cases with the syndrome of stagnation of liver qi in GAD Patients with PPS were randomly assigned into study group (n=40), treated by Chaihu Guizhi Decoction and control group (n=40), treated by Flupentixol and Melitracen Tablets for6weeks. HAMA, SF-MPQ, SDSS and self-designed TCM Syndromes Scale were used to evaluate the efficacy of Chaihu Guizhi Decoction. Treatment Emergent Symptom Scale (TESS) was used to assess side effects. Assessments began at baseline, and the2nd,4th and6th weekend as well as2week later after a withdrawal.
All statistical analyses were performed by SPSS13.0software, including t-tests, Wilcoxon singed-rank tests, Wilcoxon rank sum tests, x2tests and tests of Fisher's exact probability.
Results
1. There are no difference on Age, gender, blood type, marital status between GAD patients with PPS and the group without PPS (P>0.05), but occupation, educational background, economic conditions, course of the disease, TCM syndromes, HAMA scores, SDSS scores were found some difference (P<0.05).
2. In the Full Analysis Set (FAS), we found that HAMA score of both2groups decreased significantly after treatment (P<0.01).
In the4th weekend after treatment, the effect of study group was better than in the2nd weekend (P<0.01). The effect in study group had no significant difference in the4th and6th weekend after treatment (P>0.05), as well as in the6th weekend after treatment and2nd weekend after withdrawal (P>0.05).
The effect of control group had no significant difference in the2nd,4thweekend after treatment (P>0.05), as well as in the4th,6thweekend after treatment (P>0.05), and had no significant difference between the6th weekend after treatment and2nd weekend after withdrawal (P>0.05).
In the2nd,4thweekend after treatment, the effect between2groups had no significant difference (P>0.05). At the6th weekend after treatment and2nd weekend after withdrawal, the effect of study group was better than that in control group (P<0.05).
But Per-Protocol Population Set (PPS), revealed a different result. In the2nd,4th,6th weekend after treatment, the effect between2groups had no significant difference (P>0.05). In the2nd weekend after withdrawal, the effect of study group was better than control group (P<0.05).
3. Full Analysis Set (FAS) showed that SF-MPQ score of both groups decreased significantly after treatments (P<0.01).
The effect of study group in the4th weekend was better than that in the2nd weekend after treatment (P<0.01), and that in the6th weekend was better than that in the4th weekend (P<0.01), and there was no significant difference between the6th weekend and2nd weekend after withdrawal (P>0.05).
In the4th weekend after treatment, the effect of control group was better than that in the2nd weekend (P<0.05), but has no significant difference compared with that in6thweekend (P>0.05), and no difference between that in the6th weekend and that in2nd weekend after withdrawal (P>0.05).
In the2nd,4thweekend, the effect between2groups had no significant difference (P>0.05). In the6th weekend after treatment and2nd weekend after withdrawal, the effect of study group was better than control group (P<0.01).
This study gained the same results from the Per-Protocol Population Set (PPS).
4. In the Full Analysis Set (FAS), we found that SDSS score of both2groups after therapy decreased significantly (P<0.01).
In the4th weekend after treatment, the effect of study group was better than in the2nd weekend after treatment (P<0.01). In the6th weekend after treatment, the effect of study group was same as in the4th weekend after treatment (P>0.05). The effect of study group had no significant difference in the6th weekend after treatment and2nd weekend after withdrawal (P>0.05). The effect of control group had no significant difference in the2nd,4thweekend after treatment (P>0.05).
The effect of control group had no significant difference in the4th6thweekend after treatment (P>0.05). The effect of control group had no significant difference in the6th weekend after treatment and2nd weekend after withdrawal (P>0.05).
In the2nd,4thweekend after treatment, the effect between2groups had no significant difference (P>0.05). In the6th weekend after treatment and2nd weekend after withdrawal, the effect of study group was better than comparative group (P<0.05).
There were same results in the Per-Protocol PoPulation Set (PPS).
5. In the Full Analysis Set (FAS), we found that TCM syndromes score of both2groups decreased significantly after treatment (P<0.01).
In the4th weekend, the effect of study group was better than that in the2nd weekend (P<0.01), and that in the6th weekend was better than that in the4th weekend (P<0.05). Study group had no different results in the6th weekend and in the2nd weekend after withdrawal (P>0.05).
The effect of control group had no significant difference in the2nd and the4thweekend after treatment (P>0.05), and no significant difference in the4th and the6thweekend (P>0.05), and no significant difference in the6th weekend and in the2nd weekend after withdrawal (P>0.05).
In the2nd weekend, the effect between2groups had no significant difference (P>0.05). But in the4th,6th weekend after treatment and2nd weekend after withdrawal, study group was better than control group (P<0.01).
Otherwise, Per-Protocol Population Set (PPS), revealed some difference. In the2nd and the4th weekend after treatment, the effect between2groups had no significant difference (P>0.05), but study group was better than control group in the6th weekend and the2nd weekend after withdrawal (P<0.05, P<0.01, P<0.01).
6. There were no serious side effects in both groups. The side effects found in study group were dry mouth, anorexia, and found in control group were insomnia, dry mouth, tremor, anxiety, dizzy, anorexia, fatigue. TESS evaluation revealed that the side effect between two groups had no significant difference(P>0.05).
Conclusion
1. The poorly educated, low income level, jobless, retiree, farmer, self-employed, Stagnation of liver Qi are risk factors for PPS. The patients of GAD with PPS are more anxious and have a longer history and worse social disability than ones without PPS. The main TCM pathogenesis for PPS is stagnation of qi activity.
2. Chaihu Guizhi Decoction has certain effect in the treatment of Liver Qi Stagnation GAD with PPS. This therapy is more effective in releasing symptoms such as anxiety and pain, and has less side-effect compared with Deaxit after6weeks of treatment.
3. Chaihuguizhitang Recipe is an effective therapy in improving anxiety, pain, social disability and chinese symptoms.
4. Chaihuguizhitang Recipe and Deaxit has the same short-time efficacy, but Chaihuguizhitang Recipe are better in long-time.
5. There is minor side-effect in treatment with Chaihuguizhitang Recipe.
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