电针结合耳穴埋针对双相抑郁心境稳定作用的临床研究
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摘要
1、背景资料
双相抑郁是指双相情感障碍病程中的抑郁发作,是情感障碍疾病谱系中很重要的一部分,是一种病期长、共病率高、较单相抑郁复发率更高、自杀风险和致残率均更高、平均寿命亦更短的慢性疾病。据调查,双相抑郁在普通人群中的终身患病率为1.5%～1.8%,复发率约为90%,死亡率亦较高,约25%-50%自杀未遂,10%-15%自杀身亡,高居各类精神障碍之首。2002年全球疾病负担调查结果显示双相抑郁排在非致命性疾病负担榜的前十位。近年来,对双相抑郁的研究越来越受到精神学界的关注和重视,寻找有效、副作用少、病人依从性高的治疗手段成为研究的焦点。
双相情感障碍的病因复杂,大量研究资料提示遗传因素、生物学因素和心理社会因素对其发生有明显影响,但确切病因仍不清楚。发病机制方面目前的研究主要集中在生化研究、神经内分泌研究和基因遗传研究等方面。其中,情感障碍的神经生化研究是近30年来研究最多、了解最深的领域之一。生物胺学说认为情感障碍患者存在生物胺水平或生物胺神经通路功能乃至结构的异常。如经典的神经递质中5-羟色胺的异常及其受体的基因调控,去甲肾上腺素和多巴胺及其受体的变化等。近年来特别关注谷氨酸和γ-氨基丁酸及多种神经肽与抑郁症的关系。神经内分泌研究认为内分泌异常可能是情感障碍的病因。研究发现,双相障碍患者存在皮质醇亢进,甲状腺机能减退等内分泌紊乱现象。基因遗传学研究认为双相情感性障碍是一种多基因遗传性疾病,其机理涉及多基因的相互共同作用及环境因素,认为生活应激事件与基因遗传易感性相互作用共同参与了双相障碍的发病。
双相抑郁的治疗非常棘手,其治疗的复杂性与困难性已日益受到重视,单纯抗抑郁药治疗诱发躁狂的风险高(转躁率约为3.7%—30%),是本病在治疗学上的难题众多双相抑郁的治疗规范和指南均指出：心境稳定剂是双相抑郁治疗的基础,在双相抑郁的急性发作期和维持期,都特别强调心境稳定剂的应用。事实上,强调与心境稳定剂的联合应用已经是世界生物精神病学协会基金会(WFSBP)和美国精神病学会(APA)双相抑郁治疗指南中的主要精神。
抗癫痫药是目前临床应用最为广泛的心境稳定剂,丙戊酸钠在北美已经成为治疗双相抑郁的一线药物。丙戊酸钠作为心境稳定剂,其药理作用与脑内氨基酸神经递质含量的调控有关。丙戊酸钠具有增加5-羟色胺能,抑制NE能,拟γ-氨基丁酸能效应；还可慢性耗竭谷氨酸能,理论上能预防长期谷氨酸能亢进引起的神经损害。而针刺治疗癫痫病的临床和实验研究均显示：针刺能调节皮质兴奋性氨基酸与抑制性氨基酸的平衡,调节皮质γ-氨基丁酸和谷氨酸(GABA／Glu)的比值,从而发挥抗癫痫作用。这些研究基础表明：针灸抗癫痫的作用机制与抗癫痫药作为心境稳定剂的药理基础相似。
针灸对单相抑郁的治疗作用已得到临床和实验研究的肯定,但临床少见针灸对双相抑郁的专项研究,针灸对双相抑郁的心境稳定作用值得探讨。在方法上我们选择电针结合耳穴埋针,由于双相抑郁是多种因素综合作用的结果,缠绵难愈,需长期服药,单一针灸疗法治疗双相抑郁有着各自的局限性。因此,多靶点作用的综合治疗方法,无疑是一种较佳的选择。以往众多的研究表明：电针对抑郁症的疗效肯定,电针能改善抑郁症患者的神经、内分泌、免疫功能,从而起到抗抑郁的作用。虽然以往的研究多限于单相抑郁的病例或仅包含双相抑郁的病例,而未对电针治疗双相抑郁进行专项研究,但对电针对双相抑郁的治疗和研究仍提供了很好的借鉴意义。耳穴作为全息疗法的一种,其对内分泌的调节作用优势明显,临床有报导耳穴埋针可改善弱智儿童甲状腺功能低下的状况,双相抑郁患者存在皮质醇功能亢进和甲状腺功能低下等内分泌功能的改变,基于以上原因,选择电针结合耳穴埋针替代心境稳定剂治疗双相抑郁。
2临床研究
2.1研究目的
鉴于双相抑郁治疗既要抗“抑郁”,又要防“转躁”,而腧穴具有双相调节作用以及西药治疗副反应大,患者难于长期坚持等的局限性；本研究从抑郁症状的改善,转躁率,及药物副反应等方面,探讨电针结合耳穴埋针对双相抑郁患者心境稳定作用的疗效。
2.2研究方法：
采取随机对照试验,将符合《中国精神疾病障碍分类和诊断标准》(第三版)(CCMD-3)“双相障碍,目前为无精神病性症状的抑郁发作的诊断标准”的60例患者随机分为电针结合耳穴埋针组(治疗组)和口服丙戊酸钠组(对照组),每组30例。两组均以抗抑郁治疗作为基础治疗,抗抑郁剂选用舍曲林、帕罗西汀、氟西汀等SSRIs类药物中的一种,常规剂量口服。电针结合耳穴埋针组采用电针和耳穴埋针作为心境稳定治疗,电针主穴：百会、印堂、丝竹空、率谷、大陵、三阴交。头部腧穴百会与印堂,丝竹空与率谷连接上海产的G6805型电针治疗仪,选用连续波,频率为80次／M1N,刺激量以患者能耐受为度。留针30分钟,隔日1次,每周3次,疗程8周。耳穴埋针取穴：神门、皮质下、内分泌、颞、肝。取已消毒好的图钉型皮内针,用止血钳夹住针柄,将针尖对准选定穴位轻轻刺入,然后用小块胶布粘贴。留针3天,左右交替。疗程8周。对照组口服心境稳定剂丙戊酸钠,用药剂量从0.4g／d开始,周内递增至治疗剂量(0.8g／d—1.2g／d),疗程8周。
采用Hamilton-17项抑郁量表(HAMD-17), Bech-Rafaelsen躁狂量表(BRMS),临床总体印象量表(CGI)和药物副反应量表(TESS)分别于治疗前及治疗后1、2、4、6、8周各评定1次,从抑郁症状的改善,转躁率,及药物副反应等方面进行评定。
2.3研究结果：
本研究结果显示：治疗第1周至治疗第8周,各时点HAMD抑郁量表总分组间比较无显著性差异(P>0.05)。通过计算HAMD减分率进行疗效比较,治疗组和对照组的临床治愈率分别为10.00%和16.67%,显效率分别为33.33%和36.67%,有效率分别为26.67和30.00%,经Ridit分析,两组间疗效比较无显著性差异(P>0.05)。通过Bech-Rafaelsen躁狂量表评定转躁率,治疗组与对照组分别为20.00%和10.00%,经卡方检验,两组间无显著性差异(P>0.05)。电针结合耳穴埋针对躯体症状(躯体性焦虑,全身症状)的改善起效较快且优于西药组(P<0.01),并在改善认知障碍因子方面的作用优于西药组(P<0.05),丙戊酸钠对精神性焦虑症状的改善较快且优于治疗组(P<0.01)。两组对睡眠障碍的改善无显著性差异(P>0.05)。
两组TESS副反应量表总分比较,从治疗后第1周至第8周,各时点比较均有显著性差异(P<0.01)。治疗结束后临床总体印象疗效指数量表(CGI-EI)评定,两组间比较亦有显著性差异(P<0.05)。治疗结束时两组TESS量表副反应种类比较,治疗组的口干、恶心呕吐等的发生率低于对照组,经卡方检验两组间有显著性差异(P<0.05)。
3结论
电针结合耳穴埋针疗法对双相抑郁具有一定的心境稳定作用,总体疗效与西药丙戊酸钠相当；但电针结合耳穴埋针对躯体症状(躯体性焦虑,全身症状)的改善起效较快且优于西药组,并在改善认知障碍因子方面的作用优于西药组,且副作用小,对SSRIs类抗抑郁药引起的副作用,尤其是胃肠道副反应可能有改善作用。
1. Background information
Bipolar Depression prefers to the depressive episode of Bipolar affective disorder. It is the important parts of Mood Disorder Pedigree. It is a long-term chronic disease with high comorbidity rate. Compared with unipolar depression, It has a higher recurrence rate, suicide risk and morbidity rate and shorter average life expectancy. According to the survey, In the general population, The lifetime prevalence rate of bipolar depression is 1.5%～1.8%, the recurrence rate is about 90%, mortality is higher, about 25% to 50% of suicide attempts,10% to 15% of suicide death, the highest in the mental disorders. Global burden of disease survey in 2002 showed that bipolar depression came in non-fatal burden of disease list of the top ten. In recent years, Research on bipolar depression is more and more concerned and attended by academia of spirit diseases. to find a effective, less side effects, patients with high treatment compliance therapy become the focus of research.
The causes of bipolar disorder are complex. Considerable amount of research data suggests that genetic factors, biological factors and psychosocial factors have significant effect on its occurrence. but the exact cause remains unclear. Pathogenes research current focuses on biochemical studies, neuroendocrine studies and genetic research. Neural and biochemical research of affective disorders is one of the deepest areas studied most for recent 30 years. Biogenic amines in patients with affective disorder theory that the level of biogenic amines or biogenic amines neural pathways as well as the structure of the abnormal function. In the classic neurotransmitter 5-hydroxytryptamine and its receptor in the abnormal gene regulation, norepinephrine and dopamine and its receptors are also some changes. In recent years special attention to glutamate andγ-aminobutyric acid and a variety of neuropeptides and depression relationship. Neuroendocrine study suggests that endocrine abnormalities may be the cause of affective disorders. Study found that mood disorders are cortisol hyperthyroidism, hypothyroidism and other endocrine disorders. Genetics study suggests that bipolar disorder is a multi-gene genetic diseases. The mechanism involved in the mutual interaction of multiple genes and environmental factors. It shows that the stress of life events and genetic susceptibility interact to participate in the pathogenesis of BP.
The treatment of bipolar depression is very difficult.Its complexity and difficulty has been more and more attention. High risk manic switch rate of single antidepressant-induced is the world-wide difficult problem. The treatment of bipolar depression many norms and guidelines have pointed out that Mood stabilizers are the basis for treatment of bipolar depression. In the acute and maintenance phase, all the guidelines particular emphasis on the application of mood stabilizers. In fact, Stress on combination of mood stabilizers has been the main spirit of the world's biological Psychiatric Association Foundation (WFSBP) and the American Psychiatric Association (APA) treatment guidelines for bipolar depression.
Anti-epilepsy drugs is currently the most widely used mood stabilizers. Sodium valproate in North America has become the first line drug in the treatment of bipolar depression. As a mood stabilizer, its pharmacological action is related with the regulation of brain amino acid neurotransmitters. Sodium valproate can increase 5-HT and increase NE has the effect to beγ-aminobutyric acid. Sodium valproate has increased by 5-HT can inhibit NE could, to beγ-aminobutyric acid effect. Chronic depletion of glutamic acid sodium valproate may also, in theory, can prevent long-term glutamatergic nerve damage caused by hyperthyroidism.
The clinical and experimental studies on Acupuncture treatment of epilepsy have shown that:Acupuncture can regulate the cortical excitatory amino acids and inhibitory amino acid balance, regulating cortical GABA/Glu ratio, which play a role in epilepsy. The basis of these studies show that: Antiepileptic mechanism of acupuncture is similar to the pharmacological of antiepileptic drugs as mood stabilizers.
The Positive effect of acupuncture in treating unique depression has been affirmed in clinical and experimental research. The Mood-destabilizing Effect of Acupuncture on bipolar depression is worth exploring. In the method we have chosen Combination Therapy with Electro-Acupuncture and Ear Points Imbedding Needle. As the bipolar depression is the result of various factors, hard to be cured, need long-term medication. Single acupuncturetherapy has each limitations. The combination therapy as a multiple target therapy is undoubtedly a better choice. Many previous studies have shown Electro-Acupuncture has Positive effect on depression. It can improve the neural, endocrine, immune function of depressive patients, and thus play a role in depression.
Although previous studies on Electro-acupuncture are mostly just include cases of unipolar depression or involve cases of bipolar depression. There is no special study on Electro-acupuncture in treating bipolar depression without special study. but the previous studies still provides a good reference. Auricular therapy, one of holographic therapy, in the treatment of many diseases, such as ear weight, ear beauty, its role in endocrine regulation is obvious. clinical reports auricular acupuncture can improve hypofunction of Thyroid function of mentally handicapped children. Patients with bipolar depression have hyperfunction of COR and hypothyroidism Thyroid function and other endocrine endocrine function of the change. for above reasons, select the combination of auricular acupuncture needle buried in an alternative mood stabilizer treatment of bipolar depression.
2. Clinical Research
2.1 Objective
Treatment of bipolar depression needs not only anti-"depression" but also against turning mania. Acupoints has the function of biphasic regulation. Because of Great side effects of Western medicine, It is difficult for patiebts to persist in long-term Western medicine therapy. This study will explore Mood-destabilizing Effect of Combination Therapy with Electro-Acupuncture and Ear Points Imbedding Needle in the Treatment of Bipolar Depression on three aspects, improving the symptoms of depression, manic switch rate and adverse drug reactions.
2.2 Method
60 bipolar depression patients in accordance with diagnostic standard of CCMD-3 were randomly divided into 2 groups:treatment group (treated with Combination Therapy with Electro-Acupuncture and Ear Points Imbedding Needle) and control group(treated with sodium valproate),30 cases each. Groups were based on the treatment of antidepressant treatment, using one of fluoxetine, paroxetine or other SSRIs antidepressants, the conventional dose. Treatment group used Combination Therapy with Electro-Acupuncture and Ear Points Imbedding Needle as mood stabilizer. Electro-Acupuncture main point:GV20, EX-HN3, TE23, GB8, PC7, SP6. GV20 and EX-HN3, TE23 and GB8 connectied with G6805 Shanghai electric acupuncture-type instrument, using a continuous wave frequency of 80 times/MIN, stimulus degree which patients can tolerate. Needle retention for 30 minutes every other day,3 times per week for 8 weeks. Ear Points Imbedding Needle:TF4, AT4, C018, temporal, C012, AT12. keep intradermal needles that has been sterilized into the ear point, fasten with a small sticking paster for3 days. Turn another ear next time. The treatment lasted for 8 weeks.
The control group was treated with mood stabilizers sodium valproate, the dose from 0.4g/d at the beginning, increased to dose (0.8g/d-1.2g/d) in a week.8 weeks. The treatment lasted for 8 weeks.
Hamilton-17(HAMD-17), Bech-Rafaelsen Mania Scale (BRMS), Clinical Global Impression Scale (CGI) and adverse drug reaction scale (TESS) were used to measure the efficacy. Two groups would be evaluate before treatment and after treatment 1,2,4,6,8 weeks respectively.
2.3 Result
The results showed that total score of 17-item Hamilton Rating Scale between two groups was no significant difference after treatment 1,2,4,6,8 weeks (P>0.05). Compared the clinical efficacy by calculating HAMD reduction rate, clinical cure rates were 10.00% and 16.67%, markedly effective rates were 33.33% and 36.67%, efficiency 26.67 and 30.00% respectively in the treatment group and control group. There were no significant differences by Ridit analysis (P> 0.05). The rates of switching to minia calculated by Bech-Rafaelsen mania scale were 20.00% and 10.00% respectively. Two groups have no significant difference by chi-square test (P> 0.05). On somatic symptoms Combination therapy with Electro-Acupuncture and Ear Points lmbedding Needle faster onset of improvement was better than western medicine group (P<0.01), and factor in improving the role of cognitive dysfunction better than the Western medicine group. On the improvement of somatic symptoms the treatment group improved more quickly and has a better effect than the control group (P<0.01). In improving cognitive dysfunction, the treatment group was also better than the western group (P<0.05). On the mental anxiety symptoms Sodium valproate improved more quickly and has a better effect than the treatment group (P<0.01). On the improvement of sleep disorders two groups has no significant difference.
Comparison of TESS total score, Ttwo groups have significant difference after treatment 1,2,4,6,8 weeks (P<0.01). The assessment of CGI-EI between the two groups was significant difference (P<0.05). On the occurring rate of dry mouth, nausea, vomiting Treatment group was lower than the control group at the end of the treatment. Chi-square test showed significant difference (P<0.05).
3 Conclusion
Combination therapy with Electro-Acupuncture and Ear Points Imbedding Needle in the treatment of Bipolar Depression has a certain mood stabilizer. The overall therapeutic effects of it is equal with western medicine. but its side effects are less than western medicine.And particularly It can reduced gastrointestinal side effects caused by the SSRIs antidepressant.
双相抑郁是指双相情感障碍病程中的抑郁发作,是情感障碍疾病谱系中很重要的一部分,是一种病期长、共病率高、较单相抑郁复发率更高、自杀风险和致残率均更高、平均寿命亦更短的慢性疾病。据调查,双相抑郁在普通人群中的终身患病率为1.5%～1.8%,复发率约为90%,死亡率亦较高,约25%-50%自杀未遂,10%-15%自杀身亡,高居各类精神障碍之首。2002年全球疾病负担调查结果显示双相抑郁排在非致命性疾病负担榜的前十位。近年来,对双相抑郁的研究越来越受到精神学界的关注和重视,寻找有效、副作用少、病人依从性高的治疗手段成为研究的焦点。
双相情感障碍的病因复杂,大量研究资料提示遗传因素、生物学因素和心理社会因素对其发生有明显影响,但确切病因仍不清楚。发病机制方面目前的研究主要集中在生化研究、神经内分泌研究和基因遗传研究等方面。其中,情感障碍的神经生化研究是近30年来研究最多、了解最深的领域之一。生物胺学说认为情感障碍患者存在生物胺水平或生物胺神经通路功能乃至结构的异常。如经典的神经递质中5-羟色胺的异常及其受体的基因调控,去甲肾上腺素和多巴胺及其受体的变化等。近年来特别关注谷氨酸和γ-氨基丁酸及多种神经肽与抑郁症的关系。神经内分泌研究认为内分泌异常可能是情感障碍的病因。研究发现,双相障碍患者存在皮质醇亢进,甲状腺机能减退等内分泌紊乱现象。基因遗传学研究认为双相情感性障碍是一种多基因遗传性疾病,其机理涉及多基因的相互共同作用及环境因素,认为生活应激事件与基因遗传易感性相互作用共同参与了双相障碍的发病。
双相抑郁的治疗非常棘手,其治疗的复杂性与困难性已日益受到重视,单纯抗抑郁药治疗诱发躁狂的风险高(转躁率约为3.7%—30%),是本病在治疗学上的难题众多双相抑郁的治疗规范和指南均指出：心境稳定剂是双相抑郁治疗的基础,在双相抑郁的急性发作期和维持期,都特别强调心境稳定剂的应用。事实上,强调与心境稳定剂的联合应用已经是世界生物精神病学协会基金会(WFSBP)和美国精神病学会(APA)双相抑郁治疗指南中的主要精神。
抗癫痫药是目前临床应用最为广泛的心境稳定剂,丙戊酸钠在北美已经成为治疗双相抑郁的一线药物。丙戊酸钠作为心境稳定剂,其药理作用与脑内氨基酸神经递质含量的调控有关。丙戊酸钠具有增加5-羟色胺能,抑制NE能,拟γ-氨基丁酸能效应；还可慢性耗竭谷氨酸能,理论上能预防长期谷氨酸能亢进引起的神经损害。而针刺治疗癫痫病的临床和实验研究均显示：针刺能调节皮质兴奋性氨基酸与抑制性氨基酸的平衡,调节皮质γ-氨基丁酸和谷氨酸(GABA／Glu)的比值,从而发挥抗癫痫作用。这些研究基础表明：针灸抗癫痫的作用机制与抗癫痫药作为心境稳定剂的药理基础相似。
针灸对单相抑郁的治疗作用已得到临床和实验研究的肯定,但临床少见针灸对双相抑郁的专项研究,针灸对双相抑郁的心境稳定作用值得探讨。在方法上我们选择电针结合耳穴埋针,由于双相抑郁是多种因素综合作用的结果,缠绵难愈,需长期服药,单一针灸疗法治疗双相抑郁有着各自的局限性。因此,多靶点作用的综合治疗方法,无疑是一种较佳的选择。以往众多的研究表明：电针对抑郁症的疗效肯定,电针能改善抑郁症患者的神经、内分泌、免疫功能,从而起到抗抑郁的作用。虽然以往的研究多限于单相抑郁的病例或仅包含双相抑郁的病例,而未对电针治疗双相抑郁进行专项研究,但对电针对双相抑郁的治疗和研究仍提供了很好的借鉴意义。耳穴作为全息疗法的一种,其对内分泌的调节作用优势明显,临床有报导耳穴埋针可改善弱智儿童甲状腺功能低下的状况,双相抑郁患者存在皮质醇功能亢进和甲状腺功能低下等内分泌功能的改变,基于以上原因,选择电针结合耳穴埋针替代心境稳定剂治疗双相抑郁。
2临床研究
2.1研究目的
鉴于双相抑郁治疗既要抗“抑郁”,又要防“转躁”,而腧穴具有双相调节作用以及西药治疗副反应大,患者难于长期坚持等的局限性；本研究从抑郁症状的改善,转躁率,及药物副反应等方面,探讨电针结合耳穴埋针对双相抑郁患者心境稳定作用的疗效。
2.2研究方法：
采取随机对照试验,将符合《中国精神疾病障碍分类和诊断标准》(第三版)(CCMD-3)“双相障碍,目前为无精神病性症状的抑郁发作的诊断标准”的60例患者随机分为电针结合耳穴埋针组(治疗组)和口服丙戊酸钠组(对照组),每组30例。两组均以抗抑郁治疗作为基础治疗,抗抑郁剂选用舍曲林、帕罗西汀、氟西汀等SSRIs类药物中的一种,常规剂量口服。电针结合耳穴埋针组采用电针和耳穴埋针作为心境稳定治疗,电针主穴：百会、印堂、丝竹空、率谷、大陵、三阴交。头部腧穴百会与印堂,丝竹空与率谷连接上海产的G6805型电针治疗仪,选用连续波,频率为80次／M1N,刺激量以患者能耐受为度。留针30分钟,隔日1次,每周3次,疗程8周。耳穴埋针取穴：神门、皮质下、内分泌、颞、肝。取已消毒好的图钉型皮内针,用止血钳夹住针柄,将针尖对准选定穴位轻轻刺入,然后用小块胶布粘贴。留针3天,左右交替。疗程8周。对照组口服心境稳定剂丙戊酸钠,用药剂量从0.4g／d开始,周内递增至治疗剂量(0.8g／d—1.2g／d),疗程8周。
采用Hamilton-17项抑郁量表(HAMD-17), Bech-Rafaelsen躁狂量表(BRMS),临床总体印象量表(CGI)和药物副反应量表(TESS)分别于治疗前及治疗后1、2、4、6、8周各评定1次,从抑郁症状的改善,转躁率,及药物副反应等方面进行评定。
2.3研究结果：
本研究结果显示：治疗第1周至治疗第8周,各时点HAMD抑郁量表总分组间比较无显著性差异(P>0.05)。通过计算HAMD减分率进行疗效比较,治疗组和对照组的临床治愈率分别为10.00%和16.67%,显效率分别为33.33%和36.67%,有效率分别为26.67和30.00%,经Ridit分析,两组间疗效比较无显著性差异(P>0.05)。通过Bech-Rafaelsen躁狂量表评定转躁率,治疗组与对照组分别为20.00%和10.00%,经卡方检验,两组间无显著性差异(P>0.05)。电针结合耳穴埋针对躯体症状(躯体性焦虑,全身症状)的改善起效较快且优于西药组(P<0.01),并在改善认知障碍因子方面的作用优于西药组(P<0.05),丙戊酸钠对精神性焦虑症状的改善较快且优于治疗组(P<0.01)。两组对睡眠障碍的改善无显著性差异(P>0.05)。
两组TESS副反应量表总分比较,从治疗后第1周至第8周,各时点比较均有显著性差异(P<0.01)。治疗结束后临床总体印象疗效指数量表(CGI-EI)评定,两组间比较亦有显著性差异(P<0.05)。治疗结束时两组TESS量表副反应种类比较,治疗组的口干、恶心呕吐等的发生率低于对照组,经卡方检验两组间有显著性差异(P<0.05)。
3结论
电针结合耳穴埋针疗法对双相抑郁具有一定的心境稳定作用,总体疗效与西药丙戊酸钠相当；但电针结合耳穴埋针对躯体症状(躯体性焦虑,全身症状)的改善起效较快且优于西药组,并在改善认知障碍因子方面的作用优于西药组,且副作用小,对SSRIs类抗抑郁药引起的副作用,尤其是胃肠道副反应可能有改善作用。
1. Background information
Bipolar Depression prefers to the depressive episode of Bipolar affective disorder. It is the important parts of Mood Disorder Pedigree. It is a long-term chronic disease with high comorbidity rate. Compared with unipolar depression, It has a higher recurrence rate, suicide risk and morbidity rate and shorter average life expectancy. According to the survey, In the general population, The lifetime prevalence rate of bipolar depression is 1.5%～1.8%, the recurrence rate is about 90%, mortality is higher, about 25% to 50% of suicide attempts,10% to 15% of suicide death, the highest in the mental disorders. Global burden of disease survey in 2002 showed that bipolar depression came in non-fatal burden of disease list of the top ten. In recent years, Research on bipolar depression is more and more concerned and attended by academia of spirit diseases. to find a effective, less side effects, patients with high treatment compliance therapy become the focus of research.
The causes of bipolar disorder are complex. Considerable amount of research data suggests that genetic factors, biological factors and psychosocial factors have significant effect on its occurrence. but the exact cause remains unclear. Pathogenes research current focuses on biochemical studies, neuroendocrine studies and genetic research. Neural and biochemical research of affective disorders is one of the deepest areas studied most for recent 30 years. Biogenic amines in patients with affective disorder theory that the level of biogenic amines or biogenic amines neural pathways as well as the structure of the abnormal function. In the classic neurotransmitter 5-hydroxytryptamine and its receptor in the abnormal gene regulation, norepinephrine and dopamine and its receptors are also some changes. In recent years special attention to glutamate andγ-aminobutyric acid and a variety of neuropeptides and depression relationship. Neuroendocrine study suggests that endocrine abnormalities may be the cause of affective disorders. Study found that mood disorders are cortisol hyperthyroidism, hypothyroidism and other endocrine disorders. Genetics study suggests that bipolar disorder is a multi-gene genetic diseases. The mechanism involved in the mutual interaction of multiple genes and environmental factors. It shows that the stress of life events and genetic susceptibility interact to participate in the pathogenesis of BP.
The treatment of bipolar depression is very difficult.Its complexity and difficulty has been more and more attention. High risk manic switch rate of single antidepressant-induced is the world-wide difficult problem. The treatment of bipolar depression many norms and guidelines have pointed out that Mood stabilizers are the basis for treatment of bipolar depression. In the acute and maintenance phase, all the guidelines particular emphasis on the application of mood stabilizers. In fact, Stress on combination of mood stabilizers has been the main spirit of the world's biological Psychiatric Association Foundation (WFSBP) and the American Psychiatric Association (APA) treatment guidelines for bipolar depression.
Anti-epilepsy drugs is currently the most widely used mood stabilizers. Sodium valproate in North America has become the first line drug in the treatment of bipolar depression. As a mood stabilizer, its pharmacological action is related with the regulation of brain amino acid neurotransmitters. Sodium valproate can increase 5-HT and increase NE has the effect to beγ-aminobutyric acid. Sodium valproate has increased by 5-HT can inhibit NE could, to beγ-aminobutyric acid effect. Chronic depletion of glutamic acid sodium valproate may also, in theory, can prevent long-term glutamatergic nerve damage caused by hyperthyroidism.
The clinical and experimental studies on Acupuncture treatment of epilepsy have shown that:Acupuncture can regulate the cortical excitatory amino acids and inhibitory amino acid balance, regulating cortical GABA/Glu ratio, which play a role in epilepsy. The basis of these studies show that: Antiepileptic mechanism of acupuncture is similar to the pharmacological of antiepileptic drugs as mood stabilizers.
The Positive effect of acupuncture in treating unique depression has been affirmed in clinical and experimental research. The Mood-destabilizing Effect of Acupuncture on bipolar depression is worth exploring. In the method we have chosen Combination Therapy with Electro-Acupuncture and Ear Points Imbedding Needle. As the bipolar depression is the result of various factors, hard to be cured, need long-term medication. Single acupuncturetherapy has each limitations. The combination therapy as a multiple target therapy is undoubtedly a better choice. Many previous studies have shown Electro-Acupuncture has Positive effect on depression. It can improve the neural, endocrine, immune function of depressive patients, and thus play a role in depression.
Although previous studies on Electro-acupuncture are mostly just include cases of unipolar depression or involve cases of bipolar depression. There is no special study on Electro-acupuncture in treating bipolar depression without special study. but the previous studies still provides a good reference. Auricular therapy, one of holographic therapy, in the treatment of many diseases, such as ear weight, ear beauty, its role in endocrine regulation is obvious. clinical reports auricular acupuncture can improve hypofunction of Thyroid function of mentally handicapped children. Patients with bipolar depression have hyperfunction of COR and hypothyroidism Thyroid function and other endocrine endocrine function of the change. for above reasons, select the combination of auricular acupuncture needle buried in an alternative mood stabilizer treatment of bipolar depression.
2. Clinical Research
2.1 Objective
Treatment of bipolar depression needs not only anti-"depression" but also against turning mania. Acupoints has the function of biphasic regulation. Because of Great side effects of Western medicine, It is difficult for patiebts to persist in long-term Western medicine therapy. This study will explore Mood-destabilizing Effect of Combination Therapy with Electro-Acupuncture and Ear Points Imbedding Needle in the Treatment of Bipolar Depression on three aspects, improving the symptoms of depression, manic switch rate and adverse drug reactions.
2.2 Method
60 bipolar depression patients in accordance with diagnostic standard of CCMD-3 were randomly divided into 2 groups:treatment group (treated with Combination Therapy with Electro-Acupuncture and Ear Points Imbedding Needle) and control group(treated with sodium valproate),30 cases each. Groups were based on the treatment of antidepressant treatment, using one of fluoxetine, paroxetine or other SSRIs antidepressants, the conventional dose. Treatment group used Combination Therapy with Electro-Acupuncture and Ear Points Imbedding Needle as mood stabilizer. Electro-Acupuncture main point:GV20, EX-HN3, TE23, GB8, PC7, SP6. GV20 and EX-HN3, TE23 and GB8 connectied with G6805 Shanghai electric acupuncture-type instrument, using a continuous wave frequency of 80 times/MIN, stimulus degree which patients can tolerate. Needle retention for 30 minutes every other day,3 times per week for 8 weeks. Ear Points Imbedding Needle:TF4, AT4, C018, temporal, C012, AT12. keep intradermal needles that has been sterilized into the ear point, fasten with a small sticking paster for3 days. Turn another ear next time. The treatment lasted for 8 weeks.
The control group was treated with mood stabilizers sodium valproate, the dose from 0.4g/d at the beginning, increased to dose (0.8g/d-1.2g/d) in a week.8 weeks. The treatment lasted for 8 weeks.
Hamilton-17(HAMD-17), Bech-Rafaelsen Mania Scale (BRMS), Clinical Global Impression Scale (CGI) and adverse drug reaction scale (TESS) were used to measure the efficacy. Two groups would be evaluate before treatment and after treatment 1,2,4,6,8 weeks respectively.
2.3 Result
The results showed that total score of 17-item Hamilton Rating Scale between two groups was no significant difference after treatment 1,2,4,6,8 weeks (P>0.05). Compared the clinical efficacy by calculating HAMD reduction rate, clinical cure rates were 10.00% and 16.67%, markedly effective rates were 33.33% and 36.67%, efficiency 26.67 and 30.00% respectively in the treatment group and control group. There were no significant differences by Ridit analysis (P> 0.05). The rates of switching to minia calculated by Bech-Rafaelsen mania scale were 20.00% and 10.00% respectively. Two groups have no significant difference by chi-square test (P> 0.05). On somatic symptoms Combination therapy with Electro-Acupuncture and Ear Points lmbedding Needle faster onset of improvement was better than western medicine group (P<0.01), and factor in improving the role of cognitive dysfunction better than the Western medicine group. On the improvement of somatic symptoms the treatment group improved more quickly and has a better effect than the control group (P<0.01). In improving cognitive dysfunction, the treatment group was also better than the western group (P<0.05). On the mental anxiety symptoms Sodium valproate improved more quickly and has a better effect than the treatment group (P<0.01). On the improvement of sleep disorders two groups has no significant difference.
Comparison of TESS total score, Ttwo groups have significant difference after treatment 1,2,4,6,8 weeks (P<0.01). The assessment of CGI-EI between the two groups was significant difference (P<0.05). On the occurring rate of dry mouth, nausea, vomiting Treatment group was lower than the control group at the end of the treatment. Chi-square test showed significant difference (P<0.05).
3 Conclusion
Combination therapy with Electro-Acupuncture and Ear Points Imbedding Needle in the treatment of Bipolar Depression has a certain mood stabilizer. The overall therapeutic effects of it is equal with western medicine. but its side effects are less than western medicine.And particularly It can reduced gastrointestinal side effects caused by the SSRIs antidepressant.
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