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Generalized anxiety disorder

Treatment of Geriatric Generalized Anxiety Disorder
with Acupuncture: A Case Study
Laura D Varga, LAc
BACKGROUND: While the general public is more familiar with geriatric depression, Generalized Anxiety Disorder (GAD) affects a significant portion of the elderly population with prevalence rates possibly higher than that for depression1. One study reports a prevalence rate of 3.6% of GAD for people over the age of 60.2 CASE DESCRIPTION: A 62 year old male with GAD was treated with acupuncture from September 2009 - August 2010 at the OCOM Master’s Acupuncture and Herbal Clinic. The frequency of visits was 2x/week for 20 visits and 1x per week thereafter for a total of 37 visits. RESULT: Improvement in anxiety symptoms was reported by subjective and objective measures. Subjectively, the patient and his wife reported improvement in his anxiety and irritability. Objectively, the patient was also able to discontinue two anxiolytic medications under his physician’s supervision without adverse effect. CONCLUSION: This case study adds to the body of literature that suggests acupuncture may be of use in the treatment of anxiety. More specifically, it supports the use of acupuncture as a means of treatment for anxiety in the elderly that does not contribute to the problems of polypharmacy and its adherent risks of adverse drug interaction and side effects. ______________________________________________________________________________ According to the Diagnostic and Statistical Manual of Psychiatric Disorders IV, Generalized anxiety disorder (GAD) is characterized by “excessive worry and anxiety that is difficult to control, causes significant distress and impairment, and occurs on more days than not for at least six months”.3 Francisco Fernandez M.D, a psychiatrist at the University of San Francisco Medical School, describes the disease as, “over-arousal, irritability, poor concentration, poor sleeping, and worry about several areas most of the time.” Reports on community prevalence rates for anxiety disorders in older adults ranges from 3.5% 4 to 10.2% 5. These numbers may be higher as older adults have the proclivity to underreport psychological symptoms.6 Anxiety is also related to decreased quality of life in the elderly regardless of demographics and comorbid disease. 7, 8, 9, 10, 11, 12, 13 From a biomedical point of view, GAD may be explained as “a maladaptive neuroendocrine response to stressful stimuli”. The primary neurotransmitters involved in GAD are believed to be: norepinephrine, serotonin, gamma-aminobutyric acid (GABA) and cholecystokinin.14 GAD is also implicated in neurophysiological changes of the amygdala, part of the limbic system involved with emotion. Recent f-MRI studies suggest decreased amygdala connectivity bilaterally with the insula, dorsal/midcingulate, supplemental motor area, thalamus, caudate putamen, superior temporal gyrus, and ventrolateral prefrontal cortex.15 Other imaging studies in patients with GAD have shown differences in regional brain activity. One study using positron emission tomography (PET) found higher metabolic rates in parts of the occipital, temporal, and frontal lobes, and cerebellum, during a passive viewing task in subjects with GAD relative to control subjects.16The goal of biomedical treatment is to improve neurophysiological imbalance and relieve symptoms of anxiety. Treatment of anxiety with a benzodiazepine has been shown to decrease glucose metabolism in the cortex, especially in the occipital cortex, limbic system, and basal ganglia, compared with placebo.14 This class of drugs offers significant acute relief from anxiety. However issues of dependence and increased tolerance have limited their use. 17,18 Selective Serotonin Reuptake Inhibitors (SSRIs) are now the primary drug in the treatment of anxiety disorders. However their efficacy remains uncertain. A systematic review concluded that five patients with GAD would need to be treated with an SSRI (rather than placebo) for one patient to achieve a clinical response. Moreover, few studies have examined the treatment of GAD with antidepressant medications in the older population (wetherell). In addition, their side effects may interfere with compliance for some patients.19Polypharmacy, the prescription and use of multiple medications, is of concern in the elderly. Many patients over the age of 60 are taking medications for multiple conditions: cardiovascular disease, arthritis, diabetes, gastrointestinal disorders and bladder dysfunction. The elderly fill 32% of prescriptions and yet are only 12% of the population. Of additional concern, liver and kidney function slows down as we age resulting in decreased metabolism and excretion of drugs and increased risk for over-doseage.20 There are only a small number of clinical trials that have examined the effect of pharmacologic treatment for anxiety disorders in older patients (wetherell). This is of importance as there is a greater potential consequence of adverse events among older patients due to the increased frequency of comorbidities that complicate treatment. (wetherell) Furthermore, according to the American Geriatrics Society 2012 Updated Beers Criteria, there is a high quality of evidence and a strong recommendation to avoid the use of benzodiazepines in older adults except for severe generalized anxiety and end of life care. They report that all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults. In addition, selective serotonin re-uptake inhibitors are to be prescribed with caution as they may exacerbate or cause inappropriate antidiuretic hormone secretion or hyponatremia.21 While biomedicine can provide significant relief from acute anxiety symptoms, chronic anxiety may be difficult to treat. Some patients who are poor responders, experience significant side effects from prescription medications, or who are on multiple medications may benefit from complimentary non-pharmacological treatment for their anxiety. For these patients, acupuncture may be a prudent intervention. _____________________________________________________________________________________________________________________ Traditional or classical terminology for anxiety include: “Fear and Palpitations” (Jing Ji); “Panic Throbbing” (Zheng Chong); and “Rebellious qi of the penetrating vessel” (Li Ji). .22 Other interpretations include: “Fright Palpitations” (Jing Ji); “Fearful Throbbing” (Zheng Chong); and “Fright and Fear” (Jing Kong). And the term, Shan You Si refers to “worry and continuous or excessive thinking”. 23 In addition to definitive, descriptive classification, a differential diagnosis for the patient experiencing anxiety is made according to Traditional Chinese Medicine (TCM) theory and encapsulates a multitude of possibilities including dysfunction of the the zang-fu (heart/small intestine, spleen/stomach, lung/large intestine, kidney/bladder, liver/gallbladder), external influences (wind, heat, cold, damp, dryness) and internal causes (emotions and constitution).
Emotions have the ability to alter the movement of qi. The disturbed movement of qi will first alter the function of the zang fu and ultimately harm or injure the jing of the organ.24 The Liver is especially vulnerable to damage by the emotions. Its ability to drain, release and course the qi is easily affected. And stagnation of qi and blood usually follow.25 This stagnation of qi may give rise to heat or fire which can disturb the shen/heart; or create phlegm accumulation which blocks the portals of the heart; or at the end stage, cause stasis of blood and blockage of nourishment to the heart. 24 Some common patterns of anxiety include: heart qi vacuity and blood stasis pattern; liver depression and phlegm fire pattern; heart qi stagnation and blood stasis pattern; heart-spleen dual vacuity pattern; and yin vacuity fire effulgence pattern. Over-thinking damages the spleen (and the Liver as it binds the qi) and worry and anxiety particularly damage the spleen.23 In addition to the theory found in the texts of traditional chinese medicine, current research suggests acupuncture may be efficacious in the treatment of GAD. A review article on the treatment of anxiety with acupuncture published in 2007 by Pilkington and colleagues reported positive findings, although firm conclusions could not be drawn. The authors reviewed ten Randomized Controlled Trials, four on generalized anxiety disorder/anxiety neurosis and six on perioperative anxiety.26 Following is a brief review of the four randomized controlled trials examining the use of acupuncture in the treatment of GAD/anxiety neurosis. Liu and colleagues treated 240 subjects with: acupuncture only; acupuncture + behavioral desensitization (BD); or BD only. Patients received 10-40 sessions. Each acupuncture session used 3-6 points chosen from the following: ST36, PC6, ST25, LV3, BL23, GV4, LI11 + 4 ear points xin (MA-IC), shen (MA-SC), shenmen, and neifenmi (MA-IC3). Results found the greatest improvements in the combined treatment group with no difference between the acupuncture only or BD only groups. This study suggests an integrative approach of acupuncture and BD may be more helpful than acupuncture or BD alone. In addition, acupuncture may be as effective as BD in the treatment of GAD. 27 Eich and colleagues conducted a fixed protocol, verum versus sham acupuncture study. Verum points were GV20, sishencong, HT7, PC6, and BL62. Sham, non-verum points were located on the head, hand and foot. Thirteen subjects received 10 acupuncture sessions. Results showed a statistically significant improvement in anxiety for the verum acupuncture group only.28 Chao-Ying and colleagues compared electro-acupuncture (EA) at yin tang, GV20, GB5, GB20 for 45 minutes daily for six weeks to trazadone 100-150mg per day. Outcome measures were the Hamilton Anxiety Scale (HAMA). At six weeks, no differences between groups were detected. Pilkington and colleagues rightfully point out the low feasibility of this treatment protocol. 29 Zhang and colleagues evaluated the efficacy of acupuncture versus doxepin, a tricyclic antidepressant, in the treatment of “anxiety neurosis” for 296 subjects. The acupuncture treatment group received two of four treatment protocols: (1) GV20, PC6, GV26 and SP6 for “restoring consciousness and inducing resuscitation”; (2) 2-3 back shu points and their corresponding “emotion point” BL42 (LU), BL44 (HT), BL47 (LV), BL49 (SP), or BL52 (KD); (3) si shen cong (EX-HN1), GB13, GV24, BL44, and GV12 for “tranquilization and controlling emotion”; and (4) one back shu point injected with the herbs tian ma or dang gui. Subjects received 30 minutes of acupuncture 6 days per week for 5 weeks. Point prescription was explained as follows: for anxiety and fear BL15, BL44, PC6, and HT7 were used to regulate Heart qi; for restlessness and insomnia, GV12, GV20, GV24, GV26 and si shen cong (EX-HN1) were chosen to free the flow of qi in the Du meridian. BL23 and BL52 were used to regulate the Kidney qi and Marrow formation. SP6 was chosen to free the flow of the qi in the three yin meridians of the foot. GV12 and GB13 are empirical points for mental disease. Outcome measures were the SAS-CR (self rating anxiety scale). Scores in both groups decreased significantly (p<.001) with no statistical significance between the groups (p<.05). This study suggests acupuncture may be as effective as doxepin in the treatment of “anxiety neurosis”. 30 In additional studies, Yuan and colleagues examined the effects of acupuncture on anxiety as measured by the Clinical Global Impression Scale (CGI); plasma corticosteroid levels, adrenocorticotropic hormone (ACTH) levels, and platelet 5-HT levels. Their study design had 3 treatment arms: western medicine only, fluoxetine or paroxetine + alprazolam; acupuncture only: si shen zhen (M-HN-1) (also known as si shen cong) (Four Spirits Needles) 4 points located 1.5 cun lateral, anterior and posterior to DU20; ding shen zhen (Stabilizing the Spirit Needles) located 5 inches above Yin Tang (M-HN-3) and Yang Bai (GB14), PC6, HT7 and SP6; and western medicine + acupuncture. Similar improvement was reported in all three groups after six weeks of treatment, suggesting that acupuncture or acupuncture plus medication may be as efficacious as medication alone.31 Agelink and colleagues looked at the effects of acupuncture on the cardiac autonomic nervous system (ANS) function. Subjects received either verum acupuncture at HT7, PC6, DU20, BL62, and Ex6; or sham acupuncture defined as epidermal needling at “non acupuncture points”. Compared to the sham acupuncture group, the verum acupuncture group showed a significant increase in cardiovagal modulation of heart rate and an improvement in physiological regulatory ANS function.32 Wang and colleagues evaluated the use of acupuncture versus medication in the treatment of GAD with acupuncture. Point selection was individualized. The main points used were: Yin tang (EX-HN3), GV20, PC6, HT7, CV17 and SP6 and were retained for 30 minutes. BL15, BL20, and BL23 were also used but with no retention. Subjects received acupuncture treatment once per day for 30 consecutive days. The medication control group received: lorazepam 0.5mg-2.0mg bid or tid + oryzanol tid; or 10-20mg of propranolol (a beta-blocker) tid. The anxiety symptom scores of both groups decreased (p<0.01) with statistically significant similarities between groups (p<0.05). Rationale for point selection was to: regulate qi, relieve mental stress and tranquilize the mind.33 This study suggests acupuncture may be as effective as using a benzodiazepine or beta blocker in the treatment of GAD. Errington-Evans reported a case series of 4 patients with chronic anxiety/depression un-responsive to standard treatment including medication and cognitive behavioral therapy. Acupuncture points used were LI4, LI11, and HT7. Subjects received 6, 30 minute sessions over 6 weeks. All patients showed an improvement in anxiety symptoms by Visual Analogue Scale (VAS), life changes and attitude. 34 In additional to clinical studies, biomedical correlate studies using Functional Magnetic Resonance Imaging (fMRI) have provided interesting data on the effects of acupuncture in the brain. Modulation of subcortical structures related to anxiety and mood with acupuncture have been reported in several studies.35,36,37 _____________________________________________________________________________________________ Description: A 63 year old male with a chief complaint of anxiety first presented to me in September 2009. The patient reported a “nervousness that had been under the surface for 20-25 years and now has become very apparent since retiring 2-3 years ago”. Despite concurrent use of a benzodiazepine and SSRI the patient continued to suffer from significant anxiety. He described his condition at initial intake as “my nerves are out of control”. The patient’s Medical History includes: bilateral hearing aids since 23 years of age, hypertension (HTN), hypercholesterolemia, benign prostatic hyperplasia (BPH), hemorrhoids, sexual difficulties, nocturia, diabetes mellitus type II, intermittent rashes, acid reflux 2-3x/wk, chronicxerostomia (since taking enablex), ptosis (R eyelid) / Horton’s syndrome, seasonal allergies/wheezing (1978-2006), and double pneumonia at 4 weeks old. Past surgical history includes “removal of a tumor on his thalamus” in 2006. A large incision was visible in his R hypochondriac area. Patients height is 5’11” and weight is 205 lbs. His Blood pressure was 120/65 mm/Hg while on antihypertensives. Current Medications and supplements include: Temazepam (restoril) prn 30 mg, 4 years; Terazasin (hytrin) 10mg, 2 years; Enablex (darifenacin) 7.5 mg, 3 months; metformin (glucophage) 500mg, 5 years; lexapro (escitalopram oxalate) 5mg, 4 years; lisinopril (primivil, zestril), 4 years; lovostatin (altocor, mevacor) lactone, 1 year; amlodipine besylate (norvasc), 4 years; metamucil later prescribed for constipation caused by enablex; Prilosec, prn; and proventil inhaler, prn.
Additional Traditional Chinese Medicine Diagnostic Information
Patient reported: a neutral temperature, normal perspiration, occasional orthostatic hypotension, no gas or bloating, normal thirst, moderate energy level, disrupted sleep due to nocturia and waking early with anxiety.
At first visit the patient appeared visibly distressed. His tongue body was puffy with scallops, and slightly purple with a central crack and petechiae. The tongue coating was thick and yellow toward the back and thin and white in the front. His pulse was wiry and slippery overall; weaker in the chi positions; and weaker on the left side. Changes in his pulse occurred: at visit 15, “much more relaxed” without a pronounced wiry quality; and at visit 21, “calm”. Changes in his tongue varied and were not permanent: at visit 15, the tongue did not have purple coloring; at visit 18, it appeared purple again, disappeared at visit 19, and returned again at visit 22.
Diagnosis and Rational
Although anxiety can present with a multifactorial diagnosis, I found my patient to have a simple diagnosis of Liver qi stagnation with Kidney deficiency. I gave him the diagnosis of Liver qi stagnation due to his pronounced wiry left pulse, slightly purple tongue, and significant irritability. I also gave him a secondary diagnosis of Kidney yin and yang deficiency due to his weak pulses in both chi positions, his history of severe illness in infancy and need for bilateral hearing aides at the young age of 23 years old. Etiology and Pathogenesis
The patient reported that since he retired, his nervous energy and over-thinking “had no where to go”. Pent up or unfulfilled desires will create liver qi stagnation. Poor diet and lack of exercise will also create stagnation, and inhibit the coursing and dispersing function of the Liver. Liver qi depression is closely related to blood and yin vacuity, spleen qi vacuity, and kidney yang qi vacuity. And as blood, yin, and kidney yang all decrease as we age, older persons are naturally more vulnerable to the pattern of liver qi stagnation.23 In addition, severe illness at a very young age and overwork can prematurely deplete the Kidneys. And as the Kidney and Liver have a close relationship our patients Liver was more susceptible to imbalance.
Treatment Principles, Rational, and Plan
Course the Liver qi, relieve stagnation, calm shen and tonify the Kidneys.
Acupuncture Treatment
The most common points, used more than 75% of visits were: KD3, ST36, LV3, and LI4. KD3 was used to tonify both Kidney yin and yang. ST36 to engender postnatal qi. The 4 gates: LV3 and LI4 to course the qi and blood and relieve stagnation. LV3 also calms the mind and settles the ethereal soul. LI4 also regulates the ascending and descending of qi to and from the head and clears heat.38 Other points used were: DU20 and DU24 to descend the qi and calm the mind; si shen cong and yin tang to calm the spirit; HT7, shenmen, to calm the mind and relieve anxiety; SP6 to nourish blood and yin and calm the mind, especially the emotions of pensiveness and worry; CV6, CV4, and LV8 were used to nourish the Liver and Kidney and tonify qi and Blood. 38 SP9 and ST40 were used to drain damp and disperse phlegm. ST40 also calms the mind and relieves anxiety and is useful for a feeling of tightness in the chest. To help with urinary difficulty, CV3 and BL65 were used. To treat his scar pain, 6 needles were placed superficially around the scar, with the needles pointing towards the scar using the “surround the dragon” technique. CV14 and CV17 were also used to relieve tension caused by the scar. To treat ptosis of his right eyelid: GB14, ST2, tai yang, GB37, yu yao, and SJ23 were used. To treat episodes of GERD: CV12, GB34, GB41, PC6, ST34, ST44, and PC8 were used. Other points used infrequently, less than 15%, were: ST34 and SP10 for knee pain; LU9, LI10 to tonify the Lungs and qi; SJ17 for disorientation; BL7 sinus congestion; ST25 loose stool; SJ6 constipation; LI2 and LU5 for dry mouth; BL57 and Er Bai for hemorrhoids; and KD7 to tonify Kidney yang. 38 Herbal Formula Therapy None. Acupuncture only.
Dietary and Lifestyle Adjustments Despite encouragement and education, the patient’s diet and
exercise practices remained relatively unchanged. The patient would vacillate between healthy
and non healthy eating habits. Exercise was intermittent at best.
______________________________________________________________________________ The patient responded well to treatment with significant subjective reports from himself and his wife of improvement in his anxiety. Objectively, he was able to discontinue his benzodiazepine within a few weeks of treatment and discontinue his SSRI under the supervision of his M.D. after 8 months of acupuncture treatment. The patient reported the following qualitative descriptions during his treatment: visit 2 - irritability decreased, wife comments on how less irritable he is; visit 6 - stopped xanax; visit 12 “feels really good”; visit 18 “feels relaxed”; visit 19 “sleep is excellent”; visit 20 “feels acupuncture has balanced out his nerves” (patient decreases frequency of visits from 2x/wk to 1x/wk visit); visit 21 - begins to decrease doseage of Lexapro under the guidance of his M.D.; visit 36 he is off lexapro (7/8/10); and at final visit reports that he “feels better than he has felt in a long time”.
Generalized anxiety disorder can be a difficult disorder to treat. Short term anxiety may be effectively treated with benzodiazepines. However their long term use is not recommended as they have a high risk for dependency, drug tolerance and adverse events. SSRIs may offer relief to some patients. However others may not respond to treatment or are unable to tolerate the side effects of medication. This case is an example of GAD successfully treated with acupuncture. Anxiety symptoms improved concurrently with supervised discontinuance of anxiolytic medications by his M.D. As stated throughout this paper, any medication changes were made by his M.D. And the desire to discontinue these medications was initiated by the patient. GAD may significantly affect a patient’s quality of life and prove difficult to treat with biomedicine. Clinical trials and case studies show promising results for the treatment of generalized anxiety with acupuncture. As polypharmacy is a safety concern especially in the geriatric population, acupuncture may prove to be a viable treatment option. _________________________________________________________________________ 1. Wetherell JL, Lenze EJ, Stanley MA. Evidence-based treatment of geriatric anxiety disorders. Psychiatr Clin N Am. 2005;28:871-896.
2. Kessler RC, Chiu WT, Demler O, Walters EE. Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCR-R). Arch Gen Psychiatry, 2005;62(6);617-27. 3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, American Psychiatric Association, Washington, DC, 2000.
4. Bland RC, Newman SC, Orn H. Prevalence of psychiatric disorders in the elderly in Edmonton. Acta Psychiatr Scand Suppl. 1988;338:57-63.
5. Beekman AT, Bremmer MA, Deeg DJ, et al. Anxiety disorders in later life: a report from the Longitudinal Aging Study Amsterdam. Int J Geriatr Psychiatry. 1998;13(10):717-26.
6. Gurian BS, Minor JH. Anxiety in the elderly: treatment and research. In: Salzman C, Lebowitz BD, editors. Clinical presentation of anxiety in the elderly. New York: Springer; 191. p. 31-44.
7. deBeurs E, Beekman AT, van Balkom AJ, Deeg DJ, et al. Consequences of anxiety in older persons: its effect on disability, well-being and use of health services. Psychol Med 1999;29(3):583-93.
8. Kim HF, Kunik ME, Molinari VA, et al. Functional impairment in COPD patients: the impact of anxiety and depression. Psychosomatics 2000;41(6):465-71. 9. Brenes GA, Guralnik JM, Williamson JD, et al. The influence of anxiety on the progression of disability. J Am Geriatr Soc 2005;53(1)34-9.
10.Lenze EJ, Rogers JC, Martire LM, et al. The association of late-life depression and anxiety with physical disability: a review of the literature and prospectus for future research. Am J Geriatr Psychiatry 2001;9(2):113-35.
11.Bourland SL, Stanley MA, Snyder AG, et al. Quality of life in older adults with generalized anxiety disorder. Aging Ment Health 2000;4(4):315-23.
12.Stanley MA, Diefenbach GJ, Hopko DR, et al. The nature of generalized anxiety in older primary care patients: preliminary findings. Journal of Psychopathology and Behavioral Assessment 2003;25(4):273-80. 13.Wetherell JL, Thorp SR, Patterson TL, et al. Quality of life in geriatric generalized anxiety disorder: a preliminary investigation. J Psychiatr Res 2004;38(3):305-12. 15.Etkin A, Prater KE, Schatzberg AF, Menon V, Greicius MD Disrupted amygdala subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder.Arch Gen Psychiatry. 2009;66(12):1361.
16.Wu JC, Buchsbaum MS, Hershey TG, Hazlett E, Sicotte N, Johnson JC. PET in generalized anxiety disorder. Biol Psychiatry. 1991;29(12):1181.
20.Rosemary D. Laird, MD Assistant Professor of Medicine, Universtiy of Kansas Medical Center, Center on Aging, power point presentation.
21.American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults: The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. JAGS. 2012;60(4):616-631. 22.Maciocia, Giovanni. The Practice of Chinese Medicine. Churchill Livingston. New York. 23.Flaws B and Lake J. Chinese Medical Psychiatry: A textbook and clinical manual. Colorado: 24.Rossi E. Shen: Psycho-Emotional Aspects of Chinese Medicine. China: Churchill Livingstone 25.Li Q and Liu D. Zhongyi jingshen bingxue (Psychiatry in Chinese medicine). China: Tianjing 26.Pilkington K, Kirkwood G, Rampes H, Cummings M, Richardson J. Acupuncture for anxiety and anxiety disorders - a systematic review. Acu in Med 2007;25(l-2):l-10.
27.Liu G, Zhang Y, Liu A. Observation of the curative effect of acu-moxibustion plus systematic desensitization on anxiety neurosis. Shanghai J Acupuncture Moxibustion 1998; 17(4): 17-8.
28.Eich H, Agelink MW, Lehmann E, Lemmer W, Klieser E. Acupuncture in patients with minor depressive episodes and generalized anxiety. Results of an experimental study. Fortschr Neurol Psychiatr 2000;68(3):137-44.
29.Chao-Ying W et al. The electroacupuncture treatment of 20 cases of anxiety disorder. Hunan Journal of Chinese Medicine 2003;3:26. (abstracted and translated by Wolfe HL. Anxiety Disorder & Electroacupuncture. Blue Poppy Press 2003).
30.Zhang H, Zeng Z, Deng H. Acupuncture treatment for 157 cases of anxiety neurosis. J Tradit 31.Yuan Q, Li JN, Liu B, Wu ZF, Jin R. Effect of jin-3-needling therapy on plasma corticosteroid, adrenocorticotrophic hormone and platelet 5-HT levels in patients with generalized anxiety disorder. Chin J Integr Med 2007;13(4):264-8.
32.Agelink MW, Sanner D, Eich H, Pach J, Bertling R, Lemmer W, Klieser E, Lehmann E. Does acupuncture influence the cardiac autonomic nervous system in patients with minor depression or anxiety disorders. Fortschr Neurol Psychiatr 2003;71(3):141-9.
33.Wang Z, Li Y, and Lin H . Acupuncture treatment of generalized anxiety disorder. J Tradit 34.Errington-Evans N. Acupuncture in chronic non-responding anxiety/depression patients: a case series. Acu in Med 2009;27(3):133-134.
35.Fang J, Wang X, Liu H, et al. The limbic-prefrontal network modulated by electroacupuncture at CV4 and CV12. Evidenced-Based Complementary and Alternative Medicine. 2012;2012:515893. Epub 2012 Jan 16.
36.Feng Y, Bai L, Zhang W et al. Investigation of acupoint specificity by multivariate granger causality analysis from functional MRI data. J Magn Reson Imaging. 2011;34(1):31-42.
37.Duan DM, Tu Y, Jiao S, Qin W. The relevance between symptoms and magnetic resonance imaging analysis of the hippocampus of depressed patients given electro-acupuncture combined with fluoxetine intervention - a randomized controlled trial. Chin J Integr Med. 2011;17(3):190-199. 38.Deadman T and Al-Khafaji M. A Manual of Acupuncture. England: Journal of Chinese


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