A systematic review was conducted to examine the extent to which research supports the use of acupuncture in treating insomnia. Of the thirty studies included in the review, twelve were clinical trials with only three double-blinded. High-quality randomized clinical trials of acupuncture in treating insomnia, with proper sham and blinding procedures, will be required in the future.
A systematic review was conducted to examine the extent to which research supports the use of acupuncture in treating insomnia. Of the thirty studies included in the review, twelve were clinical trials with only three double-blinded. High-quality randomized clinical trials of acupuncture in treating insomnia, with proper sham and blinding procedures, will be required in the future.
A systematic review was conducted to examine the extent to which research supports the use of acupuncture in treating insomnia. Of the thirty studies included in the review, twelve were clinical trials with only three double-blinded. High-quality randomized clinical trials of acupuncture in treating insomnia, with proper sham and blinding procedures, will be required in the future.
in treating insomnia Wei Huang a, *, Nancy Kutner b , Donald L. Bliwise c a VA Medical Center at Atlanta, Department of Physical Medicine and Rehabilitation, Emory University School of Medicine, 1670 Clairmont Road, Decatur, GA 30033, USA b Department of Rehabilitation Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA c Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA KEYWORDS Acupuncture; Insomnia; Sleep; Traditional Chinese Medicine Summary To examine the extent to which research supports the use of acupunc- ture in treating insomnia, a systematic review was conducted that included not only clinical trials, but also case series in both English and Chinese literature. Thirty studies were included in the review, 93% of which showed positive treatment effects of acupuncture in improving various aspects of sleep. Although acupuncture has been demonstrated to be safe and holds great potential to be an effective treatment modality for insomnia, the evidence is limited by the quality of these studies and mixed results from those with sham (or unreal treatment) controls. Of the thirty studies, twelve were clinical trials with only three double-blinded. Only ve used sham controls, and of these, four showed statistically signicant differences favoring real treatments; however, none evaluated the adequacy of sham assignment. Three studies used actigraphy or polysomnography as objective outcome measures. The considerable heterogeneity of acupuncture techniques and acupoint selections among all studies made the results difcult to compare and integrate. High-quality randomized clinical trials of acupuncture in treating insomnia, with proper sham and blinding procedures will be required in the future. This review highlights aspects of acupuncture treatments important to guide future research and clinical practice. Published by Elsevier Ltd. Introduction Insomnia is dened as sleep onset, sleep mainte- nance, and early awakening problems in the presence of adequate opportunity and circum- stance for sleep. 1 It affects more than 60 million Americans each year. Approximately 1/3 of * Corresponding author. E-mail addresses: wei.huang@emoryhealthcare.org (W. Huang), nkutner@emory.edu (N. Kutner), dbliwis@emory.edu (D.L. Bliwise). 1087-0792/$ - see front matter Published by Elsevier Ltd. doi:10.1016/j.smrv.2008.04.002 Sleep Medicine Reviews (2009) 13, 73e104 www.elsevier.com/locate/smrv general population 2 and half of managed care patients report insomnia. 3 Many risk factors have been identied for insomnia including female gender, older age, comorbid chronic medical conditions and psychiatric disorders, various medications, and life style factors, e.g., caffeine intake, smoking, and reduced physical activity. 1 Due to limitations and concerns with current available insomnia treatments, a sizable propor- tion of the population, especially in Europe and China, has turned to complementary alternative medicine, including acupuncture, in searching for a treatment modality with potential efcacy and few side effects. 4 In the US, acupuncture has seen very limited use in sleep and there have been limited literature reviews to examine this modal- ity. 5e7 The most recent review of acupuncture in sleep 5 attempted a meta-analysis and failed to demonstrate signicant efcacy of acupuncture compared with various control treatments. That review was limited because the studies included were selected from English literature only and different acupuncture techniques, control groups, and outcome measures were not reviewed systematically. Acupuncture is a clinical treatment modality in an independent medical system of Traditional Chinese Medicine (TCM), 8 which was developed over 3000 years ago under the inuence of oriental philosophical theories, such as Yin-Yang, Five Elements and Dialectical Unity. It has progressed through many years of clinical observations and practice. In TCM, there is no concept of isolated organ function but rather a focus on interactions among different organ systems. TCM diagnoses connote syndromes in Western medicine, with a combination of symptoms. For instance, heart is not just the 4-chambered blood-pump. It not only controls vascular circulation but also is dened as the center of life as well as mind, with its external manifestations on tongue and face. Although these connections are not intuitive in Western medicine, they arise from long-term clinical observations. For example, TCM teaches that people with cardiac conditions often have abnormal facial complexion and tongue color, anxiety, sleep problems and cognitive dysfunc- tion. 9 Heart deciency is one of the TCM diagnoses for insomnia (Table 1). Interestingly, in Western medicine, such associations also play a role in physical diagnosis. For instance, blue lips and ngers in children may indicate cyanosis as a part of congenital heart disease. In addition, Western medicine increasingly acknowledges the relationship of insomnia to both cardiovascular diseases and psychological disturbances. 10,11 In TCM, poor sleep can also be associated with other organ system dysfunction. By performing a complete review of all symptoms, in combination with physical examination, particularly pulse and tongue examinations, one arrives at a TCM diag- nosis for insomnia (Table 1). 9,12 The TCM diag- noses can also change from time to time due to progression or resolution of various symptoms. Therefore, TCM treatments, including acupunc- ture, are targeted towards regulating and balancing the functions of different organ systems. In clinical practice, patients with the same sleep problem can get different acupuncture treat- ments, depending on individual differences in both presumed etiology and dynamic changes of symp- toms over time. Basic acupuncture technique is to insert acupuncture needles into selected acupoints along meridians, which are the channels believed to guide the ow of bio-energy in human bodies. Through many years of practice, with various interpretations and innovations worldwide, acupuncture has evolved into numerous treatment techniques with acupoint selections varying from practitioner to practitioner 13 (see Table 2 for those techniques included in this review). Given the challenge of this complex diagnostic and therapeutic system for treating insomnia using acupuncture, a more complete and systematic review of available literature is necessary to further guide future clinical and research directions. By widening our perspective on the range of study designs and types of broadly dened acupuncture techniques, we hope, in this review, to highlight critical areas that should be addressed in future clinical trials and studies of underlying mechanisms. Materials and methods Search methods for identication of studies Computerized databases, including MEDLINE (1950e2007), All Evidence-Based Medicine (EBM) ReviewsdCochrane Database of Systematic Reviews (DSR), American College of Physicians (ACP) Journal Club, Database of Abstracts of Reviews of Effects (DARE), and Cochrane Controlled Trials Register (CCTR) (through July 2007), PsycINFO (1806e2007), CINAHLdCumula- tive Index to Nursing & Allied Health Literature (1982e2007) were searched under key words acupuncture, and insomnia or sleep. In addition, relevant references in the reviewed articles were also included, if obtainable via 74 W. Huang et al. Table 1 Traditional Chinese Medicine insomnia diagnoses and acupuncture treatment rules TCM diagnoses Common clinical symptoms and signs Common sleep problems Possible disease condition Acupuncture treatment rules Heart and spleen deciency Palpitation, easy fatigue, vertigo/dizziness, sweaty, no taste in mouth, anorexia, amnesia, females with menstruation abnormalities; pale complexion, pale tongue proper with thin-whitish covering, ne and weak pulse Insomnia with difculty remaining asleep: frequent dreams and awakenings, hard to go back to sleep once awake Acute (from extreme worries and fatigue), chronic To nourish heart and to strengthen spleen Incoordination between the heart and the kidney; or kidney Yin deciency; or Yin deciency leading to excessive re Vexation, vertigo/dizziness, tinnitus, palpitation, amnesia, low back ache, nocturia, feverish sensation in the chest, palms and soles, dry mouth, sore throat, impotence if severe; abscesses over the mouth and tongue, red tongue proper, thready pulse Insomnia of all kinds Chronic, usually from long-term medical conditions To nourish Yin and drain re Heart and gallbladder Qi a deciency Palpitation, alertness, fearful, shortness of breath, lassitude; pale tongue proper, thin-whitish covering, taut-ne pulse Insomnia with frequent dreams and mid-sleep startling awakenings Acute, chronic To nourish Qi, calm down spirits and mind Disturbance of liver yang; or excessive liver re due to emotional suppression Anxiety/depression, angry (internal or external), irritable, dry mouth or having bitter taste in mouth, dizziness/headaches, bloating feeling or pain in the chest, constipation; red eyes, dark yellow urine, red tongue proper, yellowish covering, taut-rapid pulse Insomnia with onset difculty, if asleep, wakes up early Acute, chronic To drain liver re, calm down mind Liver and kidney Yin deciency Dizziness, headaches, anxiety and irritability, back and leg soreness and weakness, yellowish urine; tongue proper red with thin yellow coating, deep and ne pulse Insomnia with frequent dreams Chronic To nourish kidney and liver Yin, drain re if present Disturbance of heart due to phlegm heat Always feeling bad, worrisome, c/o vertigo/dizziness, fullness in the head/chest, bitter taste in mouth, sputum production, aversion to food, acid regurgitation, hypochondria; reddish tongue proper (tip), yellow and greasy coating, slippery and rapid pulse Insomnia Chronic To drain heat, dissolve sputum, regulate stomach function, and calm the mind Unsynchronized spleen and stomach Fullness in the stomach, anxious and cannot calm down, hiccups/belching, regurgitation. If chronic: bad breaths, thick and greasy tongue coating, slippery pulse Sleep onset difculty Acutedusually food stagnation; if chronicdusually long- term GI conditions To stimulate stomach motility, assist in digestion All abbreviations, except for those representing different study groups as indicated in the table, are listed in the Appendices. a Qi: a concept in Traditional Chinese Medicine that refers to the vital energy that sustains life activities and physiological functions of viscera and organs. A c u p u n c t u r e f o r i n s o m n i a 7 5 Table 2 Introduction of acupuncture techniques mentioned in the included studies Acupuncture techniques Description Regular body acupuncture Fine gauge acupuncture needles, usually of gauge 28e38*, penetrate the skin at selected acupoints out of 14 main meridians and extra-meridian points to achieve desired treatment effects. Different schools of acupuncture practice use different manipulations, such as manual thrusting and twirling, electrical stimulation, or simply leaving the needles in for certain amount of time. In TCM, the depth of the needles depends on the chosen acupoint, goal of treatment, age of the patients, and other variables. *A regular injection needle is of gauge 22e25; the larger the number, the smaller the needle size. Special body acupuncture Intradermal needle This technique leaves acupuncture needles embedded in the acupoints for prolonged period of time, from 24 h to a week. Plum blossom needle A piece of equipment made of 5e7 needles at one end (plum blossom shaped) and a handle at the other end is used to tap usually a large skin area, such as back, shoulder, or gluteal region. The stimulation intensity depends on the tapping intensity. The goal result ranges from skin redness to slight bleeding. Rolling needle A new type of multiple-needle equipment with dull needle-shaped spikes attached to a round shaft, which can be rolled to stimulate an entire meridian, for instance back gall-bladder meridian. The goal is to produce skin redness. Hydro-needle Instead of dry needle, hydro-needle technique injects various medications, such as herbal medications or local anesthetics into acupoints. Herbal acupoint taping Use herb soaked tapes to cover acupoint(s). The idea is to have the herb penetrating into the body and produce treatment effects. Because skin is impermeable to outside material, this technique is only commonly used at umbilical region. Dual-acupoints needling Use one needle to penetrate two acupoints at the same time. Auricular acupuncture Auricular acupoints, initially described in TCM and later advanced into a microsystem by a French physician, Paul Nogier, can be used to treat diseases with various techniques. The ones used in the reviewed studies include needling, semen vaccariae seeds taping and pressing to produce pressure, magnetic pearls taping to give presumed continuous magnetic eld stimulation, lidocaine injection, laser irradiation, blood letting, all of which are designed to induce or block stimulation at the auricular acupoints. Scalp acupuncture Although there are many scalp points along some traditional acupuncture meridians, scalp acupuncture is a specic terminology used internationally to describe a specic acupuncture treatment system, developed initially by Chinese acupuncturists and later systematized by a Japanese physician, Toshikatsu Yamamoto. This system is similar to the auricular system where zones of the body are reected on the scalp regions. Needles are usually inserted within a thin layer of loose tissue beneath the scalp surface at a low angle, many times with electro-stimulation. The most used applications are neurological conditions. Moxibustion Moxa is made of dry and grounded mugwort herb, which is believed to increase blood circulation. Moxibustion is the burning of moxa directly or indirectly at acupoints. Direct application can cause scarring, which was used originally but is now less acceptable. Indirect application is more commonly used to transmit heat from moxibustion to the acupoints via various ways. In TCM, this technique is commonly used to purge cold and warm up meridian for the treatment of certain conditions. Sham acupuncture A technique that is only used in acupuncture research to mimic similar psychological experience for the subjects that could happened when they interact with the interventionist, assuming the acupuncture is done to them. Various ways of achieving this have been adopted throughout the acupuncture research history, such as applying pressure or needling at different points than real acupoints, using the same acupoints but without needle penetration, using fake needles, and etc. The details of sham acupuncture that were used in the studies included in this review 15,19,20,22,24 are listed with each of those individual studies in Table 3. All abbreviations, except for those representing different study groups as indicated in the table, are listed in the Appendices. 7 6 W . H u a n g e t a l . interlibrary loan within the US. Due to the limita- tion on Chinese databases access, we were unable to retrieve the entire body of Chinese literature on acupuncture and insomnia and only included studies published in peer-reviewed journals that are searchable through the above-mentioned databases. A total of 332 articles were screened initially according to the following selection criteria: Inclusion criteria: 1. Articles written in English or Chinese languages. 2. Human studies. 3. Original case series or clinical trials published in peer-reviewed journals. Exclusion criteria: 1. Although acupuncture was mentioned, the main treatment modality was complemen- tary alternative medicine. 2. Treatments focused on other sleep disorders such as sleep apnea, night terrors, or somnambulism. 3. Multiple publications reporting the same group of participants or their subsets. After applying these criteria, 30 articles of insomnia treated with acupuncture were selected and reviewed in detail in the following categories: 1. Clinical trials with or without blinding (n12). 2. Case series (n18). Methods of review We attempted to extract the following data when possible: 1. Author, year of publication 2. Country 3. Study design: a. Clinical trials: group assignment method, control groups, blinding (single, double) and blinding process assessment, risk of bias. b. Case series: control of confounders, expo- sure bias, attrition bias, measurement bias, risk of bias. 4. Population studied: age, gender, referral sources, sleep difculty description or insomnia diagnosis criteria, duration of the condition 5. Total number of subjects 6. Study groups and number of subjects in each group 7. Detailed regimen for intervention or control 8. Acupoints used, including acupuncture techniques 9. Outcome measurements 10. Evaluation time points 11. Results 12. Notes: dropouts description, missing data and other relevant notes Quality assessment The quality of the studies was assessed in the following areas according to the Cochrane Hand- book for Systemic Reviews of Interventions 14 : 1. Selection bias: systematic differences in comparison groups (adequacy of randomiza- tion process or control of confounders). 2. Performance bias: systematic differences in care provided apart from the intervention being evaluated (treatment blinding process or measurement of exposure). 3. Attrition bias: systematic differences in with- drawals/dropouts from the trial or complete- ness of follow-up. 4. Detection bias: systematic differences in outcome assessment (outcome measure blinding process or the bias of measurements). The overall quality of the studies is summarized into the following three categories after assessing the above four areas: A. Low risk of bias: all the validity criteria were met. B. Moderate risk of bias: at least one validity criterion was only partly met. C. High risk of bias: at least one validity criterion was completely not met. Results Clinical trials of acupuncture in treating insomnia (details see Table 3) 1. Included studies: 12. 15e26 2. Groupassignment method: 8/12 16,18,20e24,26 not reported; for the remaining 4 studies, 15,17,19,25 reported methods vary signicantly from participation date convenience to computer- ized randomization. Acupuncture for insomnia 77 Table 3 Clinical trials of acupuncture in treating insomnia Author (year, area) Study design Population N Study groups Treatment Acupoints Eval F/U Results Notes Chen (1999, Taiwan) 15 RCT: Group assignment method: Randomized block; Control: a. sham acupressure, b. conversation; Blinding: single blinding of real and sham groups (subjects); Risk of bias: category B. Age: 61e98 yr; Gender: F:M32:52; Referral: a public assisted- living facility; Sleep difculty: insomnia with PSQI >5; Duration of the condition: NR. 84 3 groups (n28 for each group): acupressure group (ACU); sham acupressure group (SHAM), and control group (CON). Both ACU & SHAM groups: 5 min nger & 10 min acupoint massage, Rx 1e10 pm, 5 per wk for 3 wks (total 15Rx); ACU: real acupoints with Deqi a . SHAM: 1 cm to 3cun b away from true ones. CON: talk only. GV20, GB20, Anmian, Shenmen in the ears and hands. Subjective: PSQI Chinese version. Pre- and post- intervention. Signicant differences in PSQI scores of nocturnal awakening and night wakeful time in the ACU group in comparison to the other two groups, which did not have statistical difference. However, there were improvements in all groups. 84 out of 124 subjects nished the project. Each group had 6 dropouts, other 22 unnished NR. Cui (2003, China) 16 CT: Group assignment method: NR; Control: medication control; Blinding: Not blinded; Risk of bias: category C. Age: 28e67 yr; Gender: F:M58:72; Referral: outpt; Sleep difculty: insomnia of TCM Dx interior- stirring by phlegm-heat, self-report SE <60%; Duration of the condition: NR. 120 2 groups (n60 for each group): acupuncture treatment group (ACU); and medication control group (MED). Both groups: estazolam 1e2 mg daily; ACU: acupuncture with manual manipulations (duration NR), daily Rx10 days1 course, total 3 courses (30Rx). MED: medication only. GV20, GV24, Sishen cong, HT7, PC6, CV12, ST40, SP4. Subjective: Therapeutic effects: cureddSE> 75% without med; markedly effectivedSE improve by 10e20% without med; improvede SE improve by <10% with reduced med dose by 3/4; ineffectived no obvious improvement. Post- intervention. Cured and markedly improved signicantly more in the ACU group than the MED group. 7 8 W . H u a n g e t a l . da Silva (2005, Brazil) 17 CT: Group assignment method: participation day of the week; Control: study/ education control; Blinding: Not blinded; Risk of bias: category C. Age: 15e39 yr; Gender: Females; Referral: pregnant women attending prenatal program; Sleep difculty: insomnia due to pregnancy and not taking hypnotics; Duration of the condition: 15e30 wks of gestation. 22 >2 groups: acupuncture (ACU, n17 initial); control (CON, n13 initial). Both groups: sleep hygiene education; ACU: plus acupuncture 1e2x/wk for 8 wks, each session average 12 needles for 25 min, Deqi with manipulation. Total 8e12Rx. CON: education only. HT7, PC6, GB21, GV20, CV17, Anmian, and Yintang optional (up to 4 points each session). Subjective: numerical rating scale from 0 to 10 for severity of insomnia. Baseline, q2wks (5 evals). The change in the insomnia scores during the course of acupuncture treatment was signicantly higher than the control group; no difference in new-born babies data and no severe side effects. Dropouts (27%): 5 from ACU group, 3 from CON group. Gao (1995, China) 18 CT: Group assignment method: NR; Control: a. body acupuncture, b. medication; Blinding: none; Risk of bias: category C. Age: 18e62 yr; Gender: F:M76:180*; Referral: outpt clinic; Sleep difculty: insomnia; Duration of the condition: 5 days to 21 yr. 258* 3 groups: auricular seeds pressure (AUR, n128); body acupuncture (BOD, n65); medications (MED, n65). AUR: auricular vaccaria seeds pressing 2e3x per day, each 3e 5 min (qhs more), every other or 2 days change; 1e12Rx. BOD: individualized daily body acupuncture 20e 30 min; 5e20 Rx. Both groups: No meds. MED: Surazepam 2e 4 mg qhs; 10 days1 course. AUR: Main: shenmen, HT, brain; adjunct (1e2): SP, LR, GB, ST, KI. BOD: individualized treatments. Subjective: curedd shortened sleep onset, symptoms resolve, and sleep 6e8 h per night; improvedd improved symptoms, sleep 4e5 h per night; no responsedno symptom improvements; sleep <4 h/night. One case reported in the article had 2 yr of f/u. Statistical signicant difference in clinical effectiveness: best in AUR group, then in BOD group, then MED group. *Inconsistent totals on number of cases. (continued on next page) A c u p u n c t u r e f o r i n s o m n i a 7 9 Table 3 (continued) Author (year, area) Study design Population N Study groups Treatment Acupoints Eval F/U Results Notes Kim (2004, Korea) 19 RCT: Group assignment method: random digits; Control: sham acupuncture control; Blinding: independent evaluator single blinded, no blinding process evaluation reported; Risk of bias: category B. Age: RA 65.19.0, SA 68.310.4; Gender: F:M13:17; Referral: stroke inpatients; Sleep difculty: persistent insomnia > 3 nights in a row, ISI > 15, patients on hypnotics were excluded. Duration of the condition: post stroke-onset. 30 2 groups (n15 each group): real acupuncture group (RA); and sham acupuncture group (SA). Real: intradermal acupuncture needle taped down for 2 days; Sham: same points and taping but needles did not penetrate the skin. Total 1 Rx. b/l HT7 and PC6. Subjective: Questionnaires, Insomnia Severity Index (ISI), and Athens Insomnia Scale. Morning before, 1 and 2 days after. All assessed sleep outcomes improved signicantly in the RA group compared to the SA group, except for sleep latency and ease of falling asleep after wakening. Li (2005, China) 20 CT: Group assignment method: NR; Control: sham and medication control; Blinding: single blinded (subjects), no blinding process evaluation reported; Risk of bias: category B. Age: 58e79 yr; Gender: F:M28:22; Referral: outpatient acupuncture clinic; Sleep difculty: primary insomnia* Duration of the condition: 2 months to 9 yr. 50 2 groups (n25 each): treatment group and control group. Treatment: gingkgo leaf preparation taped on acupoint, VitC po daily; Control: starch taped on the same acupoint, estazolam (regular dosage) po daily. Both groups: tape change every 3 days, total 7Rx. CV8 Subjective: SEsleep time/ bed time (%). 5 stages: stage 0: SE>80%; stage 1: SE 70e80%; stage 2: SE 60e70%; stage 3: SE 50e 60%; stage 4 SE 40e50%; stage 5 SE <40%. Pre and post- treatments. Sleep improvement rates (changes of stages): treatment group 84% and control group 68% (no statistical signicance). Sleep quality, however, is signicantly better in the treatment group. *Dx by WHO International Statistical Classication of Diseases and Related Health Problems (10th edition, 1993). 8 0 W . H u a n g e t a l . Lian (1990, China) 21 CT: Group assignment method: NR; Control: medication control group; Blinding: none; Risk of bias: category C. Age: mean 21- over 51; Gender: F:M92:68; Referral: outpts; Sleep difculty: insomnia; Duration of the condition: 20 days to 7 yr. 160 2 groups (n80 each): auricular pressing (AP) group and medication (MED) group. AP: semen vaccariae seeds taped at auricular points bilaterally, changed every 3 days, patients to press the points 1 h before sleep qhs, total 30 days. MED: diazepam 10 mg qhs30 days. b/l ear points: shenmen, HT, LR, Endocrine, sub-cortex, sympathetic, cervical vertebrae. Subjective: Clinical effective criteria: cureddsleep well 7e8 h/night with symptoms disappeared; improvedd sleep 4e5 h/ night; ineffectived insomnia not ameliorated. Post-treatments. During initial stage, MED was more effective, but efcacy reduced with time; on the contrary, AP could be enhanced with time. At the end, there was signicantly increased response rate in the AP group. Suen (2002, Hong-Kong) 22 CT: Group assignment method: NR; Control: a. seed taping with pressure, b. no pressure sham control; Blinding: double blinded (both evaluator and participants), no blinding process evaluation reported; Risk of bias: B. Age: 60 yr (mean 81.7); Gender: F: M110:10; Referral: 12 homes for the elderly; Sleep difculty: 3 nights qw; actigraphic SE<85%; no severe medical or psych conditions. Duration of the condition: 6 months to > 20 yr. 120 3 study groups: Junci Medulla (no weight or active physiology-sham, n30); Semen Vaccariae (pressure, n30); experimental: auricular magnetic pearls (n60). Subjects were asked not to take any sleeping pills during the study period; all three groups had taping of material to the auricular acupoints on alternating ear every 3 days for 3 wks total. Ear points: Shenmen, HT, KI, LR, SP, occiput, sub-cortex. Objective: wrist actigraphy monitoring, Subjective: Sleep questionnaire (including daily habits that might potentially affect sleep), and sleep diary lled out by staff of the homes for the elderly. 3 days baseline, 3 days during the intervention, 3 days post- intervention. 1. Signicant improvement in actigraphic SE, and nocturnal sleep time only in the experimental group. In addition, a signicant Y sleep latency and wake after sleep, [ total wake time. There was no difference b/w the 2 control groups. 2. TCM dx did not affect Rx results; 3. the younger age the better result. Dropouts were all replaced; Suen 2003 27 followed 15 subjects at 1-, 3-, and 6-month and showed sustained effects. (continued on next page) A c u p u n c t u r e f o r i n s o m n i a 8 1 Table 3 (continued) Author (year, area) Study design Population N Study groups Treatment Acupoints Eval F/U Results Notes Tsay (2004, Taiwan) 23 CT: Group assignment method: NR; Control: a. TEAS: transcutaneous electrical acupoint stim, b. usual care; Blinding: double blinded (subjects, care providers and interviewer), blinding process evaluation NR; Risk of bias: category B. Age: 58.1612.19; Gender: F:M66%:34%; Referral: ESRD outpt on HD 3 months, c/o fatigue, with no major chronic and psych conditions, or dementia; Sleep difculty: PSQI 5, BDI 10; Duration of the condition: NR. 106 3 groups (n36 to start with each group): acupressure (ACU), TEAS, and usual care control. Both ACU & TEAS: 3x/wk4 wks (12 Rx), each session of relaxation massage (5 min)Rx 3 min at each acupoint. ACU: nger acupressure (3e 4 kg) with Deqi sensation; TEAS: 2/100 Hz stim. b/l KI1, ST36, GB34, SP6. Subjective: Piper Fatigue Scale, PSQI, and BDI. Pre-baseline, 11 data points during Rx, and post- intervention. No difference b/w ACU and TEAS groups, both signicantly better than control group in fatigue level, PSQI total score, self-reported sleep quality, and depression scores. Dropouts: 1 in ACU, 1 in usual care control. Tsay (2003, Taiwan) 24 CT: Group assignment method: NR; Control: a. sham control, b. usual care; Blinding: double blinded (subjects, care providers and interviewer), no blinding process evaluation reported; Risk of bias: category B Age: 55.5212.98; Gender: F:M56:42; Referral: ESRD outpt on HD, with no major chronic and psych conditions, or dementia; Sleep difculty: PSQI 5; Duration of the condition: NR. 98 3 groups (n35 each to start with): real acupressure group, sham acupressure group, and usual care control group. Both real and sham: 3x/wk4 wks (12 Rx), each session of relaxation massage 5 min plus acupressure 3 min each point (total 14 min); nger pressure of 3e4 kg. Real: at acupoints; Sham: 1 cm away from real points HT7, KI1, and ear Shenmen Subjective: PSQI, subject sleep log, Medical outcome study SF-36. Pre-treatment; 8 data points during intervention; post-treatment. Acupressure group did signicantly better than the control; no difference b/w real and sham; quick improvement was observed after 2e3 sessions. Dropouts: 3 in sham, 4 in control. 8 2 W . H u a n g e t a l . Wang (2006, China) 25 RCT: Group assignment method: computerized random number generation; Multicenter: 3; Control: medication control group; Blinding: none; Risk of bias: category C. Age: mean 16e75; Gender: F:M108:72; Referral: outpts; Sleep difculty: primary insomnia with sleep latency > 30 min more than 3x/wk, PSQI > 7; Duration of the condition: NR. 180 2 groups (n90 each): rolling needle and medication. Rolling needle: slow rolling 10 for 15e20 min to produce skin redness, 5x/wk for 4 wks (20 Rx), while tapering down/off sleeping medications; medication group: Clonazepam 4e6 mg qhs. Along the back Bladder meridian 1st and 2nd line (rolling up to down) and GV Meridian (rolling down to up). Subjective: Spitzer QoL Index; clinical eval: cured e[ SE >75% with disappearance of symptoms; improvede[ sleep duration and [ SE 25e74%, with improvement of symptoms; no effecte[ SE<25%, no obvious symptom improvement. Before, after, and 3 months f/u Signicantly improved CGI in the rolling needle group compared to medication group in the post-treatment eval but NOT at 3 months f/u; QoL was improved signicantly in the rolling needle group, lasting through f/u. Dropout 1 case during 3 months f/u in the control group. Yang (1988, China) 26 CT: Group assignment method: NR; Control: non- herbal soaked seeds in a. specic and b. non-specic treatment groups; Blinding: NR; Risk of bias: category C. Age: 62e91 yr; Gender: Only reported on treatment group: F:M39:23; Referral: outpts; Sleep difculty: insomnia; Duration of the condition: 2 wks to 20 yr. 127 3 groups: treatment group (TG, n62); control group I (CG-I, n40); control group II (CG-II, n25). TG: compositus Semen Vaccariae (cooked and soaked in herbs) and taped according to specic TCM dx; CG-I: Semen Vaccariae seeds taped according to specic TCM dx; CG-II: Semen Vaccariae seeds taped at xed points. All groups: 2e3 min qhs auricular seeds pressing (Purging or tonication) alternating ear 2e3x/wk, 10 Rx1 course; total 1e3courses. TG & CG-I: LR, KI for LR and KI Yin deciency; HT, SP for HT and SP deciency; HT, KI for Yin re due to Yin deciency; HT, SP, LU for phlegm-re. Frontal points if HA and dizziness. CG-II: HT, Shenmen, occiput, Sub- cortex. Subjective: markedly effective: Y latency, sleep 6e 8 h/night, resolved symptoms; improved: sleep >5 h/night, alleviation of symptoms; ineffective: no evident improvements. In the one case reported, 6 months f/u. There was signicant difference of therapeutic effects in the treatment group compared to the 2 control groups. There was no statistical difference b/w the 2 control groups. All abbreviations, except for those representing different study groups as indicated in the table, are listed in the Appendices. a Deqi: a term in acupuncture to describe the sensation of feeling energy owing through the inserted needle. See page 95 for detail and discussion. b cun: a measurement used in acupuncture to nd acupoints in relation to the patients own body size. For instance, the distance between the centre of the patella and the lateral malleolus is 16 cun and this 16 cun can be used to nd acupoints on the legs. Here, 3 cun is 4 nger breadths. A c u p u n c t u r e f o r i n s o m n i a 8 3 3. Control groups: 5/12 employed sham control (with or without other control groups) 15,19,20,22,24 ; other studies include usual care, 23,24 conversation, 15 education, 17 medi- cation, 16,18,20,21,25 or other active treatments. 22,26 4. Blinding process: 3/12 22e24 double-blinded and 3/12 15,19,20 single-blinded, but none of these studies reported an evaluation process of the adequacy of the blinding. 5. Subject age range: above 15 years old. 6. Sample size: 22e258. 7. Insomnia conditions: a. Primary insomnia (n2). 20,25 b. Comorbid insomnia (n4): e.g., post- stroke, 19 pregnancy, 17 and end-stage renal disease (ESRD) patients on hemodialysis (HD). 23,24 c. Unspecied insomnia (i.e., neither primary or comorbid specied) (n5) 15,18,21,22,26 : 2 of which employed TCM diagnoses during treatments. 18,26 d. Insomnia associated with a particular TCM diagnosis (n1): e.g. interior-stirring by phlegm-heat. 16 8. Study quality: 6 studies 15,19,20,22e24 with cate- gory B evidence, and 6 studies 16e18,21,25,26 with category C evidence. 9. Acupuncture treatments: techniques varied, including regular body acupuncture, 16,17 roll- ing needle or intradermal needle, 19,25 acu- point taping with herbal preparation, 20 auricular treatment with seed pressing or magnetic pearls, 18,21,22,26 and acupres- sure. 15,23,24 Points varied from 1 to entire meridian, including body or auricular treat- ments. Most of these studies used a standard- ized treatment paradigm, except for three studies 17,18,26 which employed an individual- ized approach. Duration ranged from 1 to 30 treatments. 10. Sleep outcomes: Most used subjective evalua- tions alone (n11), e.g., single administration sleep questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), 15,17,19,22e24 some form of a clinical global impres- sion, 16,18,20,21,25,26 and sleep diary. 22,24 Only 1 study 22 also used actigraphy as an objective sleep evaluation; none used polysomnography (PSG). 11. Effects of acupuncture for sleep: a. Compared to education control: da Silva et al. 17 treated pregnancy insomnia with sleep hygiene education alone versus a combination of acupuncture and educa- tion; they showed the combination therapy being more effective. However, without a sham acupuncture group, one cannot conclude whether this additional effect was due to acupuncture itself or from the moti- vational/placebo effects due to the perception that something had been per- formed by physicians to help. b. Compared to medication control: medica- tions used for comparison in the included studies were benzodiazepine receptor agonists, e.g., estazolam, 16,20 sur- azepam, 18 diazepam. 21 These studies all showed better treatment effects of acupuncture compared to medications, although Lian et al. 21 indicated that medi- cation had shorter duration of treatment to achieve benet and acupuncture required more treatments to surpass the effective- ness of medication. c. Compared to sham control: results are mixed. Chen et al. 15 used acupressure at sham versus real acupoints, Kim et al. 19 used sham versus real acupuncture nee- dles, Li et al. 20 used our (sham) versus Gingkgo leaf preparation (real) taping at acupoint, and Suen et al. 22 used Junci Medulla (sham) versus magnetic pearls (real) auricular treatments; all showed signicant sleep improvements in the real groups. However, Tsay et al. 24 showed no difference between sham and real acupressure, although both groups signi- cantly improved sleep when compared to the usual care control. d. Compared to other types of control: Gao 18 compared auricular and body acupuncture and showed better clinical effectiveness in the auricular group. Tsay et al. 23 compared acupressure and transcutaneous electrical acupoint stimulation (TEAS) and showed no difference between the two groups, although both did signicantly better than the usual care group. Yang 26 compared herb- soaked seeds at specic acupoints according to TCM diagnoses and two controls with regular Semen Vaccariae seeds at specic versus non-specic acupoints, and demon- strated stronger treatment effects with herb-soaked seeds but with no difference between the two control groups. 12. Maintenance of efcacy: only 2 studies 25,27 reported follow-up periods of 3e6 months; both maintained the improvements found at the end of intervention. Anecdotal cases 18 reported benecial effects lasting for 2 years at follow-up. 84 W. Huang et al. Case series of acupuncture in treating insomnia (details see Table 4) 1. Included studies: 18. 28e45 2. Subject age range: 12e83 years old. 3. Sample size: 16e2485. 4. Insomnia that was treated by acupuncture: a. Primary insomnia (n2) 32,34 : both employed TCM diagnoses during treatments. b. Comorbid insomnia (n2): e.g., AIDS, 35 anxiety. 40 c. Unspecied insomnia (i.e., neither primary or comorbidspecied) (n13) 28e31,33,36e39,41,43e45 : 6 of which had TCM diagnoses. 28,30,36,38,44,45 d. One study used the same acupuncture treatments for patients with either insomnia or excessive sleep. 42 5. Study quality: all studies with category C evidence. 6. Acupuncture treatments: techniques varied; half of the studies used auricular treatments, e.g., seeds taping and pressure applica- tions, 31,36,42 in combination with education 32 or auricular blood letting, 29 lidocaine injection at auricular points, 33 laser irradiation, 44 in combination with body acupuncture. 35,38 The other half used body acupuncture alo- ne, 30,37,39e41 in combination with plum blossom needle tapping 45 or adjunct thera- pies, 43 or combination acupuncture (e.g., body, scalp and moxibustion). 28,34 Points varied from 2 to entire meridian. All except 4 studies 37,40,41,43 reported individualized treat- ment paradigms. Duration ranged from 3 to 60 treatments in the reported data. 7. Sleep outcomes: most of these stu- dies 28e34,36e39,41e45 used some formof a clinical global impression alone (n16). Only 2 st- udies 35,40 used objective sleep evaluations, PSG or wrist actigraphy, in addition to single admin- istration questionnaires including PSQI. 8. Effects of acupuncture for sleep: a. Case series: demonstrated positive treatment effects of acupuncture in reducing sleep latency, 36,40 improving sleep and wake ratio/ sleep efciency, 35,39,40 increasing sleep dura- tion and quality 28e30,32,33,35e37,39e45 and reso- lution of insomnia symptoms 28e30,37,39e43,45 using clinical global impression. Interestingly, the two studies that used objective measurements showed different results in sleep latency. Phillips study 35 in AIDS patients used wrist actigraphy and showed no signi- cant difference in sleep latency after acupuncture treatments; while Spence et al. 40 used PSG recording and showed signicant improvement in sleep onset latency in insomnia with anxiety as a comor- bid condition. The difference could be due to different comorbidities, or different out- come measures with different measurement sensitivity. b. Case series with controls: Lu 34 showed signicantly better outcome with acupunc- ture, compared to the combination of Western and herbal medications. c. Wu 42 used the same primary acupoints to treat either insomnia or excessive sleep and showed improvements in both groups with 85% and 100% effective rates, respectively. 9. Maintenance of efcacy: 4 studies 33,34,41,45 reportedfollow-upperiods of 2 months toa year; all maintained the improvements found at the end of intervention. Anecdotal cases 29,36,37 reported benecial effects lasting for 2e3.5 years at follow-up. Discussion What are the methodological limitations of existing studies of acupuncture treatment for insomnia? Inconsistent sham controls and deciency in blinding Very few studies 15,19,20,22,24 have used sham control groups. Four of these studies demonstrated positive impact on sleep with real treatments relative to sham; one study, 24 although showing signicant improvements over usual care, reported absence of differences between real and sham acupressure. However, in this study, relaxation massage was also applied in the sham group, which may have exerted treatment effects. Furthermore, the shamacupoints were only 1 cmaway fromthe true meridians, which represents a small distancebetweensites, especially when using nger acupressure technique. Because wedonot knowhowfar away thetreatment gradient would extend fromthe true acupoints (in distance or depth), manipulations such as nger pressure may still have elicited physiological effects in this study. This could explain why another study 15 using the same technique found signicant differences between real and sham acupressure treatments. In that study, the sham points were up to 3 cun (about four nger breadths) away from the true acupoints on the body. The inconsistencies of choosing sham acupoints may have led to inconsistent results. Another relevant study was Suen et al., 22 who Acupuncture for insomnia 85 Table 4 Case series of acupuncture in treating insomnia Author (year, area) Study design Population N Treatment Acupoints Eval F/U Results Notes Cheng (1986, China) 28 Case series: Control of confounders: no. Exposure bias: yes. Attrition bias: yes. Measurement bias: yes. Risk of bias: category C. Age: 12e83 yr; Gender: F:M892:1593; Referral: outpts since 1954; Sleep difculty: insomnia of various etiology and divided into 5 TCM dx: a. deciency of HT and SP; b. HT and GB Qi deciency; c. KI deciency; d. disharmony b/w ST and mid-Jiao; e. upward invasion of LR Yang; Duration of the condition: mean 149 days. 2485 Daily acupuncture with manual stimulation and Deqi, needles retained for 20e 40 min, 12e15x1 course, plus moxibustion of selected points in certain conditions. Total Rx NR. Main: HT7*, GB12, ST36. Adjunct: a. PC7, SP6; b. GB40, GV20*; c. KI6, KI3; d. CV12, PC6; e. LR2, BL18, CV20. *20 min moxibustion in long-term decient patients. Subjective: Clinical evaluation: cureddnormal sleep with resolution of daytime symptoms; improveddsubjective improvements in sleep quality and quantity as well as some amelioration of symptoms; ineffectivedno change. After one month All 327 patients who were on hypnotic meds went off meds after 10 Rx. Simple insomnia with averaged disease course 29days, the treatment effective rate was 74.65%; Other etiologies averaged 167 days, the effective rate was 41.18% statistically signicant difference b/w. Prior to the study, 1274 cases failed to respond or maintain the response to hypnotic meds, herbs, or physical therapy. Dang (1995, China) 29 Case series: Control of confounders: none. Exposure bias: no. Attrition bias: yes. Measurement bias: yes. Risk of bias: category C. Age: 16e68 yr; Gender: F:M30:28; Referral: outpts; Sleep difculty: insomnia; Duration of the condition: 7 days to 30 yr. 58 Bloodletting at auricular tip; then other b/l auricular acupoints with vaccaria seeds taping, pressed 5e6 x/day, more intensity at qhs, once a week visit to change out the seeds. All sleep related meds are stopped during treatment. 5Rx1 course (Total NR). Auricular tip plus the following auricular acupoints: shenmen, sub- cortex, occipital, HT, shenshuai; adjunct points were used if with symptoms, e.g., LR, GB, KI, ST. Subjective: Clinical eval: cureddnormal sleep with no recurrence after stop of Rx; improvede signicant improvements with >5 h per night sleep, slight recurrence after stop of Rx but improved with reinforcement Rx; ineffectivedno obvious improvements. One case reported in the article had 2 yr of f/u. 38 cases cured; 19 cases improved; 1 case no response. Unknown total Rx that were needed, for instance for 7- day insomnia versus for 30 yr of insomnia. 8 6 W . H u a n g e t a l . Gao (1997, China) 30 Case series: Control of confounders: no. Exposure bias: yes. Attrition bias: no. Measurement bias: yes. Risk of bias: category C. Age: 16e72 yr; Gender: NR; Referral: outpt form June 1991 to May 1994; Sleep difculty: insomnia divided into 5 TCM dx: a. deciency of HT and SP; b. incoordination b/w HTand KI; c. insufciency of HT and GB; d. disturbance of LR Yang due to emotional distress; e. phlegm heat; Duration of the condition: 7 days to 6 yr. 288 Daily acupuncture with needles retained for 30 min, 25 min of which the needles were manually manipulated. Total Rx NR. Main: HT7, KI7; Adjunct: a. BL15, BL14, BL20; b. BL15, BL23, KI3, SP6; c. BL15, BL19, PC7, GB40; d. BL18, PC5, LR3; e. BL21, ST36. Subjective: Clinical effects: cureddsleep 7e 8 h/night with resolution of all symptoms; excellentd6e7 h/night with resolution of all symptoms; improveddsleep 5 h/ night with occasional symptoms; no effecteno change or worse. In the one case reported, f/u 1/ 2 yr. 90.96% case cured, 5.56% cases with excellent effect, 2.08% cases improved, 1.39% with no effect. Gao (1996, China) 31 Case series: Control of confounders: none. Exposure bias: yes. Attrition bias: yes. Measurement bias: yes. Risk of bias; category C. Age: NR; Gender: NR; Referral: outpts; Sleep difculty: insomnia; Duration of the condition: NR. 25 Auricular vaccaria seeds taping change Qd with alternating ear, pressed 3e 4x/day, each time 1e2 min with moderately strong stimulation. 10 changesone course (10 days). Resting for 3e5 days. Then next course if needed. Ear points: Shenmen, HT, sub-cortex (which can be eliminated if no pain on probing). Additional points (2e3): brain, sympathetic, endocrine, SP, LR, ST, KI. Subjective: Clinical evaluation details NR. 18 cases cured with 1 course; 3 cases cured with 2 courses; 2 cases received 3 courses but still with 2 h of sleep onset latency; 2 cases no response. (continued on next page) A c u p u n c t u r e f o r i n s o m n i a 8 7 Table 4 (continued) Author (year, area) Study design Population N Treatment Acupoints Eval F/U Results Notes Ju (1997, China) 32 Case series: Control of confounders: no. Exposure bias: yes. Attrition bias: yes. Measurement bias: yes. Risk of bias: category C. Age: 14e55 yr; Gender: F:M32:21; Referral: outpts; Sleep difculty: primary insomnia with 4 TCM dx-a. re due to LR depression; b. phlegm heat; c. excessive re due to Yin deciency; d. deciency of HT and SP; Duration of the condition: 2 months to 11 yr. 53 Education: modication of life style, such as the use of tea, coffee. Auricular vaccaria seeds taping: one ear/ alternating q5 days, massage each point 2e 3x/day, each at least 50 times, more qhs, till Deqi. 10 Rx1 course. Total Rx NR. Main: Shenmen, sub-cortex, endocrine, brain, sympathetic; Adjunct: according to TCM dx-a. LR, GB; b. HT, SP, ST; c. KI, BL; d. HT, SP, SI. If female add Jing Gong. Subjective: Clinical eval: cureddsleep return to pre-morbid condition; effectivedboth sleep duration and depth improved; ineffectivedno change of insomnia symptoms. NR 29 cases cured, 19 cases effective, 3 cases ineffective. 2 dropouts. Lee (1977, USA) 33 Case series: Control of confounders: no. Exposure bias: yes. Attrition bias: no. Measurement bias: no. Risk of bias: category C. Age: 26e69 yr; Gender: F:M7:9; Referral: outpts with insomnia as chief complaint, with or without medical comorbidities; Sleep difculty: sleep 3e4 h/ night with daytime symptoms; Duration of the condition: 2 wks to 34 yr. 16 All sleep meds discontinued prior to the treatments. Lidocaine injection at auricular acupoints (alternating ear); frequency initially 3x/wk later changed depending on responses. Patients to be active physically for about 20 min post- injection. Ear points: Main: HT, KI, adrenal, sub- cortex, endocrine, TH, Shenmen; adjunct: sympathetic, occiput, GB depending on individual patient. Objective: heart rate; Subjective: Sleep duration. Pre- and post treatments, 3 months f/u. Total Rx vary from 2 to 28, mostly below 15 (only one 28)dnot correlated with severity of insomnia. All patients reported substantial improvement. 68.7% cases had >7 h sleep per night without meds which sustained during f/u and were considered to be cured. Hypothesis was that lidocaine (blocking sensory input) is good for relative excess of Yang and also good for those who did not respond to regular acupuncture. 8 8 W . H u a n g e t a l . Lu (2002, China) 34 Case series: Control of confounders: comparable b/w group acupuncture (ACU) and group medication (MED) but statistical data NR. Exposure bias: unknown. Attrition bias: unknown. Measurement bias: yes. Risk of bias: category C. Age: 53e79 yr; Gender: F:M35:48; Referral: outpt; Sleep difculty: primary insomnia of 4 types TCM dx: a. deciency of HT and SP (n25 vs. 11), b. incoordination of HT and KI (n24 vs. 10), c. LR re aming up (n17 vs. 8), d. disharmony of ST (n17 vs. 6); Duration of the condition: 1e 20 yr. 118 (ACU 83; MED 35) ACU: TCM Dx- specic body and scalp acupuncture, with manual manipulation and moxibustion* in certain cases qd10d1 course, total of 30Rx. MED: 2.5e 5.0 mg qhs of nitrazepam and 10 ml bid of An Shen Bu Nao Ye (herb). Treatment duration NR. All: scalp MS1, MS2, plus a. scalp anterior 2nd line, body BL20*, BL*, HT7, ST36. b. scalp MS3, body KI3, HT7, PC7, LR3. c. scalp MS5, body LR2, GB44, 20, HT7. d. scalp MS5, body CV12, ST40, 45, SP1. Subjective: Clinical eval: Cureddsleep normally with no recurrence during f/u; markedly effectivedsleep normally but with occasional insomnia; effectiveds/s improved; no effectdno improvement at all. f/u 1 yr. There was signicant difference of effective rates b/w groups. There was also a tendency to favor excess syndromes than deciency syndromes. Phillips (2001, USA) 35 Case series: Control of confounders: no. Exposure bias: yes. Attrition bias: no. Measurement bias: no. Risk of bias: category C. Age: 29e50 yr; Gender: NR; Referral: AIDS support organization and a private medical clinic; Sleep difculty: with sleep disturbances 3 nights/wk and PSQI > 5. Duration of the condition: NR. 21 Individualized acupuncture (combined body and auricular) with 10e15 needles, for 30e 45 min, Deqi senses, 2 evenings/ wk5wks (delivered in group sessions). Total of 10 Rx. Body: HT7, SP6, KI3, PC6; auricular: Shenmen, HT, LU, sympathetic. Adjunct: points are selected if with peripheral neuropathy and pain. Objective: Wrist actigraph; Subjective: PSQI, CSQI, visual analog pain rating and demographic data form. 2 nights before and 2 nights after treatments. In addition to subjective sleep improvements, signicant improvements seen in actigraphy TST, # of min spent awake, and SE. Not signicant in sleep latency, # of mid-sleep awakenings, and WASO. Dropouts: 1 died and 1 left due to distance. Pain measurement comparison NR. (continued on next page) A c u p u n c t u r e f o r i n s o m n i a 8 9 Table 4 (continued) Author (year, area) Study design Population N Treatment Acupoints Eval F/U Results Notes Qiu (1996, China) 36 Case series: Control of confounders: no. Exposure bias: yes. Attrition bias: yes. Measurement bias: yes. Risk of bias: category C. Age: NR; Gender: NR; Referral: outpts; Sleep difculty: insomnia with 4 TCM dx-a. deciency of HT and SP; b. disharmony of HT and KI; c. deciency of HT Qi; d. LR Qi stagnation;. Duration of the condition: NR. 65 Auricular vaccaria seeds taping one ear/alternating q3e5 days, massage each point 25 x/day till Deqi. 10 Rx1 course. Total Rx NR. Main: Shenmen, occiput, HT, sub-cortex, insomnia; Adjunct: a. SP, SI; b. LR, KI; c. LR, KI, GB; d. LR, TE Subjective: cureddsleep onset normal, sleep normal; signicantly improveddsleep onset improved, sleep normal but easy midnight wakening; improveddsleep improved; ineffectivedno obvious improvements after 1 course. In the one case reported, 2 yr f/u with no reoccurrence. 32 cases cured, 18 cases signicantly improved, 11 cases improved, 4 cases ineffective and were stopped after 1 course. Ren (1985, China) 37 Case series: Control of confounders: no. Exposure bias: yes. Attrition bias: yes. Measurement bias: yes. Risk of bias: category C. Age: NR; Gender: NR; Referral: outpt clinic; Sleep difculty: insomnia; Duration of the condition: NR. 86 Needling 2 acupoints with 1 needle and manually stimulated to get Deqi sensation, then the needle was retained for 5e 15 min with manual stim q5 min; Rx qd7 days1 course, then 3 days of rest. In the one case reported, total 5 courses; others NR. PC7 towards TE5. Subjective: Clinical effects: curedd>6 h/night sleep with complete relief of symptoms; markedly improvedd>4 h/night sleep, with marked diminution of symptoms; improveddable to get some sleep but awakens often with some improvement of symptoms; unimproveddno change. In the one case reported, f/u 3.5 yr. Of the 86 cases, 39 cured, 36 markedly improved, 11 improved. 9 0 W . H u a n g e t a l . Shen (2004, China) 38 Case series: Control of confounders: no. Exposure bias: yes. Attrition bias: yes. Measurement bias: yes. Risk of bias: category C. Age: 17e54 yr; Gender: F:M94:106; Referral: outpt clinic; Sleep difculty: insomnia, primary n156 and secondary n44, divided into 4 TCM dx: a. incoordination b/wHTand KI; b. ST disorders; c. deciency syndrome; d. deciency of HT and SP; Duration of the condition: 2e245 days. 200 Combination of 1. auricular pressure and 2. acupuncture (for cases with duration of more than 2 months). 1. Vaccaria seeds taping alternating ear q3e4 d, points pressed 3e4x/ day. 2. Daily Rx with manual manipulation, needles retained for 5e20 min. Both: 5 days1 course; total 3e 4 courses (15e 20Rx). Main ear Shenmen, HT, Shenshuai, brainstem. Optional ear LR, ST, HT, KI, endocrine. a. HT7, SP6; b. BL21, ST36, Yintang, GB20, HT7; c. Anmian, SP6, HT7, BL23; d. ST36, GV20, Yintang, Anmian. Subjective: Clinical eval details NR. Post- treatments. 75% cases were cured, 15% cases were effective, 7% were improved, and 3% were ineffective. Better results in patients with shorter duration of disease, but detailed analysis NR. Shi (2003, China) 39 Case series: Control of confounders: none. Exposure bias: yes. Attrition bias: yes. Measurement bias: no. Risk of bias: category C. Age: 18e69 yr; Gender: F:M17:11; Referral: outpts; Sleep difculty: insomnia; Duration of the condition: 3 months to 1 yr. 28 Individualized body acupuncture according to TCM Dx. Detailed frequency and total Rx NR. Main points: HT7, GB13, SP6, PC6. Adjunct points depending on TCM diagnoses (5 examples given): e.g., LR3, LI4, KI7, ST36, LU7, BL20. Subjective: Clinical effects*: cureddgrade 1 sleep with no med, symptoms resolved; markedly effectivedgrade 2 sleep with no med, symptoms greatly improved; improveddgrade 3 sleep with over 3/4 Y of med doses, and symptoms improved; faileddstage 4 or 5 sleep, med dependence, symptoms still exist. In the one case reported, 6 months f/u. 17 cases cured, 7 cases markedly improved, 4 cases improved, 0 failed. *5 grades of sleep quality by WHO standard: 1: SE 70e80%; 2: SE 60e70%, sleep onset difculty; 3: SE 40e50%, mild sleep dis; 4: 40e 50%, moderate sleep dis; 5: 30e 40%, severe sleep dis. (continued on next page) A c u p u n c t u r e f o r i n s o m n i a 9 1 Table 4 (continued) Author (year, area) Study design Population N Treatment Acupoints Eval F/U Results Notes Spence (2004, Canada) 40 Case series: Control of confounders: yes. Exposure bias: yes. Attrition bias: NR. Measurement bias: no. Risk of bias: category C. Age: 18e55 yr; Gender: F:M11:7; Referral: volunteers; Sleep difculty: insomnia associated with anxiety, scoring >50 on the Zung Scale but not meeting DSM-IV criteria for anxiety dis. Duration of the condition: at least 2 yr. 18 2x/wk acupuncture5 wks (total of 10 Rx) NR Objective: PSG recordings, urine aMT6s measurements (metabolite of melatonin); Subjective: questionnaires on sleepiness, fatigue, alertness, anxiety, depression; complex verbal reasoning task. Before and after treatments. Signicant [melatonin secretion with improvements in PSG sleep onset latency, arousal index, TST, SE, stage 3 sleep; reduction in morning fatigue and sleepiness, anxiety, and depression; and decreased performance time for complex verbal reasoning task. Also seen decreased daytime alertnesse hypothesized as being more adaptive. Wang (1992, China) 41 Case series: Control of confounders: no. Exposure bias: yes. Attrition bias: no. Measurement bias: yes. Risk of bias: category C. Age: 16e63 yr; Gender: F:M21:29; Referral: outpt clinic; Sleep difculty: insomnia; Duration of the condition: 0.5 month to 13 yr. 50 All sleep meds were discontinued prior to Rx. Daily acupuncture with needle tips reaching periosteum and needles retained for 20 min; 10x1 course with 3 days in b/ w courses. Total Rx NR. CV20, and Sishencong. Subjective: cureddsleep [ of 4 h/night, and >6 h/night at 2 months f/u, with all symptoms relieved. Excellentd sleep [ of 3 h/night, and >4 h/night at 2 months f/u with remarkedly improved symptoms; improvedd temporary improvements of sleep and symptoms with Rx; no effectdno noted improvements. Post- treatments and f/u at 2 months. 40% cases cured, 46% cases with excellent response, 10% cases improved during treatments, 4% cases with no response. 9 2 W . H u a n g e t a l . Wu (1998, China) 42 Case series: Control of confounders: none. Exposure bias: yes. Attrition bias: yes. Measurement bias: yes. Risk of bias: category C. Age: 19e68 yr; Gender: F:M22:38; Referral: outpts; Sleep difculty: 2 groups: insomnia (INS, n40) and excessive daytime sleepiness (EDS, n20); Duration of the condition: 3 days to 5 yr. 60 Auricular vaccaria seeds taping, pressed 5e6 x/day, each time 2e3 min (until feeling warm or barely painful), no heavy massage. QOD alternating ear. 3 changes1 course. 1e3 courses (total 3e9 Rx). No medication during Rx. Main: HT, Shenmen, endocrine, sub-cortex. Additional points were used only when very typical symptoms occur: LR, Jiang ya groove, ST, KI, LI. Subjective: INS: cureddsleep >7 h per night with disappearance of symptoms; effectivedsleep >5 h per night; EDS: cureddsleep 8 h/day with disappearance of symptoms; effectivedsleep about 10 h/day; Both Groups: no responsedno obvious improvements. Two cases reported in the article had 2e3 months of f/u. INS: 23 cases cured; 11 effective; 6 no response; EDS: 16 cases cured; 4 cases effective; 0 case no response Difference of the condition duration b/w the groups NR. Xie (1994, China) 43 Case series: Control of confounders: none. Exposure bias: yes. Attrition bias: yes. Measurement bias: yes. Risk of bias: category C. Age: 21e48 yr; Gender: F:M67:57; Referral: outpts; Sleep difculty: dyssomnia failed prior therapies, including med (n92), herbal drugs (n69), PT (n12), breathing exercises (n12); Duration of the condition: 1 wk to 4 yr. 124 30 min Rx of acupuncture with manual manipulations q10 min, 7e10 Rx1 course, rest 3 days. Total 1e4 courses (7e 40Rx), averaging 3 courses. If no improvements after 2 courses, other adjuvant modalities were administered (details NR). Main points: Sishencong, GV20; Adjunct points: HT7, KI3. Subjective: Therapeutic effects: cureddnormal sleep with resolution of symptoms; markedly improvedd[ sleep by 2 h/night, signicant amelioration of symptoms; effectivedsome improvements of sleep and symptoms; ineffectivedeno improvements or short- lasting benets. In the one case reported, 3 months f/u. 73 cases cured, 26 cases markedly improved, 10 cases effective, 15 cases ineffective (7 of which did not nish the 1st course). (continued on next page) A c u p u n c t u r e f o r i n s o m n i a 9 3 Table 4 (continued) Author (year, area) Study design Population N Treatment Acupoints Eval F/U Results Notes Yao (1999, China) 44 Case series: Control of confounders: none. Exposure bias: yes. Attrition bias: yes. Measurement bias: yes. Risk of bias: category C. Age: 23e55 yr; Gender: F:M27:19; Referral: outpts; Sleep difculty: insomnia with 3 types of TCM dx: deciency of HT and SP (n18), disharmony of HT and KI (n15), LR re upward invasion (n13); Duration of the condition: 1 month to 12 yr. 46 Daily b/l auricular semiconductor laser irradiation of 1 min at each acupoint till a local warm sensation was felt, 12 Rx1 course with 5e7 days b/w courses. Total of 1e3 courses. Auricular main: Shenmen, Endocrine, Sub-cortex, Brain; Adjunct points were according to TCM diagnoses: e.g., HT, KI, SP, ST, LR. Subjective: Clinical eval: cureddsleep >7 h/ night; improveddsleep 5e6 h/night; ineffectivedsleep <3 h/ night. 32 cases cured; 13 cases improved; 1 case ineffective. No side effects. Zhang (2003, China) 45 Case series: Control of confounders: none. Exposure bias: yes. Attrition bias: yes. Measurement bias: yes. Risk of bias: category C. Age: 20e68 yr; Gender: F:M21:14; Referral: outpts; Sleep difculty: insomnia with 3 types of TCM dx: deciency of HT and SP (n12), incoordination of HT and KI (n15), upward attack by LR re (n8); Duration of the condition: 10 days to 10 yr. 35 Daily body acupuncture with Deqi sensation, manipulation q10 min, total 40 min; then, Plum blossom needle tapping till ush of the local skin. 10 Rx1 course. 1e 6 courses (10e 60Rx) with 2e3 days b/w courses. Quit other therapies during Rx. Body points: Anmian, GV20, HT7, SP6, BL62, KI6; adjunct points were chosen by TCM dx e.g., ST36, KI3, GB20, LR3. Tapping was along back Huatuojiaji and the 1st and 2nd lines of BL meridian (from top downward). Subjective: Clinical eval: cureddsleep >5 h/night without med, all symptoms resolved, and no recurrence in 6 months f/u; improveddsleep 3e5 h/ night without med, alleviation of symptoms; ineffectivedsleep <3 h/ night without obvious symptom improvements. 6 months f/u. 27 cases cured, 6 cases improved, 2 cases ineffective All abbreviations, except for those representing different study groups as indicated in the table, are listed in the Appendices. 9 4 W . H u a n g e t a l . showed signicant treatment effects when active treatment (magnetic pearls) was compared to sham (Junci Medulla). However, Suen et al. also reported no difference when Semen Vaccariae (typically used in auricular acupressure treatments) was compared to Junci Medulla (sham). These data suggest that there is not a simple and consistent answer regarding the effects of acupuncture or acupressure when compared to sham. They also raise a methodological and an ethical question: if sham control did better than usual care, no matter how the effects were produced, would that imply that sham acupuncture could be used for treatment? Another major decit of the reviewed studies was lack of blinding or lack of evaluation of the blinding process. Three studies 22e24 were double- blinded and three 15,19,20 single-blinded; no study reported assessment of blinding effects. Obviously, in reviewing these studies, one must consider the high likelihood of reporting and/or evaluating bias. Heterogeneity in study designs and outcomes Inmanystudies, therewas lackof consistent denition of insomnia leading to non-specied primary versus comorbid insomnia 15,18,21,22,26,28e31,33,36e39,41,43e45 and a mixture of acute and chronic condi- tions, 18,21,26,29,30,33,38,41e43,45 all of which could contribute to lack of equivalence across the studies. There was also signicant heterogeneity in acupuncture techniques and acupoint selec- tions, although most produced positive effects on sleep. Does this mean that the treatments produce non-specic effects so that the tech- niques or acupoint choices do not matter? Only 3 of the 30 studies 22,35,40 included in this review utilized wrist actigraphy or PSG. Most studies used some form of a clinical global impression (n22) as the outcome measure, which varied widely. For instance, the outcome of the study 45 using the criterion of sleeping over 5 h/ night as being cured is obviously different from the outcome of the study 30 that used the criterion of sleeping 7e8 h/night as being cured, although the reported effective rate was similar (94.28% versus 98.61%). What are the factors that need to be considered in future research studies when using acupuncture to treat insomnia? Acupuncture has great potential to be used to treat insomnia, although the support is limited by the quality of current available studies. Future vigorous research is needed to clarify acupuncture effects and the clinical indications. In order to help guide the technical directions for future studies, we consider the following. Technical factors Acupuncture techniques: Acupuncture techniques vary widely from study to study included in this review (Table 2). The selection of the tech- niques depends on the practitioners preference and practice feasibility. Is there any acupuncture technique that is most effective in treating insomnia? Auricular treatments were used alone or in combination with body acupuncture in 14 studies. Gao 18 showed better results with auricular treat- ments compared to body treatments. Among auricular treatments, techniques varied, such as auricular acupuncture, 35 vaccaria seeds taping and pressing, 18,21,26,31,32,36,38,42 magnetic pearls, 22 blood letting in addition to auricular pressure, 29 lidocaine injection, 33 and laser irradiation. 44 All produced similar results, except in two studies where better results were obtained with magnetic pearls (Suen et al. 22 ) and herb-soaked seeds (Yang 26 ), when compared to vaccaria seeds. Nine studies 16,17,28,30,34,39e41,43,45 used mainly tradi- tional body acupuncture, with or without combi- nation of other treatments, such as moxibustion, scalp acupuncture, or plum blossom needle tapping. They also showed positive treatment effects. Other special treatments, such as intradermal needle 19,20,25,37 also showed good results in selected patient populations. Acupressure treat- ments, 23,24 on the other hand, showed good results compared to usual care, but not signicantly better when compared to sham or electrical stimulation. The heterogeneity of treatment techniques poses a challenging question for future research. A reasonable recommendation would be to focus on the most commonly used auricular treatments with or without body acupuncture to search for the best treatment combination. Elicitation of Deqi: All body acupuncture studies tried to elicit Deqi (da Chee, meaning getting the energy) sensation with manual manipulations of needles. Is this a vital determinant of responsiveness? In acupuncture practice, Deqi sensation describes patients feeling of soreness, heaviness, and many times, a radiating sensation when the needle is inserted, which can be associated with practitioners feeling of needle being dragged. In TCM, it is believed that when Deqi sensation occurs, the energy is guided towards the needle, and thus better treatment response. However, it is less acceptable and tolerable by patients and also Acupuncture for insomnia 95 creates difculty in conducting studies with sham control. Moreover, whether or not Deqi is the vital determinant of responsiveness is still debatable. For instance, Lees study using lidocaine injection 33 obviously eliminated any feeling in the acupoint but still produced treatment effects. Psychometric studies of the sensation elicited by Deqi would aid in understanding its clinical efcacy. Acupoints selection: From the current insomnia studies, we can see that although acupoints selection varies signicantly, certain points are used more frequently than others (Table 5). Do specic acupuncture points produce the best treatment effects for insomnia? In TCM, acupoints can have different treatment functions when used in different conditions. Some- times the same acupoints can be used to affect two contrasting conditions, as shown in the study of insomnia versus excessive sleep. 42 One approach to answer the question of whether certain points can specically produce sleep benets is to examine the studies in which acupuncture was used to treat other conditions, using the same acupoints as in the insomnia studies. If sleep also improved in those studies as a secondary outcome, this might imply treatment specicity of these acupoints. Table 6 lists such studies in adults 46e54 but excluded pain studies, because pain and sleep have a particularly complex interdependence. 55 Most of these studies demonstrated efcacy in improving sleep; however, there were exceptions. In Cohens study of menopausal symptoms 48 some acupoints that are used for insomnia were applied (e.g., GV20, HT7, PC6, SP6, LR3; auricular shen- men, LR, KI); however, their effects on sleep in post-menopausal women seemed to be dependent on their different combinations. Schneider et al. 51 reported no signicant improvements in sleep with either real or sham acupuncture in irritable bowel syndrome. Therefore, the question of acupoint specicity for insomnia remains and can be possibly explored further in future studies using acupuncture to treat two different conditions. Treatment paradigm: As mentioned previously, in most clinical practice, acupuncture treatments are individualized. Most of the studies included in this review (17/30) used individualized treatments. Nevertheless, standardized treatments also have emerged and are particularly preferred in research protocols to further generalizability. Yang 26 demonstrated that there was no signicant differ- ence between individualized and standardized auricular treatments. On the basis of this single study, however, we cannot yet discount that the differential diagnoses guided by TCM, taking into account each individuals symptom composition and physiological conditions, are useful in affecting the treatment effects of acupuncture on insomnia. Further comparison of these two treatment para- digms is needed in future research. Treatment duration: How many treatment sessions are needed to produce acupuncture effects? Table 5 Acupoints selection in treating insomnia Use frequency Acupoints Body acupuncture Most commonly used (in >75% of studies) HT7 Commonly used (in 25e75% of studies) SP6, ST36, GV20, PC6, KI3, PC7, LR3 Sometimes used (in 10e25% of studies) Sishencong, Anmian, CV12, BL20, GB20, Yintang, ST40, KI1, GB40, KI6, LR2, BL18, CV20, KI7, BL15, BL23, BL21, entire back bladder and GV meridians Rarely used (in <10% of studies) GV24, SP4, GB21, CV17, CV8, GB34, GB12, BL14, BL19, PC5, GB44, ST45, SP1, TE5, GB13, LI4, LU7, BL62 Auricular acupuncture Most commonly used (in >75% of studies) HT, Shenmen, LR, KI Commonly used (in 25e75% of studies) Sub-cortex, SP, ST, endocrine Sometimes used (in 10e25% of studies) GB, sympathetic, occiput, brain Rarely used (in <10% of studies) LU, Shenshuai, SI, TE, cervical vertebrae, BL, Jinggong, adrenal, insomnia, brainstem, Jiangya groove, LI Scalp acupuncture Only one study used scalp acupuncture MS1, 2, 3, 5, scalp anterior 2nd line Note: The percentages were calculated with the reviewed studies. All abbreviations, except for those representing different study groups as indicated in the table, are listed in the Appendices. 96 W. Huang et al. Table 6 Studies of acupuncture in treating various non-sleep conditions with sleep as a secondary outcome Author (year, area) Study design Population N Study groups Treatment Acupoints Eval F/U Results Notes Alraek (2001, Norway) 46 Prospective case series. Age: 18e60 yr; Gender: all females; Referral: subjects with recurrent cystitis (3 episodes in past 12 months); Duration of the condition: NR. 67 NA Prophylactic acupuncture treatments: 2x/wk for 4 wks, each session 20 min, Deqi with intermittent manual manipulation. Main: ST36, SP6, SP9, LR3, KI3, BL23, BL28; Adjunct: vary depending on TCM dx. Open-ended, free text questionnaire. 2 wks after intervention. 39 reported improvements, including bladder emptying, bowel movements, abdominal discomfort, stress level, sleep pattern, relief of painful conditions, menstrual pain, and more free ow of menstrual blood. Only 46 were sent a questionnaire at the end. Berman (2004, Sweden) 47 RCT: Randomization method: manual lottery; Control: comparison acupuncture; Blinding: NR. Age: mean 33.5 yr; Gender: F:M61:97; Referral: inmates in two prisons with substance abuse history; Duration of the condition: NR. 163 2 groups: 1. National Association for Detox Acupuncture (NADA) Auricular acupuncture (specic); 2. Helix auricular acupuncture (non-specic). 5x during rst wk, 3x/wk for 3 wkstotal of 14 sessions in 4 wks, each lasts 40 min. NADA: b/l Shenmen, sympathetic, KI, LR, LU; Helix: b/l 5 points on the helix, not avoiding the liver yang points. Drug use questionnaire, SCL-90, TCS. ATAS before and after each treatment. Urine drug tests every other day. Interviews before and after 4 wk. Before and after each 4 wk treatments. No major differences b/w groups. Better abstinence from helix, condence in treatment grows with NADA. For sleep: 77% with better sleep in NADA; 50% with better sleep in helix. Randomization results were lost for 5 subjects and therefore they were excluded. Out of 158, 76 completed the Rx. Cohen (2003, USA) 48 RCT: Randomization method: priori determined assignment per participant number in sealed envelopes; Control: comparison acupuncture; Blinding: double blinded (subjects and evaluators), blinding evaluation NR. Age: NR; Gender: all females; Referral: post- menopausal women, off other treatments for 3 months; Duration of the condition: 3 months to 2 yr. 17 2 groups: experimental acupuncture (EA) group (n8); comparison acupuncture (CA) (n9). Intervention: qw3 wks, then qow3 (total of 6Rx), each treatment 20e30 min. EA: needling of acupoints related to treatment of menopausal symptoms; CA: designed for general tonication. EA: BL15, BL23, BL32, GV20, HT7, PC6, SP6, LR3, SP9; CA: HT7 LR4, KI7, ear Shenmen, sympathetic, KI, LR, LU. Daily diary monthly for 4 months, scores 0e3 given to various symptom categories, mean monthly scores among subjects were used for statistical analysis. Baseline, every month4 (including 3 wks post- intervention). EA: signicant Yhot ushseverity, but rebound at f/u; signicant improvements in sleep and mood, lasting through f/u; CA: Mood borderline improved during Rx. No change in hot ush severity or sleep during Rx but both improved during f/u. 1 dropout after baseline. Baseline data not comparable b/w groups. No statistical analyses b/w groups. (continued on next page) A c u p u n c t u r e f o r i n s o m n i a 9 7 Table 6 (continued) Author (year, area) Study design Population N Study groups Treatment Acupoints Eval F/U Results Notes Jackson (2006, UK) 49 n1 design controlled trials; control: within subject. Age: 32e79 yr; Gender: F:M1:5; Referral: outpts with tinnitus; Duration of the condition: 12 months to over 20 yr. 6 NA Individualized acupuncture at 6e13 points each session. Moxibustion and auricular acupuncture were also applied. 5x/ wk2wks (total of 10 treatments). Main: TE17, GB2; either KI3 and BL23, or LR3. Other points were selected according to other symptoms. Daily diary to score 4 tinnitus- related symptoms including quality of sleep in 0e10 scale. THI and MYMOP at 5 times points. 14 days pre-, at the start, at the end, 14days post-, and 6 wks post-Rx. Total of 5 time points. The combined treatment effects of acupuncture supported a more consistent and signicant improvement in the reduction of waking hours and improved quality of sleep. The THI and MYMOP showed a trend of improvement. A hierarchical Bayesian model for analysis of n1 trials was used. Janssen (2005, Canada) 50 Prospective case series. Age: 30e49 yr; Gender: M>F; Referral: Canadian poorest urban population with high use of drugs; acupuncture offered at 2 community agencies; Duration of the condition: NR. 39 NA Voluntary drop-in up to 5 days/wk; each session 35e40 min. b/l ear points: sympathetic, shenmen, LR, KI, LU. Weekly questionnaire on Fridays. Once a week during Rx. Signicant reduction in self-reported frequency of substance use. Signicant decrease in intensity of withdrawal s/s, including insomnia, shakes, stomach cramps, hallucinations, muddle- headedness, muscle aches, nausea, sweating, feeling suicidal, heart palpitations. *3months period with total 2755. visits; 39 subjects nished all 4 wks of Rx. 9 8 W . H u a n g e t a l . Schneider (2006, Germany) 51 RCT: Randomization method: block randomization; Control: sham control; Blinding: double blinded (subjects and evaluator), no blinding process evaluation reported. Age: mean for AC 47.63 and SAC 47.14; Gender: F:M34:9; Referral: Outpt GI clinic; Condition: Rome II classication for IBS; Duration of the condition: over 55% >10 yr. 43 2 groups: acupuncture (AC; n22); sham acupuncture (SAC; n21). Intervention: 2x/ wk for 5 wks (total 10 Rx). AC: with Deqi sensation at acupoints, SAC: Streitberger needle at 2 cm away from acupoints. LR3, ST36, SP6, CV12, ST21, ST25, HT7, GV20. FDDQL (including sleep eval), SF-36. Pre-, post- treatment, 3 months f/u. Many areas of FDDQL got signicant improvements in both groups, not including sleep. SF-36 improved signicantly only in pain in both groups. There was with no difference b/w groups. 2 female subjects dropout during the course of study. Poor sleep and low coping capacity predict non- response to placebo effects. Shulman (2002, USA) 52 Pilot study Age: mean 68 yr; Gender: F:M8:12; Referral: Outpts with diagnosis of Parkinsons Disease stages Ie III, on stable med dose 1 month; Duration of the condition: mean 8.5 yr. 20 NA Rx: Combination of body, scalp, and electro- acupuncture. 1 h/session, 2x/wk. First 7 subjects received 10 Rx; last 13 pts received 16 Rx. Body: LI4, GB34, ST36; KI3, KI7, SP6, SI3, TE5. (*main) Scalp: 9 needles in chorea- trembling control area. Electro: NR. Patient questionnaires, SIP, UPDRS, H&Y, S&E, BAI, BDI, quantitative motor tests, and adverse events. Before, within 5 days after all treatments. The only signicant improvement seen post- acupuncture is sleep and rest. 85% patients reported also subjective improvements in other s/s, e.g., tremor, handwriting, pain, walking, slowness, anxiety, depression. No adverse effects. Subjective improvements not veried by objective assessments. (continued on next page) A c u p u n c t u r e f o r i n s o m n i a 9 9 Table 6 (continued) Author (year, area) Study design Population N Study groups Treatment Acupoints Eval F/U Results Notes Wang (2006, China) 53 RCT: Randomization method: according to the admission date (odd- treatment vs. even-control); Control: medication only; Blinding: None. Age: 21e68 yr; Gender: F:M23:22; Referral: inpt diagnosed with depression according to CCMD-3, with HDS > 18; Duration of the condition: NR. 45 2 groups: 1. treatment group: acupuncture with medication (n23); 2. control group: medication only (n22). Acupuncture with Qi conducting maneuver: 2e3 min per acupoints along the GV, plus adjunct body points by TCM dx; Qd4 wks (28Rx); medications: individualized Sertraline 50e 100 mg/day, Venlafaxine 75e 100 mg/day, or Remeron 15e 45 mg/day. Main: GV24, GV20, GV14, GV11, GV9; Adjunct points vary to TCM dx. HDS; PSQI Pre- and post- treatments. Both groups had signicant decrease of HDS scores, but only the treatment group had signicant decrease of PSQI. Comparability of med use in the two groups: NR. Article also reported more signicant YHDS scores in the treatment group than the control group, but no data. Yang (2007, Taiwan) 54 Within subject crossover. Age: over 65 yr; Gender: F:M7:13*; Referral: NH residents 13 wks, with dementia and severe agitation (CMAI 40); Duration of the condition: 12 months to over 20 yr. 31* Within subject crossover: 1. Study: pretest 1wk, acupressure treatment 4 wks, post 1 wk; 2. Washout: rest 1 wk; 3. Control: pretest 1 wk, visiting and conversation 4 wks, post 1 wk. Acupressure: 5 min warm-up (rubbing palms/ ngers of both hands), 2 min massage each acupoint (10 min) with average force of 3.68e3.82 kg; 2x/day for 5 days, rest 2 days, total of 4 wks (40Rx). Control: daily visit and conversation for 15 min/each. GB20, GV20, HT7, PC6, SP6. CMAI, and ease of care inventory were evaluated 4 times during the study. Also, daily agitated behaviors were recorded. 1 wk pre-test, 1 wk post- test. 2 rounds during the study, before and after crossover. All aspects of agitation behavior were signicantly improved; although after 6wks control, scores worsened, most trends of improvement lasted till the end. Patients were also observed to fall asleep naturally with acupressure (no specic measurements). During the 13wksdstudy period, there were 11 dropouts: due to hospitalization or discharge * of subjects do not match. All abbreviations, except for those representing different study groups as indicated in the table, are listed in the Appendices. * # of subjects do not match. 1 0 0 W . H u a n g e t a l . The reported number ranges from 1 to 60, with a median of 11 and a mean of 15 treatments, although the most optimal treatment duration remains an uncertain issue. Insomnia diagnosis What is the association between insomnia diag- nosis and acupuncture efcacy? Insomnia can be diagnosed according to Western or TCM systems. In Western medicine, insomnia is divided into primary and comorbid insomnia. Both in studies that specied primary insomnia 20,25,32,34 and comorbid insomnia, e.g., AIDS, 35 anxiety, 40 pregnancy, 17 stroke, 19 and ESRD patients on HD, 23,24 acupuncture treatments were shown to be effective. In addition, Lees study 33 illustrated that a positive response to acupuncture treatments was not affected by multiple concur- rent medical problems. In TCM, however, there are many insomnia diagnoses, according to the involvement of different organ systems in excessive or decient forms. Lu 34 reported that certain TCM syndromes (e.g., excess) were more easily treated with acupuncture than other types (e.g., deciency). This nding is very interesting and is consistent with the rst authors (WH) clinical practice experience. It remains to be seen whether research proto- cols employing Western insomnia diagnoses versus those based on TCM differentials will lead to the most successful clinical trials and possibly eluci- date underlying mechanisms. How safe is acupuncture in treating insomnia? Studies that reported side effects of acupuncture have reported local ecchymoses at needle inser- tion points, 17 and skin irritation and mild pain at vaccaria seeds taping area. 42 There have been no serious side effects reported to be associated with acupuncture treatments for insomnia. This could be one of the unique features of acupunc- ture in comparison with other medical treat- ments, especially in selected populations such as the elderly and patients with multiple medical comorbid conditions and taking multiple medications. What are possible underlying mechanisms of acupuncture in treating insomnia? Acupuncture offers great potential for enhancing our understanding of the pathophysiologic basis for insomnia that may not be available using other treatment modalities. For example, acupuncture treatments that were targeted at other medical or psychological conditions (see Table 6) also improved sleep, indicatingpossiblecommonendocrinemarkers and/or neurotransmitter systems across these conditions that can be regulated by acupuncture. Melatonin was suggested in one study 40 as such a factor. Perhaps the most intriguing aspect of insomnia that could be elucidated by the use of acupuncture treatment would be direct manipulation of the autonomic nervous system (ANS). ANS dysregula- tion of cardiac function may be particularly rele- vant for poor sleep 56,57 ; individuals with insomnia have also been recognized to have higher heart rates than good sleepers 58,59 and short sleep duration may be associated with hypertension. 60,61 To the extent that TCM has long suggested that heart is a main organ system controlling sleep, this opens up many avenues of research. For example, Lee 33 demonstrated that modulation of heart rate correlated with improvements of insomnia. Sleep also improved when stimulating the paraspinal bladder meridian in some studies, 25,45 while Teitelbaum 62 observed a corre- lation between this meridian and the anatomical ANS efferent locations along the spine. ANS involvement in acupuncture treatment of insomnia is also implicated by the use of auricular acu- points, which are thought to be able to regulate autonomic sympathetic/parasympathetic tone, 63 and, as a consequence, produce benecial effects on sleep. These ndings warrant further investi- gational efforts in clinical trials, to both test acupunctures efcacy and to enhance our under- standing of pathophysiologic mechanisms contrib- uting to poor sleep. Conclusion The currently available studies have demonstrated the safety and potential benecial effects of acupuncture in treating most forms of insomnia. However, the evidence is severely limited by study bias and signicant heterogeneity of acupuncture techniques and acupoint selections. Future acupuncture research will require more vigorous study designs to evaluate not only the effects of acupuncture in treating insomnia in comparison to sham acupuncture, but also to search for better treatment paradigms and to understand possible underlying mechanisms, all of which can elucidate whether acupuncture can contribute to the clinical care of patients with insomnia. Acupuncture for insomnia 101 Acknowledgment Supported in part by the Southeast Center of Excellence in Geriatric Medicine, Hartford Foun- dation Grant #97333-G. Practice points 1. Current evidence does not yet provide unequivocal support of theuseof acupuncture intreatinginsomniaas mainmedical modality, although there has been some observed clin- ical effectiveness in certain patients. 2. Acupuncture is safe when used to treat insomnia; auricular and body acupuncture or their variants, withanaverage 15 treatments, are the most commonly used treatment techniques. Research agenda 1. More vigorously designed randomized clin- ical trials will be needed to demonstrate the effectiveness of acupuncture in treating insomnia, with particular attention to insomnia denition, sham control process, blinding, treatment paradigm, outcome measurements and follow-up periods. 2. Mechanistic evaluation of acupuncture in treating insomnia should also be pursued. Appendix I. Acupuncture nomenclature used in this review BL bladder CV conception vessel meridian GB gall bladder GV governing vessel meridian HT heart KI kidney LI large Intestine LR liver LU lung PC pericardial SI small intestine SP spleen ST stomach TE triple energizer (triple heater) Note: when these are used alone, they represent acupoints (usually auricular); when these are used with a number following, they represent meridians, e.g., HT7 is the 7th point on the Heart meridian. Appendix II. Abbreviations in alphabet- ical order # number AHI Apnea/Hypopnea Index AI Apnea Index AIDS Acquired Immune Deciency Syndrome ATAS Acupuncture Treatment Assessment Scale measuring worry, muscle tension, drug craving, physical well-being, and psychological well-being b/l bilateral b/w between BAI Beck Anxiety Inventory BDI Beck Depression Inventory bid twice a day c/o complain of CCMD-3 China Classication of Mental Disorders Third Revision CGI Clinical Global Impression CMAI Cohen-Manseld Agitation Inventory CSQI Current Sleep Quality Index CT clinical trial dis disorder/disease(s) Dx diagnosis ESRD end-stage renal disease eval evaluation f/u follow-up FDDQL Functional Digestive Diseases Quality of Life Questionnaire GI gastroenterology h hour(s) H&Y Hoehn and Yahr HA headache(s) HD Hemodialysis HDS Hamilton Depression Scale IBS Irritable Bowel Syndrome Inpt Inpatient ISI Insomnia Severity Index med medication(s) min minute(s) MYMOP Measure Your Medical Outcome Prole NA not applicable NH nursing home NR not reported Outpt Outpatient(s) PGS polysomnography po take by mouth PSQI Pittsburgh Sleep Quality Index psych psychiatric PT physical therapy Qd once a day qhs every night before bedtime QOD every other day QoL quality of life qow once every other week qw once a week/per week RCT randomized clinical trial Rx treatment 102 W. 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