Abstract
Randomized, Blinded, Sham-Controlled Trial of Acupuncture for the Management of Aromatase Inhibitor–Associated Joint Symptoms in Women With Early-Stage Breast Cancer.
Crew KD, Capodice JL, Greenlee H, Brafman L, Fuentes D, Awad D, Tsai WY, Hershman DL. J Clin Oncol 2010;28(7):1154–1160
Participants were randomly assigned to 12 true acupuncture (TA) or sham acupuncture (SA) sessions over 6 weeks. Acupuncture protocol was selected based on a standard Traditional Chinese Medicine (TCM) point prescription to treat musculoskeletal pain and the National Acupuncture Detoxification Association (NADA) protocol applied to one ear to relieve pain and decrease stress. A standardized set of acupuncture points (full body and auricular acupuncture in alternating ears. In addition to specific points tailored to treat 3 of the patient's most painful joint areas) were given for 30 minutes twice weekly over 6 weeks. The sham intervention used superficial needle insertion at body locations not recognized as true acupoints. The TA and SA points were chosen based on the concept of treatment manualization to facilitate the systematic delivery of standardized acupuncture treatments.
Participants were asked to complete a baseline questionnaire covering demographic information and reproductive history. Patients were also surveyed on their use of complementary and alternative medicine (CAM), at baseline and again at 3 and 6 weeks. Self-administered questionnaires included the Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]; hands Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands [M-SACRAH]; Functional Assessment of Cancer Therapy–General (FACT-G) which measures physical, social/family, emotional, and functional well-being and a general 14-item questionnaire pain scale used in cancer patients that asks to rate pain over the prior week and the degree to which it interferes with activities (BPI-SF). Additional efficacy end points included change in analgesic use and the frequency and severity of adverse events (according to the National Cancer Institute Common Terminology Criteria) assessed by telephone interviews conducted every 2 weeks for 6 weeks. The primary objective was to compare the mean BPI-SF worst pain score at 6 weeks between groups. All other analyses were secondary objectives.
Forty-three women (median age was 58 years; range, 37 to 77 years) were randomized. Baseline demographic and clinical characteristics were comparable between the 2 groups. At 6 weeks, the mean BPI-SF worst pain score was 3.0 and 5.5 (P = .002) for the TA and SA groups, respectively, corresponding to a 50% improvement in scores compared with baseline for the TA group. Similar 6-week differences were seen for pain severity (2.59 vs 4.53; P < .001) and pain-related interference (2.48 vs 4.54; P < .002). Eighty percent of participants in the TA group reported at least a 2-point improvement in the BPI-SF worst pain score as compared with 22% with SA (P < .001). Similar findings were also seen comparing the 6-week mean scores for the WOMAC and M-SACRAH subscales (70% decrease from baseline). Although the physical well-being measured by the FACT-G showed a significant improvement for TA compared with SA (19.8 vs 15.4; P < .03), no significant differences were observed for the FACT-G social/family, emotional, and functional wellbeing subscales.
This is one of first studies looking at management of arthralgias in patients with cancer. Some limitations of this study, as identified by the authors, are the relatively small sample size, larger than anticipated drop-out, possible selection bias, and that the primary and secondary outcomes relied on patient-reported outcomes, although many have been repeatedly validated. This study supports a favorable effect of acupuncture in the management of postmenopausal women with AI-induced arthralgias. Improvement was noted in joint pain, stiffness, functional ability, and physical well-being after 6 weeks of acupuncture therapy.
Acupuncture for depression during pregnancy: a randomized controlled trial.
Manber R, Schnyer RN, Lyell D, Chambers AS, Caughey AB, Druzin M, Carlyle E, Celio C, Gress JL, Huang MI, Kalista T, Martin-Okada R, Allen JJ. Obstet Gynecol. 2010 Mar;115(3):511–20.
Depressed pregnant women with viable pregnancies were recruited between 2003 and 2008 through advertising in parent and baby publications and from local clinics. Inclusion criteria were: 1) participants had to be between 12 and 30 weeks of gestation; 2) 18 years or older; 3) meet criteria for major depressive disorder according to DSM-IV-TR, and score at least 14 on the 17-item Hamilton Rating Scale for Depression. Exclusion criteria were: 1) other current primary Axis I psychiatric disorders, except social phobia; 2) seasonal affective disorder or psychotic features; 3) abnormal thyroid panel or drug screen results; 4) serious uncontrolled medical conditions or conditions that may be a medical basis of depression; 5) cluster B personality disorders (determined by the Structured Clinical Interview for DSM-IV interview for Axis II disorders 24); 6) current psychotherapy, herbs, or psychotropic medications; 7) electroconvulsive therapy or vagal nerve stimulation in the past year; 8) current active suicidal potential necessitating immediate treatment; 9) absence of prenatal care; and 10) conditions necessitating bed rest.
A total of 183 participants were enrolled, 150 were randomized, and 141 began treatment. Participants were randomized to acupuncture specifically designed to address depression or to 1 of 2 control treatments: acupuncture that was not specific for depression and prenatal massage. Treatments were provided 2 times per week for the first 4 weeks, and weekly for 4 more weeks. Each treatment lasted approximately 25 minutes. Acupuncture specific for depression was tailored individually to address each participant's depression according to the principles of Traditional Chinese Medicine (TCM). Acupuncture, not specific for depression, was also standardized and needles were inserted in real acupuncture points that did not address depression according to TCM. Swedish massage was provided in a standardized fashion and included effleurage and petrissage strokes. Approximately 5 minutes was spent on each of the following: back, face, head, neck and shoulder, and feet while participants were lying on their side.
Treatment outcome was assessed by blinded raters. The primary measure of outcome was the 17-item Hamilton Rating Scale for Depression (HRS-D), administered at baseline and after 4 and 8 weeks of treatment by raters blind to treatment group. Demographic characteristics were similar except for the racial composition of groups, with a higher proportion of blacks in the group receiving acupuncture not specific for depression than the other 2 groups. Depression severity and history were similar in all groups.
Participants in the active acupuncture group experienced a significantly greater reduction in HRS-D scores than the participants in the combined control interventions (P < .05; Cohen's d effect size for change in HRS-D = 0.39; 95% confidence interval [CI] 0.01 − 0.77), and there were no differences between the 2 control conditions (P = .43; Cohen's d = 0.13; 95% CI −0.32 to 0.58). The observed average reduction in the HRS-D in the active group was 10 points. The number needed to treat (NNT) effect size was 5.3 (95% CI 2.8 − 75.0) for the group receiving acupuncture specific for depression compared with the combined control groups and 8.0. Remission rates were not significantly different between the active and the control groups. Discontinuation of treatment occurred in 33 of 141 participants who started treatment (23%), of whom 10 of 33 (30%) were for pregnancy-related reasons (early delivery or pregnancy complications). The proportion of participants who dropped out did not differ by group (P > .52). Ten unexpected/adverse events occurred including premature delivery, pregnancy loss, congenital defects, preeclampsia, and hospitalization for different reasons. The rates of adverse events were not significantly different for the 3 treatment groups (P = .69). Side effects of any type were reported by 43 participants (4 in the group receiving prenatal massage, 19 in the group receiving acupuncture not specific for depression, and 20 in the group receiving acupuncture specific for depression). The group receiving prenatal massage reported significantly fewer side effects than the 2 acupuncture groups (P < .01).
In this study, acupuncture specific for depression was associated with a significantly greater decrease in depression symptom severity and a higher rate of response compared with the combined control groups. The authors felt that overall, the acupuncture protocol yielded a response rate comparable to the rates observed in standard treatments for depression and was associated with relatively few and mild side effects, suggesting that this standardized acupuncture protocol could be a viable treatment option for depression during pregnancy.
Use of a conventional acupuncture treatment protocol rather than a standardized protocol allows for realistic clinical application. However, despite the positive findings, this study encompasses several limitations such as a weak blinding protocol and a high number of dropouts (23%). Overall, results from this study validate findings from other studies and meta-analyses confirming that acupuncture engenders good symptomatic improvement with fewer side effects than pharmaceutical treatments.
Acupuncture versus venlafaxine for the management of vasomotor symptoms in patients with hormone receptor-positive breast cancer: a randomized controlled trial.
Walker EM, Rodriguez AI, Kohn B, Ball RM, Pegg J, Pocock JR, Nunez R, Peterson E, Jakary S, Levine RA. J Clin Oncol. 2010 Feb 1;28(4):634–40. Epub 2009 Dec 28.
The aim was to evaluate the effect of acupuncture in reducing/eliminating vasomotor symptoms in patients with breast cancer who received antiestrogen hormone therapy as compared with venlafaxine and to determine whether acupuncture has fewer adverse effects.
Patients were recruited from oncology clinics of Henry Ford Health System, from September 2004 through June 2007. The inclusion criteria were as follows: (1) stage 0-III pre- or postmenopausal breast cancer patients on hormone therapy with tamoxifen or anastrozole (premenopausal patients must not have menstruated for at least 6 months); (2) ≥14 hot flashes per week; (3) ≥18 years of age; (4) may have been treated locally with surgery and/or radiation and must have completed chemotherapy; (5) may be receiving radiation therapy but otherwise must be within 5 years after treatment; (6) must be on a stable dose of hormone therapy for 4 weeks or more without plans to discontinue therapy for the duration of the study; (7) Karnosky performance status (KPS) >70; (8) life expectancy >6 months.
Health outcomes were measured using: a) the Hot Flash Diary11; b) the Menopause Specific Quality of Life Questionnaire (MenQOL); the Short Form 12-Item Survey (SF-12); the Beck Depression Inventory-Primary Care (BDI-PC); and the National Cancer Institute Common Toxicity Criteria scale.
This RCT compared 12 weeks of acupuncture or venlafaxine treatment. The primary end point was hot flash frequency. Patients were observed for 1 year post-treatment. Patients in the acupuncture arm received treatments twice per week for the first 4 weeks, then once per week for the remaining 8 weeks. All patients were treated using primary acupuncture points of urinary bladder 23, kidney 3, and spleen 6 for general menopausal symptoms. Secondary points were used as needed according to the TCM diagnosis: DU 14, gallbladder 20, lung 9, liver 3, DU 20, stomach 36, Ren 6, pericardium 7, and heart 7. No electrical stimulation was used. Patients in the control arm took venlafaxine 37.5 mg orally at night for 1 week, then 75 mg at night for the remaining 11 weeks.
Fifty subjects were equally randomized to each arm. They ranged in age from 35 to 77 years, with a median of 55 years; 82% were postmenopausal. Although both groups started out differently (the acupuncture group had more hot flashes at pretreatment), both groups experienced similar changes across time (P < .001), including significant decreases in hot flashes from pre- to post-treatment of 50% (P < .036), followed by a return toward baseline at follow-up time points. At 2 weeks post-treatment the venlafaxine group experienced significant increases in hot flashes, whereas the acupuncture group remained low.
The results of the ANOVA for secondary outcome measures showed a significant effect of time for hot flash severity (P < .001), BDI-PC (P < .001), MenQOL (P < .002), and SF-12: Mental (P < .007). There were no significant effects of group or significant interactions. Eighteen adverse effects were reported in the venlafaxine treatment group vs. zero in the acupuncture group.
Despite the small number of participants, results of this study are very encouraging demonstrating a beneficial effect of acupuncture on hot flashes similar to venflaxine. The hot flash frequency remained low up to the 3-month visit after discontinuation of treatment for the acupuncture group, while it was back to baseline at the 2-week visit for the venflaxine group.
Efficacy of acupuncture in fibromyalgia syndrome–a systematic review with a meta-analysis of controlled clinical trials.
Langhorst J, Klose P, Musial F, Irnich D, Häuser W. Rheumatology (Oxford). 2010 Apr;49(4):778–88. Epub 2010 Jan 25.
To be considered, studies were required to meet the following inclusion criteria: 1) randomized and quasi-randomized study designs; 2) 3 types of acupuncture: Chinese acupuncture, Western acupuncture, and Japanese acupuncture; 3) acupuncture points should be stimulated by needle insertion or laser "verum acupuncture;" 4) trials comparing verum acupuncture with the following control interventions were included: sham acupuncture (penetration of the skin with and without stimulation of non-acupuncture points), and simulated acupuncture (simulated non-penetrating stimulation of the skin at acupuncture or non-acupuncture points); and 5) outcome measures included at least 1 key symptom of FMS, namely pain, fatigue, sleep disturbances, and physical function was required as outcome measure. Secondary outcome measures were adverse events.
Studies were excluded if acupuncture points were stimulated by acupressure, transcutaneous electrical nerve stimulation, and infrared light for verum acupuncture.
After screening of titles and abstracts, full text articles were reviewed independently by 2 authors for appropriateness. In preparation for the meta-analysis, 2 authors independently extracted the data using standard extraction forms. Discrepancies were rechecked and consensus achieved by discussion; if necessary, a third author reviewed the data to reach consensus. Internal and external validity were assessed using the modified Cochrane Collaboration tool.
Literature search initially produced 124 citations; of these, 9 were excluded, 64 did not evaluate acupuncture in FMS, 27 were duplicates of controlled studies, and 2 were reviews. After a review of these 27 initially-selected articles, a further 20 papers were excluded either because they had no control arm or because acupuncture, used as an adjuvant to medical therapy, was compared with medical therapy.
The median age of the participants was 47 (range 44–55) years; median of the percentage of women was 95% (range 90–100%). The review found strong evidence for the reduction of pain at post-treatment (SMD −0.25; 95% CI −0.49 to −0.02; P = .04), while there was no evidence for a positive effect on other main symptoms of FMS, i.e., fatigue and sleep disturbances, or physical function at post-treatment. Moderate evidence was reported indicating that the positive effects could not be maintained at follow-up. There was significant heterogeneity in the outcomes of sleep and physical function at post-treatment and in pain at latest follow-up studies; however, due to the small number of studies, the source of heterogeneity could not be identified.
Subanalysis of data found that trials with individual selection of acupuncture points, with electro-stimulation and less than 10 sessions, had significant effects on pain at post-treatment, but not studies with standardized selection of acupuncture points, manual stimulation, and more than 10 sessions.
Adverse events were inconsistently reported. Acupuncture treatment received good acceptance by patients as evidenced by the low dropout rate. Acupuncture was also not found to be associated with serious harmful events.
Results of this meta-analysis should be interpreted with caution. There was great variability of the methodological quality of studies included. One trial, identified as high quality in which sham and simulated acupuncture were superior to verum acupuncture, differed from the others: acupuncture was delivered by 8 acupuncturists in private settings rather than by 1 or 2 acupuncturists. Conclusions in this review differ from those reported in previously published systematic reviews, highlighting the difficulty in conducting standardized acupuncture research and interpreting results from existing trials.
Acupuncture in poststroke rehabilitation: a systematic review and meta-analysis of randomized trials.
Wu P, Mills E, Moher D, Seely D. Stroke. 2010 Apr;41(4):e171–9. Epub 2010 Feb 18.
Nine databases (including 2 in Chinese) were searched from inception to September 2009. Articles were included if they were conducted: 1) including adult patients (>18 years) with disability due either to ischemic or hemorrhagic stroke; 2) participants had to be randomly allocated to either active Acupuncture (Ac) treatment or a control group given sham Ac or no Ac treatment; 3) any co-interventions had to be reported as the same in both groups. Studies were excluded if: 1) only laboratory values rather than clinical responses were included; and 2) comparisons in which Ac was not independently assessed. Eligibility was assessed based on review of the full-text papers. Data were extracted independently by reviewers using a standard pre-piloted form.
A total of 56 randomized clinical trials (35 in Chinese and 21 in English) containing independent data fit the criteria for inclusion. The 56 publications included 5,650 patients, (3,156 in the treatment groups; 2,494 in the control group). Four trials assessed hemorrhagic stroke, 24 trials assessed ischemic stroke, and 28 trials assessed either hemorrhagic or ischemic stroke (mixed). Sixteen trials used electroacupuncture, 24 studies used both scalp and body Ac, 28 studies used body Ac, and 4 studies used scalp Ac only. Sham Ac was used as control in 7 studies only.
The intervention duration ranged from 2 to 10 weeks (mean, 4.5 weeks; standard deviation 1.6). Thirty-nine of the 56 studies provided detailed information based on the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines. Overall, the quality of the studies was “fair” and most studies were small (median n = 86; range, 16 to 241).The trials used various motor impairment scales, generalized stroke scales, and disability assessments.
Positive results were reported in 45 of the 56 studies. Six studies reported a positive benefit only in a subgroup analysis. Thirty-eight trials provided numeric data for meta-analyses, the results of which yielded a highly significant or demonstrating efficacy in post-stroke rehabilitation with Ac compared with no Ac (OR = 4.33, 95% CI: 3.09 to 6.08). The OR for studies conducted in China was 4.49 (95% CI = 3.16 to 6.39); while in the 3 studies conducted outside of China, the OR was 3.33 (95% CI = 0.75 to 14.88). Studies conducted in mainland China, the use of manual vs electric Ac, the use of sham controls, and the reporting of randomization contributed to study heterogeneity. No significant effects were found of allocation concealment on heterogeneity.
Despite several weaknesses, the overall evidence suggests that Ac may have a role in post-stroke rehabilitation. As has been noted in other trials, no difference in efficacy was noted between Ac and sham Ac. The authors concluded that given concerns about study quality, they were reticent to strongly endorse Ac from this review, but argue that there is compelling evidence for a large and well-conducted randomized clinical trial to support implementation of Ac within clinical practice for post-stroke rehabilitation.