Abstract
Imbalance between pro- and anti-inflammatory cytokines, and between Th1 and Th2 cytokines in depressed patients: the effect of electroacupuncture or fluoxetine treatment.
Song C, Halbreich U, Han C, Leonard BE, Luo H. Pharmacopsychiatry. 2009;42:182–188.
The aim of the present study was to (1) study cytokine changes in untreated depressed patients, including proinflammatory cytokines IL-1β (from macrophages), TNF-α (from macrophage and Th1 cells), and IFN-γ (from Th1), and anti-inflammatory cytokine IL-10 (from Th2 cells) and IL-4 (from Th2 cells); (2) assess the effect of treatments with electroacupuncture (EA) vs the SSRI (selective serotonin reuptake inhibitor) fluoxetine on plasma cytokine concentrations; and (3) compare these cytokine changes in treatment responders and non-responders.
Ninety-five Chinese patients (mean [SD] age, 31.8 [12.1] years) and 30 healthy Chinese controls were recruited from outpatient clinics of the Beijing Mental Health Institute. Hamilton Depression Rating Scale (HDRS) 21 item scores and Clinical Global Impression (CGI) were used to assess severity and therapeutic effects each week for 6 weeks. Patients were assessed with the Structured Clinical Interview for DSM IV (SCID) and met DSM-IV criteria for major depressive disorder.
Depressed patients were randomly and blindly assigned to 1 of 3 groups: (1) EA and placebo capsules; (2) fluoxetine and sham EA; and (3) sham EA and placebo capsules. The 3 depression groups did not differ in the duration of depression, duration of current episode, and number of depressive episodes. Baseline blood samples from controls and patients were withdrawn at 7:00–9:00
EA treatment was performed by placing needles at Bai Hui and at Yin Tang acupuncture points on the forehead, which have been demonstrated to be effective for relief of depression. The acupuncture needles were then connected to an EA machine for 45 minutes, 3 times per week. The sham acupuncture was performed by placing the needles at nontherapeutic points, 1 cm beside the Bai Hiu and Yin Tang acupoints. The needles were connected with the same EA machine, which simulated the same oscillation waves as the active EA. The treatment procedure was the same as for the EA group. Fluoxetine (20 mg) or matched placebo capsules were taken after breakfast once daily for 6 weeks.
At baseline the HDRS scores in the 3 groups (EA, fluoxetine, and placebo groups) did not differ. Following 6 weeks of treatment, mean (SD) HDRS scores were as follows: EA, 10.2 (5.9); fluoxetine, 11.3 (6.6); and placebo 13.9 (6.3), demonstrating a statistically significant (P < .01) improvement in depressive symptoms for the EA and fluoxetine treatment groups. Similar scores were found on the CGI. Before treatment scores were EA, 4.03 (0.41); fluoxetine, 4.0 (0); placebo, 4.03 (0.18), and posttreatment scores were EA, 2.10 (0.94); fluoxetine, 2.25 (1.08); and placebo, 2.84 (1.27).
Compared with controls, untreated depressed patients showed higher concentrations of IL-1β than controls (P < .01). In the posttreatment groups, the reduction of this proinflammatory cytokine was statistically significant when compared with pretreatment (P < .01). Tukey/Kramer post hoc testing revealed this reduction occurred in patients treated with EA and fluoxetine but not in the placebo group. By contrast, the concentration of Th1 cells produced proinflammatory cytokine TNF-α and IFN-γ were lower in depressed patients than these cytokines in controls (TNF: P < .001; IFN: P < .001). EA treatment significantly normalized the level of TNF-α (P < .05), while treatment with fluoxetine or placebo lacked an effect. The change in IFN-γ in patients receiving EA was almost significant (P = .06) when compared with untreated patients. The comparison between nonresponders and responders showed that serum TNF-α concentration was significantly reduced (nonresponders: 11.03 [0.67] and responders: 8.95 [0.36]) (P < .01), while IFN-γ was not significantly changed in patients who responded to the treatments (nonresponders: 3.64 [0.37] and responders: 5.21 [0.65]).
These results suggest an imbalance between proinflammatory and anti-inflammatory cytokines (IL-1 and IL-10) as well as between Th1 and Th2 cytokines (IFN-γ and IL-4) in depressed patients. The antidepressant treatment with fluoxetine showed an anti-inflammatory effect by reducing proinflammatory cytokines, while EA treatment not only reduced proinflammatory cytokines but also modified Th2 cytokine synthesis and restored the balance in the Th1/Th2 ratio. Sham acupuncture also partially reduced depression-associated increase in IL-1β concentration (P = .06).
Acupuncture versus venlafaxine for the management of vasomotor symptoms in patients with hormone receptor-positive breast cancer: a randomized controlled trial [published online ahead of print].
Walker EM, Rodriguez AI, Kohn B, et al. J Clin Oncol. December 28, 2009.
The study evaluated the effect of acupuncture in reducing/eliminating vasomotor symptoms in patients with breast cancer who received anti-estrogen hormone therapy as compared with venlafaxine and to determine whether acupuncture has fewer adverse effects.
Participants were recruited from the oncology clinics of Henry Ford Health System. The inclusion criteria were as follows: (1) stage 0-III premenopausal or postmenopausal breast cancer patients taking hormone therapy with tamoxifen or arimidex (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 receiving a stable dose of hormone therapy for 4 weeks or more without plans to discontinue therapy for the duration of the study; (7) Karnofsky performance status (KPS) >70; (8) life expectancy >6 months.
In this study the authors compared 12 weeks of acupuncture or venlafaxine (37.5 mg orally for 1 week, then 75 mg at night for the remaining 11 weeks). Patients were observed for 1 year after 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 BL 23, KI 3, and SP 6 for general menopausal symptoms. Secondary points were used as needed according to the TCM diagnosis: Du 14, GB 20, LU 9, LR 3, Du 20, ST 36, Ren 6, PC 7, and HT 7. The primary end point was hot flash frequency. Additional end points were the hot flash diary (measuring the number and severity of hot flashes); the Menopause Specific Quality of Life Questionnaire (MenQOL), Short Form 12-Item Survey (SF-12), the Beck Depression Inventory-Primary Care (BDI-PC), and the National Cancer Institute Common Toxicity Criteria scale (measuring adverse effects of treatment).
Fifty women were initially randomized to the 2 arms (24 completed the treatment in the acupuncture arm and 20 in the venlafaxine arm). At the 12-month follow-up, data from 14 participants in the acupuncture group and 13 in the venlafaxine group were available for analysis. Participants ranged in age from 35 to 77 years (median, 55 years); 82% were postmenopausal. Women were evenly distributed between the 2 arms, although participants in the venlafaxine arm were slightly older (56 vs 50 years).
ANOVA analysis of the primary outcome (hot flash frequency from before to posttreatment and at 3-, 6-, 9-, and 12-month follow-up points) showed a significant effect of group (P < .036) and time (P < .001), but no significant interaction effect. Similar changes were noted across time, including significant decreases in hot flashes from before to posttreatment of 50%, followed by a return toward baseline at follow-up time points. Two weeks after treatment the venlafaxine group experienced significant increases in hot flashes, whereas the acupuncture group remained low until 2 months following treatment. 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. National Cancer Institute Common Toxicity Criteria scale data showed 18 incidences of adverse effects in the venlafaxine group in contrast to 0 adverse effects in the acupuncture group (P < .002).
In this study acupuncture was noted to be as effective as venlafaxine in decreasing the number of vasomotor symptoms in patients with breast cancer who receive anti-estrogen hormone therapy. Women in the acupuncture arm experienced fewer side effects and a longer duration of symptom relief after discontinuation of treatment. These findings should be interpreted with caution due to the small number of subjects and high dropout rates on follow-up; however, it should be noted that these results are consistent with findings from similar previously published studies. Clinicians looking for a safe, effective, and potentially less expensive treatment may want to consider acupuncture as an alternative to medications.
Does acupuncture have a place as an adjunct treatment during pregnancy? a review of randomized controlled trials and systematic reviews.
Smith CA, Cochrane S. Birth. 2009;36(3):246–253.
English-language texts of randomized controlled trials (RCTs) and systematic reviews were searched in PubMed, CINAHL, and the Cochrane Library, from database inception to November 2008. Studies were included if they were RCTs or systematic reviews comparing acupuncture with a control group (sham or placebo control acupuncture, no additional treatment, standard treatment, or other treatment). Additional RCTs were included if they were published since the last published systematic review. Quasi-randomized and crossover trials were excluded. The validity of each trial was assessed according to criteria in The Cochrane Handbook for Systematic Reviews of Interventions. Assessment of systematic reviews and meta-analyses was undertaken using the Overview Quality Assessment Questionnaire (OQAQ).
Sixteen studies were included (8 were RCTs and 8 were systematic reviews). Articles evaluated back pain, nausea, depression, breech presentation, cervical ripening, induction of labor, and pain management in labor.
Nausea
Trials were heterogeneous, making it hard to pool the results. Overall findings indicated that acupressure and electrostimulation had better control than manual acupuncture in the treatment of nausea and vomiting.
Emotional Disorders During Pregnancy
One study was identified that reported a significantly larger proportion of participants responded to acupuncture treatment than to massage (P = .03), with a number-to-treat (NTT) of 2.7. No difference was seen between acupuncture and the control group (P = .18; NTT = 4.7).
Back and Pelvic Pain
One RCT was published since the prior systematic reviews. Overall the findings from the reviews and recent RCT highlight promising evidence for the effectiveness of acupuncture to manage back and pelvic pain and the need to conduct further high-quality trials.
Breech Presentation Use of Moxibustion
Two reviews concluded that the current literature shows a beneficial effect from using acupuncture-type interventions on acupuncture point BL 67 to induce correction of a breech presentation compared with expectant management.
Cervical Ripening, Induction of Labor, and Augmentation of Labor
Two RCTs were identified since the Cochrane review (2004) that found that fewer women receiving acupuncture required use of induction methods compared with standard care. One study (N = 106) evaluated the augmentation effect from acupuncture after prelabor rupture of membranes compared with standard of care. The study found no difference in outcome between the groups. The other high-quality study (N = 364) concluded that no difference was found between groups (acupuncture to sham acupuncture) in women in spontaneous labor, or in the need for induction methods.
Pain Management in Labor
Two systematic reviews were identified. Both reviews concluded that the evidence for acupuncture as an adjunct to conventional pain control during labor was promising, but further research is still needed. A more recent RCT randomized 144 healthy nulliparas in the active phase of labor to real or control minimal acupuncture (20 minutes). The study concluded that acupuncture reduced labor pain 2 hours after the study intervention (P < .01), and that the active phase of labor was shorter in the acupuncture group compared with the control group (P < .001).
Based on the results of this review, a small but growing body of acupuncture research confirms the potential benefit from acupuncture to treat nausea in pregnancy. A review of acupuncture to treat back pain, pain management in labor, and the use of moxibustion to turn a breech baby demonstrated encouraging but limited findings. The use of acupuncture to stimulate the onset of labor showed mixed results.
Correction of nonvertex presentation with moxibustion: a systematic review and metaanalysis.
Vas J, Aranda JM, Nishishinya B, et al. Am J Obstet Gynecol. 2009;201(3):241–259.
The aim of the present review was to assess the available scientific evidence on the effectiveness and safety of moxibustion, compared with a control (ie, either doing nothing or applying a different approach, such as postural methods or acupuncture; studies that evaluated the combined effects of moxibustion and another technique were also included), to correct the nonvertex presentation of a fetus. Randomized or semi-randomized controlled studies were examined. Several databases were searched without language restrictions through June 2007. The principal outcome measure considered was the proportion of versions to cephalic presentation following the period of moxibustion intervention.
Seven articles (from a total of 60 references) met the inclusion criteria and were included in this review. Five studies were deemed of moderate quality and 2 were of low quality. Four studies were conducted in China and 3 in Italy. Six studies compared moxibustion (alone or in association with acupuncture and/or postural measures) with no treatment, or with postural measures, whereas 1 compared moxibustion with acupuncture. Studies had a high degree of heterogeneity.
Moxibustion (6 studies with a total of 1087 pregnant women) demonstrated a high rate of cephalic version of 72.5% vs 53.2% in the control group (RR, 1.36; 95% CI, 1.17–1.58). The number needed to treat (NNT) was 5 with a 95% CI between 4 and 7. Analysis by subgroups isolated a subset of studies (4 studies; 635 subjects) with no significant heterogeneity (women with a gestational age of 32 weeks or greater). In this subset analysis a significant difference was seen between the moxibustion and the control groups (RR, 1.31; 95% CI, 1.03–1.66; NNT of 6, 95% CI, 4–12).
Analysis by subgroups, depending on geographic location of the studies, revealed an RR that was higher for the studies carried out in Asia (RR, 1.40; 95% CI, 1.16–1.68) than those performed in Europe (RR, 1.21; 95% CI, 0.81–1.80).
No statistically significant differences were found in the comparison of moxibustion with any other technique, with respect to rates of cesarean delivery, premature births, Apgar score less than 7 at 5 minutes, operative deliveries (by vacuum or forceps), or premature rupture of the membranes. In addition the treatment group had a tendency for a lower number of complications.
This systematic review, despite identifying several areas of weakness and heterogeneity, strongly supports the benefit of moxibustion applied at the acupuncture point BL 67 for achieving cephalic version, particularly in women with pregnancies of 32 weeks' gestation or more.
A single point acupuncture treatment at large intestine meridian: a randomized controlled trial in acute tonsillitis and pharyngitis.
Fleckenstein J, Lill C, Lüdtke R, et al. Clin J Pain. 2009;25(7):624–631.
In a pilot study, 30 patients with clinically diagnosed sore throat due to acute tonsillitis or pharyngitis were randomized into 2 groups. One group received 1 single-needle acupuncture treatment, whereas the other group received 1 sham laser acupuncture treatment. Acupuncture treatment was administered between acupuncture points LI 8 and LI 10. In this pilot study, acupuncture reduced pain immediately after treatment as compared with the control group. This study is an extension of the pilot study and was designed to confirm its effects.
Sixty patients with acute tonsillitis or pharyngitis were recruited from Ludwig Maximilians University Munich, Munich, Germany, and from 6 private practices. Patients were told they would receive either acupuncture or a laser acupuncture treatment, and group assignment was not revealed to them. Inclusion criteria included patients older than 18 years having had a sore throat for a maximum of 5 days. The diagnosis of acute tonsillitis or pharyngitis was confirmed by a specialist from the study center using the Schachtel Score. Patients were excluded from the study if 1 or more of the following criteria was fulfilled: local and general contraindications for treatment such as participation in other studies, pregnancy, coagulopathies, psychosis, or other severe diseases. The treatment was standardized and performed by the same acupuncturist on the upper part of the forearm at the Meridian section between the acupuncture points LI 8 and LI 10. At the most tender site assessed, the needle was administered tangentially along the cutis in an easy and gently dabbing movement to achieve a slight petechial bleeding. Treatment duration was approximately 1 minute. The recovery time after treatment was 15 minutes for both acupuncture and sham laser groups. Sham laser acupuncture was applied at equivalent points.
Pain on swallowing (using a 10-point visual analog scale) was defined as the main outcome parameter in this study. Patients were also asked to evaluate whether their satisfaction and expectations were met by means of a standardized questionnaire according to Vincent and Lewith, which comprised 4 items: (1) Alleviation: How confident do you feel that this treatment can alleviate your complaint? (2) Recommendation: How confident would you be in recommending this treatment to a friend who suffered from similar complaints? (3) Logic: How logical does this treatment seem to you? (4) Other: How successful do you think this treatment would be in alleviating other complaints?
Due to recruitment problems and since the triangular test did not yield a final conclusion, researchers terminated the trial prematurely and subsequently switched to a conventional statistical analysis relying on a priori fixed patient numbers. Outcomes were analyzed on an intention-to-treat basis by univariate ANCOVA.
Sixty patients (32 female, 28 male; mean [SD] age, 30.5 [10.7] years) were finally randomized. Treatment groups did not significantly differ with respect to sex, age, severity and duration of disease, pretreatments, accompanying diseases, and experiences with acupuncture.
Pain intensity provoked by swallowing was reduced in both groups but ANCOVA resulted in a nonsignificant group difference of 0.9 points on the VAS (confidence interval: 0.2-2.0; P = .12). Patients reported relief of provoked pain in both groups 2 hours and 24 hours after treatment concerning pain on swallowing. The nonsignificant trend in favor of the acupuncture group was also observed 2 hours, but not 24 hours, after treatment. There was no statistically significant difference between groups in the number of analgesics or supplementary treatment used. Patients' satisfaction with treatments was comparable and high in both groups on the VAS (acupuncture group: 7.9 [1.9] points; sham group: 7.9 [2.1] points).
Although the findings of this study are interesting, results should be interpreted with caution. The study had several difficulties in recruitment and logistics and had to be modified from its original plan. In addition, as with many other trials reviewed here, a question is raised regarding the effect of sham acupuncture and the expectation of pain relief.