By William C. Haas III, MD, MBA
Integrative Medicine Fellow, Department of Family and Community Medicine, University of Arizona, Tucson
Dr. Haas reports no financial relationships relevant to this field of study.
Summary Points
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Acupuncture produces a greater placebo response than pills in the treatment of hot flashes among breast cancer survivors.
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Pending additional research, electroacupuncture may prove to be an effective treatment for hot flashes.
Synopsis: Electroacupuncture produces a greater placebo affect than oral medication when attempting to treat hot flashes in breast cancer survivors.
Source: Mao J, et al. Electroacupuncture versus gabapentin for hot flashes among breast cancer survivors: A randomized placebo-controlled trial. J Clin Oncol 2015; [Epub ahead of print].
Hot flashes affect millions of menopausal women world wide,1 but these vasomotor symptoms tend to be more severe among breast cancer survivors. Breast cancer survivors often suffer from premature menopause as a result of their treatment, which may include surgery, chemotherapy, and estrogen blockers. Unfortunately, due to their cancer history, hormone replacement therapy is not an option for these patients. Although several non-hormonal treatments are available, such as venlafaxine and gabapentin, many women prefer to avoid medications that may have additional adverse effects.2
Among the non-pharmacologic therapies, acupuncture may hold promise for the treatment of hot flashes, especially those caused prematurely in breast cancer survivors. More specifically, electroacupuncture, which introduces low-voltage electrical current through needles inserted into the skin, is hypothesized to improve hot flashes due to a stimulated release of endorphins and other neuropeptides.3 However, the use of acupuncture always raises the question of the placebo response. Interestingly, the placebo effect has been shown to be greater with acupuncture vs pills in the field of pain management.4 These findings prompted a group of researchers to compare the placebo effects of electroacupuncture vs gabapentin for hot flashes in breast cancer survivors. Their primary focus was to evaluate both placebo and nocebo responses with the secondary goal of assessing long-term durability of treatment.
Nearly 500 women in remission from early-stage breast cancer (stage 1-3) were screened for participation in the study. Women considered for the study were required to experience hot flashes for at least 1 month prior to enrollment, with a minimum of two hot flashes per day during the 7-day screening period. Additionally, premenopausal women had to be willing to use non-hormonal contraception during the study. Exclusion criteria were extensively outlined in the methods section. Patients not considered were those actively undergoing cancer treatment, anticipating changes to hormone based adjuvant therapy, or those with a relative contraindication to gabapentin therapy (allergy, renal failure, etc.)
After the initial screening, 120 patients were randomized to one of four interventions: 1) electroacupuncture (EA), 2) sham acupuncture (SA), 3) gabapentin (GP), or 4) placebo pill (PP). For both the EA and SA groups, treatments occurred twice per week for 2 weeks followed by once per week for an additional 6 weeks. Treatments were performed by two licensed, non-physician acupuncturists using a semi-standardized protocol that allowed for four of the acupuncture points to be chosen based on individual patient symptoms (e.g., fatigue or insomnia). Further clarification regarding differences between EA points and SA points were not discussed. Both acupuncture needles and sham needles were left in place for 30 minutes, with the EA group receiving a 2-Hz current through the needles using a transcutaneous electrical nerve stimulation unit. The stimulation unit was also connected to the sham needles with the dial turned to a position that did not emit current, but still showed the unit to be operational. The GP group was titrated to a dose of 300 mg three times per day, using capsules that appeared identical to the placebo pills. The GP and PP groups took the pills for the entire 8-week intervention. The primary outcome was a weekly average hot flash composite score (HFCS) measured by the daily hot flash diary. Frequency and severity of hot flashes were recorded daily during the 8-week intervention and then daily for 1 week at weeks 12 and 24.
There were no significant differences between the groups at baseline. Upon completion of the 8-week intervention, significant differences were observed among all treatment groups with regard to HFCS score (-7.4 for EA, -5.9 for SA, -5.2 for GP, and -3.4 for PP; P < 0.001). Between groups, acupuncture produced a significantly greater placebo effect than did the use of pills, with the SA group having a significantly lower HFCS score than the PP group (-2.39; 95% confidence interval [CI], -4.60 to -0.17; P = 0.035). Compared to the PP group, the EA group also experienced an improvement in hot flashes (-4.1; 95% CI, -7.0 to -1.3; P < 0.005), whereas the GP group showed a non-significant improvement (-1.8; 95% CI, -3.9 to -0.2; P < 0.085). Four months after treatment, the EA group experienced the best long-term effect with the GP group experiencing the least (-8.5 for EA, -6.1 for SA, -4.6 for PP, and -2.8 for GP; P < 0.001). No serious adverse events were observed in any treatment group, although both pill groups reported more treatment-related side effects (dizziness and fatigue) compared to the acupuncture groups (39.3% for GP, 20.0% for PP, 16.7% for EA, 3.1% for SA; P = 0.005).
COMMENTARY
Before discussing the subtleties of the paper, the principle finding should be reiterated — researchers found that acupuncture was associated with enhanced placebo effects and lower nocebo effects when compared with taking pills for hot flashes among breast cancer survivors. It is important to note that the study was not designed to determine the efficacy of acupuncture or gabapentin therapy, primarily as a result of being underpowered as well as the lack of a no-treatment group. Hence, definitive statements regarding the superiority of acupuncture over gabapentin in treating hot flashes should be limited. With that said, EA produced the greatest reduction in hot flashes at the end of the treatment period as well as 4 months off treatment. These findings certainly warrant additional evaluation using more patients and a longer follow-up period.
Overall, the study was well-designed; however, a few potential limitations should be discussed. First, acupuncture treatments were not completely standardized, which may have contributed to variations in treatment response, although individualized acupuncture treatments are part of other acupuncture study protocols. Moreover, as with all acupuncture trials, blinding could not occur when comparing the intervention to an oral medicine. Another potential limitation was that 25% of patients were receiving an antidepressant during the study, which could have independently accounted for improvements in hot flashes.
Regardless of any limitations in study design or inability to generalize the efficacy of electroacupuncture, the study enhances our knowledge of acupuncture and its potential areas for application. The fact that acupuncture elicited a greater placebo effect than pills suggests that there is something intrinsically different about acupuncture, especially as similar findings have been observed in other areas of medicine4,5 The researchers suggest that the enhanced placebo effect may be due to a combination of positive expectancy, patient-provider interaction (including touch), relaxation, and light sensory stimulation by sham needling. Interestingly, EA produced further symptom improvement beyond the treatment period when compared to SA. These findings are supported by separate research that real acupuncture causes an increased µ-opioid receptor binding potential in brain structures, which is not observed with sham acupuncture.6 Ultimately, additional clarification in the methods regarding the different points chosen for both EA and SA would have provided greater insight about the difference between EA and SA for hot flashes.
The general takeaway from this study is that electroacupuncture produces a greater placebo effect than oral medication when attempting to treat hot flashes in breast cancer survivors. In fact, electroacupuncture may provide a better response than gabapentin with fewer adverse effects; however, additional research needs to be conducted to confirm this possibility. A large study that is appropriately powered would allow for more definitive conclusions. Acupuncture should certainly reside in the clinician’s toolbox for treating hot flashes among breast cancer survivors.
REFERENCES
- Stearns V, et al. Hot flashes. Lancet 2000;360:1851-1861.
- Mao JJ, et al. Acupuncture for hot flashes: Decision making by breast cancer survivors. J Am Board Fam Med 2012;25:323-332.
- Han JS. Acupuncture and endorphins. Neuro Sci Lett 2004;361:258-261.
- Kaptchuk TJ, et al. Sham device v inert pill: Randomized controlled trial of two placebo treatments. BMJ 2006;332:391-397.
- Meissner K, et al. Differential effectiveness of placebo treatments: A systematic review of migraine prophylaxis. JAMA Intern Med 2013;173:1941-1951.
- Harris RE, et al. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs). Neuroimage 2009;47:1077-1085.
Electroacupuncture produces a greater placebo effect than oral medication when attempting to treat hot flashes in breast cancer survivors.
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