Acupuncture vs. Venlafaxine for Hot Flashes in Breast Cancer Patients

Abstract & Commentary

By Judith L. Balk, MD, MPH, FACOG. Dr. Balk is Associate Professor, Magee-Women's Hospital, University of Pittsburgh; she reports no financial relationship to this field of study.

Synopsis: This RCT compared acupuncture to venlafaxine for management of hot flashes in breast cancer patients. Both acupuncture and venlafaxine were given for 12 weeks, and then the subjects were followed. Both groups had improvements in their symptoms, but the venlafaxine group had side effects, and the acupuncture group did not.

Source: Walker EM, et al. Acupuncture versus venlafaxine for the management of vasomotor symptoms in patients with hormone receptor-positive breast cancer: A randomized controlled trial. J Clin Oncol 2009 Dec 28; Epub ahead of print.

Vasomotor symptoms like hot flashes are common in breast cancer patients who are taking anti-estrogen medications. Hormone therapy is contraindicated in these patients, so non-hormonal approaches are used. One popular non-hormonal approach is the medication venlafaxine, which is an antidepressant. However, some women experience side effects on this medication, and others simply choose not to use it. Thus, a non-pharmaceutical agent may be preferred by some women.

Fifty subjects with a history of hormone receptor-positive breast cancer were randomized to receive 12 weeks of either acupuncture or venlafaxine. After the 12-week treatment period, subjects were followed for up to 1 year. The primary outcome was hot flash frequency, and secondary outcomes included depressive symptoms and quality of life.

Both groups had significant improvements in hot flashes, depressive symptoms, and other quality-of-life symptoms. During the 12 weeks of treatment, the groups had similar outcomes. At 2 weeks post-treatment, the venlafaxine group had significant increases in hot flashes; the acupuncture group did not. At the other follow-up time points (3, 6, 9, and 12 months), the groups did not differ from each other, with both groups improving over time. The venlafaxine group had 18 incidences of adverse effects; the acupuncture group had none. In addition, in about 25% of women in the acupuncture group, improved libido was experienced.

Acupuncture appears to be at least equivalent to venlafaxine in reducing the frequency of hot flashes, without having adverse effects. Both groups improved over time after a 12-week course of treatment.


Effective treatment of hot flashes for breast cancer patients is an important problem. Women who have been diagnosed with breast cancer often have challenging menopausal symptoms, which can be due to discontinuing hormone therapy after their diagnosis, being placed into menopause from the chemotherapy, and taking anti-estrogen drugs like selective estrogen receptor modulators or aromatase inhibitors. Hormone therapy with estrogen and progestogens is contraindicated in women who have had breast cancer. Thus, finding non-hormonal treatment for menopausal symptoms is very important.

Many different pharmacologic and non-pharmacologic approaches have been studied, including clonidine,1 fluoxetine,2 venlafaxine,3 gabapentin,4 paroxetine,5 relaxation training,6,7 and acupuncture.8 Clinical trials with medications can readily be placebo-controlled, but research on complementary modalities such as acupuncture and relaxation training is often plagued with difficulty in finding appropriate control groups. Recently, sham acupuncture has been questioned as to whether it is truly an inactive control group;9,10 thus, identifying other appropriate control groups will manifest in better research on the effectiveness of various modalities. One approach to studying complementary modalities is to compare the modality with a known effective treatment. With this type of research, one can make an equivalency statement, i.e., whether one treatment appears to be equivalent to another treatment. However, whether the positive effects are due to attention or expectation (placebo effects) cannot be assessed with this type of study. Studying acupuncture relative to a known effective treatment for hot flashes, such as venlafaxine, is thus an excellent study design due to the limitations of sham-controlled acupuncture research.

Venlafaxine is effective for treating hot flashes.3 One double-blind, placebo-controlled, randomized trial enrolled women who either had a history of breast cancer or were reluctant to take hormones, to study the effect of placebo or venlafaxine at different dosages: 37.5 mg, 75 mg, or 150 mg. The primary outcome variable was the hot flash score at 4 weeks. Subjects were stratified based on age, current tamoxifen use, duration of hot flash symptoms, and average frequency of hot flashes per day. One hundred ninety-one subjects had evaluable data over the entire study period. The groups receiving venlafaxine had a greater decrease in hot flashes than did the placebo group. Side effects that were significantly higher in the venlafaxine group compared to the placebo group include mouth dryness, decreased appetite, nausea, and constipation, and were more frequently reported at the 150 mg dosage than at the 75 mg dosage. Overall quality of life increased in all the venlafaxine groups, and decreased in the placebo group. Thus, it appears that venlafaxine is more effective than placebo, at least after 4 weeks, in treating hot flashes, but side effects may limit its utility.

Acupuncture also has placebo-controlled research supporting its effectiveness in treating hot flashes.8,11 In one study, women on tamoxifen received 10 weeks of either true acupuncture or sham acupuncture. During the treatment period, the mean number of hot flashes at day and night was significantly reduced by 50% and almost 60%, respectively, from baseline in the true acupuncture group, and was further reduced by 30% both at day and night during the next 12 weeks. In the sham acupuncture group, hot flashes decreased 25% during the day over the 12 weeks of treatment, but this decrease was reversed during the following 12 weeks. No reduction was seen in hot flashes at night. In another study, 72 women with breast cancer experiencing three or more hot flashes per day were randomly assigned to receive either true or sham acupuncture. True acupuncture was associated with 0.8 fewer hot flashes per day than sham at 6 weeks, but this difference did not reach statistical significance (95% confidence interval, -0.7 to 2.4; P = 0.3). When participants in the sham acupuncture group were crossed over to true acupuncture, the frequency of hot flashes further decreased. The reduction in hot flash frequency persisted for up to 6 months after the completion of treatment. Thus, it appears that acupuncture is effective for hot flashes, and it appears to be well tolerated.

When advising a breast cancer patient regarding options to treat her hot flashes, one must consider both effectiveness and side effect profile. Direct comparisons, such as the study presented, which compare two viable options, often yield very helpful advice. This study has many strengths. First, the researchers employed randomized design with clear statements of the eligibility criteria. The outcome measures are well described, and the CONSORT diagram is clear. The acupuncture points are clearly stated, and the analysis is thorough and appropriate. Most importantly, this study has high clinical significance because it is a comparative effectiveness study, which can improve decision-making between two options.

This study also has limitations. First, the sample size is fairly small, including only 50 subjects. No power analysis is presented to determine the necessary sample size to detect a meaningful difference. The most important limitation is that while the acupuncture intervention likely mimics usual care, the venlafaxine arm does not. Patients may not electively choose to stop medication for hot flashes after 12 weeks, if the medication is tolerated and working well. That said, hot flashes rapidly returned after 12 weeks in the venlafaxine group, but the acupuncture effect was of longer-lasting duration. This is clinically significant, and it may be cost-effective to consider acupuncture rather than medication.

Overall, this is an excellent study that used a sound design to test a very significant question. The authors conclude the paper stating their hope that this study will lead to a change in the typical pattern of practice of treating vasomotor symptoms in patients with breast cancer. I agree with the authors, with the caveat that the small sample size precludes making equivalency conclusions. That said, acupuncture vs. venlafaxine? When conservatively weighing therapeutic risks and benefits, acupuncture comes out ahead.


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2. Loprinzi C, et al. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol 2002;20: 1578-1583.

3. Loprinzi C, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: A randomised controlled trial. Lancet 2000;356:2059-2063.

4. Guttuso T, Jr, et al. Gabapentin's effects on hot flashes in postmenopausal women: A randomized controlled trial. Obstet Gynecol 2003;101:337-345.

5. Stearns V, et al. Paroxetine controlled release in the treatment of menopausal hot flashes: A randomized controlled trial. JAMA 2003;289:2827-2834.

6. Freedman R, et al. Biochemical and thermoregulatory effects of behavioral treatment for menopausal hot flashes. Menopause 1995;2:211-218.

7. Irvin JH, et al. The effects of relaxation response training on menopausal symptoms. J Psychosom Obstet Gynaecol 1996;17:202-207.

8. Hervik J, Mjaland O. Acupuncture for the treatment of hot flashes in breast cancer patients, a randomized, controlled trial. Breast Cancer Res Treat 2009;116: 311-316.

9. Lund I, et al. Minimal acupuncture is not a valid placebo control in randomised controlled trials of acupuncture: A physiologist's perspective. Chin Med 2009;4:1-27.

10. Balk J, Horn B. Why we should change the course of acupuncture research. J Chinese Med 2008;78:54-59.

11. Deng G, et al. Randomized, controlled trial of acupuncture for the treatment of hot flashes in breast cancer patients. J Clin Oncol 2007;25:5584-5590.