Research Review By Dr. Ceara Higgins©

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Date Posted:

July 2017

Study Title:

The Long-term Effect of Acupuncture for Migraine Prophylaxis: A Randomized Clinical Trial

Authors:

Zhao L, Chen J, Li Y, et al.

Author's Affiliations:

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China; The Chinese Cochrane Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, China; Acupuncture and Tuina School, Hunan University of Traditional Chinese Medicine, Hunan, Changsha, China; Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China; Department of Traditional Chinese Medicine, Ningxia Medical University, Ningxia, Yinchuan, China.

Publication Information:

JAMA Internal Medicine 2017; 177(4): 508-515.

Background Information:

Migraines have a prevalence of 14.9% in the United States (1) and 8.4-12.7% in Asia (2), causing significant individual and societal burdens. 25-38% of individuals with migraines need preventive therapy (3), including phamacotherapies. However, pharmacotherapies increase the risk of adverse events (AEs), which can include weight gain, fatigue, sleep disturbance, and gastrointestinal intolerance (4). Excessive use of some medications can also lead to overuse-headaches and increased headache frequency (3).

Several small trials have shown true acupuncture (TA) to be more effective than sham acupuncture (SA) for the reduction of migraine intensity, frequency of attacks and number of migraine days, while others have found no differences. This study aimed to determine if TA is more effective than SA in preventing future migraine attacks.

Pertinent Results:

249 patients (245 in the final analysis, ~75% women) were randomized to the true acupuncture (TA, n=83), sham acupuncture (SA, n=80) or wait list control (WL, n=82) groups.

The frequency of migraine attacks decreased by 3.2 (attacks) in the TA group, 2.1 in the SA group, and 1.4 in the wait list (WL) group between baseline and 16 weeks. The TA group also showed significantly lower frequency of migraine attacks, migraine days and VAS scores than the other two groups at each interview during weeks 4 to 24. Significant differences in frequency of migraine attacks and migraine days were only seen between the SA and WL groups at weeks 8, 12, and 20.

At the end of week 4, the TA and SA groups showed no differences in the migraine-specific quality-of-life questionnaire (MSQ), the Zung self-rating anxiety scale (SAS), and the Zung self-rating depression scale (SDS) scores. All three groups showed decreased usage of acute pain medications, however, with the TA and SA groups demonstrating larger reductions compared to the WL group.

Seven patients reported AEs during the 24 weeks: 5 in the TA group and 2 in the SA group. In the TA group, 3 patients reported a tingling sensation in acupoints in the head after insertion and 1 reported swelling in the left ankle after a needle was removed from GB40. The final patient in the TA group and 2 patients from the SA group reported subcutaneous hemorrhage (bruising) in the needle insertion area. All of these AEs were reported as mild or moderate and all the patients fully recovered.

Clinical Application & Conclusions:

True (electro-) acupuncture showed persistent, clinically significant benefits that were superior to sham acupuncture or wait list interventions for patients with migraine without aura. This included reductions in migraine frequency, number of days with migraine and intensity of migraine pain. Patients in the TA group also showed improvements in the emotional domain of quality of life.

This study demonstrated higher efficacy of true compared to sham acupuncture than some previous studies. The authors speculate this may be due to the addition of electrostimulation, as it has been shown to be more effective than manual acupuncture for pain relief (9) and is thought to induce a longer-lasting effect (10). In addition, this study only included patients with migraine without aura. Is it possible that patients with migraine with aura may not respond to TA in the same way?

While SA was inferior to TA in this study, it was still associated with clinical improvement. Interestingly, SA was better for controlling migraine frequency and number of days with migraine within 8 weeks after treatment compared to no treatment (this is seen in many trials where the “sham” acupuncture intervention involves actual needle insertion). It is possible that this is a result of nonspecific physiological effects from needling or the result of the placebo effect. More research is needed to clarify this.

This study concluded that true electro-acupuncture creates superior and clinically relevant benefits in migraine prophylaxis for at least 24 weeks in patients with migraine headache without aura.

Study Methods:

Patients with migraine without aura were recruited from the outpatient unit of the Department of Acupuncture and Neurology from three clinical centers in China between October 2012 and September 2014. Patients complaining of recurrent, unilateral headaches, lasting 4-72 hours, with a pulsating quality, and aggravated by routine physical activity, were identified and diagnosed using the International Headache Society classification criteria (6). The following inclusion and exclusion criteria were also utilized for this trial.

Inclusion Criteria:
  • Men or women between 18 and 65 years of age
  • Initial onset of migraines prior to age 50
  • Acute migraine attacks at a frequency of 2-8 times per month in the three months prior to inclusion
  • Migraine attacks for at least 1 year
  • Completion of a baseline headaches diary
  • Completion of written, informed consent
Exclusion Criteria:
  • Patients with headaches caused by organic disorders (ex. subarachnoid or cerebral hemorrhage, cerebral embolism, etc.)
  • Patients with neurological diseases, immunodeficiency, bleeding disorders, or allergies
  • Prophylactic treatment with medication during the previous 3 months
  • Pregnancy, lactation, or plans to become pregnant within 6 months
  • Involvement in other clinical trial
249 patients were randomly assigned in a 1:1:1 ratio to receive true acupuncture (TA) treatment, sham acupuncture (SA) treatment, or to be placed on a waiting list (WL, the control group). Individuals in the TA and SA groups were blinded, however those in the WL group were not able to be blinded. Acupuncturists were also unable to be blinded, given the nature of the interventions. Outcome assessors, data collectors, and statisticians were blinded.

TA and SA treatment was provided by licensed acupuncturists who had a minimum of 5 years of training and 4 years of clinical experience and included 20 sessions of electro-acupuncture, once per day for 5 consecutive days, followed by a 2-day break, for 4 weeks. Each treatment lasted 30 minutes. Individuals in the TA and SA groups were not allowed to take and prophylactic medications, but in cases of intolerable headache could take 300-mg, sustained release ibuprofen capsules. Usage was recorded in their headache diaries. Both groups were treated at four acupoints per treatment. These always included GB20 and GB8 with the other 2 points chosen according the practitioners expertise from a list of potential points which included SJ5 (“triple burner”), GB34, BL60, SI3, LI4, ST44, LR3, and GB40 (7). No additional acupoints were allowed. These points were picked based upon a systematic review of ancient and modern literature (8), consensus meetings with clinical experts, and experience from a previously conducted study (5). Therapy was applied unilaterally, alternating use of the right and left side points at each session.

In the TA group single-use, sterile filiform acupuncture needles with a length of 25-40mm and a diameter of 0.25mm were used and inserted to achieve the De qi sensation (described as a sensation of soreness, numbness, distention, or radiating). Once this sensation was achieved, the HANS acupoint nerve stimulator was applied with a frequency of 2/100 Hz (alternating every 3 seconds), and an intensity varying from 0.1 to 1.0 mA based on patient comfort. The SA group received identical treatment, except that no attempt was made to elicit the De qi sensation and four non-points were utilized according to a previous study (7).

Patients in the WL group received no treatment for the duration of the clinical trial, but were provided with 20 free sessions of acupuncture at the end of the 24 weeks.

All participants completed a headache diary, including the time of migraine onset, duration, severity based on the visual analog scale (VAS) score, and medication use. Headache diaries were collected every 4-weeks and the frequency of migraine attacks, migraine days, and intensity of each attack were calculated. Changes in the frequency of migraine attacks between baseline and 16 weeks after randomization was used as the primary outcome measure and the number of migraine days, average headache severity, and medication intake were used as secondary outcome measures. As well, individuals were asked to complete the migraine-specific quality-of-life questionnaire (MSQ), the Zung self-rating anxiety scale (SAS), and the Zung self-rating depression scale (SDS) at baseline and 4-weeks. Finally, acupuncture-associated adverse events (AEs) were recorded at each treatment session.

Study Strengths / Weaknesses:

Strengths:
  • This study is one of the largest trials to date to use rigorous methods and a long follow-up period to test the efficacy of true acupuncture.
  • This study only lost 1.6% of subjects to follow-up.
Weaknesses:
  • This study used a semi-standard prescription limited to only four acupoints. Since the study did not utilize the individual acupuncturists’ experience to create personalized treatment plans, it is possible that performance bias may have influenced the treatments.
  • Blinding was not possible for the waitlist group, which makes it possible that the difference between the TA and WL groups and the SA and WL groups may have been overestimated due to the nonspecific effects of needling.
  • The authors employed a relatively intense treatment schedule – 5 times per week with a two day break, for 4 weeks (so, treatment every weekday, essentially). This intense treatment plan may not be reasonable from a time, nor financial perspective for some patients.
  • This study didn’t test the comparative effect of acupuncture combined with standard therapy on migraine prophyaxis.

Additional References:

  1. Burch RC, Loder S, Loder E, et al. The prevalence and burden of migraine and severe headaches in the United States: updated statistics from government health surveillance studies. Headache 2015; 55(1): 21-34.
  2. Wang SJ. Epidemiology of migraine and other types of headache in Asia. Curr Neurol Neurosci Rep 2003; 3(2): 104-108.
  3. Pringsheim T, Davenport W, Mackie G, et al. Canadian Headache Society Prophylactic Guidelines Development Group. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci 2012; 39(2)(suppl 2): S1-S59.
  4. Tfelt-Hansen PC. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2013; 80(9): 869-870.
  5. Li Y, Zheng H, Witt CM, et al. Acupuncture for migraine prophylaxis: a randomized controlled trial. CMAJ 2012; 184(4): 401-410.
  6. International Classification of Headache Disorders, 2nd edition. Cephalalgia 2004; 24(suppl 1): 9-160.
  7. Chen J, Zhao L, Zheng H, et al. Evaluating the prophylaxis and long-term effectiveness of acupuncture for migraine without aura: study protocol for a randomized controlled trial. Trials 2013; 14: 361.
  8. Chen Q, Wu X, Zhu H, et al. Analysis of acupuncture points used in clinical controlled trials of acupuncture for migraineurs. J Chengdu Univ Trad Chinese Med 2007; 30: 1-9.
  9. Schliessbach J, van der Klift E, Arendt-Nielsen L, et al. The effect of brief electrical and manual acupuncture stimulation on mechanical experimental pain. Pain Med 2011; 12(2): 268-275.
  10. Zheng Z, Feng SJ, Costa CD, et al. Acupuncture analgesia for temporal summation of experimental pain: a randomized controlled study. Eur J Pain 2010; 14(7): 725-731.