Migraine, a highly prevalent primary headache, affects 11%–16% of the population [
To date, no “cure” exists for migraine. Although the pharmacotherapies provide some relief, they are associated with adverse events (AEs) such as low blood pressure, nausea, depression, drowsiness, and rarely renal damage. For this reason, 50% of chronic migraineurs and 27% of episodic migraineurs prefer nonpharmacotherapies and have used complementary therapies for migraine [
To date, clinical trials have shown that acupuncture is an effective alternative treatment for tension-type headache [
The present trial aimed to determine the short- and long-term effects and safety of acupuncture, compared with sham acupuncture for migraine sufferers who have headache more than 5 days per month.
All participants were volunteers suffering from migraine and recruited from the greater Melbourne area using a series of media releases and advertisements. Those who met the inclusion criteria of migraine according to the International Headache Society (IHS) [
After a four-week baseline, eligible participants were randomly allocated to real acupuncture (RA) or sham acupuncture (SA) groups. Block randomization was used, eight participants in each block, with a 1 : 1 ratio. An independent researcher prepared a computer-generated sequence of random numbers and processed the randomization. The opaque sealed envelopes were stored in a locked cabinet, and each block of envelopes (up to eight) was hand out to let the next eligible participant pick an envelope from the block. Participants were informed this being a randomized trial that compared the effect of real acupuncture with that of sham treatment without being told the block or the block size. They were also informed that sham treatment produced minimal effect in addition to the placebo effect. Only the treating acupuncturist was aware of the treatment allocation. Furthermore, independent assistants in charge of data entry or assessment were blinded to the treatment allocation. During the treatment period, any discussion related to treatment between the participants and the acupuncturist was restricted to a minimum of necessary explanations in order to ensure the success of the blinding procedure. After the first week of treatment, credibility of the acupuncture procedure was assessed with a questionnaire.
During the 20-week treatment period, a total of 16 treatment sessions were delivered to participants. This occurred twice per week for four weeks (eight sessions) followed by once per week for another four weeks (four sessions), then once every two weeks for four weeks (two sessions), then once per month for another two months (two sessions). The location of acupoints adopted in the present study followed the Standard Acupuncture Nomenclature published by the World Health Organization [
A semistandardised acupuncture treatment protocol was used for both groups. This protocol consisted of a set of mandatory acupoints that were used for all participants and a set of supplementary acupoints that were selected based on individual diagnosis of Chinese medicine syndromes of migraine (Table
Acupoints selection for the real acupuncture group.
Syndromes | Mandatory acupoints (unilateral) | Supplement acupoints (bilateral) |
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Ascending hyperactivity of liver yang | Fengchi (GB20, bilateral) |
Baihui (DU20), Xingjian (LR2), Taichong (LR3), Taixi (KI3), Xuanzhong (GB39), and Sanyinjiao (SP6) |
Deficiency of both Qi and blood | Baihui (DU20), Shang Xing (DU23), Zusanli (ST36), and Sanyinjiao (SP6) | |
Wind phlegm blocking the meridians | Feng Long (ST40), Zhongwan (CV12), and Yinlingquan (SP9) | |
Blood stasis | Sanyinjiao (SP6), Xuehai (SP10), and Ashi point |
For RA, needles were inserted transversely, obliquely, or perpendicularly to a depth of 10–30 mm depending on the specific locations of acupoints. De Qi sensation was induced. Needles were retained for 25 minutes, with further stimulation given every 10 minutes.
For SA, combined insertion and noninsertion procedures were used (Table
Method of sham acupuncture.
Local sham points on the scalp, face, and neck | Distal sham points on the four extremities | |
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Technique | Noninvasive, using a blunted cocktail-stick | Minimal acupuncture, 2 mm depth insertion |
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Sham point | 1-2 cm away from the real acupoints | 1-2 cm away from the real individual distal supplementary points according to the syndrome differentiation |
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Stimulation | The stick was tapped | No needling manipulation, avoid De Qi |
The type of outcome measures and when they were measured are listed in Table
Outcome measures used in the trial.
Outcome measures | Instruments | Baseline (4 weeks) | Treatment (20 weeks) | Follow-up (phase 1* and phase II#) |
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Primary outcomes | ||||
Frequency of migraine | Headache diary | Daily for 4 weeks | Daily for 20 weeks | Phase I: daily for 12 weeks and this is between 21st week and 32nd week after randomization. |
Duration of migraine | 24-hour Visual Analogue Scale (VAS) | |||
Intensity of migraine | 0–10 VAS and a Six-Point Likert Scale | |||
Response rate | Percentage of patients with more than 50% reduction in the number of days with migraine attack per four weeks | Calculated based on the frequency data and reported on weekly basis | ||
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Secondary outcomes | ||||
Relief medication usage | Pill count and the Medication Quantification Scale | Daily for 4 weeks | Daily for 20 weeks | Phase I: daily for 12 weeks and this is between 21st week and 32nd week after randomization. |
Severity and quality of migraine | McGill pain questionnaire [ |
At the last week of baseline | At the 4th, 8th, 12th, 16th, and 20th week after randomization | Phase I: at the 24th, 28th, and 32nd week after randomization. |
Quality of life | Migraine Specific Quality of Life questionnaire [ | |||
Pressure pain threshold | A handheld pressure algometer | Before the 1st treatment | After the last treatment |
*Phase I follow-up period: 3 months from the end of the treatment.
#Phase II follow-up period: one year from the end of the treatment.
The secondary outcome measures included the relief medication usage for migraine, the severity and quality of migraine [
The points used for testing pressure pain threshold.
Number 1 | Left | 2 cm inferior to the external occipital protuberance and 2 cm lateral to the midline |
Number 2 | Right | |
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Number 3* | Left | GB20: in a depression between the upper portions of the sternocleidomastoid muscle and the trapezius |
Number 4* | Right | |
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Number 5 | Left | 2 cm lateral to GV20, which locates on the head, 5 cun# directly above the midpoint of the anterior hairline, at the midpoint of the line connecting the apexes of both ears |
Number 6 | Right | |
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Number 7* | Left | EX-HN5: in the temple region, in a depression about 1 cun posterior to the midpoint between the lateral end of the eyebrow and the outer canthus of the eye |
Number 8* | Right | |
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Number 9 | Left | ST6: one finger width anterior and superior to the angle of the mandible at the belly of the masseter muscle when teeth clenched |
Number 10 | Right | |
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Number 11 | EX-HN3: at the midpoint of the line connecting the medial ends of the eyebrows |
*Also indicates the acupoints needled in the RA group.
Intention to treat (ITT) analyses were performed for all the outcome measurements of post treatment and follow-up I. Per protocol (PP) analyses of outcome measures were conducted with follow-up II data. Chi-square or
The significance level used was
Any missing data in the headache diary, MPQ, or PPT was replaced by using the “Missing Value Analysis” function under “Analysis function” in the Statistical Package for the Social Sciences (SPSS, version 15.0 for windows) software program. MSQOL missing data was dealt with according to the instruction manual.
The sample size was calculated based on an acupuncture trial on migraine [
Figure
Comparisons of demographic variables at baseline.
Variables | RA ( |
SA ( |
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Demographic data | |||
Age (years) mean (SD) | 41.6 (14.9) | 43.8 (13.4) | 0.58 |
Migraine history (years) mean (SD) | 18.4 (12.7) | 21.1 (13.3) | 0.47 |
Gender |
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Female | 18 (75%) | 19 (73.1%) | 0.88 |
Acupuncture experience |
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No | 10 (41.7%) | 14 (53.9%) | 0.39 |
Yes | 14 (58.3%) | 12 (46.1%) | |
Marital status |
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Partnered | 17 (70.8%) | 17 (65.4%) | 0.68 |
Single | 7 (29.2%) | 9 (34.6%) | |
Education level ( |
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H: university or higher | 10 | 12 | 0.52 |
S: 9 or more years of formal education | 12 | 14 | |
L: less than 9 years | 1 | 0 | |
M: missing data | 1 | 0 | |
Type of migraine |
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MO: migraine without aura | 16 (32%) | 13 (26%) | 0.46 |
MA: migraine with aura | 3 (6%) | 6 (12%) | |
Both: MO and MA cooccurrence | 5 (10%) | 7 (14%) | |
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Outcomes measures# | |||
Migraine days (number of days with migraine per 4 weeks) | 11.8 (5.8) | 12.4 (6.4) | 0.73 |
Duration (hours /attack) | 9.0 (3.6) | 8.9 (4.8) | 0.91 |
Highest pain-VAS | 6.0 (1.1) | 5.3 (2.0) | 0.11 |
Lowest pain-VAS | 3.1 (1.8) | 2.7 (1.9) | 0.39 |
Average pain-VAS | 4.6 (1.4) | 4.0 (2.0) | 0.21 |
Severity of pain (six-point Likert scale) | 3.2 (0.4) | 3.2 (0.6) | 0.79 |
McGill | |||
PRI-S | 18.3 (8.9) | 21.3 (7.5) | 0.20 |
PRI-A | 5.4 (2.7) | 6.7 (3.2) | 0.14 |
PRI-E | 3.5 (1.3) | 3.6 (1.1) | 0.73 |
PRI-M | 6.7 (3.0) | 7.6 (3.2) | 0.34 |
Total | 33.9 (13.4) | 39.0 (13.2) | 0.19 |
MSQOL | |||
FR | 54.2 (17.2) | 46.7 (18.9) | 0.15 |
FP | 71.0 (19.0) | 61.7 (20.6) | 0.10 |
EF | 54.7 (24.8) | 48.5 (24.2) | 0.40 |
Medication | |||
MQS | 93.8 (81.1) | 87.0 (110.2) | 0.81 |
Pill count | 13.50 (20.27) | 7.27 (13.50) | 0.54 |
Number of participants who took pain killers | 22 | 23 | 0.71 |
Number of participants who took specific antimigraine drugs | 4 | 3 | 0.60 |
Number of participants who took prophylactic drugs | 12 | 11 | 0.59 |
RA: real acupuncture group; SA: sham acupuncture group; #Clinical data were summarized as mean (SD); PRI-S: sensory components; PRI-A: affective components; PRI-E: evaluative components; PRI-M: miscellaneous components; FR: function-restrictive in Migraine Specific Quality of Life questionnaire; FP: function-preventive in Migraine Specific Quality of Life questionnaire; EF: emotional function in Migraine Specific Quality of Life questionnaire; PPT: pressure pain threshold; MQS: Medication Quantification Scale.
Number of participants in different stages of trial. EOI: expression of interest.
The number of days with migraine (migraine days) was significantly reduced in both groups over the 20-week treatment period [
Primary outcome measurements.
After treatment ( |
At three months follow-up period I ( |
One-year follow-up period II ( |
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RA mean (SD) | SA mean (SD) | 95% CI for difference |
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RA mean (SD) | SA mean (SD) | 95% CI for difference |
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RA mean (SD) | SA mean (SD) | 95% CI for difference |
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Migraine days (number of days with migraine per 4 weeks) | 5.2 (5.0) | 10.1 (7.1) | (−8.5, −1.3) | 0.008* | 5.1 (3.7) | 9.5 (6.2) | (−7.2, −1.4) | 0.005* | 11.3 (5.5) | 12.3 (5.6) | (−5.8, 3.7) | 0.660 |
Duration (hours/attack) | 6.0 (3.3) | 8.0 (4.5) | (−4.3, 0.2) | 0.073 | 8.2 (2.8) | 8.81 (4.1) | (−2.6, 1.3) | 0.520 | 7.51 (2.6) | 7.61 (3.5) | (−2.6, 2.4) | 0.930 |
Highest pain-VAS | 5.0 (1.8) | 4.5 (1.9) | (−0.2, 1.6) | 0.350 | 4.8 (1.4) | 4.66 (2.0) | (−0.9, 1.1) | 0.800 | 5.81 (1.0) | 4.91 (2.4) | (−1.8, 1.2) | 0.710 |
Lowest pain-VAS | 2.3 (1.9) | 2.5 (1.7) | (−1.2, 0.9) | 0.820 | 2.6 (1.1) | 2.62 (1.7) | (−0.9, 0.7) | 0.860 | 2.77 (1.5) | 3.04 (2.1) | (−1.0, 2.8) | 0.310 |
Average pain-VAS | 3.0 (1.8) | 3.2 (1.8) | (−1.3, 0.8) | 0.650 | 3.9 (1.0) | 3.60 (1.9) | (−0.6, 1.7) | 0.480 | 4.21 (1.1) | 3.39 (2.1) | (−0.8, 2.5) | 0.290 |
Severity of pain (six-point Likert scale) | 2.2 (1.1) | 2.9 (0.6) | (−1.2, −0.3) | 0.004* | 2.6 (0.4) | 2.9 (0.6) | (−0.5, 0.0) | 0.087 | 3.11 (0.5) | 3.3 (0.7) | (−0.7, 0.3) | 0.420 |
Responder+ | 19 (73.1%) | 7 (29.2%) | 0.020# | 17 (65.4%) | 5 (20.8%) | 0.034# | 1 (6.3%) | 0 (0%) |
*Statistical significance assessed at 0.05/4 = 0.0125 (Bonferroni correction) for both intention to treat (
+Responder: participants with 50% or greater reduction in days with migraine.
#Indicates statistical significance assessed at 0.05.
The number of days with migraine per four weeks in each group across all treatment time points (mean and SE). Tw4, Tw8, Tw12, Tw16, and Tw20 correspond to the treatment weeks 1–4, weeks 5–8, weeks 9–12, weeks 13–16, and weeks 17–20, respectively; Pw4, 8, and 12 correspond to the posttreatment weeks 1–4, weeks 5–8, and weeks 9–12;
The time course of the average pain measured with a six-point Likert scale over the five treatment phases (mean and SD). Tw4, Tw8, Tw12, Tw16, and Tw20 correspond to the treatment weeks 1–4, weeks 5–8, weeks 9–12, weeks 13–16, and weeks 17–20, respectively; Pw4, 8, and 12 correspond to the posttreatment weeks 1–4, weeks 5–8, and weeks 9–12;
There was no group difference in McGill pain questionnaire data except for PRI-emotional, which was better in the RA group (Table
Secondary outcome measurements.
After treatment ( |
At three months follow-up period I ( |
One year follow-up period II ( |
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RA mean (SD) | SA mean (SD) | 95% CI for difference |
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RA mean (SD) | SA mean (SD) | 95% CI for difference |
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RA mean (SD) | SA mean (SD) | 95% CI for difference |
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McGill | ||||||||||||
PRI-S | 13.1 (8.8) | 15.8 (11.6) | (−8.6, 3.1) | 0.350 | 11.1 (4.2) | 14.1 (9.0) | (−7.1, 1.1) | 0.150 | 21.6 (8.1) | 19.7 (10.8) | (−6.0, 9.8) | 0.620 |
PRI-A | 3.96 (3.0) | 4.8 (2.8) | (−2.5, 0.8) | 0.320 | 3.3 (2.1) | 4.4 (3.1) | (−2.6, 0.4) | 0.163 | 6.5 (2.5) | 6.2 (3.4) | (−2.2, 2.7) | 0.820 |
PRI-E | 2.08 (1.3) | 2.8 (1.5) | (−1.53, .02) | 0.056 | 1.6 (0.9) | 2.6 (1.3) | (−1.6, −.38) | 0.002* | 3.6 (1.2) | 3.8 (1.2) | (−1.2, 0.8) | 0.700 |
PRI-M | 5.6 (3.4) | 6.1 (3.5) | (−2.47, 1.45) | 0.60 | 5.5 (0.9) | 5.9 (2.9) | (−1.9, 1.2) | 0.651 | 7.3 (2.5) | 8.1 (2.9) | (−3.2, 1.4) | 0.440 |
Total | 20.8 (15.7) | 33.4 (17.4) | (−22.1, −3.2) | 0.010* | 15.0 (4.5) | 22.4 (14.5) | (−13.5, −1.4) | 0.017 | 38.9 (11.8) | 37.8 (16.0) | (−10.4, 12.7) | 0.843 |
MSQOL | ||||||||||||
FR | 72.2 (16.4) | 58.0 (21.0) | (3.6, 24.9) | 0.010* | 74.2 (15.3) | 56.3 (23.2) | (6.5, 29.2) | 0.003* | 46.4 (15.2) | 50.1 (19.0, −0.5) | (−18.0, 10.6) | 0.600 |
FP | 77.1 (16.8) | 68.3 (22.7) | (−2.7, 20.3) | 0.13 | 80.8 (15.3) | 63.1 (23.2) | (5.1, 30.2) | 0.007* | 62.0 (15.4) | 64.3 (17.8) | (−16.3, 11.71) | 0.740 |
EF | 78.3 (19.3) | 60.5 (25.6) | (4.98, 30.6) | 0.007* | 79.3 (18.7) | 58.8 (27.3) | (7.1, 34.0) | 0.002* | 49.5 (17.0) | 56.6 (21.0) | (−23.1, 8.8) | 0.370 |
Medication | ||||||||||||
MQS | 20.8 (46.4) | 68.9 (81.2) | (−85.4, −10.9)* | 0.012 | 11.0 (24.3) | 54.3 (62.4) | (−69.8, −16.8) | 0.002* | 78.2 (79.1) | 75.1 (50.8) | (−59.5, 67.7) | 0.920 |
Pill count | 4.54 (12.21) | 10.54 (19.31) | (−15.12, 3.11) | 0.192 | 3.46 (9.84) | 10.10 (17.63) | (−14.93, 1.64) | 0.113 | 10.56 (14.81) | 7 (9.90) | (−7.91, 15.03) | 0.530 |
Number of participants who took pain killers | 9 | 18 | 8.2∧ | 0.004# | ||||||||
Number of participants who took specific antimigraine drugs | 1 | 4 | 2.28∧ | 0.13 | ||||||||
Number of participants who took prophylactic drugs | 7 | 9 | .64∧ | 0.42 |
*Indicates statistical significance assessed at 0.05/4 = 0.0125 (Bonferroni correction) for both intention to treat (
At the end of treatment, more participants in the RA group used less pain killers as relief medication than in the SA group (
Percentage changes in PPT varied significantly among the 11 sites. Generally, the two groups showed similar trends in the PPTs changes across the sites [
The percentage change of PPTs at 11 sites in the two groups after the treatment (mean and SE, RA,
In the RA group, mean increases in PPTs ranged from 15.84% at Number 11 (EX-HN3) to 229.48% at Number 7. In the SA group, the range was from a decrease of 0.66% at Number 7 to an increase of 66.86% at Number 9 (left ST-6). No significant correlations were detected between changes in frequency, duration, and intensity of migraine with changes of PPTs at all 11 selected sites.
At the end of the one-year follow-up period, only 25 out of 47 participants completed the headache diary, consisting of 16 from the RA group and nine from the SA group. No statistically significant group difference was detected in any outcome measures (Table
Thirty-seven AEs were reported out of 400 sessions (9.25%) in the RA group and 14 of 374 sessions (3.74%) in the SA group (Table
The adverse events reported by participants in each treatment group.
Type of event | RA (number of cases) | SA (number of cases ) |
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Dizziness | 4 | 3 |
Bruising | 3 | 1 |
Pain | 3 | 2 |
Cold and sweaty | 8 | 5 |
Tingling | 11 | 1 |
Recurrent headache | 7 | 2 |
Mild spasm in the calf muscle induced by tapping on the thigh by the patients after the treatment | 1 | 0 |
Total of AEs | 37 | 14 |
Total of treatment sessions | 400 | 374 |
Accidences per treatment | 9.25% | 3.74% |
Credibility of the blinding was assessed at the end of the first treatment week after two sessions. All 50 participants completed a three-item questionnaire. The credibility of sham needling at the early stage of the trial was successful with no statistically significant difference between the two groups (
The reason of guessing group allocation.
RA group | SA group | Total |
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No selection (participants indicate they could not guess the group allocation) | 9 | 8 | 17 | 1.88 | 0.76 |
Manner, attitude, or words of acupuncturist | 3 | 4 | 7 | ||
Manner, attitude, or words of the personnel in the clinic | 5 | 6 | 11 | ||
Results of the treatment | 8 | 4 | 12 | ||
Others | 1 | 2 | 3 | ||
Total | 26 | 24 | 50 |
The present trial showed that acupuncture was effective in reducing migraine days, as well as effecting a reduction of medication consumption and improvement in quality of life, when compared with sham acupuncture. The effect lasted up to three months but seems to have ceased one year after the termination of the treatment. However this conclusion about a lack of the long-term is based on data from less than 50% of the participants who returned the diary. There were no serious adverse events that necessitated withdrawal of participants from the trial. The incidence and severity of minor adverse effects were comparable between the two groups. The participants were properly blinded. The above results demonstrated that manual acupuncture can be an effective and a safe prophylaxis for frequent migraine sufferers. Because the findings of the present study were based on self-selected community-based participants; the results discussed here are limited to this specific group.
The current RCT is unique when compared with previous studies of acupuncture for migraine in the following four aspects. First, these participants all experienced a minimum of five days of migraine or more during the four-week baseline period. People with frequent migraine attacks were chosen because the effect of acupuncture on this group of population has not been well studied [
Second, the current study has the longest treatment period (20 weeks) of any in the literature and incorporated gradual decrease in treatment frequency. This treatment regime reflects how acupuncture is practiced in a clinical setting and has been shown to be effective in one positive acupuncture trial for osteoarthritis in the knee [
Third, we adopted an innovative sham acupuncture design. In published acupuncture trials, it is often difficult to establish a true placebo intervention, as sham acupuncture is not an inert treatment [
Forth, we measured PPT on 11 sites on the scalp and face during nonmigraine days in addition to pain measurement. It is interesting to note that the PPTs at only two sites, Numbers 7 and 8, statistically significantly increased more than those in the SA group. These two sites are located on either side of the m. temporalis, over the superficial temporal artery and vein and near the second and third branches of the trigeminal nerve. The temporal artery [
Finally, in order to ensure the credibility of the sham acupuncture, participants with limited acupuncture experience were recruited, and it was demonstrated that they could not identify real from sham acupuncture according to past experience.
The main limitation is the small sample size. Inadequate sample size can skew findings [
Another potential limitation is that frequent migraine sufferers might have a higher expectation of acupuncture than those less affected by the condition. Previous studies have shown that the expectation caused greater treatment activation than skin prick [
The findings of the current study on migraine days demonstrated that the RA was significantly better than SA, which is supported by some studies [
Although RA acupuncture reduced the duration of each migraine attack in the RA group, there was no group difference on this measure in the current study. Two studies conducted by Alecrim-Andrade and her colleagues demonstrated that acupuncture reduced the total hours in pain per four weeks [
Acupuncture can be used as alternative and safe prophylaxis for frequent migraine. Our recommendation is that practitioners treat migraine sufferers twice per week for at least eight weeks. Reduced medication usage is expected during acupuncture treatment. Future studies need to assess if regular follow-up treatments, perhaps at a monthly or bimonthly interval after an initial three-month hiatus, might provide long-term prophylaxis for this group of patients.
The authors declare no conflict of interests.