NEWS

In the current study, trained and experienced acupuncturists used nonpenetrating placebo needles with a blunt tip at nonacupuncture points. Patients in this control group felt a pricking sensation; but instead of puncturing the skin, the needles retracted up into the shaft.

This approach, said Wang, avoided segmental analgesia and minimized any physiological effect in the sham group.

Earlier, Larger, Longer Effects

As much as possible, the timing and patterns of treatment were the same for the manual and sham acupuncture groups.

All participants received usual care, which included information on lifestyle changes and migraine self-management. Those randomly assigned to the UC group received acupuncture after waiting 24 weeks.

After a 4-week assessment period, all patients received 20 sessions of 30-minute acupuncture treatment or UC over 8 weeks, followed by 12 weeks of follow-up, for a total trial period of 24 weeks. About 98% of those enrolled completed the study.

Main outcomes were change in the mean number of migraine days and migraine attacks per 4-week cycle during weeks 1 to 20 after randomization compared with baseline.

Compared with participants receiving sham acupuncture, those receiving manual acupuncture had a significantly greater reduction in migraine days during weeks 13 to 20, with a group difference of -1.4 days (95% confidence interval [CI], -2.4 to -0.3; P = .005) at weeks 13 to 16 and -2.1 days (95% CI, -2.9 to -1.2; P < .001) at weeks 17 to 20.

The manual acupuncture group also had a significantly greater reduction in migraine attacks vs the sham group at weeks 17 to 20, with a group difference of -1.0 attacks (95% CI, -1.5 to -0.5; P < .001).

"Overall, the therapeutic effects in the manual acupuncture group occurred earlier, were larger, and might last longer," the investigators write.

Better than Prophylactic Meds?

Wang noted that the difference in reduced migraine days between manual and sham acupuncture was larger than that seen in studies of prophylactic drugs, such as monthly subcutaneous injections of fremanezumab (-1.5 days per month vs placebo) or galcanezumab (about -1.1 days vs placebo).

Sham acupuncture in the current study resulted in a significantly greater reduction in migraine attacks during weeks 5 to 20 compared with UC.

A secondary outcome was the proportion of patients achieving at least a 50% reduction in mean number of migraine days. Such responder rates were significantly higher in the manual acupuncture group than in the two control groups during weeks 17 to 20.

In addition, all subscales of the Migraine-Specific Quality-of-Life Questionnaire were improved significantly more in the manual acupuncture group at weeks 20 vs the two control groups.

Total scores on the Pittsburgh Sleep Quality Index and Migraine Disability Assessment Score were significantly lower in the manual acupuncture group than in the usual care group at week 20.

Although the study didn't directly explore what difference in migraine reduction between actual acupuncture and sham acupuncture would be clinically important, improvements in these secondary outcomes imply that patients would notice the change, Wang said.

There was no significant difference in the mean dose of rescue medication or in Beck Anxiety Inventory and Beck Depression Inventory II scores among the three groups at week 20.

Multiple Mechanisms

Acupuncture's mechanism of action in relieving migraine is unclear, but "multiple mechanisms could contribute," Wang said.

One possibility is that acupuncture blocks central processing of pain through alternative stimulation, similar to transcutaneous electrical nerve stimulation and other nonpharmacologic pain treatments.

"Pain-sensitive structures in the head and neck connect with cells in the spinal cord, thalamus, and cortex. These same cells also receive input from the limbs, including from established acupuncture points. This convergence might explain acupuncture's effects," said Wang.  

Acupuncture also activates the limbic system, which is important in emotional responses, and releases endorphin, a transmitter that potentially reduces pain, said Wang.

Asked if 20 acupuncture sessions over 8 weeks is sufficient to assess the efficacy of manual acupuncture, Wang said it is "long enough" according to Chinese acupuncture experts.

"Longer treatment might increase efficacy, but it might reduce patient compliance," he noted. However, because migraine is a highly recurrent disease, "a considerable number of patients" are likely to require repeated acupuncture treatment.

Future trials with longer follow-up periods will be needed to assess how long the effects of acupuncture last, he added.

At the end of the study, there was no significant difference between the manual and sham acupuncture groups in correctly guessing their allocation.

In the manual group, 8% of patients reported at least one acupuncture-related adverse event (AE) compared with no patients in the sham acupuncture group. One patient withdrew from the study because of an AE, but no patients in either acupuncture group reported a severe AE.

A study limitation was that it didn't include an additional group of patients who took a prophylactic drug. That would have enabled a head-to-head comparison between acupuncture and such a drug, but would have meant a larger sample size and been more difficult to conduct, Wang said.

Encouraging Findings

Commenting on the findings for Medscape Medical News, W. Clay Jackson, MD, chief of palliative medicine, West Cancer Center, Memphis, Tennessee and past president of the Academy of Integrative Pain Management (AIPM), said the study provides useful information about acupuncture in migraine.

Although it was a relatively small study, "you did see the active intervention separate from the sham placebo," said Jackson, who was not involved with the research.

An ongoing concern in acupuncture studies has been the ability of patients to differentiate sham from actual acupuncture, but patients in this new study couldn't perceive the difference, Jackson noted.

"The new results are very encouraging from a statistical standpoint and a study design standpoint," he said. "This is probably one of the better studies I've seen in terms of multiple sites and the statistically significant separation between the real acupuncture and the sham acupuncture."

In addition, the results suggest that manual acupuncture is more effective than previous migraine preventive therapies, Jackson said, adding that acupuncture might come out on top in terms of cost–benefit analysis because some migraine drugs can be quite costly.

If manual acupuncture works, "it will be a useful tool in the armamentarium of an integrative practitioner," Jackson said.

In an accompanying editorial, Heather Angus-Leppan, MD, consultant neurologist, Royal Free London NHS Foundation Trust, United Kingdom, said the study provides a solid evidence base for acupuncture, which is "often dismissed" as an unproven complementary therapy.

"Given that almost 90% of people with frequent migraine have no effective preventive treatment, acupuncture provides a useful additional tool in our therapeutic armour," Angus-Leppan writes.

She agrees that a strength of this study is the successful masking of the sham procedure. However, the effects of acupuncture, shown with 2.1 fewer migraine days per month, were modest and "it is difficult for clinicians to know whether this level of benefit would be noticeable to patients."

Angus-Leppan also notes that the study period of 20 weeks was "relatively short" and that it's not known "whether acupuncture resets sensory pathways for a sustained improvement or whether it must be repeated to maintain its effects."

The study was funded by grants from the National Natural Science Foundation of China and the Hubei University of Chinese Medicine/Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion. Wang and Jackson have disclosed no relevant financial relationships. Editorialist Angus-Leppan reports that her salary is partly funded by the National Institute for Health Research (NIHR), that she serves on the advisory board of the Medicines and Healthcare products Regulatory Agency, was on the Sanofi women and epilepsy education board 2018, and has received nonpharmacologic research grants from Eisai, Royal Free Charity, Epilepsy Action, and NIHR.

BMJ. Published online March 25, 2020. Full text , Editorial

For more Medscape Neurology news, join us on Facebook and Twitter