Inspired by Liu et al 2022.
MRM – menstrual-related migrainekey to acronyms
MA – manual acupuncture
RCT – randomised controlled trial
RR50 – responder rate (% of patients with a reduction in headache days of 50% or more)
AP – acupuncture point
I almost skipped past this paper when it showed up in my daily search of PubMed as yet another trial of acupuncture in migraine.
I checked the size and the results, and something made me pause… It was the size of the reduction in migraine days – less than one in the acupuncture group. This was not what I expected. Normally we see reductions of 50% or more in days with headache in the acupuncture group of a trial, and that usually amounts to anywhere from 3 to 10 days in a month. What was going on here?
The reduction was in migraine days per menstrual cycle rather than per 28 days, as is usually the case in headache studies. Then I realised that this was the first time I had recalled seeing such a paper focussing on menstrual migraine. Also, Prof Jing is on the author list, so I thought I better take it seriously.
It is a sham controlled double dummy trial with 2 parallel arms (n=172). In their introduction the authors note that there has been one previous study (that I must have missed), and that was from 2004 and included only 31 women (28 finished the trial).
Double dummy trials are rather unusual in acupuncture. In this case MA was combined with placebo naproxen and compared with sham MA and real naproxen. The naproxen was taken in a sustained-release formulation at a dose of 500mg once a day for 3 days before the predicted onset of each menstruation. Women were allowed to take acute pain medication throughout the trial and were asked to record the details.
The acupuncture treatment consisted of two sessions per week (preventative treatment) and at least 3 sessions in the 10 days before the predicted onset of menstruation (premenstrual conditioning treatment). The protocol of points for preventative treatment included 10 needles in the head – 2 midline (GV20, GV24) and 4 bilateral points (GB20, TE20, GB13, GB8) and a choice of points in the upper (PC6, TE5, LI4, SI3) and lower limbs (GB34, GB40, BL60, ST44, LR3) based on syndrome differentiation. The premenstrual conditioning treatment points were all in the suprapubic region (CV3, KI12, ST29). I guess these were in addition to the other points, although this is not clear in the paper.
The sham acupuncture was administered in exactly the same way as the real MA but at points in the arms and legs only – points not considered effective in migraine or menstruation. Apart from the lack of points on the head, this was a strange choice from a physiological perspective, not least because, in the first large RCT of acupuncture in migraine prophylaxis, a minimal sham in the limbs was associated with a responder rate (RR50) of 53%.
The primary outcome was the change from baseline of the average number of migraine days per perimenstrual period over cycles 1 to 3. The perimenstrual period was defined as 2 days before menstruation and the first 3 days of menstruation. The baseline average was just under 2 days of migraine during the perimenstrual period, and this reduced in the real MA group by 0.94 (0.82 to 1.07) and in the naproxen group by 0.61 (0.50 to 0.71), p=0.0001.
So, this is a clearly positive result, but it does leave us with a question from the physiological perspective related to the relative lack of effect of proper needling at so-called non-effective points.
In a previous double dummy RCT of migraine prophylaxis by the same team, the RR50 in the flunarizine plus sham MA group was just 40% – the sort of value you might expect from the drug on its own. In the real MA group of this trial the RR50 was 59%.
In the biggest sham controlled trial of acupuncture (n=960), which was performed in Germany as part of the Modellvorhaben Akupunktur, the RR50 at 6 weeks was 52% in the real MA group, 49% in the minimal sham group, and 39% in the medication group.
Again, the big difference between the West and the East appears to be in the magnitude of the sham MA effect. Furthermore, minimal needling in the West seems to be associated with considerably larger effects than robust AP needling in the East.
1 Liu L, Zhang C-S, Liu H-L, et al. Acupuncture for menstruation-related migraine prophylaxis: A multicenter randomized controlled trial. Front Neurosci 2022;16:992577. doi:10.3389/fnins.2022.992577
2 Linde M, Fjell A, Carlsson J, et al. Role of the needling per se in acupuncture as prophylaxis for menstrually related migraine: a randomized placebo-controlled study. Cephalalgia 2005;25:41–7. doi:10.1111/j.1468-2982.2004.00803.x
3 Linde K, Streng A, Jürgens S, et al. Acupuncture for patients with migraine: a randomized controlled trial. JAMA 2005;293:2118–25. doi:10.1001/jama.293.17.2118
4 Wang L-P, Zhang X-Z, Guo J, et al. Efficacy of acupuncture for migraine prophylaxis: a single-blinded, double-dummy, randomized controlled trial. Pain 2011;152:1864–71. doi:10.1016/j.pain.2011.04.006
5 Diener H-C, Kronfeld K, Boewing G, et al. Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial. Lancet Neurol 2006;5:310–6. doi:10.1016/S1474-4422(06)70382-9
6 Cummings M. Modellvorhaben Akupunktur–a summary of the ART, ARC and GERAC trials. Acupunct Med 2009;27:26–30. doi:10.1136/aim.2008.000281