Acupuncture, drugs or Botox for chronic migraine?

Stimulated by Zheng et al 2021,[1] Giovanardi et al 2020,[2] and Yin et al 2020.[3]

Photo by Andrea Piacquadio on

Botox – botulinum toxin type A
CI – confidence interval
EBM – evidence based medicine
fMRI – functional magnetic resonance imaging
GRADE – grading of recommendations, assessment, development and evaluation
IF – impact factor
MWoA – migraine without aura
NMA – network meta-analysis
RCT – randomised controlled trial
SMD – standardised mean difference
zALFF – z-transformed amplitude of low frequency fluctuation

key to acronyms

I was drawn to look at the results of this network meta-analysis from the interventions mentioned in the title, and because a very small and inadequate NMA in CG150 estimated that topiramate was twice as good as acupuncture in migraine prophylaxis.[4] Plus, there are few direct comparisons of acupuncture with Botox,[5] and NMAs allow you to perform good indirect comparisons.

It is important to note that this NMA compared topiramate, acupuncture and Botox in chronic migraine. No mixed migraine populations were allowed, so all the patients had to start out with at least 15 headache days per month, of which at least 8 had to be migraine.[6]

This NMA included 15 RCTs, but only 2 of them involved acupuncture,[5,7] and most were Botox versus placebo, topiramate versus placebo or Botox versus topiramate. Despite the limited data representing acupuncture, I was pleased to see no mention of the dreaded sham acupuncture, and no conflation of sham acupuncture with placebo drugs as NICE is so fond of doing.[8]

the SMD for acupuncture exceeded that for topiramate and Botox

Where there was data to pool, the SMD for acupuncture always exceeded that for the other interventions, apart from for adverse events, in which it was the lowest. However, the CIs overlapped so this trend in favour of acupuncture did not reach significance for any outcome.

I was a little alarmed at first to see the paper conclude that Botox was still the primary preventative treatment for chronic migraine, but then I remembered a neurologist from the north of England commenting on CG150 at a meeting on headache. He wearily questioned why NICE had bothered to recommend acupuncture at all, as it was not available to be prescribed on the NHS, at least not in his area.

There is no mention of Botox in CG150. Botox is recommended in a technology assessment devoted entirely to the topic,[9] which came out at the same time as CG150 in 2012, and the recommendation is limited to chronic migraine.

acupuncture versus drugs in migraine prophylaxis

The second paper I am highlighting comes from a group in Italy, and the first author is president of the Italian Federation of Acupuncture Societies (FISA). This is a systematic review (SR) of acupuncture versus drugs in migraine prophylaxis. It included 9 RCTs and concludes that acupuncture is mildly more effective than drugs and much safer. That is probably true given the data, and this review has been performed well, although if I was to criticise with an entirely uncompromising EBM approach, I would say that the certainty of the evidence in the GRADE assessments is rather generous (I’ll explain in the webinar).

A previous SR on the topic with authors from Stanford and Harvard published in the journal Headache (IF 3.23) towards the beginning of 2020 included 7 RCTs and chose not to pool data,[10] but it was cautiously optimistic, and presented a conclusion rather similar to the Cochrane review of 2016 led by Klaus Linde.[11]

Another large narrative review of acupuncture in migraine with authors from Harvard was published in Neurology & Therapy (IF 3.65) later in 2020,[12] so it looks as though there is a positive will in favour of acupuncture developing in respectable authors in the US. Let’s hope it finds its way across the Pond.

middle occipital gyrus activity could predict the response to acupuncture

To close, I want to mention a recent fMRI study on migraine without aura (MWoA).[3] It is a bit complex, so I’ll keep it brief. The team from Chengdu first studied the differences in various brain regions between patients with MWoA and healthy subjects. They then went on to measure a specific parameter that could predict the response to acupuncture based on activity in the middle occipital gyrus of patients. That parameter is called zALFF!


1          Zheng H, Huang S-L, Chen Y-Y, et al. Topiramate, acupuncture, and BoNT-A for chronic migraine: a network meta-analysis. Acta Neurol Scand Published Online First: 3 January 2021. doi:10.1111/ane.13391

2          Giovanardi CM, Cinquini M, Aguggia M, et al. Acupuncture vs. Pharmacological Prophylaxis of Migraine: A Systematic Review of Randomized Controlled Trials. Front Neurol 2020;11:576272. doi:10.3389/fneur.2020.576272

3          Yin T, Sun G, Tian Z, et al. The Spontaneous Activity Pattern of the Middle Occipital Gyrus Predicts the Clinical Efficacy of Acupuncture Treatment for Migraine Without Aura. Front Neurol 2020;11:588207. doi:10.3389/fneur.2020.588207

4          Recommendations | Headaches in over 12s: diagnosis and management | Guidance | NICE. (accessed 9 Jan 2021).

5          Naderinabi B, Saberi A, Hashemi M, et al. Acupuncture and botulinum toxin A injection in the treatment of chronic migraine: A randomized controlled study. Casp J Intern Med 2017;8:196–204. doi:10.22088/cjim.8.3.196

6          ICHD-3 1.3 Chronic migraine. (accessed 9 Jan 2021).

7          Yang C-P, Chang M-H, Liu P-E, et al. Acupuncture versus topiramate in chronic migraine prophylaxis: A randomized clinical trial. Cephalalgia 2011;31:1510–21. doi:10.1177/0333102411420585

8          White A, Cummings M. Inconsistent placebo effects in NICE’s network analysis. Acupunct Med 2012;30:364–5. doi:10.1136/acupmed-2012-010262

9          Botulinum toxin type A for the prevention of headaches in adults with chronic migraine | Guidance | NICE. (accessed 9 Jan 2021).

10        Zhang N, Houle T, Hindiyeh N, et al. Systematic Review: Acupuncture vs Standard Pharmacological Therapy for Migraine Prevention. Headache 2020;60:309–17. doi:10.1111/head.13723

11        Linde K, Allais G, Brinkhaus B, et al. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev 2016;:CD001218. doi:10.1002/14651858.CD001218.pub3

12        Urits I, Patel M, Putz ME, et al. Acupuncture and Its Role in the Treatment of Migraine Headaches. Neurol Ther Published Online First: October 2020. doi:10.1007/s40120-020-00216-1

Declaration of interests MC