MD, PhD, FMedSci, FRSB, FRCP, FRCPEd

migraine

A new study published in JAMA investigated the long-term effects of acupuncture compared with sham acupuncture and being placed in a waiting-list control group for migraine prophylaxis. The trial was a 24-week randomized clinical trial (4 weeks of treatment followed by 20 weeks of follow-up). Participants were randomly assigned to 1) true acupuncture, 2) sham acupuncture, or 3) a waiting-list control group. The trial was conducted from October 2012 to September 2014 in outpatient settings at three clinical sites in China. Participants 18 to 65 years old were enrolled with migraine without aura based on the criteria of the International Headache Society, with migraine occurring 2 to 8 times per month.

Participants in the true acupuncture and sham acupuncture groups received treatment 5 days per week for 4 weeks for a total of 20 sessions. Participants in the waiting-list group did not receive acupuncture but were informed that 20 sessions of acupuncture would be provided free of charge at the end of the trial. Participants used diaries to record migraine attacks. The primary outcome was the change in the frequency of migraine attacks from baseline to week 16. Secondary outcome measures included the migraine days, average headache severity, and medication intake every 4 weeks within 24 weeks.

A total of 249 participants 18 to 65 years old were enrolled, and 245 were included in the intention-to-treat analyses. Baseline characteristics were comparable across the 3 groups. The mean (SD) change in frequency of migraine attacks differed significantly among the 3 groups at 16 weeks after randomization; the mean (SD) frequency of attacks decreased in the true acupuncture group by 3.2 (2.1), in the sham acupuncture group by 2.1 (2.5), and the waiting-list group by 1.4 (2.5); a greater reduction was observed in the true acupuncture than in the sham acupuncture group (difference of 1.1 attacks; 95% CI, 0.4-1.9; P = .002) and in the true acupuncture vs waiting-list group (difference of 1.8 attacks; 95% CI, 1.1-2.5; P < .001). Sham acupuncture was not statistically different from the waiting-list group (difference of 0.7 attacks; 95% CI, −0.1 to 1.4; P = .07).

The authors concluded that among patients with migraine without aura, true acupuncture may be associated with long-term reduction in migraine recurrence compared with sham acupuncture or assigned to a waiting list.

Note the cautious phraseology: “… acupuncture may be associated with long-term reduction …”

The authors were, of course, well advised to be so atypically cautious:

  • Comparisons to the waiting list group are meaningless for informing us about the specific effects of acupuncture, as they fail to control for placebo-effects.
  • Comparisons between real and sham acupuncture must be taken with a sizable pinch of salt, as the study was not therapist-blind and the acupuncturists may easily have influenced their patients in various ways to report the desired result (the success of patient-blinding was not reported but would have gone some way to solving this problem).
  • The effect size of the benefit is tiny and of doubtful clinical relevance.

My biggest concern, however, is the fact that the study originates from China, a country where virtually 100% of all acupuncture studies produce positive (or should that be ‘false-positive’?) findings and data fabrication has been reported to be rife. These facts do not inspire trustworthiness, in my view.

So, does acupuncture work for migraine? The current Cochrane review included 22 studies and its authors concluded that the available evidence suggests that adding acupuncture to symptomatic treatment of attacks reduces the frequency of headaches. Contrary to the previous findings, the updated evidence also suggests that there is an effect over sham, but this effect is small. The available trials also suggest that acupuncture may be at least similarly effective as treatment with prophylactic drugs. Acupuncture can be considered a treatment option for patients willing to undergo this treatment. As for other migraine treatments, long-term studies, more than one year in duration, are lacking.

So, maybe acupuncture is effective. Personally, I am not convinced and certainly do not think that the new JAMA study significantly strengthened the evidence.

A new study tested the efficacy of chiropractic spinal manipulative therapy (CSMT) for migraine. It was designed as a three-armed, single-blinded, placebo -controlled RCT of 17 months duration including 104 migraineurs with at least one migraine attack per month. Active treatment consisted of CSMT (group 1) and the placebo was a sham push manoeuvre of the lateral edge of the scapula and/or the gluteal region (group 2). The control group continued their usual pharmacological management (group 3).

The RCT began with a one-month run-in followed by three months intervention. The outcome measures were quantified at the end of the intervention and at 3, 6 and 12 months of follow-up. The primary end-point was the number of migraine days per month. Secondary end-points were migraine duration, migraine intensity and headache index, and medicine consumption.

The results show that migraine days were significantly reduced within all three groups from baseline to post-treatment (P < 0.001). The effect continued in the CSMT and placebo groups at all follow-up time points (groups 1 and 2), whereas the control group (group 3) returned to baseline. The reduction in migraine days was not significantly different between the groups. Migraine duration and headache index were reduced significantly more in the CSMT than in group 3 towards the end of follow-up. Adverse events were few, mild and transient. Blinding was strongly sustained throughout the RCT.

The authors concluded that it is possible to conduct a manual-therapy RCT with concealed placebo. The effect of CSMT observed in our study is probably due to a placebo response.

Chiropractors often cite clinical trials which suggest that CSMT might be effective. The effects sizes are rarely impressive, and it is tempting to suspect that the outcomes are mostly due to bias. Chiropractors, of course, deny such an explanation. Yet, to me, it seems fairly obvious: trials of CSMT are not blind, and therefore the expectation of the patient is likely to have major influence on the outcome.

Because of this phenomenon (and several others, of course), sceptics are usually unconvinced of the value of chiropractic. Chiropractors often respond by claiming that blind studies of physical intervention such as CSMT are not possible. This, however, is clearly not true; there have been several trials that employed sham treatments which adequately mimic CSMT. As these frequently fail to show what chiropractors had hoped, the methodology is intensely disliked by chiropractors.

The above study is yet another trial that adequately controls for patients’ expectation, and it shows that the apparent efficacy of CSMT disappears when this source of bias is properly accounted for. To me, such findings make a lot of sense, and I suspect that most, if not all the ‘positive’ studies of CSMT would turn out to be false positive, once such residual bias is eliminated.

Case reports of adverse effects after chiropractic spinal manipulation usually come as publications in peer-reviewed medical journals. As such they tend to documents that are factual, detached and clinical. This is an intended effect and is meant to increase objectivity; at the same time it omits all of the directness and emotions that are associated with such incidences which can, of course, be important. Here is a case report that is dramatically different. It is a story told by a sibling of the victim (both had been having manipulations for migraines regularly) on this website. As I think it is poignant, I have not changed anything except for shortening it slightly.

My youngest brother has been receiving chiro for… long, however last week he received very, very aggressive neck adjustments 3 times in a row. The last one left him feeling off and he felt like it worsened his migraine. He called me asking if I had ever had an adjustment worsen a headache and I said yes, once or twice. He then told me it was creating a different vision issue than his regular migraine aura. I told him get to emergency ASAP. He had a full stroke 15 minutes later. At the age of 29 years. Thank God he went to ER, he told me he almost went to try to sleep it off after he hung up the phone.

An MRI and CT scan showed that the stroke was NOT a clot that was already formed and agitated/released by the neck adjustment. But that the adjustment had actually caused a large tear in his vertebral artery and that it had in turn caused bleeding into his brain and consequently the stroke.

The doctor told him that had he not come in right when he did, he would most certainly have died or in the best case scenario, been a vegetable.

I realize that perhaps the chiropractor did not realize how aggressive he was being or even consider the trauma he could cause. Or maybe, he made a poor judgement call, he is only human. I have since consulted my own chiropractor, who sadly, is of the opinion that it’s just not possible for a chiropractor to cause such trauma and that it simply was an issue waiting to happen and that the adjustment just ‘helped’ it along. He stated over and over that chiro CANNOT cause a stroke. I am scared enough to not go back. I find physio to help my neck more anyway.

The other part is, the ER doctor told my brother that he has seen what he considers to be an alarming increase in chiropractic related strokes and vertebral artery tears. I realize that nowhere NEAR even 90% of all patients adjusted have this issue, but it definetely exists and it IS scary.

I expect that several apologists will now accuse me again of being alarmist, but I do wonder how often such cases happen and remain unreported. I am certainly not aware that this case has been published in a peer-reviewed journal.

Osteopathy is a difficult subject. In the US, osteopaths are (almost) identical with doctors who have studied conventional medicine and hardly practice any manipulative techniques at all. Elsewhere, osteopaths are alternative healthcare providers specialising in what they like to call ‘osteopathic manipulative therapy’ (OMT). As though this is not confusing enough, osteopaths are doing similar things as chiropractors but are adamant that they are a distinct profession. Despite these assertions, I have seen little to clearly differentiate the two – with one exception perhaps: osteopaths tend to use techniques that are less frequently associated with severe harm.

Despite this confusion, or maybe because of it, we need to ask: DOES OMT WORK?

A recent study was aimed at assessing the effectiveness of OMT on chronic migraineurs using HIT-6 questionnaire, drug consumption, days of migraine, pain intensity and functional disability. All patients admitted to the Department of Neurology of Ancona’s United Hospitals, Italy, with a diagnosis of migraine and without chronic illness, were considered eligible for this 3-armed RCT.

Patients were randomly divided into three (1) OMT+medication therapy, (2) sham+medication therapy and (3) medication therapy only and received 8 treatments during 6 months. Changes in the HIT-6 score were considered as the main outcome measure.

A total of 105 subjects were included. At the end of the study, OMT significantly reduced HIT-6 score, drug consumption, days of migraine, pain intensity and functional disability.

The investigators concluded that these findings suggest that OMT may be considered a valid procedure for the management of migraineurs.

Similar results have been reported elsewhere:

One trial, for instance, concluded: “This study affirms the effects of OMT on migraine headache in regard to decreased pain intensity and the reduction of number of days with migraine as well as working disability, and partly on improvement of HRQoL. Future studies with a larger sample size should reproduce the results with a control group receiving placebo treatment in a long-term follow-up.”

Convinced? No, I am not.

Why? Because the studies that do exist seem a little too good to be true; because they are few and far between, because the few studies tend to be flimsy and have been published in dodgy journals, because they lack independent replications, and because critical reviews seem to conclude that OMT is nowhere near as promising as some osteopaths would like us to believe: “Further studies of improved quality are necessary to more firmly establish the place of physical modalities in the treatment of primary headache disorders. With the exception of high velocity chiropractic manipulation of the neck, the treatments are unlikely to be physically dangerous, although the financial costs and lost treatment opportunity by prescribing potentially ineffective treatment may not be insignificant. In the absence of clear evidence regarding their role in treatment, physicians and patients are advised to make cautious and individualized judgments about the utility of physical treatments for headache management; in most cases, the use of these modalities should complement rather than supplant better-validated forms of therapy.”

Lots of alternative therapies are advocated for migraine. Few of them are supported by good evidence. An exception could be the herbal remedy FEVERFEW.

This review is an update of a previously published review in the Cochrane Database of Systematic Reviews on ‘Feverfew for preventing migraine’. Feverfew (Tanacetum parthenium L.) extract is a herbal remedy, which has been used for preventing attacks of migraine. Our aim was to systematically review the evidence from double-blind, randomised, clinical trials (RCTs) assessing the clinical efficacy and safety of feverfew monopreparations versus placebo for preventing migraine.

For this updated version of the review we searched CENTRAL, MEDLINE, EMBASE and AMED to January 2015. We contacted manufacturers of feverfew and checked the bibliographies of identified articles for further trials.

We included randomised, placebo-controlled, double-blind trials assessing the efficacy of feverfew monopreparations for preventing migraine in migraine sufferers of any age. We included trials using clinical outcome measures, while we excluded trials focusing exclusively on physiological parameters. There were no restrictions regarding the language of publication.

We systematically extracted data on patients, interventions, methods, outcome measures, results and adverse events. We assessed risk of bias using the Cochrane ‘Risk of bias’ tool and evaluated methodological quality using the Oxford Quality Scale developed by Jadad and colleagues. Two review authors independently selected studies, assessed methodological quality and extracted data. We resolved disagreements concerning evaluation of individual trials through discussion.

We identified one new study for this update, resulting in a total of 6 trials (561 patients) meeting the inclusion criteria. Five of the 6 trials reported on the main outcome measure which was migraine frequency. Although 5 of the trials were generally of good methodological quality, all studies were either of unclear or high risk of bias with regards to sample size. Pooled analysis of the results was not possible due to the lack of common outcome measures and heterogeneity between studies in terms of participants, interventions and designs. The most recent trial added to this update was rigorous and larger (n = 218) than previous studies. It used a stable feverfew extract at a dose determined by a previous dose-finding trial. It reported that feverfew reduced migraine frequency by 1.9 attacks from 4.8 to 2.9 and placebo by 1.3 from to 4.8 to 3.5 per month. This difference in effect between feverfew and placebo was thus 0.6 attacks per month. For the secondary outcome measures such as intensity and duration of migraine attacks, incidence and severity of nausea and vomiting, and global assessment no statistically significant differences between feverfew and placebo were reported.

The results of previous trials were not convincing: three trials reporting positive effects of feverfew were all of small sample size (17 to 60 participants), while two rigorous trials (n = 50, 147) did not find significant differences between feverfew and placebo.

Only mild and transient adverse events of feverfew, most commonly gastrointestinal complaints and mouth ulcers, were reported in the included trials.

We concluded that, since the last version of this review, one larger rigorous study has been included, reporting a difference in effect between feverfew and placebo of 0.6 attacks per month. This adds some positive evidence to the mixed and inconclusive findings of the previous review. However, this constitutes low quality evidence, which needs to be confirmed in larger rigorous trials with stable feverfew extracts and clearly defined migraine populations before firm conclusions can be drawn. It appears from the data reviewed that feverfew is not associated with any major safety concerns.

So, good or bad news for migraine sufferers? I suppose it depends on whether you are an optimist or a pessimist. I would say that, considering the mostly bad news about alternative medicine for migraine, it is relative good news: patients who want to try something ‘natural’ could do so, particularly in view of the lack of serious risks.

“If ever there was a permanent cure for migraine, homeopathic medicines are the only one that can do this miracle. It may sound like an overstatement and quite quackerish, but it’s true. Long term treatment with homeopathy has an excellent cure for migraine headaches.” Statements like this can be found by the thousands on the internet, not just in relation to migraine but also about osteoarthritis. Both migraine and osteoarthritis are important domains for homeopathy, and most homeopaths would not doubt for a second that they can treat these conditions effectively. This is why it is so important to highlight the few sources which are not misleading consumers into making the wrong therapeutic decisions.

‘Healthcare Improvement Scotland’ (HCIS) have just published advice for patients suffering from migraine and osteoarthritis (the full document with all the evidence can be found here). I think it is worth having a close look and I therefore cite it in full:

Homeopathic remedies are prepared by repeated dilution and vigorous shaking of substances in water. Remedies are prepared from substances that in healthy people cause the signs and symptoms of the condition being treated. The more dilute the remedy is the more potent it becomes so that the most potent remedies are unlikely to contain any of the original substance.

People in Scotland have access to homeopathy through some GPs or a referral to homeopaths in the private sector, regional NHS clinics or the Centre for Integrative Care (CIC) (formerly Glasgow Homeopathic Hospital). Not all NHSScotland health boards provide funding for homeopathy; investment varies widely among those that do, and individual boards have begun to review funding for homeopathy services.

Clinical effectiveness

  • Evidence of clinical effectiveness was reviewed from systematic reviews of four placebo controlled randomised trials of homeopathy for migraine published between 1991 and 1997; and systematic reviews of four active treatment controlled randomised trials of homeopathy for osteoarthritis published between 1983 and 2000. The quality of the evidence was low to moderate.
  • Homeopathy for migraine has not been compared with active treatment in randomised controlled trials (RCTs). Of four RCTs comparing homeopathy with placebo, only one found homeopathy to be superior.
  • Three RCTs in osteoarthritis comparing homeopathy with medicines for pain relief found either no difference between the interventions, or that analgesic treatment had a better effect than homeopathy. A further RCT comparing intra-articular injection of a homeopathic remedy with hyaluronic acid injections showed similar pain reduction in both groups.

Safety

  • Published systematic reviews of homeopathy for migraine and osteoarthritis contain insufficient information to inform conclusions about safety.

Cost effectiveness

  • No evidence on the cost effectiveness of homeopathy for migraine was identified; and the evidence from a single cost-minimisation analysis of one homeopathic preparation for osteoarthritis is not generalisable to the UK.

Context/conclusion

  • Homeopathy for migraine has not been compared with standard care in RCTs and no evidence of cost effectiveness has been identified..
  • There is insufficient evidence to determine whether or not homeopathic treatment for osteoarthritis is clinically effective compared with standard care, and no relevant evidence of cost effectiveness has been identified.
  • The evidence does not support treating migraine or osteoarthritis with homeopathy.

Before the fans of homeopathy start shouting “THIS IS ALL RUBBISH AND DISREGARDS IMPORTANT EVIDENCE!!!”, I should mention that the top experts in homeopathy were asked to contribute their evidence and were unable to find any convincing data that would have changed this negative verdict. And it is important to point out that HCIS is a respected, independent organisation that issues statements based on thorough, unbiased reviews of the evidence.

As I reported a while ago, the Australian ‘NATIONAL HEALTH AND MEDICAL RESEARCH COUNCIL’ has assessed the effectiveness of homeopathy. The evaluation looks like the most comprehensive and most independent in the history of homeopathy. Its draft report  concluded that “the evidence from research in humans does not show that homeopathy is effective for treating the range of health conditions considered.”

So, the HCIS is in excellent company and I have no doubt whatsoever that this new statement is correct – but I also have little doubt that homeopaths will dispute it.

 

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