MD, PhD, FMedSci, FSB, FRCP, FRCPEd

systematic review

My aim with this blog is to eventually cover most of the 400 or so different alternative therapies and diagnostic techniques. So far, I have focused on some of the most popular modalities; and this means, I have neglected many others. Today, it is time, I think, to discuss aromatherapy, after all, it is one of the most popular forms of alternative medicine in the UK.

Aromatherapists use essential oils, and this is where the confusion starts. They are called “essential” not because humans cannot do without them, like essential nutrients, for instance; they are called “essential” because they are made of flower ESSENCES. The man who ‘discovered’ aromatherapy was a chemist who accidentally had burnt his hand and put some lavender essence on the burn. It healed very quickly, and he thus concluded that essential oils can be useful therapeutics.

Today’s aromatherapists would rarely use the pure essential oil; they dilute it in an inert carrier oil and usually apply it via a very gentle massage to the skin. They believe that specific oils have specific effects for specific conditions. As these oils contain pharmacologically active ingredients, some of these assumptions might even be correct. The question, however, is one of concentration. Do these ingredients reach the target organ in sufficient quantities? Are they absorbed through the skin at all? Does smelling them have a sufficiently large effect to produce the claimed benefit?

The ‘acid test’ for any therapeutic claim is, as always, the clinical trial. As it happens a new paper has just become available. The aim of this randomised study was to determine the effects of inhalation aromatherapy on pregnant women. Essential oils with high linalool and linalyl acetate content were selected and among these the one preferred by the participant was used. Thirteen pregnant women in week 28 of a single pregnancy were randomly assigned into an aromatherapy and a control group. The main outcome measures were several validated scores to assess mood and the heart-rate variability. The results showed significant differences in the Tension-Anxiety score and the Anger-Hostility score after aromatherapy. Heart rate variability changes indicated that the parasympathetic nerve activity increased significantly in the verum group. The authors concluded that aromatherapy inhalation was effective and suggest that more research is warranted.

I have several reasons for mentioning this study here.

1st research into aromatherapy is rare and therefore any new trial of this popular treatment might be important.

2nd aromatherapy is mostly (but not in this study) used in conjunction with a gentle, soothing massage; any outcome of such an intervention is difficult to interpret: we cannot then know whether it was the massage or the oil that produced the observed effect. The present trial is different and might allow conclusions specifically about the effects of the essential oils.

3rd the study displays several classic methodological mistakes which are common in trials of alternative medicine. By exposing them, I hope that they might become less frequent in future.

The most obvious flaw is its tiny sample size. What is an adequate size, people often ask. This question is unfortunately unanswerable. To determine the adequate sample size, it is best to conduct a pilot study or use published data to calculate the required number of patients needed for the specific trial you are planning. Any statistician will be able to help you with this.

The second equally obvious flaw relates to the fact that the results and the conclusions of this study were based on comparing the outcome measures before with those after the interventions within one intervention group. The main reason for taking the trouble of running a control group in a clinical trial is that the findings from the experimental group are compared to those of the control group. Only such inter-group comparisons can tell us whether the results were actually caused by the intervention and not by other factors such as the passage of time, a placebo-effect etc.

In the present study, the authors seem to be aware of their mistake and mention that there were no significant differences in outcomes when the two groups were compared. Yet they fail to draw the right conclusion from this fact. It means that their study demonstrated that aromatherapy inhalation had no effect on the outcomes studied.

So, what does the reliable trial evidence on aromatherapy tell us?

A clinical trial in which I was involved failed to show that it improves the mood or quality of life of cancer patients. But one swallow does not make a summer; what do systematic reviews of all available trials indicate?

The first systematic review was probably the one we published in 2000. We then located 12 randomised clinical trials: six of them had no independent replication; six related to the relaxing effects of aromatherapy combined with massage. These 6 studies collectively suggested that aromatherapy massage has a mild but short-lasting anxiolytic effect. These effects of aromatherapy are probably not strong enough for it to be considered for the treatment of anxiety. We concluded that the hypothesis that it is effective for any other indication is not supported by the findings of rigorous clinical trials.

Since then several other systematic reviews have emerged. We therefore decided to summarise their findings in an overview of all available reviews. We searched 12 electronic databases and our departmental files without restrictions of time or language. The methodological quality of all systematic reviews was evaluated independently by two authors. Of 201 potentially relevant publications, 10 met our inclusion criteria. Most of the systematic reviews were of poor methodological quality. The clinical subject areas were hypertension, depression, anxiety, pain relief, and dementia. For none of the conditions was the evidence convincing. Our conclusions therefore had to be cautious: due to a number of caveats, the evidence is not sufficiently convincing that aromatherapy is an effective therapy for any condition.

Finally, we also investigated the safety of aromatherapy by assessing all published data regarding adverse effects. Forty two primary reports met our inclusion criteria. In total, 71 patients had experienced adverse effects after aromatherapy which ranged from mild to severe and included one fatality. The most common adverse effect was dermatitis. Lavender, peppermint, tea tree oil and ylang-ylang were the most common essential oils responsible for adverse effects. We concluded that aromatherapy has the potential to cause adverse effects some of which are serious. Their frequency remains unknown.

And what is the conclusion of all this? To me, it seems fairly straight forward: Aromatherapy is not demonstrably effective for any condition. It also is not entirely free of risks. Its risk/benefit profile is thus not positive which can only mean that it is not a useful or recommendable treatment for anybody who is ill.

As I have mentioned before, I like positive news as much as the next person. Therefore, I am constantly on the look-out for recently published, sound evidence suggesting that  some form of alternative medicine is effective and safe for this or that condition. This new systematic review fits that description, I am pleased to report.

Its authors evaluated the effectiveness of massage therapy (MT) for neck and shoulder pain. Their extensive literature searches identified 12 high-quality studies. The meta-analyses showed significant effects of MT for neck pain and shoulder pain compared to inactive therapies. MT did not yield better effects for neck pain or shoulder pain than other active therapies administered to the control groups. Shoulder function was not significantly affected by MT. The authors concluded that “MT may provide immediate effects for neck and shoulder pain. However, MT does not show better effects on pain than other active therapies. No evidence suggests that MT is effective in functional status”.

Massage therapy is thus a promising treatment, particularly as this systematic review is by no means the only piece of encouraging evidence. It is not better than other effective treatments, but it is not associated with frequent or serious adverse effects. This means that the demonstrable benefits are likely to outweigh its risks; in other words, the risk benefit balance is positive. Regular readers of this blog will appreciate the importance of this point.

Massage is practiced by several professions: mostly, of course, by massage therapists, but occasionally also by nurses, osteopath, chiropractors etc. Chiropractors, in particular, have recently tried to make much – I think too much – of this fact. They tend to claim that, as they use treatments which are evidence-based, such as massage, chiropractic is an evidence-based profession. I think this is akin to surgeons claiming that all of surgery is evidence-based because surgeons use medications which effectively reduce post-operative pain. Chiropractors foremost employ spinal manipulation and surgeons foremost use surgery; if they want us to believe that their practice is evidence-based, they need to show us the evidence for their hall-mark interventions. In the case of surgery, the evidence is mostly established; in the case of chiropractic, it is mostly not.

Massage is backed by reasonably sound evidence not just for neck and shoulder pain but for a range of other conditions as well. WHAT DO WE CALL AN ALTERNATIVE MEDICINE THAT WORKS? WE CALL IT MEDICINE!

So why is massage not a mainstream therapy? The answer is simple: in many countries, massage therapy has long been considered to be entirely conventional. Twenty years ago, I was chair of rehabilitation medicine at the university of Vienna. Amongst my staff, there always were about 5-8 full time massage therapists and nobody thought this to be unusual in any way. Similarly, in Germany, massage is entirely conventional.

Perhaps it is time that the English-speaking countries catch up with Europe when it comes to massage therapy and the evidence that supports it?

Still in the spirit of ACUPUNCTURE AWARENESS WEEK, I have another critical look at a recent paper. If you trust some of the conclusions of this new article, you might think that acupuncture is an evidence-based treatment for coronary heart disease. I think this would be a recipe for disaster.

This condition affects millions and eventually kills a frighteningly large percentage of the population. Essentially, it is caused by the fact that, as we get older, the blood vessels supplying the heart also change, become narrower and get partially or even totally blocked. This causes lack of oxygen in the heart which causes pain known as angina pectoris. Angina is a most important warning sign indicating that a full blown heart attack might be not far.

The treatment of coronary heart disease consists in trying to let more blood flow through the narrowed coronaries, either by drugs or by surgery. At the same time, one attempts to reduce the oxygen demand of the heart, if possible. Normalisation of risk factors like hypertension and hypercholesterolaemia are key preventative strategies. It is not immediate clear to me how acupuncture might help in all this – but I have been wrong before!

The new meta-analysis included 16 individual randomised clinical trials. All had a high or moderate risk of bias. Acupuncture combined with conventional drugs (AC+CD) turned out to be superior to conventional drugs alone in reducing the incidence of acute myocardial infarction (AMI). AC+CD was superior to conventional drugs in reducing angina symptoms as well as in improving electrocardiography (ECG). Acupuncture by itself was also superior to conventional drugs for angina symptoms and ECG improvement. AC+CD was superior to conventional drugs in shortening the time to onset of angina relief. However, the time to onset was significantly longer for acupuncture treatment than for conventional treatment alone.

From these results, the authors [who are from the Chengdu University of Traditional Chinese Medicine in Sichuan, China] conclude that “AC+CD reduced the occurrence of AMI, and both acupuncture and AC+CD relieved angina symptoms and improved ECG. However, compared with conventional treatment, acupuncture showed a longer delay before its onset of action. This indicates that acupuncture is not suitable for emergency treatment of heart attack. Owing to the poor quality of the current evidence, the findings of this systematic review need to be verified by more RCTs to enhance statistical power.”

As in the meta-analysis discussed in my previous post, the studies are mostly Chinese, flawed, and not obtainable for an independent assessment. As in the previous article, I fail to see a plausible mechanism by which acupuncture might bring about the effects. This is not just a trivial or coincidental observation – I could cite dozens of systematic reviews for which the same criticism applies.

What is different, however, from the last post on gout is simple and important: if you treat gout with a therapy that is ineffective, you have more pain and eventually might opt for an effective one. If you treat coronary heart disease with a therapy that does not work, you might not have time to change, you might be dead.

Therefore I strongly disagree with the authors of this meta-analysis; “the findings of this systematic review need NOT to be verified by more RCTs to enhance statistical power” — foremost, I think, the findings need to be interpreted with much more caution and re-written. In fact, the findings show quite clearly that there is no good evidence to use acupuncture for coronary heart disease. To pretend otherwise is, in my view, not responsible.

There might be an important lesson here: A SEEMINGLY SLIGHT CORRECTION OF CONCLUSIONS OF SUCH SYSTEMATIC REVIEWS MIGHT SAVE LIVES.

This week is acupuncture awareness week, and I will use this occasion to continue focusing on this therapy. This first time ever event is supported by the British Acupuncture Council who state that it aims to “help better inform people about the ancient practice of traditional acupuncture. With 2.3 million acupuncture treatments carried out each year, acupuncture is one of the most popular complementary therapies practised in the UK today.

Right, let’s inform people about acupuncture then! Let’s show them that there is often more to acupuncture research than meets the eye.

My team and I have done lots of research into acupuncture and probably published more papers on this than any other subject. We had prominent acupuncturists on board from the UK, Korea, China and Japan, we ran conferences, published books and are proud to have been innovative and productive in our multidisciplinary research. But here I do not intend to dwell on our own achievements, rather I will highlight several important new papers in this area.

Korean authors just published a meta-analysis to assess the effectiveness of acupuncture as  therapy for gouty arthritis. Ten RCTs involving 852 gouty arthritis patients were included. Six studies of 512 patients reported a significant decrease in uric acid in the treatment group compared with a control group, while two studies of 120 patients reported no such effect. The remaining four studies of 380 patients reported a significant decrease in pain in the treatment group.

The authors conclude “that acupuncture is efficacious as complementary therapy for gouty arthritis patients”.

We should be delighted with such a positive and neat result! Why then do I hesitate and have doubts?

I believe that this paper reveals several important issues in relation to systematic reviews of Chinese acupuncture trials and studies of other TCM interventions. In fact, this is my main reason for discussing the new meta-analysis here. The following three points are crucial, in my view:

1) All the primary studies were from China, and 8 of the 10 were only available in Chinese.

2) All of them had major methodological flaws.

3) It has been shown repeatedly that all acupuncture-trials from China are positive.

Given this situation, the conclusions of any review for which there are only Chinese acupuncture studies might as well be written before the actual research has started. If the authors are pro-acupuncture, as the ones of the present article clearly are, they will conclude that “acupuncture is efficacious“. If the research team has some critical thinkers on board, the same evidence will lead to an entirely different conclusion, such as “due to the lack of rigorous trials, the evidence is less than compelling.

Systematic reviews are supposed to be the best type of evidence we currently have; they are supposed to guide therapeutic decisions. I find it unacceptable that one and the same set of data could be systematically analysed to generate such dramatically different outcomes. This is confusing and counter-productive!

So what is there to do? How can we prevent being misled by such articles? I think that medical journals should refuse to publish systematic reviews which so clearly lack sufficient critical input. I also believe that reviewers of predominantly Chinese studies should provide English translations of these texts so that they can be independently assessed by those who are not able to read Chinese – and for the sake of transparency, journal editors should insist on this point.

And what about the value of acupuncture for gouty arthritis? I think I let the readers draw their own conclusion.

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