St John's Wort and why it scares me, despite the fact that it works.

Hi all,

It's lovely for once to be able to write about something that works, instead of something which has little to no evidence of it working. However, I wanted to share with you some reasons why I would tend to steer people away from a "natural" remedy, despite the evidence being positive. Why St John's Wort today? Well, my RSS feed today popped up with:

31/12/2012
Daily Telegraph
By: Presswatch
GPs prefer herbal remedies to Prozac, says survey
A survey by Schwabe Pharma found that GPs are increasingly likely to prescribe herbal remedies such as St John's wort for depression rather than Prozac.	(

(http://www.presswatch.com/health/index.php?d=2012-12-31#3)

I haven't been able to find the actual story, or the press release from Schwabe Pharma (who, incidentally, produce St John's Wort, so wouldn't be without bias), but it got me thinking anyway.

Is it because of a big pharma conspiracy? Is it because I'm in cahoots with the evil drug companies and all I want is money? Is it because I'm just too close-minded to be able to accept anything other than conventional medicines? Is it because I love seeing patients suffer? Well, in short no.

I find herbal medicines really interesting. Unlike homeopathy, which has no theoretical possibility of working, herbal medicines contain plant material with high enough levels of chemical constituents to cause a pharmacological effect. There's something quite beautiful about the concept of using plants for medicinal purposes. The problem with them lies in the fact that there just aren't enough studies done for us to be able to say whether they work, or more importantly, whether they harm. Whilst herbal remedies have enough "medicine" in them to make them work, this also means they have enough in them to cause adverse reactions, to interact with other herbs, medication, illnesses and so on. Without Big Pharma funding, though, its not that likely that large, well designed trials will be undertaken on them, so using herbal medicines can be a bit like shooting in the dark. Even if we don't find any documented issues with a herb, this doesn't mean none exist, it may just mean that nobody has looked at (or published) any issues yet.

St John's Wort is different. There is now a pretty large body of evidence to suggest that it works, and that it works better than placebo and as well as conventional antidepressants like the SSRIs. We also know a fair bit about its interactions and its adverse drug reactions... So that's great then, yes? That means healthcare professionals should all consider it as a better choice than the conventional medicines, with all their nasty side effects etc, right?

Well, in my opinion: not always. Whilst we know a fair amount about it, the problem here lies with production, and the inherent variability in herbal medicines. Because they're made from plant materials, there can be a huge amount of variability in what each tablet contains.. Even if you're using a product licensed under the Traditional Herbal Registration scheme, there can still be variability between each batch, depending on where the plant was grown, the time of year/ day it was harvested, and what it was treated after it was harvested. So, if you get stabilised on one batch of medicine, the next batch may contain differing amounts of active ingredients, which could mean a whole host of things might happen: it might work better, it might start interacting with your other meds, it might trigger a side effect etc. Then, just when you're getting used to that batch, the next one is different too, etc etc.

I've come across a few enquiries where a patient wants to use St John's Wort as add-on therapy along with their antidepressants. It maybe doesn't occur to the patient or their GP/pharmacist etc that it actually works in a very similar way to a conventional antidepressant. Combinations of antidepressants are usually only done under specialist care (with a few exceptions) because combining them increases the risk of some very severe side effects such as serotonin syndrome- the same applies to St John's Wort. The fact it's "natural" seems to blindside people into forgetting the usual principles of how medicines work.

This is before we even get into the territory of risks associated with self-treatment of what can be a very, very serious disease. Would I exclude use of St John's Wort entirely, for everyone? No, because it does appear to work. But do I treat it with as much (if not more) caution than I would an SSRI? Yes, because there's still not that much information about its safety in the grand scheme of things. So this sort of negates the point of it, to be honest.

Hopefully that explains a bit about why I'm cautious about herbal medicines.

Have a lovely New Year's Eve folks, see you again in 2013. 

Halotherapy: the return

Ages and ages and ages ago I wrote an initial blog post on halotherapy (salt cave therapy), and i promised you a follow up once I have looked at the available data for it.

In short, I always meant to get round to following it up, but kept forgetting or getting embroiled in something else instead. So here, dear friends, is the follow up post.

As you may recall, www.saltcave.co.uk were claiming their clinically tested, drug free treatment meant that many of their patients stopped taking their medications becuase they because symptom free. They claimed it would work for asthma, COPD, and sinusitis. So, I thought I'd test their claim for COPD, particularly since this illness can be particularly devastating and debilitating.

So here's what I did: had a look at their website, which attempts to helpfully provide a list of published studies. I the proceeded to ignore this entirely, and did my own search of Medline and Embase, the two leading medical literature databases in the world. If there was going to be any robust evidence, I would find it in those.

Now I'm interested in human clinical studies mainly as a starting point, because these are the ones that can actually tell us best whether or not something works. So I limited the searches to human trials: after all, The Salt Cave are claiming that it's a clinically tested therapy, right? I then combined the results for halotherapy, with results for chronic obstructive pulmonary disease, to see what would come up.

In Embase, I found one study. Unfortunately, it was in Russian, so I have to rely on the abstract. The study included 29 patients, and that's pretty much all that we know. The authors claim a significant positive effect, with no other information or data reported in the abstract. But frankly, a study with 29 patients in is neither here nor there- it's far too small to use to make any claims of benefit.It's worth noting, by the way, that these patients were in a "sanatorium" setting, which is likely to be a rather different setting to the middle-class-Ikea-£35 a go-UK based version that is being sold here. What other treatments would be given in a Russian sanatorium setting? How would any of this affect the patient's condition? How has this been controlled for in this study? Unfortunately, there's no way of knowing given how badly presented the abstract is.  

Okay, so what did I find in Medline? Well, in short, nothing. No results at all.

So then I went back to the references provided by www.saltcave.co.uk and found very little to add. Another Russian-based sanatorium study, in abstract only, providing no data at al. Likewise, the study that they use on the "results" page of their website only include 26 patientswith COPD: again, too limited to draw any secure conclusions from.

So my conclusion? The evidence for the use of salt cave therapy in COPD is far too limited to claim any benefit at this point in time. More research needs to be done in this area to be able to claim that it works. And this evidence base certainly doesn't justify £35 per hour. They can put as many testimonials as they like on their website but it still doesn't add up to good, robust clinical evidence.

Hopefully this is a step to debunking some of the claims they are making on this website. Whilst there is a possibility that it might work, at the moment we just don't have enough information to justify the claims- and the cost.

Further reading on halotherapy can be found at The 21st Floor and Sceptical Letter Writer

For transparency, here's my search terms:
EMBASE: halotherapy.ti.ab AND Chronic obstructive ling disease/ 
MEDLINE: halotherapy.ti.ab AND Pulmonary disease, chronic obstructive

Christmas Dinner Conversation: An Anecdote

Hi all,

Hope you all had a lovely festive period, whatever religion (or lack of) you may follow.

I spent christmas day with my parents and remaining grandparents, and thought I'd regale you with the tale of part of our christmas dinner conversation.

Having been asked what I was doing in life at the moment, one of the things that was mentioned was the Newcastle Skeptics in the Pub talk that my good friend and Helper Dog Nancy and I are doing in February. This prompted Mum to state that she thought that homeopathy might work, after all plants had been used for many years in medicine. Now, I have written before about the case of the magic crystals, and do remember mum trying homeopathic remedies on me as a child (out of desperation due to my awful car sickness. Out of interest, I also remember them not working) when I was a bit older, so this stopped me short. I do have a suspicion that the majority of users of homeopathy have little knowledge of how it is made, and therefore no idea how unreasonable it is to expect it to work. And here was living proof that this was, indeed the case. Dad was aware of the like-cures-like principle, but they had no idea at all of the serial dilutions used in homeopathy.

Cue a demonstration (involving wine), and an explanation that beyond 12C there is virtually no likelihood of any molecules of the "active" ingredient appearing, and the general consensus was that they were amazed at this turn of events, and couldn't understand how on earth it could work and how anyone could possibly be taken in by such nonsense.

And so it seems to me that a general lack of good information about what homeopathy is, and what the principles of it are, may well be responsible for the majority of people who may believe it still works.

What do you think? I wonder if there is any way to measure this? If you have any ideas, do give me a shout.

H x

A Call To Arms: Pharmacists should call for Open Data

Pharmacists of the world, unite and take over.

Pharmacy has been hit hard over the past few weeks. We've had MPs accusing us of being smartie counters, and a badly written BBC News expose implying that we are all merrily dealing benzo's to make a quick buck. (I may attempt another blog post on this at some point)

I believe that historically, pharmacy has drawn the short straw. In my opinion. our professional body, the Royal Pharmaceutical Society, seems to lag behind other bodies when it comes to media savviness, and it often feels like we have very little impact or voice when it comes to the healthcare profession as a whole. Even now, its still a rare occastion that a pharmacy-related story will actually have a pharmacist commenting on it in the news- GPs, doctors and nurses are simply much more vocal and recognisable to an audience.

But here is an opportunity, and it has been handed to us on a silver platter by Ben Goldacre and the BMJ. I'm sure you may have heard by now, but there is a pretty large campaign on the go to allow for more transparent reporting of clinical trial data. This has been prompted by the case of Roche's Tamiflu, but its wider implications on patient safety and care are huge.

All the information you need about the BMJ's Open Data campaign can be found here. 

Today I tweeted Ben Goldacre to ask what involvement there has been from the pharmacy bodies. The answer? A big fat zero. There has been no involvement at all, from any of them.

So here is my call to arms. If you are a pharmacist, or if you are affiliated with the pharmacy profession, lets contact the RPS, the GPhC, NPA, PSNC, and anyone else who will listen. Lets tell them how important this is to us and how we want them to represent us and get our voice heard.

After all, to be experts in medicine, we need to have access to information about medicine. And that information has to be accurate, reliable, accessible, and unbiased. Without open data, we simply cannot do our jobs properly or with the degree of safety that we would like to. It may seem like a trial not being published is far removed from handing over a prescription to a patient over the counter, but the fact of the matter is that patients are dying due to the lack of transparency. How can we counsel a patient on side effects, for example, when patient level data from trials has been withheld? How can a patient be prescribed the best medicine for their condition when most of the trials involving the drug haven't been published?

Moreover, what a great way to represent ourselves as a profession who, more than anything, care about the health- and safety- of our patients, and who are willing to speak up when it counts. What a fantastic opportunity for our professional bodies to prove what they can do.

H xxx

The importance of being human

The more I talk to homeopaths and other alternative medicine practitioners, the more I realise that the distinction between in vitro and in vivo testing is unclear to many.

It may be due to ignorance, or it may be in a desperate bid to pad out the lack of real-life clinical evidence, or to stun us all into silence with impressive looking sciencey stuff, but it seems that alternative medicine supporters are desperate to throw in vitro studies my way as "evidence" that their treatments work. But here's the thing: it's not evdience that it works at all. In fact, for the purposes of informing treatment decisions, any in vitro data might as well be discarded before you even bother reading it.

Why do i say this? Well, the easiest way to explain this is in picture form (drawings are courtesy of my marvellous friend Haymond Lam) :

Figure 1: A Petri dish, with some cells in it. (in vitro)

Figure 2: A human being  (well, okay, I know some people might think scientists aren't quite human beings but, y'know, we thought we'd still use one as an example). (in vivo)

As you can see from these pictures, a few cells in a petri dish actually look (and act) rather differently to a functioning, whole human body. So positive (or negative) results in an in vitro study actually bear very little resemblance to real life clinical situations. What  in vitro testing is great for is as preliminary evidence- to make new discoveries and to guide further research, and to find out the all-important details of how something may work. But we can't use some cells in a petri dish to say "Yes, this will definitely work for this or that illness". The only sort of evidence that we can use to decide if a drug is effective in any particular illness is a robustly designed clinical trial, and even then we can't use that as a cast iron guarantee.

I'm hoping that you will forgive me for this horrendous oversimplification, but it is hopefully a useful point to make. So, the next time you come across some in vitro studies being used as "evidence" that homeopathy works, you know that they're actually scraping the barrel, particularly gievn the fact that homeopathis is supposed to have been around for 2000 years. I'd expect after that amount of time that they'd have more than cell culture studies to their name.

H x

Alternative medicines and brain tumours

There's been a lot of press attention in recent days about the case of  Neon Roberts, whose mother had apparently ran away with him in order to avoid him being given post-surgery radiotherapy.

I will admit at this point that I haven't looked too closely into the case. I'm writing this on my lunch break so don't have time to go into all the details, but it appears that after being found, Neon has been taken into foster care and has been given the treatment he requires.

If the press reports are to be relied upon (and bear in mind my main source is the Daily Fail), this seems like a striking case of the sort of harm misinformation about alternative medicines can cause. Reportedly, the mother only wanted him to receive "natural remedies" as he recovers from his surgery. The implication is that natural remedies would be safer for the child, whereas conventional treatments like radiotherapy and chemotherapy are evil, toxic poisons.

And yet this distinction between "natural" and conventional medicines is highly blurred, particularly when it comes to chemotherapy. Some of our most powerful (and potentially toxic) chemotherapeutic agents are derived from plants- the taxols for example. Ultimately, the main difference between these agents and alternative medicines is that they have been tested and have been proven to work. If other natural, alternative medicines went through the same testing processes and also had positive results, they too would cease to be alternative and would become conventional medicines. Radiation, similarly, is an ultimately natural process. So how do the public at large decide what constitutes a "natural" remedy? We can see from this case the potential consequences of such misinformation.

Another thought that occurs to me is the distinction between complementary and alternative medicines. I think we can all agree that there is a potential benefit from some natural remedies for some cancer-associated symptoms or problems. So as an example I have no problem with a patient who decides to try a herbal remedy to treat say anxiety alongside their conventional treatment, providing they are doing so with a knowledge of the pros and cons of the treatment, and with their healthcare provider's knowledge. Complementary therapy, in other words. What's infinitely more worrying is the concept of alternative therapy, e.g. where a patient makes a decision to not use conventional medicine but to use a herbal remedy(or homeopathy, or acupuncture etc) instead. The evidence base for alternative medicines is absolutely nowhere near the level required to justify a patient using them instead of conventional medicines for something as serious as cancer.

And this brings me on to homeopathy. Yes, homeopathy again. I'm not going to cover how homeopathy works, as its been done much better at this site: http://www.howdoeshomeopathywork.com/ . What is particularly worrying about this modality is the advice given that conventional medicines need to be avoided to allow the homeopathy to work. This is bandied about in an inocuous sort of a way by websites such as this. So, by recommending a homeopathic treatment for a serious condition, homeopaths are directly harming their patient by encouraging them to not take conventional medicines (which may have a chance of working at least) and to replace them with Magic Woo Memory Water Sugar Pills (which have zero chance of working). One of the most heart-breaking things i have ever read on the internet are the letters of Penelope Dingle to her homeopath, who treated her pancreatic cancer. If you haven't seen this already, I highly recommend that you have a look, but warn you that it is likely to induce tears, then rage.

I've noticed that a few homeopaths on twitter have already picked up on the story of Neon Roberts, and are gleefully tweeting things like "UK Boy to Be Forced Into Chemotherapy" (forgetting the fact that it's actually radiotherapy that he will be receiving). Of course I'm Not Actually A Doctor Nancy Malik is involved. So I thought I'd have a look at what evidence there is that homeopathy can treat brain tumours, before they all start claiming that it can. So I've checked Medline and Embase, the leading medical literature databases in the world. My search stratedy was: Search for homeopathy. Search for brain tumours, and limit to therapy or treatment. Add the two together. See what comes out.  Makes sense, right?

So here are the results for EMBASE (links are only available to athens users):

	1	EMBASE	*HOMEOPATHY/	4263
	2	EMBASE	BRAIN TUMOR/dt, th [dt=Drug Therapy, th=Therapy]	7758
	3	EMBASE	1 AND 2	0

And here are the results for MEDLINE:

	1	MEDLINE	HOMEOPATHY/	3941
	2	MEDLINE	BRAIN NEOPLASMS/th [th=Therapy]	7433
	3	MEDLINE	1 AND 2	0

Now, you don't have to be an expert in literature searching to realise that that's a bit fat zero.

I'm Not Really A Dr Nancy Malik, however, has other ideas, and has helpfully sent me links to 4 sources that she claims are evidence that homeopathy can work in brian cancer treatment. Three of which are studies looking at  tissue cell culture, and one of which is for treatment of side effects (ergo as complementary, rather than alternative therapy, and which bears no resemblance to whether or not it could actually treat a brain cancer). The in vitro studies are very interesting i'm sure, but to use them as evidence that homeopathy can treat brain cancers in humans is an enormous stretch. With something so serious, would you really be willing to base a treatment decision on what happens to a couple of cells in a lab? Or would you rather base it on what happens to thousands, if not millions of other people in real-life? I know which one I would go with.

One other footnote to this news story is one which I fear may have been forgotten about. Imagine being a child, who has just undergone surgery for a brain tumour. Imagine the fear this poor boy feels on a daily basis, not to mention how physically ill he may be. Now imagine being taken by your mother on a trip elsewhere, then being taken into foster care and having to be given radiotherapy, whilst a court case battles on around you. I can't even begin to imagine what this child is feeling. This time would have been bad enough for him as it was, without any of this being added onto his trauma.