The King’s New Medicine: on the soporific effect of homeopathy

This is the story of the King’s new clothes.

Now there was once a king who was absolutely insane about

new clothes and one day, two swindlers came to sell him what

they said was a magic suit of clothes. Now, they held up this

particular garment and they said, “Your Majesty, this is a magic suit.”

Well, the truth of the matter is, there was no suit there at all.

But the swindlers were very smart, and they said,

“Your Majesty, to a wise man this is a beautiful raiment

but to a fool it is absolutely invisible.”

THE KING’S NEW CLOTHES, From the film “Hans Christian Andersen” (1952)

 It’s Homeopathy Awareness Week (HAW) again in the UK from the 14^th to 21^st June.  This is an annual publicity campaign run by homeopathy organizations and a potion maker.  It’s an attempt to convince potential customers that homeopathy is useful for something significant.  The two main problems are: there is no real evidence that homeopathy can help with any specific health issue, and they are peddling magic pills that typically contain no medicine.

This event always gives me a strong sense of déjà vu: after failing to produce any proper evidence for being able to help with women’s health (2010) and hay fever (2009), this year it’s sleeplessness (insomnia).

The campaign’s website, ‘heal through homeopathy’, highlights the undoubted importance of the topic by claiming that, “… sleeplessness … affects an estimated 77% of people in GB.”  However, according to a National Health Service (NHS) publication, “Sleeplessness – A Self Help Guide” the figure is around 30%.  Perhaps the homeopaths are overstating the problem?

A summary of a recent YouGov poll^* put it this way:

“The majority of the British public need between six and nine hours’ sleep a night to feel fully rested, according to a recent survey. 43% claim they need 6-7 hours and another 33% of the population stated they require 8-9 hours to feel fresh the following day. This appears to be consistent with the hours of sleep the public normally get with a huge 79% claiming they get between 6-9 hours each night. However, almost one in five respondents (18%) state that they get a just a maximum of five hours of sleep a night and just seven percent claim that they feel fully rested with this amount.”

This seems to suggest that a smaller percentage of the population feel they are not getting enough sleep than the homeopaths are suggesting.

Isn’t it grand! Isn’t it fine!

As for what the campaign think they can do for people with problems sleeping, Ranjni Janda is quoted as saying:

“… there are many homeopathic remedies which can be used to help. Chamomilla can help if you are feeling tired but cannot sleep and Cocculus can help if sleeplessness is caused by mental and physical exhaustion. Coffea may be beneficial for those suffering from restless sleep that regularly wake during the night, especially when too many thoughts are running through the mind, and Nux Vomica is useful for those that overindulge in food, drink and smoking to counter mental strains and worries resulting in sleeplessness.”

Is there any reason to think that these ‘remedies’ could help, or even heal, sleeplessness?  Given that all these remedies will likely be diluted down to nothing, no.  In fact, by the time the dilutions are done, there will be no way to distinguish between these potions.  At the (im)potencies typically dispensed in the UK, they will contain nothing of the alleged medicine.

Setting this aside for the moment, is there any robust evidence from clinical trials to support the claims made by this campaign?  To raise my level of awareness I searched PubMed for “homeopathy” and “sleep”, and did a little additional googling.

… it’s altogether the most remarkable evidence

Recent claims

Long et al (2001) solicited the opinions of the opinions of 223 professionalCAM organizations as to what therapies benefitted which conditions.  It lists therapies for which 2 or more responses were received and where the therapy was recommended by at least one respondent.  Homeopathy was not listed for insomnia.  So it looks like official homeopathic enthusiasm for treating insomnia is a recent phenomenon.

A case in point?

Perhaps the least informative type of evidence comes from case reports – accounts of treating individual patients.  They have legitimate uses, of course, but don’t say anything about the effectiveness of an intervention.

In my search, I came across a single case report. Rogers(1997) looked at treating alcohol-related problems with homeopathy.  The author claimed that, “… Examples of some specific homoeopathic treatments, together with a case report, are given to illustrate the potential uses of this form of therapy. It is concluded that homoeopathy can provide a valid and effective therapy to help clients break the cycle of dependence on alcohol.”

Given that this appears to be a single case report, then drawing this conclusion is unwarranted.  Neither does t have any relevance to issues not related to alcohol.

Trials and tribulations

Well conducted, large, double-blind randomised control trials (DBRCT) are a very useful indicator of efficacy, particularly when they are replicated.  Given that the Society of Homeopaths, the British Homeopathic Association and Nelsons Homeopathic Pharmacy are running a campaign claiming to be able to alleviate sleeplessness I would expect that they have plenty of this kind of evidence underpinning their claim.

Starting with Over The Counter (OTC) remedies, a topic relevant to Nelsons business, Cialdella et al (2001) published a double-blind RCT of 61 subjects comparing the efficacy of homeopathic preparations, “Homéogène 46 and Sédatif PC” as an alternative to benzodiazepines (less than 10 mg/d of diazepam equivalents).  They concluded that:

“No statistically significant difference between homeopathic drugs and placebo was observed for the main outcome or for the secondary outcomes. The lack of statistical power due to accrual difficulties limits the conclusions of this trial which did not confirm the efficacy of homeopathic drugs in this indication.”

This negative result does not seem to have stopped the manufacturer, Boiron, continuing to sell Homéogène 46 or Sédatif PC.  This is a familiar theme with CAM: positive trials, whatever their quality, are justifications; negative trials are ignored.

In a similar vein, La Pine et al (2006) tested the homeopathic remedy No-Shift-Lag on ICU nurses with a “randomized, double-blind, placebo-controlled, crossover trial”.  Apparently the trial involved 34 subjects; only 28 completed a drop-out rate of close to 18%.  The remedy was administered to, “ICU nurses working 3 consecutive 12hr night shifts, and assessing for fatigue.”  The outcome was negative:

“Vigilance test was not significantly different when taking either the study preparation or the placebo.”

This may explain why La Pine et al (2006) doesn’t appear on the manufacturer’s website – which features a positive unpublished trial.

Mean differences and 95% confidence intervals for overall nighttime and daytime therapeutic effectiveness between the two treatments, and for the components of the night-time score. Positive values favor Neurexan. The dotted line indicates the border for noninferiority of Neurexan to valerian therapy. (after Waldschütz and Klein, 2008)

Another theme in the CAM literature is compromising rigour to deliver apparently positive results.  Waldschütz and Klein (2008) published the results of, “an open-label, prospective cohort study in 89 German centres offering both conventional and complementary therapies.”  The 409 subjects were given Neurexan, a homeopathic preparation, or one of a disparate collection of commercial valerian products, for 28 days.  Doses were at the physicians’ discretion.  “Sleep duration and latency were evaluated based on patients’ sleep diaries over 14 days; sleep quality was evaluated at 28 +/- 1 days.”

Interestingly, Sarris and Byrne (2011) noted, “… weak and unsupportive evidence for herbal medicines such as valerian”.  Therefore this study was essentially a non-superiority trial for a low potency homeopathic preparation against a herbal preparation that likely does not work.

There were minor differences in favour of Neurexan, but looking at Figure 2 in the paper (above) the 95% confidence intervals for the mean differences for overall nighttime and daytime therapeutic effectiveness between the two treatments, and for the components of the night-time score, cross “zero”, i.e. no statistically significant difference.

The authors also observed that, “[s]ignificantly more patients reported lack of daytime fatigue with Neurexan than with valerian therapies (49% vs. 32%; p < 0.05 for the comparison).”

Overall, this is not an impressive result for the homeopathic treatment.  In terms of insomnia treatment it works about as well as something that probably doesn’t work.  The composition of Neurexan is also interesting, in that it contains some putative therapeutic agent. It contains Passiflora incarnate (White sarsaparilla) and Avena sativa (Common oats) at D2 (1%) concentration. Zincum isovalerianicum (Valerianate of zinc) is present at D4 (0.01%), finally the much-mentioned Coffea Arabica is present at the lowest concentration (D12). However, this study provides no evidence that the homeopathic preparation actually works.

Yet another string to the CAM bow is publishing in ‘special’ journals that don’t apply any noticeable scholastic standards.  And so we come to Naudé et al (2010), a study of individualized homeopathy for Primary Insomnia in the homeopaths’ trade ‘journal’ Homeopathy.  A total of thirty subjects completed the trial.  These were randomly allocated to receive either the homeopath recommended ‘remedies’ (a range of 19 were used) or a placebo (“by an independent dispenser at [a] Homeopathic Day Clinic”).  Two subjective self-recorded outcome measures were used: a daily written record of the subjects’ sleeping pattern (SD) from which the total number of hours slept per week was extracted and a questionnaire (SII).  The results were recorded at the start of the trial (baseline) and after trial weeks 2, 3 and 4.

Although the authors make a series of comparisons within the treatment and placebo groups, the relevant comparisons are between groups.  These showed marginally positive results.  For the SD measure (total hours of sleep per week):

“Analysis between groups of total hours slept per week revealed significant differences in favour of the Treatment Group i.e. at Week 2 (p = 0.004), Week 3 (p = 0.042) and Week 4 (p = 0.036).”

The results for weeks 3 and 4 do not have very impressive P values.  It doesn’t appear that the authors have made any correction for multiple inferences (two measures).  Applying the simple Bonferroni correction, to account for this makes the differences at weeks three and four non-significant.

As for the SII questionnaire:

“Comparisons … revealed significant differences at the first follow-up consultation in 8/11 questions and 10/11 questions at the second follow-up consultation. When summary scores for the SII were compared between groups a significant difference in favour of the verum group was noted at Week 4”

However, the authors neglect to mention that the summary scores between ‘treatment’ (“verum”) and placebo at week 3 (“follow up 1”) were not significantly different (p=0.116).

The authors engage in a lot of hand waving about intra-group comparison (effectively removing the control) and trying to break down the responses to the SII questionnaire.  However, on face value, the SD measure only reached significance (correcting for the two comparisons) in one of the three weeks it was assessed.  The summary score for the SII questionnaire only returned a significant result on one of the two times it was assessed.

Ultimately this is a small study giving patients imaginary doses of ‘remedies’ (potencies varied from 30CH to 10M, 200CH being the most popular) and getting inconsistent results on subjective measurements.

To their credit, the authors acknowledge most of these limitations:

“… the external validity of this study is challenged by the relatively small sample size and limited duration of the study particularly in the light of the chronic nature of the illness.”

“Based on a power calculation, future studies should comprise a sample size of 120 in addition, is recommended that the study be conducted over a 6 month period.”

Not even these homeopathy advocates go beyond calling for more research in this paper.  It certainly doesn’t justify treating patients or the selling of pills.

On the topic of specific remedies, of the remedies promoted by Janda, Nux Vomica only represented 11.6% of the prescribed doses and Coffea a paltry 3.3%.  Chamomilla and Cocculus were not prescribed at all.

Finally, the CAM literature is replete with small trials.  It seems that some fields never progress beyond the preliminary.  Bell et al (2011) provide a nice example of this: a positive trial of two homeopathic remedies, Nux Vomica or Coffea Cruda (at 30c), on 54 young adults (18-31) with coffee related insomnia.  This month-long study has a quite complex design:

“Participants underwent a total of eight all-night PSG and actigraphic recordings in their own homes, distributed as 4 weekly pairs of consecutive nights (Week 1 baseline; Week 2 single-blind placebo pellets on night 8; Week 3 repeat baseline; Week 4 double- blind verum homeopathic remedy pellets on night 22). Thus, PSGs were performed on nights 1–2, 8–9, 15–16, and 22–23 of study participation. Subjects were instructed not to consume alcohol on the day of the recordings and not to consume caffeinated beverages or tobacco for 6 h prior to each PSG, but were otherwise encouraged to maintain their own habitual dietary and sleep–wake patterns in order to obtain naturalistic data.”

It seems odd that placebo was given single blind; this reduced methodological rigour is not helpful.  The results appear largely positive.  Again, the method of analysis is complex, based on regression, “… controlling for gender, personality scores, total time in bed, and means for combined baseline nights (1/2/15/16).”  Positive results were reported for the remedies singularly and in combination, for most of the ten outcome measures.

In summary: it’s positive, but it’s a small study with blinding problems.

The ‘evidence’, such as it is, is a microcosm of what is wrong with CAM research generally:

• Bold claims made on the basis of little more than anecdote (Rogers, 1997).
• Negative trials failing to have any impact on practise (Cialdella et al, 2001; La Pine et al, 2006).
• Comparisons against ineffective treatments (Waldschütz and Klein, 2008).
• Failure to progress beyond small, preliminary trials (Bell et al, 2011; Naudé et al, 2010).
• Unnecessarily complex trial design (Bell et al, 2011).
• Weak methodology (Waldschütz and Klein, 2008; Bell et al, 2011).
• The use of special low-quality journals, that are little more than fanzines (Naudé et al, 2010).

Taking a holistic approach

CAM advocates like to talk about ‘holism’, looking at the patient in the round.  I think that it’s important to look at the evidence in the round also.  Individual studies can appear to be positive as a result of random chance.  Looking at the balance of the evidence from the published trials, whilst not an infallible guide, is helpful.  Also, the academics who conduct these reviews don’t run up against the ‘paywall’ issues that occasionally stymie my curious nature.

Given the negative balance of the individual trials I identified, I’m not surprised that the reviews are overwhelmingly negative.  For example, Cooper and Relton (2010a) published a systematic review^**, concluding:

“The limited evidence available does not demonstrate a statistically significant effect of homeopathic medicines for insomnia treatment. Existing RCTs were of poor quality and were likely to have been underpowered. Well-conducted studies of homeopathic medicines and treatment by a homeopath are required to examine the clinical and cost effectiveness of homeopathy for insomnia.”

Similarly, Sarris and Byrne (2011) were not impressed with the supporting evidence for homeopathy.  Their review commented:

“Surprisingly, studies involving several mainstreamCAMtherapies (e.g., homoeopathy, massage, or aromatherapy) were not located or did not meet basic inclusion criteria. If CAM interventions are to be considered as viable stand-alone or adjuvant treatments for sleep disorders, future researchers are urged to use acceptable methodology, including appropriate sample sizes and adequate controls.”

Finally, Ernst (2011) conducted a review, concluding:

“Six randomised, placebo-controlled trials met the inclusion criteria. Two studies used individualised homeopathy, and four used standardised homeopathic treatment. All studies had significant flaws; small sample size was the most prevalent limitation. The results of one study suggested that homeopathic remedies were superior to placebo; however, five trials found no significant differences between homeopathy and placebo for any of the main outcomes. Evidence from RCTs does not show homeopathy to be an effective treatment for insomnia and sleep-related disorders.”

Animal magnetism

Homeopaths will point to some apparently positive trials on animal models.  For instance Ruiz-Vega and co-workers (2000, 2002, 2003) have reported a series of studies on the effect of Coffea Cruda on rats.   Whatever the merits of these papers they have no relevance to the matter at hand: treating people with insomnia.

I know I missed some bits.

I’ve not been able to access Mamtani and Cimino (2002) or Neubauer (2003), as they live behind a paywall.

Carlini et al (1987) appears to be a controlled clinical trial, but I cannot find any further details.

Finally, I haven’t been able to find any trace of the rather charmingly titled, “Homeopathy and behavior therapy. Gentle duo against sleepless nights” (Anon., 2003).

Summon the court physician!

The homeopathy awareness week campaigners make very specific, confidant claims:

“Chamomilla can help if you are feeling tired but cannot sleep and Cocculus can help if sleeplessness is caused by mental and physical exhaustion. Coffea may be beneficial for those suffering from restless sleep that regularly wake during the night, especially when too many thoughts are running through the mind, and Nux Vomica is useful for those that overindulge in food, drink and smoking to counter mental strains and worries resulting in sleeplessness.”

On the other hand, Clare Relton (2010), a well-known homeopath and researcher with the Homeopathy Research Institute (HRI) concluded a fairly comprehensive review in their newsletter:

“Homeopaths often treat insomnia, however, there is currently a lack of high-quality sufficiently powered studies assessing the effectiveness of either homeopathic medicines or treatment by a homeopath for this condition. There is a need for further well-conducted clinical trials of treatment by a homeopath in order to examine fully the clinical and cost effectiveness of the therapeutic system of homeopathy in the management of insomnia. This evidence will enable patients, clinicians and healthcare commissioners/insurers to make informed decisions regarding the homeopathic treatment of insomnia.”

The contrast is striking: the campaigners confidently claim specific homeopathic nostrums can help; Relton says that there is a lack of evidence and that better evidence is needed to enable informed decision making.  They both cannot be right.

On the other hand, unlike Relton, I don’t think further research is warranted.  There is no basic plausibility; the trials that have been done are largely negative and consequently the reviews indicate that homeopathy is ineffective.

I will say one thing about the soporific effect of homeopathy: reading many of the claims made by homeopaths may well be the most powerful inducement into the arms of Morpheus that homeopathy can offer.

The King is in the altogether

As ever, Homeopathy Awareness Week is as “wide open to ridicule and scorn”, as Hans Christian Anderson’s proverbial monarch, lacking any real evidence or basic plausibility.  Its sponsors are misinforming the public to promote their products and services.  Perhaps this is just people with vested interests seeing what they want to see, what they are afraid not to see, not wanting to appear foolish.

At any rate, it puts professional and commercial interests ahead of customers and patients, and that is just not good enough.  Let’s hope that the public can see through this charade.

Useful Information

Proper medicine

NHS Choices, Insomnia

Northumberland Tyne and Wear, NHS Foundation Trust, Sleeping Problems – Self Help Guide

Sleep Problems, Moodjuice Self Help Guide

Homeopathy Awareness Weeks Past

The Quackometer, Homeopathy Awareness Week, 14 – 21st June 2009

Stuff and Nonsense, Homeopathy Awareness Week: Bloggers versus Journalists

Edzard Ernst , Homeopathy Awareness Week: Is this the homeopaths’ last stand?

apgaylard, Homeopathy Awareness Week and hay fever

Disclaimer

I try to make sure that what I write is both accurate and fair.  If you think that I have got anything wrong please let me know.  If you are right I will happily change what I have written.

This is not medical advice.  If you need that see a properly qualified and registered doctor.

Notes

*YouGov poll: http://today.yougov.co.uk/life/brits-need-their-beauty-sleep

**They added to this with a summary of additional evidence, published after they completed their systematic review (Cooper and Relton, 2010b) but its paywalled.

Acknowledgements

With apologies for the clumsy allusions to THE KING’S NEW CLOTHES, From the film “Hans Christian Andersen” (1952) (Frank Loesser – Based on the 1837 children’s story “The Emperor’s New Clothes” by Hans Christian Andersen), Danny Kaye (Film Soundtrack) – 1952.

References

[Homeopathy and behavior therapy. Gentle duo against sleepless nights]. MMW Fortschritte der Medizin. 2003 Sep;145(35-36). Available from: http://view.ncbi.nlm.nih.gov/pubmed/14584216.

Bell IR, Howerter A, Jackson N, Aickin M, Baldwin CM, Bootzin RR. Effects of homeopathic medicines on polysomnographic sleep of young adults with histories of coffee-related insomnia. Sleep Medicine. 2011 May;12(5):505–511. Available from: http://dx.doi.org/10.1016/j.sleep.2010.03.013.

Carlini EA, Braz S, Troncone LR, Tufik S, Romanach AK, Pustiglione M, et al. [Hypnotic effect of homeopathic medication and placebo. Evaluation by double-blind and crossing technics]. AMB; revista da Associação Médica Brasileira. 1987;33(5-6):83–88. Available from: http://view.ncbi.nlm.nih.gov/pubmed/3329355.

Cialdella P, Boissel JP, Belon P. [Homeopathic specialties as substitutes for benzodiazepines: double-blind vs. placebo study]. Thérapie. 2001;56(4):397–402. Available from: http://view.ncbi.nlm.nih.gov/pubmed/11677862.

Cooper KL, Relton C. Homeopathy for insomnia: a systematic review of research evidence. Sleep medicine reviews. 2010 Oct;14(5):329–337. Available from: http://dx.doi.org/10.1016/j.smrv.2009.11.005.

Cooper KL, Relton C. Homeopathy for insomnia: summary of additional RCT published since systematic review. Sleep medicine reviews. 2010 Dec;14(6). Available from: http://dx.doi.org/10.1016/j.smrv.2010.07.004.

Ernst E. Homeopathy for insomnia and sleep-related disorders: a systematic review of randomised controlled trials. Focus on Alternative and Complementary Therapies;p. no. Available from: http://dx.doi.org/10.1111/j.2042-7166.2011.01083.x.

La Pine MP, Malcomson FN, TorranceJM, MarshNV. Night shift: can a homeopathic remedy alleviate shift lag?  Dimensions of critical care nursing : DCCN. 2006;25(3):130–136. Available from: http://view.ncbi.nlm.nih.gov/pubmed/16721192.

Long L, Huntley A, Ernst E. Which complementary and alternative therapies benefit which conditions?  A survey of the opinions of 223 professional organizations. Complementary therapies in medicine. 2001 Sep;9(3):178–185. Available from: http://dx.doi.org/10.1054/ctim.2001.0453.

Mamtani R, Cimino A. A primer of complementary and alternative medicine and its relevance in the treatment of mental health problems. The Psychiatric quarterly. 2002;73(4):367–381. Available from: http://view.ncbi.nlm.nih.gov/pubmed/12418362.

Naudé DF, Stephanie Couchman IM, Maharaj A. Chronic primary insomnia: Efficacy of homeopathic simillimum. Homeopathy. 2010 Jan;99(1):63–68. Available from: http://dx.doi.org/10.1016/j.homp.2009.11.001.

Neubauer DN. Pharmacologic approaches for the treatment of chronic insomnia. Clinical cornerstone. 2003;5(3):16–27. Available from: http://view.ncbi.nlm.nih.gov/pubmed/14626538.

Relton C. Homeopathy for Insomnia: A review of research evidence; 2010. Available from: http://www.homeoinst.org/sites/default/files/newsletters/HRI_Newsletter_Issue09_Summer%202010.pdf

Rogers J. Homoeopathy and the treatment of alcohol-related problems. Complementary therapies in nursing & midwifery. 1997 Feb;3(1):21–28. Available from: http://view.ncbi.nlm.nih.gov/pubmed/9432423.

Ruiz-Vega G, Pérez-Ordaz L, Proa-Flores P, Aguilar-Díaz Y. An evaluation of Coffea cruda effect on rats. The British homoeopathic journal. 2000 Jul;89(3):122–126. Available from: http://view.ncbi.nlm.nih.gov/pubmed/10939767.

Ruiz-Vega G, Pérez-Ordaz L, León-Huéramo O, Cruz-Vázquez E, Sánchez-Diaz N. Comparative effect of Coffea cruda potencies on rats. Homeopathy : the journal of the Faculty of Homeopathy. 2002 Apr;91(2):80–84. Available from: http://view.ncbi.nlm.nih.gov/pubmed/12371461.

Ruiz-Vega G, Pérez-Ordaz L, Cortés-Galván L, Juárez-G FM. A kinetic approach to caffeine–Coffea cruda interaction. Homeopathy : the journal of the Faculty of Homeopathy. 2003 Jan;92(1):19–29. Available from: http://view.ncbi.nlm.nih.gov/pubmed/12587991.

Sarris J, Byrne GJ. A systematic review of insomnia and complementary medicine. Sleep Medicine Reviews. 2011 Apr;15(2):99–106. Available from: http://dx.doi.org/10.1016/j.smrv.2010.04.001.

Waldschütz R, Klein P. The homeopathic preparation Neurexan vs. valerian for the treatment of insomnia: an observational study. TheScientificWorldJournal. 2008;8:411–420. Available from: http://dx.doi.org/10.1100/tsw.2008.61.

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