Adverse effects of homeopathy, what do we know? A systematic review and meta-analysis of randomized controlled trials

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Highlights

  • This review address the naive assumption that because of the generally diluted doses used homeopathy must be safe.

  • This review touches the neglected issue of the distinction between homeopathic aggravation, adverse reactions and adverse effects.

  • We found a similar risk for homeopathic treatment compared to controls such as placebo and conventional medicine

Abstract

Objectives

Homeopathy is a popular treatment modality among patient, however there is sparse research about adverse effects of homeopathy. A concept unique for homeopathy, is homeopathic aggravation that is understood as a transient worsening of the patients’ symptoms before an expected improvement occurs. From a risk perspective it is vital that a distinction between homeopathic aggravations and adverse effects is established. There is a lack of systematic information on how frequent adverse effects and homeopathic aggravations are reported in studies. Therefore, a systematic review and meta-analysis were performed.

Design and setting

Sixteen electronic databases were searched for Randomized Controlled Trials (RCTs). The searches were limited from the year 1995 to January 2011. Forty-one RCTs, with a total of 6.055 participants were included. A subtotal of 39 studies was included in the additional meta-analysis.

Results

A total of 28 trials (68%) reported adverse effects and five trials (12%) reported homeopathic aggravations. The meta-analysis (including six subgroup comparisons) demonstrated that no significant difference was found between homeopathy and control with OR 0.99, 95% CI 0.86–1.14, I2 = 54%. More than two third of the adverse effects were classified as grade 1 (68%) and two third were classified as grade 2 (25%) and grade 3 (6%) according to the Common Terminology Criteria for Adverse Effects. Homeopathic aggravation was classified as grade 1 (98%) and grade 3 (2%), suggesting that homeopathic aggravations were reported to be less severe than adverse effects. The methodological quality according to a method recommended in the Cochrane handbook for RCTs, was high.

Conclusion

Adverse effects including the concept of homeopathic aggravations are commonly reported in trials. The meta-analysis demonstrated that the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to placebo and conventional medicine.

Introduction

Homeopathy was established and developed in Germany by Samuel Hahnemann in the late 18th century, and since then the theory and practice of homeopathy have developed outside the established health services. The action of homeopathic remedies is questioned as most remedies are diluted to such a high degree that there is only a theoretical probability that molecules of the original substance are present in the remedy.1, 2, 3 Accordingly, homeopathic remedies of high dilutions are pharmacologically inactive. On the other hand some homeopathic remedies are less diluted (D6 or D12), meaning that these remedies could be pharmacologically active. However, research suggests.4 that it is low direct risk connected to homeopathic remedies. The possible risk is therefore classified as indirect, related to other aspects of clinical context and practice. In medical science, risk can be divided into direct and indirect risk. Direct risk is related directly to the intervention itself, such as the medication or the homeopathic remedy. Indirect risk is related to the treatment setting, such as the practitioner and the caring context 5, 6, 7

In the United States 2.3% of the adult population used homeopathy in 2007, and 2.9 billion USD were spent on homeopathic remedies.8 The 12 month prevalence of those who have visited a homeopath in Europe has been found to vary between 2% in Great Britain.9 to 15% in Germany10 A survey among older German adults revealed that 21% used homeopathy for their complaints.11 In Scandinavian countries the prevalence of persons who use homeopathy fluctuates between 7% and 14%.12

Being female, having higher education, suffering from health complaints and using conventional health care have all been associated with the use of Complementary and Alternative Medicine (CAM), including homeopathy.13, 14, 15 Uncontrolled studies of homeopathy document consistent and sustained patient satisfaction.15 Patients used homeopathy for chronic, physical problems, as well as emotional complaints.14, 15, 16 The most frequent diagnoses for which they seek homeopathy are allergic rhinitis in adult males, headache in adult females and atopic dermatitis in children.17 Homeopathy is one of the most common CAM therapies in cancer care in Europe, ranging from 11% across cancer diagnoses.18 up to 19% in breast cancer patients19 Among younger cancer patients in Germany, 45% reported that they have used homeopathic remedies during their illness.20 The majority of the patients used homeopathy with the aim to increase the body’s ability to fight cancer or to improve physical or emotional well-being.19

A concept specific to homeopathy is homeopathic aggravations, which is defined as “a temporary worsening of existing symptoms following the administration of a correctly chosen homeopathic remedy”. This reaction is seen as a favourable response to the treatment and is expected to be followed by an improvement.2, 21, 22, 23 In 2003, Grabia and Ernst24 published a systematic review to investigate how homeopathic aggravations was reported in RCTs. From a total of 25 trials, eight reported homeopathic aggravations and six reported adverse effects. The authors claimed that, for safety reasons, the concept should be reported in trials.

A systematic review of case reports published in 201225 found that, among the included 38 primary reports, 30 reported direct adverse effects from homeopathic remedies and eight were related to adverse effects caused by the substitution of conventional medicine with homeopathy. This review initiated a broad and controversial discussion about the safety of homeopathic treatment which has already been raised with regard to the risk of homeopathy related to practice by Dantas in 199926 In particular, Tournier et al.27 highlighted the importance of differentiation between homeopathic care and clinical negligence. Together with poor reporting quality of the primary sources (i.e. of applied potencies of the remedy) this may lead to a misinterpretation of causality. Nevertheless this scientific episode highlights the need for some criteria or guidelines that enables to document common standards of homeopathic treatment.

So far, homeopathic aggravations have mostly been reported in an anecdotal way. In one case,28 a nine-month old baby girl was given several homeopathic remedies to treat atopic dermatitis. The child developed Bullous Pemphigoid (BP) during the treatment period and when the baby was finally admitted to the hospital, the condition was life threatening. This situation occurred because the homeopath misinterpreted the worsening of the symptoms as homeopathic aggravations and continued the treatment. In this case only spars information regarding the prescription of the homeopathic remedies was documented and the author stated that “no conclusion about the role of the homeopathy in the triggering of BP can be made”. However, Posadzki et al. in their review judged Mercury intoxication as a possible explanation of the adverse effect as judged by the author of the primary report.25

This case illustrates the difficulty of judging the likelihood of homeopathic aggravations and adverse effects in homeopathy. Good data on a well-recognized, easily detectable adverse effects may be available from randomized clinical studies (RCTs),29 and since limited knowledge of how adverse effects and homeopathic aggravations are reported in trials – a systematic review is needed.

The aims of this paper are to 1. Systematically investigate how homeopathic aggravations and adverse effects are reported in randomized controlled trials. 2. Classify adverse effects and homeopathic aggravations according to the Common Terminology Criteria for Adverse Effects (CTCAE).30 3. Perform a meta-analysis to evaluate the risk for patients using homeopathy (consultation and/or homeopathic remedies) compared to controls.

Section snippets

Terminology

Not only is the homeopathic intervention itself a very complex treatment situation, which includes much more components than the remedy, there is, moreover, an astounding variety of definitions of harmful events available. This situation makes a thorough discussion of the terminology, which forms the basis of the systematic review and meta-analysis presented here, necessary.

The homeopathic intervention is a very elaborate treatment situation that consists of in-depth consultations often

Searches

The focus question was:

Is homeopathy associated with adverse effects and/or homeopathic aggravations?

The PICO format was used when searching for relevant articles, which included the following four parts

Population: Patients using homeopathy, physicians and homeopaths who reported adverse effects and homeopathic aggravations in the included studies.

Intervention: Homeopathy, including everything a homeopath does in the consultation, such as a diagnostic in-depth interview, prescription of

Outcome of the literature searches

A total of 1129 RCTs articles were identified. They were initially examined on the basis of titles and abstracts, and 1079 were excluded from further examination for the following reasons: Seventy-five articles did not record adverse effects or homeopathic aggravations, 44 described homeopathic proving trials, 324 were irrelevant (according to the criteria), 439 were multiple article registrations in databases, 62 were written in other languages than English and German and 135 were CAM studies

Discussion

In this present review we found that adverse effects were reported in 68% of the RCTs, More than two third of these events was classified as CTCAE grade 1 (minor) and one third as grade 2 and 3 (moderate and severe/significant). The meta-analysis demonstrated the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to control such as placebo and conventional medicine.

The CTCAE grading of adverse

Conclusion

Adverse effects including the concept of homeopathic aggravations are commonly reported in trials. The meta-analysis demonstrated that the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to placebo and conventional medicine. The different harm terminology applied in the included studies and lack of standard reporting procedures made this work challenging and may bias this findings.

Competing interest

The authors declare that they have no competing interests and that no financial interest exists.

Contributors

TS conceived the study, performed the searches and selected studies for inclusion and collected study data, assessed the studies for risk of bias (methodological assessment), developed the risk of bias table, prepared the data for the statistical analysis,performed the meta-analysis together with JL and drafted the manuscript. FM and AK developed the risk of bias table, prepared the data for the statistical analysis and reviewed the subsequent version of the manuscript. TA selected studies for

Acknowledgements

We want to thank Claudia Witt and Rainer Lüdtke for sharing and preparing data on homeopathic aggravations for us and Jane Ekelund, Åsa Sohlén and Kari Riddervold for technical support. We also want to thank The Norwegian Homeopathic Association for financial support.

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