Systematic reviews of complementary therapies – an annotated bibliography. Part 3: Homeopathy

  • Klaus Linde1, 2Email author,

    Affiliated with

    • Maria Hondras3,

      Affiliated with

      • Andrew Vickers4,

        Affiliated with

        • Gerben ter Riet5, 6 and

          Affiliated with

          • Dieter Melchart1

            Affiliated with

            BMC Complementary and Alternative Medicine20011:4

            DOI: 10.1186/1472-6882-1-4

            Received: 22 March 2001

            Accepted: 20 July 2001

            Published: 20 July 2001

            Abstract

            Background

            Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with homeopathy. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of homeopathy; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively.

            Results

            Eighteen out of 22 potentially relevant reviews preselected in the screening process met the inclusion criteria. Six reviews addressed the question whether homeopathy is effective across conditions and interventions. The majority of available trials seem to report positive results but the evidence is not convincing. For isopathic nosodes for allergic conditions, oscillococcinum for influenza-like syndromes and galphimia for pollinosis the evidence is promising while in other areas reviewed the results are equivocal.

            Interpretation

            Reviews on homeopathy often address general questions. While the evidence is promising for some topics the findings of the available reviews are unlikely to end the controversy on this therapy.

            Introduction

            In this third part of our series on systematic reviews in complementary therapies we report our findings on homeopathy. Homeopathy is one of the most widespread forms of complementary medicine worldwide. According to a recent survey 3.4% of Americans have used homeopathy in the past 12 months [1]. It is even more widespread in some European countries [2], some countries in South America, India or Pakistan [3]. This widespread use is in strong contrast with the position held by many in scientific medicine that homeopathy has no effect beyond placebo [4].

            The basic principle of homeopathy is the principle of similars: A patient with a specific pattern of symptoms is best treated by a remedy which causes the same or a very similar pattern in healthy subjects. Homoeopathic remedies are often prescribed in high dilutions some of which are unlikely to contain any molecules of the originally diluted agents. In consequence, homoeopathic remedies – at least when applied in high dilutions – cannot act by pharmacological means. Theories for a potential mechanism of action, therefore, postulate the storage of information in the dilution process by physical means [5].

            Methods

            A detailed description of the methods used in this review of reviews is given in the first part of this series [6]. As a specific intervention-related inclusion criterion we required that reports reviewed prospective (not necessarily controlled) clinical trials of homoeopathic medicines in humans.

            Results

            From a total of 22 potentially relevant reviews identified in the literature screening, 18 reviews published in 19 papers met the inclusion criteria [725] (see table 1). Four papers were excluded as they were only subgroup or methodological analyses of previously published papers [2629].
            Table 1

            Systematic reviews of clinical trials of homoeopathy

            Author Year

            Indication

            Homoeopathy/Control

            Studies

            Features 1 / 2 / 3 / 4 / 5

            Results

            Conclusion

            All homoeopathy in all conditions

            Cucherat

            all

            all/placebo

            17 RCT

            y / y / y /

            Combined p value for an effect

            There is some evidence that

            2000 [7]

               

            n /y

            over placebo p = 0.000036, for

            homoeopathy is more than placebo.

                 

            best trials only p = 0.08

            Studies of high quality more likely to be

                  

            negative

            Linde 97 [8]

            all

            all/placebo

            89 RCT

            y / y / y /

            OR of all trials over placebo 2.45

            Results not compatbile with the

                

            y /y

            (95%CI 2.05; 2.93), in better trials

            hypothesis that all homeo-pathy is

                 

            1.66 (1.33; 2.08)

            placebo. No firm evidence for any

                  

            single condition

            Walach 97

            all

            all/placebo,

            41 RCT

            y / p / y /

            Random effect size g = 0.259

            The effects of homoeopathy are not

            [9]

             

            conventional

             

            y / y

            (95%CI -0.319; 0.837), fixed

            different from placebo on a statistical

                 

            effects 0.295 (0.223; 0.366)

            level

            Lutz 93 [10]

            all

            all/placebo,

            21 RCT/CCT

            ? / n / y /

            Results of available studies

            No clear conclusions drawn.

              

            conventional

             

            y / p

            contradictory

            (Comment: thesis mainly discussing

                  

            problems of meta-analysis)

            Kleijnen 91

            all

            all/placebo,

            107 CCT

            y / p / y /

            81 trials reported positive results.

            Available evidence positive but not

            [11]

             

            conventional

             

            y / n

            Most trials low quality but many

            sufficient to draw definitive conclusions

                 

            exceptions

             

            Hill 90 [12]

            all

            all/placebo,

            40 RCT

            n / p / y /

            The authors of half of the studies

            The results do not provide acceptable

              

            conventional

             

            y / n

            concluded that homoeopathy was

            evidence that homoeopathy treatments

                 

            effective, further 7 promising

            are effective

            Individualized homoeopathy in all conditions

            Ernst 99

            all

            individualized/

            3 RCT, 3 CCT

            y / p / n /

            All trials were burdened with

            The relative efficacy of individualized

            [13]

             

            conventional

             

            y / n

            serious methodological flaws.

            homoeopathy compared to

                 

            Results non-uniform

            conventional treatments is not known

            Linde 98

            all

            individualized/

            32 RCT

            y / y / y /

            Responder RR vs. placebo 1.62

            Available evidence suggests effects

            [14]

             

            placebo, convent.

             

            y / y

            (95%CI 1.17; 2.23), in better

            over placebo. Evidence not convincing

                 

            quality trials 1.12 (0.87; 1.44)

            due to shortcomings and

                  

            inconsistencies

            Various homoeopathic treatments in a single condition/area

            Barnes 97

            postoperative

            various/placebo

            4 RCT, 2 CCT

            y / y / y /

            Time to first flatus in homoeopathy

            Available evidence positive but several

            [15]

            ileus

              

            y / y

            significantly shorter. Best trial

            caveats preclude definitive conclusions

                 

            negative

             

            Ernst 98

            delayed-

            various/placebo

            8 double-blind

            y / y / y /

            Most trials with severe flaws. The

            Published evidence does not support

            [16]

            onset muscle

             

            trials (3

            y / n

            3 RCT showed no significant

            the hypothesis that homoeopathic

             

            soreness

             

            explicitly RCT)

             

            effects over placebo

            remedies are effective for muscle

                  

            soreness

            Jacobs 91*

            rheumatic

            various/placebo

            4 CCT

            p / y / n /

            3 of 4 trials positive. Quality poor

            No specific conclusion on

            [17]

            diseases

              

            y / n

             

            homoeopathy (generally: no convincing

                  

            evidence for alternative therapies in

                  

            rheumat.)

            Linde 98

            asthma

            various/placebo

            3 RCT

            y / y / y /

            Trials highly heterogeneous. Two

            Currently available evidence insufficient

            [18]

               

            y / n

            report statistically significant

            to assess the possible role of

                 

            effects

            homoeopathy in the treatment of

                  

            asthma

            Arnica in various conditions (mainly various tissue traumata)

            Lüdtke 99

            all

            arnica/placebo,

            23 RCT, 14

            y / y / y /

            Quality often low. 13 of 35 studies

            Available evidence suggests that arnica

            [19]

             

            no treatment

            CCT

            n / n

            vs. placebo with significant results,

            can be efficacious. Further rigorous

                 

            10 with trend

            trials needed

            Ernst 98

            all (mainly

            arnica/placebo,

            4 RCT, 4 CCT

            y / y / y /

            2 trials positive, 2 trials positive

            Claims that homoeopathic arnica is

            [20]

            trauma)

            conventional

             

            y / n

            trend. Most studies with severe

            efficacious are not supported by

                 

            flaws

            rigorous trials

            Similar homoeopathic treatments in one condition/a group of conditions

            Taylor

            allergic

            isopathic

            4 RCT

            n / n / n /

            Pooled analysis of 100 mm visual

            Isopathic nosodes were different from

            2000** [21]

            conditions

            nosodes/placebo

             

            y / y

            analogue scores 9.8 (95%CI

            placebo on both subjective and

                 

            4.2;15.4) mm better with isopathy

            objective measures

            Vickers

            influenza-like

            oscillococcinum/

            7 RCT

            y / y / y /

            No evidence for preventative

            Oscillococcinum probably reduces the

            2000 [22]

            syndrome

            placebo

             

            y / y

            effect (3 trials) but reduction of

            duration of influenza-like syndromes.

                 

            length of illness in treatment trials

            Further trials needed

            Ernst 99

            headache

            individualized/

            4 RCT

            y / p / y /

            one trial positive, one partially

            The trial data do not suggest an effect

            [23]

            prophylaxis

            placebo

             

            y / n

            positive, 2 negative

            over placebo in the prophylaxis of

                  

            migraine or headache

            Wiesenauer

            pollinosis

            galphimia/placebo

            8 RCT, 1 CS,

            p / n / n /

            Responder RR galphimia vs.

            Galphimia is significantly more effective

            96** [24,25]

              

            2 UCS

            y / y

            placebo from 7 trials 1.25 (95%CI

            than placebo

                 

            1.09; 1.43)

             

            *Disease-focused review on a variety of complementary medicine interventions including homoeopathy; **Meta-analytic overviews of researchers of their own trials on the topic Features: 1 = comprehensive search, 2 = explicit inclusion criteria, 3 = formal quality assessment, 4 = summary of results for each included study, 5 = meta-analysis; y = yes, p = partly, n = no, - = not applicable, ? = unclear RCT = randomized controlled trials, CCT = non-randomized controlled trials, CS = cohort study, UCS = uncontrolled study; OR = odds ratio, RR = rate ratio

            Three quantitative meta-analyses addressed the general question whether homeopathy is different from placebo by pooling highly heterogeneous study samples [79]. Study samples and meta-analytic methods differed considerably (total number of trials covered 97). While two reviews reported significant effects of homeopathy [7,8] a third found no effect over placebo in the main analysis [9]. Several years before the publication of these studies a meta-analytic approach had already been tried in a thesis [10]. However, this review is mainly dealing with the problems encountered when trying to pool the data and cannot be interpreted meaningfully with respect to the effectiveness of homeopathy. Two older reviews included both placebo-controlled trials and comparisons with standard treatment [11,12] (total number of trials covered 107). Results were classified in a vote count as positive and negative. The majority of the studies had reported positive results. The conclusions were positive with reservations in one review and ambiguous in the other.

            Two reviews focused on individualized homeopathy but were not restricted in terms of conditions investigated. A review of comparisons of individualized homoeopathic and conventional treatment found that only few trials of low quality exist [13]. The other review included mainly placebo-controlled trials [14]. Overall, the results suggested that individualized homeopathy is superior to placebo but when the analysis was limited to studies of better quality the difference was no longer significant.

            Four reviews focused on a single condition or a group of conditions but included a variety of homoeopathic treatments [1518]. Positive results have been reported for the treatment of postoperative ilues and asthma but definitive conclusions are not possible.

            Arnica is the most often investigated homoeopathic remedy. Typically it is used in conditions involving tissue trauma. Two reviews with slightly different inclusion criteria have been published [19,20] (total number of trials covered 37). While the results of the available trials seem to be contradictory the more comprehensive of the two reviews had slightly more favorable conclusions.

            Systematic reviews addressing more focused questions are available for the use of isopathic nosodes (diluted allergens) in allergic conditions, Oscillococcinum for influenza-like syndromes, individualized homeopathy for headache and galphimia for pollinosis [2125]. Significant differences over placebo were reported for all but the headache review.

            Discussion

            Systematic reviews on homeopathy address, more often than in other areas of complementary medicine, general questions such as "is it more than placebo?" or "is it effective?" This is probably due to the fact that any effect of homeopathy over placebo is considered scientifically implausible. In consequence, the discussion does not primarily focus on specific clinical problems but on whether there is a real effect at all. While many overviews report that the majority of trial results are positive conclusions of reviewers are contradictory.

            With few exceptions such as arnica for trauma or individualized homeopathy for headache, the reviews (and probably the primary research) do not cover conditions and treatment approaches which are relevant in homoeopathic practice. Self-medication with Oscillococcinum for influenza-like syndromes is popular in several countries but cannot be considered representative practice.

            We want to emphasize again that it was not our primary objective to assess the effectiveness of homeopathy and the other therapies included in our series but to provide an annotated bibliography of the available systematic reviews. This provides an overall picture of the evidence but for an in-depth review readers must go back to the original reviews.

            In conclusion, the available systematic reviews on homeopathy provide little guidance for patients and doctors. They rather reflect the ongoing fundamental controversy on this therapy and strengthen the perception that, on one side, positive evidence from clinical trials will not convince skeptics, and that on the other side negative results from trials not representing actual practice will not have any impact on homoeopaths.

            Declarations

            Acknowledgements

            KL's work was partly funded by the NIAMS grant 5 U24-AR-43346-02 and by the Carl and Veronica Carstens Foundation, Essen, Germany. We would like to thank Brian Berman for his support, his help to get funding and his patience in awaiting the completion of our work.

            Authors’ Affiliations

            (1)
            Centre for Complementary Medicine Research, Department of Internal Medicine II, Technische Universität, München
            (2)
            Institute for Social Medicine & Epidemiology, Charité Hospital Humboldt University
            (3)
            Consortial Center for Chiropractic Research, Davenport
            (4)
            Royal London Homoeopathic Hospital
            (5)
            NHS Centre for Reviews & Dissemination, University of York
            (6)
            Department of Epidemiology, Maastricht University

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            30. Pre-publication history

              1. The pre-publication history for this paper can be accessed here:http://​www.​biomedcentral.​com/​content/​backmatter/​1472-6882-1-4-b1.​pdf

            Copyright

            © Linde et al 2001

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