Effect of homoeopathy on pain and other events after acute trauma: placebo controlled trial with bilateral oral surgery

PATIENTS

With approval from the regional Committee on Medical Research Ethics, 24 healthy outpatients (20 women and four men; mean (range) age 24 (19 to 28) years volunteered after they had received oral and written explanation of the events and implications of the trial. They all needed prophylactic surgical removal of identical bilaterally impacted mandibular third molars, as evaluated clinically and by means of orthopantomograms. The patients were highly motivated for the trial, 14 being students in the Norwegian Academy of Natural Medicine. There was no drop out.

SURGERY

The two operations were performed by the same surgeon (PS) at the same time of the day, and, with two exceptions, on the same day of the week. The mean (range) interval was 27 (14 to 51) days. Surgery was performed by a standardised technique.4 Before each operation 5.4 ml local anaesthetic (20 mg lignocaine plus 12.5 μg adrenaline/ml: Astra, Sweden) was injected. The time from injection to last suture averaged 10.3 minutes (range 8 to 13) for the operation followed by placebo treatment and 10.2 minutes (range 8 to 14) when followed by homoeopathy.

HOMOEOPATHIC TREATMENT

Classic homoeopathy is based on individualised treatment with a single drug selected according to the signs and symptoms of the patient. Six homoeopathic drugs were chosen as the most likely alternatives: arnica, hypericum, staphisagria, ledum, phosphorus, and plantago. They were prepared at the D30 potency according to accepted requirements for homoeopathic remedies and used for medication of sucrose tablets.10 Identical sucrose tablets served as placebo. The drugs were supplied in vials of 100 tablets (Vala Pharma Laboratorium AB, Gothenburg, Sweden). For each patient one set with six vials containing homoeopathic tablets (arnica, hypericum, etc) and one with six vials containing placebo tablets (also labelled arnica, hypericum, etc) were coded. Treatments were allocated according to a block randomisation system (four patients in each block), which ensured that half of the patients received placebo after the first operation. The study was double blind as neither the clinical investigators nor the patients had any access to the randomisation list.

Treatment started three hours after completion of surgery with the remedy selected by the homoeopaths. Each dose consisted of three tablets. One dose was administered quarterly for the first three hours, thereafter one dose per hour until bedtime, and two doses the following morning at an interval of three hours. Twenty four hours after treatment was initiated, the signs and symptoms of the patient were re-evaluated by the homoeopaths. Thereafter treatment continued with four doses before bedtime, either with the first choice or an alternative from the same set of vials. Three doses were then given daily for the next five days.

OTHER DRUGS

If an analgesic was greatly needed, the patients were allowed to take codeine tablets (codeine phosphate 25 mg) and the intake was recorded. No other drug was permitted in the period of observation.

ASSESSMENTS

Pain was rated on a visual analogue scale with lines from “no pain” (0 mm) to “pain cannot be worse” (100 mm), with 28 assessments after each operation, five of which were made before start of treatment (see fig 2). Facial swelling at the site of surgery was measured with a mechanical device (fig 1) which gives a measurement of the postoperative swelling by subtraction of recordings before operation from those afterwards.2 The maximum ability to open the mouth (distance between the edges of upper and lower incisors) was measured with a vernier gauge.2 On days 3 and 7 after surgery the patients were also examined for complications in wound healing and discolouration indicative of haematoma or ecchymoses.4 Postoperative bleeding was assessed according to the criteria indicated in table III. On each evening after the operation the patients recorded any special discomfort.

After the second operation, the patients gave an overall assessment of preference for postoperative course on a visual analogue scale with a line from “maximum preference for the first course” (0 mm) to “maximum preference for the second course” (100 mm). They were invited to state or guess after which operation they had received homoeopathic treatment. The patients indicated their attitude to and trust in homoeopathy on a visual analogue scale from “no confidence in homoeopathy” (0 mm) to “maximum confidence in homoeopathy” (100 mm), both before and at the end of the trial.

fig 1

Device for measurement of swelling in jaw region

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STATISTICAL METHODS

For pain, trismus, swelling, and bleeding the difference between the values after treatment for homoeopathy and placebo was analysed by using analysis of covariance (ANACOVA) with adjustment for period effects and for correlation with pretreatment values.11 When several measurements were made before and after treatment their mean was used.12 Due to skewness, the visual analogue score for pain was logarithmically transformed before analysis. For pain, the pretreatment mean was analysed (ANACOVA) to test for carry over effects given period effects. ANOVA was used to test the preference of patients for each treatment and period effect. Binominal tests were used to check for shifts in dichotomous variables away from the 50-50 distribution. All tests were two sided, and P values below the 5% level were regarded as significant. Treatment effects were estimated and other effects were estimated when significant. Estimates are given with 95% confidence intervals.

Results

The first choice of homoeopathic treatment in the 24 patients was arnica for nine, phosphorus for seven, hypericum for five, ledum for one, staphisagria for one, and plantago for one. When re-evaluated on day 1 after surgery the choice was arnica for 21, phosphorus for two, and ledum for one. The first choice when placebo was actually given was arnica for 12, phosphorus for six, hypericum for four, and staphisagria for two, and when re-evaluated it was arnica for 20 and phosphorus for four.

Pain—Postoperative pain was essentially the same whether the patients were treated with homoeopathy or placebo (fig 2). The mean estimated pain for the entire treatment period was 2% greater with homoeopathy as compared with placebo (95% confidence interval −27% to 42%; P=0.90). Codeine tablets were taken by seven patients. A total of 23 tablets were taken when patients were treated with homoeopathy and 16 tablets were taken during placebo treatment. One patient accounted for 18 tablets, of which 14 were taken during homoeopathic treatment.

fig 2

Mean pain assessments by visual analogue scales (VAS) after two separate “identical” oral surgical interventions in a crossover trial in 24 patients in whom placebo or homoeopathic treatment started 3 hours after surgery (no pain=0 mm; pain cannot be worse=100 mm). A: assessments on day of surgery; B; assessments on day 1-7 after surgery (m=morning, e=evening)

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Swelling and trismus—Twelve patients had greater swelling with homoeopathy and 12 with placebo (table I). Compared with placebo there was 33% less reduction in ability to open the mouth on day 3 with homoeopathy (table II), a difference of borderline significance (P=0.05).

Bleeding—Essentially there was no difference in bleeding after the two operations (table III). Eight patients exhibited haematoma or ecchymoses at the site of surgery; five after both operations, two only when treated with homoeopathy, and one only when treated with placebo.

Side effects and complaints—Wound healing was uneventful in all patients after both operations. Non-specific complaints (for example, headache, dizziness) were recorded by five patients after each operation, mostly on the evening after surgery and by the same patients after both operations.

Preference for and confidence in homoeopathy—Homoeopathy was favoured by 11 and placebo by 13 patients (fig 3). There was a non-significant preference for placebo: 0.2 mm (95% confidence interval −15.6 mm to 16.0 mm; P=0.98). Eleven of the 24 patients correctly indicated or guessed after which operation they had received homoeopathic treatment. The high confidence of the patients in homoeopathy remained essentially unchanged: mean score 79 mm (range 50 to 100) before and 82 mm (range 37 to 100) after the trial.

fig 3

Overall preference of patients for postoperative course assessed after second operation. Abscissa: assessment by 100 mm visual analogue scale. (Maximum preference for homoeopathy=-50 mm. No difference=0 mm. Maximum preference for placebo=50 mm). Ordinate: each patient ranked according to preference

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Period and carry over effects—Statistical analyses revealed significant period effects in pain and trismus before treatment but no significant carry over effect. A period effect is a general change in response from the first to the second period, whereas a carry over effect means that the effect of a treatment in the first period lasts and changes the response in the second period. Pain before treatment after the second operation was 40% lower compared with the first operation (95% confidence interval 9% to 61%; P=0.02). During treatment, the assessment of pain showed a weaker period effect, which became insignificant when adjusted for values before treatment (P=0.32). The mean ability to open the mouth was virtually the same before the two operations (48.4 mm v 48.6 mm). After the operations, however, there was a significant period effect, with less trismus after the second operation. Difference on day 3 was 5.9 mm (2.5 mm to 9.2 mm; P=0.001) and on day 7 was 3.3 mm (0.8 mm to 5.9 mm; P=0.01).

Discussion

The review of clinical trials in homoeopathy by Kleijnen et al refers to 20 studies on trauma and pain.1 In 18 of these, the outcome was interpreted as positive by the authors. Our results, however, indicated no significant effect of homoeopathy on pain and other events after an acute soft tissue and bone injury. In fact, the postoperative course with placebo was remarkably similar to that with homoeopathy (figs 2 and 3). This is in contrast with previous placebo controlled trials on analgesic and anti-inflammatory drugs in this clinical model, which have all shown significant differences.2 3 5 6 7 8 9 The power of the present trial was, however, reduced by the lower pain scores of these patients. As seen from the confidence intervals, a relative difference of about 30% to 40% would have been needed for an effect to become significant.

Generally, small sample sizes will affect power—that is, the probability of detecting small effects—and is a particular problem with negative findings. Power calculations indicate that detection of a 5% relative difference would have required a crossover study in about 1000 patients (that is, 11000 visits by the patients to the surgeon and the homoeopaths). The lack of any trend in figures 2 and 3 indicating a possible effect of homoeopathy suggests that even a large scale trial with many patients and accordingly greater power would probably not change the validity of our negative findings. Practically, attainment of clinical proof for the non-existence of a homoeopathic effect is impossible.

As the effects of treatment are claimed to last for long periods, crossover studies on homoeopathy should be examined for carry over effects.1 13 Our analyses found no significant carry over effect, but the estimate is rather insensitive, being based on comparison between patients.

Homoeopathic treatment is selected on an individual basis. The few individualising symptoms in the patients (for example, low pain) made it difficult to choose the most appropriate homoeopathic medicine. Not surprisingly, 21 of the 24 patients ended up with arnica. Arnica is recognised by homoeopaths as the remedy par excellence for wounds and injuries,14 not least to reduce the effects of dental surgery.13 14 15 16 17 18 19 20 21 22 The present potency (D30) represents a medium potency (dilution 1: 10³⁰) often used in homoeopathy. Perhaps a higher potency could have been more appropriate as several authors have recommended higher potencies of arnica for treating trauma and pain.16 17 18 20 21 22 In two pilot trials on arnica as a remedy for injuries, Campbell found arnica ineffective in a dilution of C30 (1:10⁶⁰) but apparently effective in a dilution of 10 M (1:10²⁰⁰⁰⁰).16 This would agree with homoeopathic theory, according to which a higher potency is expected to be more effective than a lower one.

Buckman, in a recent discussion in the BMJ on “What does homoeopathy do—and how?” pointed out that, besides evidence and mechanism, the important issue is whether patients feel better when they take homoeopathic remedies.23 The pain scores of our patients were remarkably low after both operations. Despite inability to identify correctly the postoperative course with homoeopathic treatment, their strong confidence in homoeopathy remained unchallenged. Conventional physicians and devoted homoeopaths cooperated without problems in this study. The physicians believe that the low pain scores and satisfaction of the patients may at least partly reflect the clinical skill of the two homoeopaths.

We acknowledge the Norwegian Research Council for funding this work. Homoeopathic drugs and corresponding placebo tablets were kindly supplied free of charge by Vala Pharma Laboratorium AB (Gothenburg, Sweden). E A Rodland (Medstat Research, Lillestrom, Norway) performed the statistical analyses.