Repetition following Amelioration in Homoeopathy: A Randomized placebo

controlled pilot study

Dr.Alok Misra, MD (Hom.)
Lecturer, Organon of Medicine,
D.N. De Homoeopathic Medical College & Hospital,
12 Gobindo Khatick Road, Kolkata-700046, West Bengal, India
dralok23@yahoo.com

Abstract
Objectives: This study attempts to ascertain benefit of repeating medicine in higher potencies, after initial
amelioration in symptom complex, over placebo.
Material and method: This study was designed with a screening phase prior to the randomized placebo controlled
phase. During screening phase individualized homoeopathic medicine was prescribed to the patient and only those
patients were included in the study, who reported amelioration in the symptom complex. Patients randomized to
Group I (intervention group) were given three doses of next higher potency of the screening phase medicine and
after every 15 days three doses of same medicine, with potency raised serially in ascending order, were given.
Patients in Group II (placebo group) were prescribed placebo after initial relief with the medicine of the screening
phase. Both groups were followed for 45 days. Follow-up assessment was done using Clinical Global Impression
(CGI) Scale (improvement and severity) and Quality of Life scale (QOLS).
Results: There was no significant difference in the severity of disease and improvement with the individualized
medicine in both the groups by the time of randomization (p = 0.878 > 0.05). After follow-up of 45 days there was
significant change in CGI-S scores in intervention group as compared to placebo group (p = 0.011 < 0.05) but the
difference in CGI-I scores was not statistically significant. Mean increase in QOLS scores in intervention group
(7.36 0.358) was higher as compared to placebo group (3.18 0.038) but this difference could not reach to the
level of statistical significance. Number of recurrences of complaints were higher in placebo group (n=9) as
compared to the intervention group (n=4).
Conclusion: Direction of result favours intervention group but this could only be partially validated on statistical
tools.
Keywords: homoeopathy; repetition; higher potency; centesimal scale.
Introduction
Samuel Hahnemann propounded the law of similars in late 18th century, since then this theory has to confront too
many controversies. The most truthful assessment of 200 years of journey is perhaps it has signally failed to
persuade the doubters to believe, but it has equally failed to persuade the believers to doubt. A meta-analysis by
Linde et al1 was a bench mark in the history of homoeopathy. This was one of the most rigorous meta-analysis,
reporting that clinical effects of homoeopathy are not due to placebo. There was great turmoil in the scientific world

and many meta-analysis and systematic reviews appeared in its repercussion to refute homoeopathy 2 - 6. To add to
the controversial avenues of homoeopathy Linde et al7 performed another meta-analysis which tumbled up their
previous findings and showed that methodologically better quality studies of homoeopathy show less positive
results.
In Homoeopathy, treatment modality differs from physician to physician. Homoeopathic medicine fails and
physician finds himself in the midst of sea, without a compass, so as to know whether his selection of medicine,
potency, dosage or repetition schedule was wrong. Homoeopathic therapeutic system lacks any clear cut guideline
for selection of medicine & potency, dosage and repetition schedule. These judgments are often left to the
discretion of physician, who fails to follow any uniform pattern and adopts multifarious ways of prescription. These
are few of the main reasons why so many meta-analyses have appeared which find action of homoeopathic
medicine nothing more than placebo 2-7. Definite guidelines for selection of medicine, potency, dosage and
repetition are lacking. Scientific world round the globe are skeptical about homoeopathy because it lacks
reproducibility due to these shortcomings8-10.
Hahnemann in his 5th edition of Organon of Medicine11, while describing centesimal scale (1:100 dilution factor),
completely precludes any repetition of the administered medicine, so long amelioration persists. But in the 6 th
edition of Organon of Medicine 12, while describing 50 millesimal scale (1: 50,000 dilution factor), he has directed to
repeat the same medicine, in somewhat renewed dynamization, so long amelioration persists.
There are few evidences in homoeopathic literature that good results were obtained when centesimal scale
medicines were repeated in increasing potency 13, 14. There are many factors which combat the action of medicine;
there are chances of exhaustion of medicinal action much before complete recovery of patient. To overcome this
very issue Hahnemann recommended using Renewed Dynamization while describing about 50 millesimal scale. If
same paradigm is used in centesimal scale better results may be anticipated. With this hypothesis of repeating
centesimal scale medicines, in increasing potencies after initial relief in the symptom complex of the patients, this
pilot study was designed
Material and methods
Setting
Study was simultaneously conducted at two private homoeopathic clinics and all patients were assessed by the
same physician.
Design
A single blind randomized placebo controlled parallel arm pilot study was conducted. Prior to the randomized
controlled phase there was a screening phase in which individualized medicine for each patient was optimized.
Same method of optimizing homoeopathic medicine in the screening phase was used by Frei et al 15.
After initial relief in the symptom complex, with the optimized homoeopathic medicine, patients were randomized to
receive either repetition of the same medicine, with which they got relief earlier, in next serially higher dilution or
placebo. Randomization was done in blocks of two using a computer random number generator available from
www.randomizer.com16. Patients of both the groups were called for follow up assessment after every fifteen days
till 45 days. Initial randomization was pursued through out the follow-up.

Sample selection
Inclusion was based on improvement in clinical assessment following 1 st prescription in the screening phase and
was not limited to clinical disease condition. Patients of all age groups were included. Patients in acute
emergencies or suffering from life threatening conditions were excluded from the study.
Homoeopathic medicine selection
In the screening phase all patients were prescribed individualistic homoeopathic medicine, selected on the basis of
their presenting totality, in 30C potency (10 -60th dilution). Homoeopathic software Radar 7.1 version, using synthesis
repertory, was also used for selection of medicine, where ever required. All medicines, in screening phase or
during study phase, were used in centesimal potency. Patients who reported relief in their symptom complex, after
screening phase medicine, were included in the study after obtaining written informed consent from them.
Study Groups
Group I (Intervention Group): After randomization, patients were prescribed three doses of 200C potency (10 -400th
dilution) of the same medicine with which they were relieved. This was followed by placebo for 15 days and again
after 15 days three doses of next higher potency of the same medicine was given. Medicines were prescribed up to
10M potency.
Group II (Placebo Group): After randomization, patients were prescribed placebo. Medicine and placebo were
identical in appearance, taste and odor.
Outcome measures
Primary outcome measure was Clinical global impression (CGI) scale17 (improvement and severity). Scores on the
Clinical global impression severity (CGI-S) subscale range from 1 = not ill at all to 7 = among the most extremely
ill. The Clinical global impression improvement (CGI-I) subscale also ranges between 1 = very much improved to
7 = very much worse. Initially in the screening phase all the patients were assessed on Clinical Global Impressionseverity scale, whereas at the time of randomization and all subsequent follow-up patients were assessed on both
the subscales of CGI scale.
All patients entering the screening phase were also evaluated on 16-item Quality of life scale (QOLS)17. Patients
were re-evaluated on QOLS at the time of randomization and finally at the completion of 45 days follow-up.
Statistical analysis
Differences in continous variable were assessed using t-test after checking for normality of distribution. Differences
in categorical variables were assessed using Mann-whitneys test. A p-value of < 0.05 was considered as
significant.

Screening Phase
(n = 104)

Eligible for randomization

(n = 67)
Consent
not given
(n = 6)

Randomized
(n = 61)
Placebo group
(n = 31)

Intervention group
(n = 30)

Completed
follow-up
(n = 28)

Loss to
follow-up
(n = 2)

Completed
follow-up
(n = 28)

Loss to
follow-up
(n = 3)

Fig. 1: Study flowchart of patients

Results
Over two months of screening phase, 67 patients were found eligible for enrolment in the study and 61 were
randomized into the study (Fig. 1). Out of this, 56 completed follow-up period with two dropouts in intervention
group and three drop-outs in placebo group. At the time of randomization, the comparison of demographic
characteristics and baseline values found no significant differences between the two groups (Table 1). The criterion
for inclusion in the study was relief after homoeopathic prescription in the screening phase and was not limited to
any particular clinical condition. As such clinical conditions in the two groups were not equally distributed (Table 2).
Patients severity of disease was measured on CGI-S scale at the time of screening, randomization and at the end
of follow-up.

At the time of screening and at the time of randomization there was no statistically significant

difference in the CGI-S scores in both the groups (Table 1)). However, CGI-S scores were significantly lowered
after a follow-up of 45 days, in the intervention group (p=0.011 <0.05) (Table 3).
Improvement score in patients symptom complex was assessed at the time of randomization and at the end of 45
days follow-up, using CGI-I. Patients in both the groups improved with the medicine prescribed in the screening
phase. By the time of randomization mean CGI-I scores of intervention (2.82 0.390) and placebo (2.86 0.357)
groups were comparable. But at the end of follow-up, patients in the intervention group improved better (mean
CGI-I 2.11 0.956) as compared to placebo group (mean CGI-I 2.86 1.335), but this difference could not reach to
the level of statistical significance (p = 0.083 > 0.05) (Table 3)

Table 1: Demographic characteristics and baseline values in both the groups

Age

Intervention group
38.14 12.048

Placebo Groups
34.57 11.980

p value
0.735

Male
Female
CGI-S at the time of randomization
CGI-I at the time of randomization
Change in severity scale (CGI-S)
score by the time of randomization
Quality of life scale score at the time
randomization

12
16
3.71 0.763
2.82 0.390

13
15
3.68 0.723
2.86 0.356

1.11 0.009

1.14 0.14

62.00 10.788

61.61 10.619

CGI-S: Clinical Global Impression-severity; CGI-I: Clinical Global Impression-improvement.

Table 2: Clinical conditions of patients in both the groups

Intervention group
1
2
5
1
1
2
1
2
1
5
4
1
2

Headache
Respiratory problem
Gastritis
Paroxysmal sneezing
Tendency to catch cold easily
Warts
Piles (bleeding or bland)
Gynaecological problems
Acne
Eczema and other skin problems
Joint problem
Urinary complaint
Psychological problems

Placebo Groups
2
2
4
1
2
1
1
3
3
7
2
-

Table 3: Clinical conditions of patients in both the groups

Intervention group
(mean rank)

Placebo Groups
(mean rank)

P value

95% Cl

At baseline

28.20

28.80

0.879

At end of study

33.71

23.29

0.011

At baseline

29.00

28.00

0.718

At end of study

31.89

25.11

0.083

Intervention group
(mean SD)

Placebo Groups
(mean SD)

P value

95% Cl

62.00 10.788

61.61 10.619

0.553

-5.342 to 6.128

69.36 11.146

64.79 10.657

0.946

-1.272 to 10.414

CGI-S

CGI-I

Table 4: Change in QOL score over time

At the time of screening

At baseline
At end of study
Difference in score

QOL was assessed at the time of screening, randomization and at the end of follow-up. QOL at the time of
screening and randomization were almost comparable in both the groups but at the end of study period QOL was

found to be better in the intervention group (mean increase 7.36 0.358) as compared to placebo group (mean
increase 3.18 0.038). However, this difference was also not statistically significant (p = 0.946 > 0.05).
Further, reappearance of complaints was reported more frequently in the placebo group (n=9) as compared to the
intervention group (n=4). As compared to intervention group, in placebo group reappearance of complaints was
more seen in diseases having periodical nature.
Discussion
This study could only address the problem partially, as there was significant reduction in CGI-S scores in
intervention group as compared to placebo group but there was no significant difference in CGI-I and QOLS
scores. Insufficient statistical power is always a consideration in a small pilot study such as this, but the direction of
effect favors the intervention group.
Moreover, recurrences of complaints were quite less in intervention group as compared to placebo group. Results
suggest that repeating medicine in serially higher potency have some potential in breaking the periodicity of
diseases. It was a drawback of our study that there was no provision for repetition of medicine in placebo group
even when there was relapse in patients condition, but classical homoeopathy advocates to repeat the medicine if
after a period of amelioration case again presents with same symptomatology. Future studies must be taken up
with the repetition model of our study in comparison to classical homoeopathy, especially in diseases of recurrent
character, to draw some conclusive evidence.
Theory of vital force is as contentious as Homoeopathy itself. The new gyroscope model of vital force, presented
by MilGrom19, suggests torque like action of homoeopathic medicines and diseases on the vital force. This model
permits disease to be represented as braking torque, decreasing the angular momentum of vital force, however,
indicated medicine provides an accelerating torque, increasing the angular momentum of vital force. It is concluded
that in order to avoid aggravations, this accelerating torque, viz. medicinal potency, should be applied gradually.
Such an approach echoes the 50 millesimal system 12. Our results propose that this gradual increase in torque like
action of medicines can be applied by centesimal scales also.
One of the major methodological flaw in studies related to classical homoeopathy is, selection of individualized
homoeopathic medicines. Many a times cases fail to respond due to wrong selection of medicine but the failure is
accredited to Homoeopathy, thus increasing the chances of type-II error. With the aim of reducing chances of error
in evaluating studies of classical homoeopathy, selection of individualized homoeopathic medicine for each patient
must be optimized before entering into randomization phase. In our study, at the time of randomization mean
improvement, with the medicine of screening phase, in both the groups were almost same (Table 1), suggesting
that selection of medicine was optimized in all patients. Similar to our method Frei et al 15 also used screening
phase to optimize selection of homoeopathic medicine before randomization.
This study had many limitations, firstly this study failed to address any specific clinical conditions. Secondly, the
assessment parameters were ambiguous, which could not judge patients condition precisely. These shortfalls can
only be prevailed over by assigning this type of study to any one clinical condition which will enable us to assess
the treatment outcome on more stringent and authoritarian parameters.

This pilot study justifies future definitive study incorporating medicine repetition in higher potency and optimization
of medicine selection model, with larger sample size but limited to any single clinical condition, so that it could be
assessed with more specific and stringent parameters.

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