Efficacy of Individualized Homeopathic Medicines in the Treatment of Sciatica Pain: Double-Blind,Randomized,Placebo-Controlled Trial

Abstract

Objectives:

Sciatica is a debilitating condition that causes pain in its distribution or in the lumbosacral nerve root that is connected to it. Although there are claims that homeopathy can reduce sciatica pain, systematic scientific proof is currently lacking. The objective of the trial was to determine whether individualized homeopathic medicines (IHMs) were as effective as identical-looking placebos in treating sciatica pain.

Design:

This is a double-blind, randomized (1:1), two parallel arms, placebo-controlled trial.

Setting:

The study was conducted at Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, Howrah, West Bengal, India.

Subjects:

Sixty participants with sciatica pain were included in this study.

Interventions:

Verum (n = 30; IHMs plus concomitant care) versus control (n = 30; placebos plus concomitant care).

Outcome measures:

Primary—Sciatica Bothersome Index (SBI) and Sciatica Frequency Index (SFI) scores and secondary—Roland Morris Pain and Disability Questionnaire (RMPDQ), Short Form McGill Pain Questionnaire (SF-MPQ), and Oswestry Low Back Pain Questionnaire (OLBPQ) scores: all of them were measured at baseline, and every month, up to 3 months.

Results:

Intention-to-treat sample (n = 60) was analyzed. Group differences were examined by two-way (split-half) repeated measure analysis of variance, primarily accounting for between groups and time interactions, and additionally, by unpaired t tests comparing the estimates obtained individually every month. The level of significance was set at p < 0.025 and <0.05 two tailed for the primary and secondary outcomes, respectively. Group differences could not achieve significance in SBI (p = 0.044), SFI (p = 0.080), and RMPDQ scores (p = 0.134), but were significant for SF-MPQ (p = 0.007) and OLBPQ (p = 0.036). Gnaphalium polycephalum (n = 6; 10%) was the most frequently prescribed medicine. No harm, serious adverse events, or intercurrent illnesses were recorded in either of the groups.

Conclusions:

The primary outcome failed to demonstrate evidently that homeopathy was effective beyond placebo, and the trial remained inconclusive. Independent replications are warranted to confirm the findings. Clinical Trial Registration Number: CTRI/2020/10/028617.

Introduction

Sciatica refers to pain along the sciatic nerve pathway that typically occurs in the distribution of a dermatome and goes below the knee to the foot. The pain sensation is characteristically shooting in nature traveling along the nerve associated with weakness.¹ The reported prevalence of sciatica varies widely, causing a significant burden on health care and the economy, and resulting in a poorer quality of life.² Although the prognosis is good for most of the patients, up to 45% continue to have symptoms for 12 months or longer.³

Conventional therapy for sciatica pain focuses on pain reduction, either by using nonsteroidal anti-inflammatory drugs, epidural steroid injections, or by using biological agents, but their application either does not improve the natural course of the disease in most patients or is expensive.⁴ Surgical options are either invasive or minimally invasive techniques, which are generally indicated in the presence of a herniated lumbar disk; however, its benefit over usual conservative care is controversial.⁵

Until now, homeopathic research has focused primarily on low-back pain,^6

–11 but not sciatica typically. This trial was aimed at evaluating the efficacy of the individualized homeopathic medicines (IHMs) against placebos in the treatment of sciatica pain.

Materials and Methods

Trial design

This two-parallel arm, double-blind, randomized (1:1), placebo-controlled study was carried out in the outpatient department of an Indian homeopathic hospital.

Ethics approval

The institutional ethics committee (IEC) gave its approval to the study protocol (reference No. 907/MBHMCH/CH/PRIN/ADM/20; dated October 6, 2020). The Clinical Trials Registry—India (CTRI) received a prospective registration for the protocol—trial registration number CTRI/2020/10/028617; the essential components of the protocol can be found online at: https://ctri.nic.in/Clinicaltrials/showallp.php?mid1=48494&EncHid=&userName=CTRI/2020/10/028617; secondary identifier (UTN): U1111-1259-5038.

The protocol complied with the Good Clinical Practice guidelines and the Declaration of Helsinki. Before enrollment, all patients received a patient information leaflet in the regional vernacular, Bengali, and all participants gave their signed informed consent before participation.

Participants

The inclusion criteria were the cases experiencing low-back pain radiating to the lower limb (unilateral or bilateral) for 3 months or more (2018/19 ICD-10-CM diagnosis code M54.3), confirmed by straight leg raising (SLR) test, participants of either sex, age between 18 and 65 years, and patients giving written informed consent to participate in the study. Exclusion criteria were those cases suffering from uncontrolled systemic diseases and/or infections; having a history of low-back surgery in the past 6 months; undergoing any medicinal treatment during 6 weeks before enrollment in the study; substance abuse and/or dependence, pregnant, puerperal, or lactating women; patients with psychiatric diseases; and self-reported immune-compromised states.

Study medications

A computer-generated random number list was used to assign the subjects to the verum group (IHMs plus concurrent nonpharmacologic management) or the control group (alike placebos and nonpharmacologic management). The centesimal potencies of the IHMs were prescribed in customized dosages following homeopathic principles. Each dose comprised six to eight cane sugar globules No. 20, moistened with the indicated medicines. The participants were directed to take them orally, with an empty stomach, and a clean tongue. In addition, they were instructed to suck the globules rather than swallow them and to abstain from handling, eating, drinking, smoking, and brushing their teeth for 30 min after consuming the globules. A 3-month follow-up period was given to every participant.

Similar to the verum group, placebos were administered to the control group. Each dose of placebo consisted of six to eight nonmedicated globules (No. 20) of cane sugar, moistened with rectified spirit.

All participants were encouraged to make postural modifications and ergonomic adjustments, applying hot fomentation to the back, using a firm bed, doing spinal extensor exercises, and avoiding lifting heavy weights regardless of the codes they were assigned.

All of the medications were purchased from Dr. Willmar Schwabe India Pvt., Ltd. (New Delhi, India), a company accredited by Good Manufacturing Practices. Every prescription was tailored and reinforced by repertorization utilizing HOMPATH Zomeo^® software when needed, with the assistance of Materia Medica and three homeopaths' consensus. As needed, subsequent visits involved adjusting the medications, potencies, and dosages following the traditional homeopathic principles.

Two of the homeopaths, T.B. and S.G., had master's degrees in homeopathy and had been practicing classical homeopathy for >5 and >20 years, respectively. The postgraduate scholars of the institution were the remaining homeopathic doctors and all were the members of their state council. Follow-up visits and weekly phone calls guaranteed adherence to recommendations. A drug accountability diary was kept up to date, recording the dosages taken and globules returned.

Outcome measures

Primary outcome measures were the Sciatica Bothersome Index (SBI) and Sciatica Frequency Index (SFI) scores.^12,13 Both are composite scores of four questions about symptoms during the previous week—both being valid, easily comprehensible, easy to administer, and less time consuming, but reflecting the symptom burden of sciatica adequately. SBI consists of the following four questions— (1) leg pain; (2) numbness or tingling in the leg, foot, or groin; (3) weakness in the leg or foot; and (4) back or leg pain while sitting. Scores are in the range of 0–6 for each item (“not bothersome” to “extremely bothersome”); thus, the total score ranges from 0 to 24; a higher score indicates worse symptoms.

SFI consists of the same four questions provided with a 0–6 scale (“not at all” to “always”), and thus total score ranges from 0 to 24; a higher score indicates worse symptoms. It was administered at baseline and the end of each month for 3 consecutive months. Secondary outcomes were the Roland Morris Pain and Disability Questionnaire (RMPDQ),¹⁴ the Short Form McGill Pain Questionnaire (SF‑MPQ),¹⁵ and the Oswestry Low Back Pain Disability Questionnaire (OLBPDQ).^16
–18 The RMPDQ is designed to measure self-rated disability due to back pain. The questionnaire is short, simple, sensitive, and reliable.¹⁴

The RMPDQ is scored by adding up the number of items the patient has ticked. Greater levels of disability are reflected by higher scores. The SF-MPQ, the shorter version of the MPQ, is a multidimensional valid and reliable measure of perceived chronic pain in adults.¹⁵ It comprises 15 words (first 11 sensory and last 4 affective), which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The SF‑MPQ also includes one item for present pain intensity (PPI; 0–5) and one item for a 10‑cm visual analogue scale (VAS) for average pain. The total pain rating index (PRI) score is obtained by summing the item scores (range 0–45).

There are no established critical cut points. As for the MPQ, a higher score indicates worse pain. The SF‑MPQ takes 2–5 min to complete. A mean improvement in total scores of >5 on the 0–45 scale demonstrated a clinically important change. The OLBPDQ is one of the most commonly used outcome measures for individuals with low-back pain and is considered to be the gold standard in the assessment of patient‑rated outcomes. It is a valid, reliable, and responsive condition‑specific assessment tool that is suited for use in clinical practice.^16
–18

It is easy to administer and score, objectify clients' complaints, and monitor the effects of therapy. For each section, the total possible score is 5, the first statement is marked = 0, and the last statement is marked = 5. Total section = 10; total possible score = 50. The minimum detectable change (90% confidence) was 10% points (a change of less than this may be attributable to an error in the measurement).

Timeline

Every outcome was monitored at monthly intervals for a maximum of 3 months.

Sample size

The absence of any clinical trial of a similar design in homeopathy hindered formal effect size and sample size calculation. Earlier, in a 3-month trial by Danazumi et al., SBI scores reduced by 31.7% from 17.51 (±4.76) to 11.97 (±5.48) after specific manual therapies.¹⁹ A mean reduction of 55% in the verum group was assumed. Thus, the post-treatment mean group difference was estimated as 4.1, close to the minimally important change of 4.4 as recommended by Grøvle et al.²⁰

The effect size (Cohen's d) was calculated as 0.742. Thus, using an unpaired t test and 1:1 allocation, a research with 2 × 30 participants would result in 80% power, based on a two-sided significance level of 5%, to identify a mean difference of 4.1 in the SBI scores between two groups after a 3-month intervention.

Randomization

An impartial third party utilized StatTrek to centrally produce a list of 60 random numbers by limiting 6 permuted blocks of fixed size 10 while preserving a balance between groups. Thus, the participants were divided equally into two groups: the control group and the verum group. This random number chart was given to the blinded pharmacist to distribute medication. Another impartial third party classified identical amber-colored glass vials as either “1” or “2,” denoting either identical placebos or medications. The random number chart determined which participant would get the vials in a sequential order. The codes were disclosed at the end of the trial after the data set was locked.

Blinding

All study participants, including treating physicians, trial recruiters, outcome assessors, pharmacists, and data entry operators, remained masked throughout the experiment. By asking the participants which group they thought they were in, the blinding was verified both before and after the study.

Allocation concealment

Participants were screened, enrolled, and assigned serial numbers by blinded postgraduate trainees and registration counter workers. The blinded homeopaths then conducted interviews with the blinded subjects to determine the prescription. As a result, allocation concealment was accomplished by keeping the random number sequence a secret from the treating physicians and the trial recruiters.

Statistical methods

All enrolled participants were included in the final analyses, which were conducted using the intention-to-treat (ITT) approach. Predicted values from a linear regression model were used to impute the missing values. Histograms, skewness and kurtosis, Q-Q plots, and Shapiro–Wilk tests were used to analyze the data distribution; no discernible deviation from normalcy was found. An examination was conducted to see how comparable the two groups were at the baseline. Using chi-squared and unpaired t tests, the baseline comparability of the two groups was investigated.

Models for analysis of covariance (ANCOVA) were used to adjust the baseline differences. Group differences were mostly assessed using the more reliable two-way repeated measures analysis of variance (ANOVA) models generally for between-group and time interactions and less reliable unpaired t tests at various points in time. Effect sizes are expressed as Cohen's d, and differences between means are presented with confidence intervals (CIs) with Bonferroni adjustments.

After a Bonferroni correction, p-values <0.025 two-tailed and <0.05 for the secondary outcomes were deemed statistically significant for the two primary outcome measures. The means and CIs of descriptive statistics were used to report intragroup variations over time. The Statistical Package for the Social Sciences for Windows (version 23.0; IBM Corp., Armonk, NY) was used for all statistical computations.

Adverse events

The subjects were advised to notify the outpatients immediately or over the phone about any adverse or serious adverse events.

Trial reporting

The Consolidated Statement for Reporting Trials²¹ and Reporting Data on Homeopathic Treatment²² were followed in the reporting of this trial (Supplementary Files S1 and S2).

Results

Participant flow

Out of the 106 screened patients, 60 were included in the study and assigned at random to either the verum group (n = 30) or the control group (n = 30). Four discontinued during the 3-month follow-up (verum: 1, control: 3). All 60 participants were included in the final analysis (Fig. 1).

FIG. 1.

Consolidated Statement for Reporting Trials study flow diagram. IHMs, individualized homeopathic medicines, ITT, intention-to-treat.

Enrollment

This trial had a 19-month phase of recruitment spanning from mid-October 2020 until mid-May 2022, followed by a treatment phase of 3 months duration. By mid-August 2022, the final patient who was enrolled had finished follow-up.

Baseline data

According to the baseline distribution of the confounding variables, the two groups were comparable (Table 1). The SBI (p = 0.022), SFI (p = 0.002), and SF-MPQ VAS scores (p < 0.001) were higher in the IHMs group than in placebo at baseline, and these were adjusted subsequently using ANCOVA.

Table 1.

Comparison of the Sociodemographic Characteristics Between Two Groups at Baseline (N = 60)

Features	IHMs group (n = 30)	Placebo group (n = 30)
Age (years)^a	44.4 ± 8.1	41.5 ± 9.0
Duration of sufferings (years)^a	6.5 ± 2.1	6.6 ± 1.9
Body mass index^a	23.6 ± 1.9	23.3 ± 2.2
Blood pressure (mm of Hg)^a
Systolic	123.5 ± 6.0	123.4 ± 5.4
Diastolic	80.2 ± 5.0	78.0 ± 5.5
Sex^b
Male	18 (60)	17 (56.7)
Female	12 (40)	13 (43.3)
Residence^b
Rural	6 (20)	10 (33.3)
Semiurban	16 (53.3)	12 (40)
Urban	8 (26.7)	8 (26.7)
Treatment taken^b
Yes	26 (86.7)	24 (80)
Education^b
8th std. or less	8 (26.7)	10 (33.3)
9–12th std.	14 (46.7)	16 (53.3)
Higher than 12th std.	8 (26.7)	4 (13.3)
Employment status^b
Service	7 (23.3)	6 (20)
Business	12 (40)	12 (40)
Dependent and others	11 (36.7)	12 (36.7)
Socioeconomic status^b
Poor	10 (33.3)	11 (36.7)
Middle class	11 (36.7)	13 (43.3)
Affluent	9 (30)	6 (20)
Comorbidities^b
Hypertension	3 (10)	4 (13.3)
Diabetes mellitus	2 (6.7)	2 (6.7)
Others	1 (3.3)	3 (10)

Continuous data presented as means ± SDs.

Categorical data presented as absolute values (percentages).

IHMs, individualized homeopathic medicines; SD, standard deviation.

Number of patients analyzed

All the 60 randomized participants entered into the final analysis on an ITT approach.

Outcomes

Sciatica Bothersome Index

Although the IHMs group achieved greater intragroup mean decreases than the placebo group for 3 months, the primary analysis could not reveal statistical significance (F _{1, 58} = 4.256, p = 0.044). Additional analysis demonstrated the statistical significance of IHMs against placebos after 2 months (mean difference: −3.0, 95% CI −4.9 to −1.1, p = 0.002) and 3 months (mean difference: −5.0, 95% CI −7.3 to −2.8, p < 0.001) (Table 2).

Table 2.

Comparison of the Sciatica Bothersome Index at Different Time Points (N = 60)

SBI total score	Baseline: mean ± SD	After 1 month: mean ± SD	After 2 months: mean ± SD	After 3 months: mean ± SD	Intragroup mean reductions over time (95% CI)
SBI total score	Baseline: mean ± SD	After 1 month: mean ± SD	After 2 months: mean ± SD	After 3 months: mean ± SD	Month 0–1	Month 0–2	Month 0–3
IHMs group (n = 30)	14.3 ± 2.3	12.7 ± 2.8	9.9 ± 4.3	7.6 ± 4.7	1.6 (1.0 to 2.2)	4.4 (3.1 to 5.7)	6.7 (5.2 to 8.2)
Placebo group (n = 30)	12.8 ± 2.6	12.7 ± 3.0	12.9 ± 2.9	12.7 ± 4.1	0.1 (−0.7 to 0.9)	−0.1 (−0.9 to 0.7)	0.1 (−0.8 to 1)
Mean group difference ± SE	1.5 ± 0.6	−0.0 ± 0.7	−3.0 ± 0.9	−5.0 ± 1.1
95% CI	0.2 to 2.8	−1.5 to 1.5	−4.9 to −1.1	−7.3 to −2.8
t ₅₈	2.348	−0.044	−3.198	−4.425
p ^a	0.022	0.965	0.002^**	<0.001^***
Effect size (Cohen's d)	—	0	0.818	1.156
Two-way repeated measure ANOVA
F _{1, 58}				4.256
p ^b				0.044
Partial eta squared				0.068

Baseline differences adjusted using ANCOVA models.

Intergroup differences detected by unpaired t tests.

Intergroup differences detected by two-way repeated measure ANOVA models.

p < 0.025; ^** p < 0.01; ^*** p < 0.001.

ANCOVA, analysis of covariance; ANOVA, analysis of variance; CI, confidence interval; IHMs, individualized homeopathic medicines; SBI, Sciatica Bothersome Index; SD, standard deviation; SE, standard error; t ₅₈, t score at 58 degrees of freedom.

Sciatica Frequency Index

Although the IHMs group's intragroup mean decreases were higher than the placebo group's until 3 months, the primary analysis was unable to detect statistical significance (F _{1, 58} = 3.165, p = 0.08). The additional analysis demonstrated the statistical significance of IHMs compared with placebos after 2 months (mean difference: −3.5, 95% CI −5.7 to −1.4, p = 0.001) and 3 months (mean difference: −5.2, 95% CI −7.7 to −2.7, p < 0.001) (Table 3).

Table 3.

Comparison of the Sciatica Frequency Index at Different Time Points (N = 60)

SFI total score	Baseline: mean ± SD	After 1 month: mean ± SD	After 2 months: mean ± SD	After 3 months: mean ± SD	Intragroup mean reductions over time (95% CI)
SFI total score	Baseline: mean ± SD	After 1 month: mean ± SD	After 2 months: mean ± SD	After 3 months: mean ± SD	Month 0–1	Month 0–2	Month 0–3
IHMs group (n = 30)	15.2 ± 2.8	13.3 ± 3.6	9.6 ± 4.9	7.7 ± 5.4	1.9 (1.3 to 2.6)	5.6 (4.2 to 7.0)	7.5 (5.9 to 9.1)
Placebo group (n = 30)	12.9 ± 2.8	13.3 ± 2.9	13.2 ± 3.1	12.9 ± 4.2	−0.4 (−1.1 to 0.3)	−0.3 (−1.2 to 0.6)	0 (−1.0 to 0.9)
Mean group difference ± SE	2.4 ± 0.7	0.0 ± 0.8	−3.5 ± 1.1	−5.2 ± 1.2
95% CI	0.9 to 3.8	−1.7 to 1.7	−5.7 to −1.4	−7.7 to −2.7
t ₅₈	3.231	0.024	−3.352	−4.177
p ^a	0.002^**	0.981	0.001^**	<0.001^***
Effect size (Cohen's d)	—	0	0.878	1.075
Two-way repeated measure ANOVA
F _{1, 58}				3.165
p ^b				0.080
Partial eta squared				0.052

Baseline differences adjusted using ANCOVA models.

Intergroup differences detected by unpaired t tests.

Intergroup differences detected by two-way repeated measure ANOVA models.

p < 0.025; ^** p < 0.01; ^*** p < 0.001.

ANCOVA, analysis of covariance; ANOVA, analysis of variance; CI, confidence interval; IHMs, individualized homeopathic medicines; SD, standard deviation; SE, standard error; SFI, Sciatica Frequency Index; t ₅₈, t score at 58 degrees of freedom.

Roland Morris Pain and Disability Questionnaire

Similar trends of nonsignificance in the primary analysis (F _{1, 58} = 2.305, p = 0.134), but significant differences in the additional analyses, were revealed in RMPDQ scores after 2 months (mean difference: −2.9, 95% CI −5.4 to −0.4, p = 0.024) and 3 months (mean difference: −3.6, 95% CI −6.7 to −0.5, p = 0.023) (Table 4).

Table 4.

Comparison of the Roland Morris Pain and Disability Questionnaire at Different Time Points (N = 60)

RMPDQ total score	Baseline: mean ± SD	After 1 month: mean ± SD	After 2 months: mean ± SD	After 3 months: mean ± SD	Intragroup mean reductions over time (95% CI)
RMPDQ total score	Baseline: mean ± SD	After 1 month: mean ± SD	After 2 months: mean ± SD	After 3 months: mean ± SD	Month 0–1	Month 0–2	Month 0–3
IHMs group (n = 30)	11.8 ± 5.4	10.0 ± 5.2	9.4 ± 5.5	9.5 ± 6.4	1.8 (1.2 to 2.4)	2.4 (1.6 to 3.3)	3.3 (2.2 to 4.4)
Placebo group (n = 30)	11.2 ± 4.5	11.8 ± 4.1	12.3 ± 4.1	12.1 ± 5.5	−0.6 (−1.7 to 0.4)	−1.1 (−2.4 to 0.2)	−0.9 (−2.2 to 0.4)
Mean group difference ± SE	0.6 ± 1.3	−1.8 ± 1.2	−2.9 ± 1.3	−3.6 ± 1.5
95% CI	−1.9 to 3.2	−4.2 to 0.6	−5.4 to −0.4	−6.7 to −0.5
t ₅₈	0.497	−1.481	−2.326	−2.339
p ^a	0.621	0.144	0.024^*	0.023^*
Effect size (Cohen's d)	—	0.384	0.598	0.436
Two-way repeated measure ANOVA
F _{1, 58}				2.305
p ^b				0.134
Partial eta squared				0.038

Intergroup differences detected by unpaired t tests.

Intergroup differences detected by two-way repeated measure ANOVA models.

p < 0.05.

ANOVA, analysis of variance; CI, confidence interval; IHMs, individualized homeopathic medicines; RMPDQ, Roland Morris Pain and Disability Questionnaire; SD, standard deviation; SE, standard error; t ₅₈, t score at 58 degrees of freedom.

Short Form McGill Pain Questionnaire

On primary analysis, the total SF-MPQ score revealed statistical significance (F _{1, 58} = 7.888, p = 0.007) favoring IHMs against placebos. Significance was achieved at all the time points on additional analyses (month 1: p = 0.005, month 2: p = 0.003, month 3: p = 0.004). Similar significant trends were also detected in the SF-MPQ sensory subscale, but not in the affective subscale. The VAS was nonsignificant on primary analysis (F _{1, 58} = 0.371, p = 0.545), but significant after the 1st (p = 0.032) and 3rd (p = 0.01) months on secondary analyses (Table 5).

Table 5.

Comparison of the Short Form McGill Pain Questionnaire at Different Time Points (N = 60)

SF-MPQ scores	Baseline: mean ± SD	After 1 month: mean ± SD	After 2 months: mean ± SD	After 3 months: mean ± SD	Intragroup mean reductions over time (95% CI)
SF-MPQ scores	Baseline: mean ± SD	After 1 month: mean ± SD	After 2 months: mean ± SD	After 3 months: mean ± SD	Month 0–1	Month 0–2	Month 0–3
Total score
IHMs group (n = 30)	10.8 ± 5.0	9.2 ± 5.6	8.9 ± 6.1	8.2 ± 6.9	1.6 (0.6 to 2.6)	1.9 (0.6 to 3.3)	2.6 (0.9 to 4.2)
Placebo group (n = 30)	12.5 ± 4.4	12.9 ± 4.0	13.2 ± 4.3	13.2 ± 5.8	−0.3 (−1.5 to 0.8)	−0.6 (−1.9 to 0.6)	−0.6 (−2.1 to 0.8)
Mean group difference ± SE	−1.7 ± 1.2	−3.7 ± 1.3	−4.3 ± 1.4	−4.9 ± 1.7
95% CI	−4.2 to 0.8	−6.2 to −1.1	−7.0 to −1.6	−8.2 to −1.6
t ₅₈	−1.388	−2.905	−3.157	−2.988
P ^b	0.171	0.005^*	0.003^**	0.004^**
Effect size (Cohen's d)	—	0.760	0.815	0.784
Two-way repeated measure ANOVA
F _{1, 58}				7.888
p ^c				0.007^**
Partial eta squared				0.120
Sensory score
IHMs group (n = 30)	8.9 ± 3.3	7.4 ± 3.9	7.0 ± 4.4	6.5 ± 5.1	1.5 (0.8 to 2.2)	1.9 (0.9 to 2.9)	2.4 (1.1 to 3.7)
Placebo group (n = 30)	10.5 ± 3.4	10.7 ± 2.9	10.9 ± 3.2	10.6 ± 4.2
Mean group difference ± SE	−1.6 ± 0.9	−3.4 ± 0.9	−3.9 ± 1.0	−4.0 ± 1.2	−0.3 (−1.2 to	−0.4 (−1.5 to	−0.1 (−1.4 to
95% CI	−3.3 to 0.2	−5.2 to −1.6	−5.8 to −1.9	−6.4 to −1.6	0.7)	0.7)	1.2)
t ₅₈	−1.826	−3.811	−3.947	−3.344
p ^b	0.073	<0.001^***	<0.001^***	0.001^**
Effect size (Cohen's d)	—	0.960	1.014	0.878
Two-way repeated measure ANOVA
F _{1, 58}				12.465
p ^c				0.001^**
Partial eta squared				0.177
Affective score
IHMs group (n = 30)	1.9 ± 1.9	1.9 ± 2.1	1.9 ± 2.0	1.7 ± 2.1	0 (−0.4 to 0.5)	0 (−0.4 to 0.5)	0.2 (−0.3 to 0.7)
Placebo group (n = 30)	2.1 ± 1.5	2.1 ± 1.5	2.3 ± 1.5	2.6 ± 1.9
Mean group difference ± SE	−0.1 ± 0.4	−0.3 ± 0.5	−0.4 ± 0.5	−0.9 ± 0.5	−0.1 (−0.3 to 0.2)	−0.2 (−0.5 to 0)	−0.6 (−0.9 to −0.2)
95% CI	−1.0 to 0.8	−1.2 to 0.7	−1.3 to 0.5	−1.9 to 0.1
t ₅₈	−0.300	−0.587	−0.857	−1.741
p ^b	0.765	0.560	0.395	0.087
Effect size (Cohen's d)	—	0.110	0.226	0.449
Two-way repeated measure ANOVA				0.889
F _{1, 58}				0.350
p ^c				0.015
Partial eta squared
VAS score
IHMs group (n = 30)	6.1 ± 0.5	5.6 ± 0.8	5.0 ± 1.1	4.2 ± 1.6	0.5 (0.3 to 0.6)	1.1 (0.8 to 1.4)	1.8 (1.4 to 2.3)
Placebo group (n = 30)	5.0 ± 1.0	5.1 ± 0.9	4.9 ± 1.0	5.2 ± 1.4
Mean group difference ± SE	1.1 ± 0.2	0.5 ± 0.2	0.1 ± 0.3	−1.0 ± 0.4	−0.1 (−0.4 to 0.2)	0.1 (−0.2 to 0.4)	−0.2 (−0.6 to 0.2)
95% CI	0.7 to 1.5	0.0 to 0.9	−0.5 to 0.6	−1.8 to −0.2
t ₅₈	5.267	2.201	0.284	−2.652
p ^b	<0.001^***	0.032^*	0.777	0.010^*
Effect size (Cohen's d)	—	0.587	0.095	0.665
Two-way repeated measure ANOVA
F _{1, 58}				0.371
p ^c				0.545
Partial eta squared				0.006

Baseline differences adjusted using ANCOVA models.

Unpaired t tests.

Intergroup differences detected by unpaired t tests.

Intergroup differences detected by two-way repeated measure ANOVA models.

p < 0.05, ^** p < 0.01, ^*** p < 0.001.

ANCOVA, analysis of covariance; ANOVA, analysis of variance; CI, confidence interval; IHMs, individualized homeopathic medicines; SD, standard deviation; SE, standard error; SF-MPQ, Short Form McGill Pain Questionnaire; t ₅₈, t score at 58 degrees of freedom; VAS, visual analogue scale.

Oswestry Low Back Pain Questionnaire

The total OLBPQ score showed statistical significance in the primary analysis (F _{1, 58} = 4.6, p = 0.036). Additional analyses demonstrated significance after the 2nd (p = 0.004) and 3rd months (p = 0.002) (Table 6).

Table 6.

Comparison of the Oswestry Low Back Pain Questionnaire at Baseline and at Different Time Points (N = 60)

OLBPQ total score	Baseline: mean ± SD	After 1 month: mean ± SD	After 2 months: mean ± SD	After 3 months: mean ± SD	Intragroup mean reductions over time (95% CI)
OLBPQ total score	Baseline: mean ± SD	After 1 month: mean ± SD	After 2 months: mean ± SD	After 3 months: mean ± SD	Month 0–1	Month 0–2	Month 0–3
IHMs group (n = 30)	35.6 ± 18.4	29.6 ± 18.1	24.0 ± 20.0	21.8 ± 22.1	6.0 (3.9 to 8.1)	11.6 (7.1 to 16.0)	13.8 (8.4 to 19.2)
Placebo group (n = 30)	35.7 ± 13.4	35.9 ± 11.2	36.9 ± 12.3	37.8 ± 15.7	−0.2 (−3.1 to 2.7)	−1.2 (−4.5 to 2.1)	(−5.9 to 1.7)
Mean group difference ± SE	−0.1 ± 4.2	−6.3 ± 3.9	−12.9 ± 4.3	−16.0 ± 5.0
95% CI	−8.4 to 8.2	−14.1 to 1.5	−21.5 to −4.3	−25.9 to −6.1
t ₅₈	−0.024	−1.622	−3.010	−3.226
p ^b	0.981	0.110	0.004^**	0.002^**
Effect size (Cohen's d)	—	0.419	0.777	0.835
Two-way repeated measure ANOVA
F _{1, 58}				4.600
p ^c				0.036^*
Partial eta squared				0.073

Unpaired t tests.

Intergroup differences detected by unpaired t tests.

Intergroup differences detected by two-way repeated measure ANOVA models.

p < 0.05, ^** p < 0.01, ^*** p < 0.001.

ANOVA, analysis of variance; CI, confidence interval; IHMs, individualized homeopathic medicines; OLBPQ, Oswestry Low Back Pain Questionnaire; SD, standard deviation; SE, standard error; t ₅₈, t score at 58 degrees of freedom.

Prescribed medications

Twenty-seven different medicines were prescribed in the beginning—Gnaphalium polycephalum (10%), Bryonia alba, and Rhus toxicodendron (8.3% each), and Hypericum perforatum and Staphysagria (6.7% each) were the most frequently prescribed remedies (Table 7). The complete list of the prescribed medicines with potencies for both groups is appended as Supplementary File 3A and B.

Table 7.

Prescribed Medicines in the Two Groups at Baseline (N = 60)

Name of the medicines	Total, n (%)	IHMs group (n = 30), n (%)	Placebo group (n = 30), n (%)
(1) Gnaphalinum polycephalum	6 (10)	4 (13.3)	2 (6.7)
(2) Bryonia alba	5 (8.3)	3 (10)	2 (6.7)
(3) Rhus toxicodendron	5 (8.3)	3 (10)	2 (6.7)
(4) Hypericum perforatum	4 (6.7)	2 (6.7)	2 (6.7)
(5) Stapghysagria macrosperma	4 (6.7)	2 (6.7)	2 (6.7)
(6) Arsenicum album	3 (5)	1 (3.3)	2 (6.7)
(7) Calcarea fluoricum	3 (5)	2 (6.7)	1 (3.3)
(8) Natrum muriaticum	3 (5)	1 (3.3)	2 (6.7)
(9) Pulsatilla nigricans	3 (5)	—	3 (10)
(10) Graphites	2 (3.3)	1 (3.3)	1 (3.3)
(11) Guaiacum officinale	2 (3.3)	1 (3.3)	1 (3.3)
(12) Causticum	2 (3.3)	—	2 (6.7)
(13) Colocynthis citrullus	2 (3.3)	—	2 (6.7)
(14) Lachesis mutus	2 (3.3)	2 (6.7)	—
(15) Sulfur	2 (3.3)	2 (6.7)	—
(16) Arnica montana	1 (1.7)	1 (3.3)	—
(17) Belladonna	1 (1.7)	—	1 (3.3)
(18) Bellis perennis	1 (1.7)	—	1 (3.3)
(19) Calcarea carbonica	1 (1.7)	1 (3.3)	—
(20) Gelsemium sempervirens	1 (1.7)	—	1 (3.3)
(21) Kali carbonicum	1 (1.7)	1 (3.3)	—
(22) Lycopodium clavatum	1 (1.7)	—	1 (3.3)
(23) Magnesium phosphoricum	1 (1.7)	—	1 (3.3)
(24) Nux vomica	1 (1.7)	1 (3.3)	—
(25) Ruta graveolens	1 (1.7)	—	1 (3.3)
(26) Silicea terra	1 (1.7)	1 (3.3)	—
(27) Strontium carbonicum	1 (1.7)	1 (3.3)	—

IHMs, individualized homeopathic medicines.

Adverse events

Only five (verum: 2, placebo: 3) minor adverse effects were noted during the trial; however, all of those appeared to be unrelated to the medication. In the experimental arm, two participants reported acute diarrhea and were treated with Podophyllum peltatum 30C, 6 doses, and Aloe socotrina 200C, 3 doses, respectively. There was a case of common cold in the control group that was treated with Hepar sulphuris 30C, 6 doses; one case of sore throat, treated with Pulsatilla nigricans 200C, 4 doses; and another case of a minor bruise on the right arm from injury, which was treated with Arnica montana 30C, 6 doses. The trial medicines were stopped during the administration of acute remedies and resumed afterward, as appropriate.

Discussion

In this double-blind, randomized, placebo-controlled trial of IHMs on 60 participants, some of the secondary outcomes (SF-MPQ total, SF-MPQ sensory subscale, and OLBPQ) showed significant effects of IHMs against placebos, despite the primary analysis of the primary outcomes failing to reveal that the treatment was superior to placebo in reducing sciatica pain. Failure to detect the difference was partly contributed by a robust significance level of 0.025, and partly by a robust statistical model such as two-way repeated measure ANOVA, mutual administration of concomitant care measures to all the randomized participants, and a short follow-up duration of 3 months only.

Additional analyses showed significant effects of the IHMs against placebos on most of the occasions, especially after the 2nd and 3rd months of intervention. The apparent discrepancies observed between the results obtained in SBI and SFI scores between the primary and additional analyses can be explained by the more robust nature of the two-way repeated measure ANOVA than unpaired t tests. However, the incongruities arising between the results of SF-MPQ total and sensory subscales with that of VAS scores cannot be explained fully but might have been contributed by mere chance, the nonsignificant outcomes in the affective subscale, and the participants' difficulties in comprehending the VASs properly.

Gnaphalium polycephalum was the most frequently prescribed medicine. Thus, an inconclusive but promising trend of IHMs could be detected over placebos in reducing sciatica pain in adults. Independent replications are required to arrive at any confirmatory conclusion.

The trial's main strengths comprised randomization, double-blinding, blinded assessment of the outcomes, allocation concealment, and ITT analyses. Two primary outcomes were taken into account—SBI and SFI, because they assessed the severity of the sciatica pain; whereas the rest of the outcomes were aimed at capturing the impact of sciatica pain on the perceived disability and quality of life. A Bonferroni correction was used to determine whether p < 0.025 for the primary outcomes was statistically significant.

The traditional principles of homeopathy were followed in the prescription of IHMs, and selection and subsequent adjustments in dosage in follow-ups. This was reinforced by the use of the consensus prescribing technique, which involves three homeopathic physicians for each visit.

Concern exists about randomized controlled trials (RCTs)’ compromised external validity. RCT patients are carefully selected, and the participants differ greatly from those seen in general practice. Several anonymous questionnaires were required for RCT participants, and they also required special consideration and care during consultations. Results of marginal significance, especially on primary analysis in the two primary outcomes, may be deceptive due to increased Type II errors for obvious reasons. Concomitant care advice, which was recommended to all the recruited participants, may have made it more challenging to identify group differences, particularly when using ANOVA models to analyze group differences while addressing between-group differences and time interactions.

Because the analyses were covariate adjusted to take into account the variations, the results are less likely to be impacted. The 3-month follow-up period for each patient may not be sufficient. In this study, all of the outcome measures were self-administered subjective questionnaires. The effect size of the SBI and SFI after 3 months of intervention was 1.156 and 1.075, respectively, suggesting that a trial with 26 (2 × 13) and 30 (2 × 15) participants would provide 80% power based on a two-sided significance level of 5%. As a result, the 60 sample size the authors were able to obtain offered adequate power to compensate for a Type II error.

Future studies should focus on independent replications with more suitable single primary outcome measures, additional time point extensions to 4 months or longer, use of 50-millesimal scales, and innovative prescription techniques (e.g., cluster-symptoms methodology, polarity analysis). Future studies might also benefit from the use of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, additional control group(s) of physiotherapy, and/or concomitant care measures.

Conclusions

No positive effect of homeopathy could be demonstrated clearly against placebos in reducing sciatica pain, thereby making the trial inconclusive. Additional analyses demonstrated a trend of superiority of homeopathy over placebos, particularly in the 2nd and 3rd months of the intervention. Future trials may benefit from several modifications, particularly when selecting the primary outcome and varying prescribing methods.

Footnotes

Acknowledgments

The heads of the academic and hospital divisions of the institutions are thanked by the authors for enabling us to carry out the trial successfully. The authors express their gratitude to pharmacists, patients, staff, and other postgraduate trainees for their unwavering support and genuine involvement in the research.

Authors' Contributions

S.K.D., T.B., S.G., and S.S. contributed to concept and literature search; T.B., S.N.T., A.S., and S.G. were involved in clinical study and data acquisition; A.N., S.S., and S.K. carried out literature search and preparation of the article; and M.K. and S.S. were in charge of design, data interpretation, statistical analysis, and preparation of the article. All the authors reviewed and approved the final article.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

The project received no external funding. The institution has no role to play in the analysis of the study results and publication of the article.

Supplementary Material

Supplementary File S1

Supplementary File S2

Supplementary File S3A

Supplementary File S3B

References

Bhat

. SRB's Manual of Surgery. 5th ed. Jaypee Brothers Medical Publishers: New Delhi, 2016; p. 364.

Maslak

, Jenkins

, Weiner

, et al. Burden of sciatica on US Medicare recipients. J Am Acad Orthop Surg, 2020; 28:e433–e439; doi: 10.5435/JAAOS-D-19-00174

Konstantinou

, Dunn

, Ogollah

, et al. Prognosis of sciatica and back-related leg pain in primary care: The ATLAS cohort. Spine J, 2018; 18:1030–1040; doi: 10.1016/j.spinee.2017.10.071

Williams

, Lewis

, Din

, et al. A systematic review and meta-analysis of biological treatments targeting tumour necrosis factor α for sciatica. Eur Spine J, 2013; 22:1921–1935; doi: 10.1007/s00586-013-2739-z

Jacobs

, van Tulder

, Arts

, et al. Surgery versus conservative management of sciatica due to a lumbar herniated disc: A systematic review. Eur Spine J, 2011; 20:513–522; doi: 10.1007/s00586-010-1603-7

Prakash

, Bhowmik

, Singh

, et al. Individualized homeopathic medicines for low back pain in lumbar spondylosis: Double-blind, randomized, placebo-controlled trial. Homeopathy, 2023; 112(4):240–250; doi: 10.1055/s-0042-1758132

Nath

, De

, Singh

, et al. The role of homoeopathic treatment in women suffering from post-caesarean backache: An open observational clinical trial. Indian J Res Homoeopathy, 2019; 13:81–90; doi: 10.4103/ijrh.ijrh_14_19

MorrisM, Pellow

, Solomon

, Tsele-Tebakang

. Physiotherapy and a homeopathic complex for chronic low-back pain due to osteoarthritis: A randomized, controlled pilot study. Altern Ther Health Med, 2016; 22:48–56.

Beer

, Fey

, Zimmer

, et al. Effectiveness and safety of a homeopathic drug combination in the treatment of chronic low back pain: A double-blind, randomized, placebo-controlled clinical trial. MMW Fortschr Med. 2012; 154:48–57; doi: 10.1007/s15006-012-0304-z

10.

Pach

, Brinkhaus

, Roll

, et al. Efficacy of injections with Disci/Rhus toxicodendron compositum for chronic low back pain—A randomized placebo-controlled trial. PLoS One, 2011; 6:e26166; doi: 10.1371/journal.pone.0026166

11.

Stam

, Bonnet

, van Haselen

. The efficacy and safety of a homeopathic gel in the treatment of acute low back pain: A multicentre, randomised, double-blind comparative clinical trial. Br Homeopath J, 2001; 90:21–28; doi: 10.1054/homp.1999.0460

12.

Grovle

, Haugen

, Keller

, et al. Reliability, validity, and responsiveness of the Norwegian versions of the Maine-Seattle back questionnaire and the Sciatica Bothersomeness and frequency indices. Spine, 2008; 33:2347–2353; doi: 10.1097/BRS.0b013e31818047d6

13.

Patrick

, Deyo

, Atlas

, et al. Assessing health-related quality of life in patients with sciatica. Spine, 1995; 20:1899–1908; doi: 10.1097/00007632-199509000-00011

14.

Roland

, Morris

. A study of the natural history of back pain. Part 1: Development of a reliable and sensitive measure of disability in low back pain. Spine, 1983; 8:141–144; doi: 10.1097/00007632-198303000-00004

15.

Hawker

, Mian

, Kendzerska

, et al. Measures of adult pain: Visual analogue scale for pain (VAS pain), numeric rating scale for pain (NRS pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), chronic pain grade scale (CPGS), short form-36 bodily pain scale (SF-36 BPS), and measure of intermittent and constant osteoarthritis pain (ICOAP). Arthritis Care Res (Hoboken), 2011; 63:S240–S252; doi: 10.1002/acr.20543

16.

Vianin

. Psychometric properties and clinical usefulness of the Oswestry disability index. J Chiropr Med, 2008; 7:161–163; doi: 10.1016/j.jcm.2008.07.001

17.

Fairbank

, Pynsent

. The Oswestry disability index. Spine (Phila Pa 1976), 2000; 25:2940–2952; doi: 10.1097/00007632-200011150-00017

18.

Davidson

, Keating

. A comparison of five low back disability questionnaires: Reliability and responsiveness. Phys Ther, 2002; 82:8–24; doi: 10.1093/ptj/82.1.8

19.

Danazumi

, Bello

, Yakasai

, et al. Two manual therapy techniques for management of lumbar radiculopathy: A randomized clinical trial. J Osteopath Med, 2021; 121:391–400; doi: 10.1515/jom-2020-0261

20.

Grøvle

, Haugen

, Keller

, et al. Reliability, validity, and responsiveness of the Norwegian versions of the Maine-Seattle Back questionnaire and the Sciatica Bothersomeness and Frequency Indices. Spine, 2008; 33:2347–2353; doi: 10.1097/BRS.0b013e31818047d6

21.

Schulz

, Altman

, Moher D; CONSORT

Group

. CONSORT 2010 statement: Updated guidelines for reporting parallel group randomised trials. BMJ, 2010; 340:c332; doi: 10.1136/bmj.c332

22.

Dean

, Coulter

, Fisher

, et al. Reporting data on homeopathic treatments (RedHot): A supplement to CONSORT. Homeopathy, 2007; 96:42–45; doi: 10.1016/j.homp.2006.11.006

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.08 MB

0.11 MB

0.12 MB

0.23 MB