NHR Jan-Mar 2019: Original Research: Effectiveness of Epiphegus virginiana 30CH in comparison with individualized homoeopathic medicines in treatment of tension type headache: An open-label, randomized, pragmatic, pilot trial

Effectiveness of Epiphegus virginiana 30CH in comparison with individualized homoeopathic medicines in treatment of tension type headache: An open-label, randomized, pragmatic, pilot trial


Nisha Ganguly1*, Abhijit Chattopadhyay2

  1. Postgraduate Trainee, Dept. of Homoeopathic Materia Medica, National Institute of Homoeopathy, Govt. of India
  2. Professor and Head, Dept. of Homoeopathic Materia Medica, National Institute of Homoeopathy, Govt. of India

*Correspondence: gangulynisha2697@gmail.com


ABSTRACT:

Background: Tension type headache remains one of the commonest primary headache disorders, with a significant impact on patient’s quality of life, which may lead to high direct or indirect financial burden. Individualised homoeopathic medicines (IH) are claimed to reveal encouraging result in management of tension type headache; on the other hand, empirically selected Epiphegus virginiana (EV) on common symptoms is also claimed to be effective, but there is no systematic research addressing the comparative effectiveness of the said interventions in tension headache. In this present study, we aimed to compare the effectiveness of EV 30cH against IH medicines in the management of tension type headache.

Method: An open label, randomized, pragmatic, pilot trial was conducted on 41 patients suffering from tension type headache. The score of TSS (tension headache scoring scale) were used as outcome measures and were assessed at baseline and after 6 month of intervention. Comparative analysis was done on the protocol-compliant sample to detect group differences.

Results: Both the treatment group showed significant improvement in TSS after 6 months of intervention (all p < 0.001, paired t test). Group differences favored IH medicines over EV [8.3 (3.4) vs. 4.4 (2.9), mean difference 3.8, SE 1.0, 95% CI 1.8, 5.8, p < 0.001, independent t test].

Conclusion: Both the treatment group seems to be effective in management of tension type headache, although, IH medicines appeared to be superior to EV. Further adequately powered equivalence trials are warranted.

Keywords: Tension type headache, homoeopathy, Epiphegus virginiana, randomized controlled trial


Introduction

Headache is one of the most common complaints encountered in Internal Medicine & Paediatric & adult neurology clinic. In a population-based study, it was observed that 93% of men and 99% of women experience headache at some point in their life. This headache disorder is a painful condition, which may affect productivity at work and school and may lead to limitation of social activities [1] and thus have a significant impact upon patient’s quality of life which causes recognizable direct or indirect financial cost [2, 3].

The International Headache Society, classified headache as primary and secondary headache disorder [4, 5] and among the primary headache disorder tension type headache (TTH) is the most common type. A population based study shows tension type headache having the largest percentage of total headache disorder [3]. Though disability caused by TTH is more than migraine, still migraine is diagnosed more often in daily practice [6], as a significant percentage of people suffering from TTH never seeks medical advice[2] and have increased tendency for the consumption of analgesic worldwide[7].

The Global Burden of Disease Study 2010 published by WHO reported that the tension type headache is the second most prevalent disease in the world [3]. The life time prevalence of tension type headache in the general population varies between 30% and 78% and it is increased 15.3% from 2005 to 2015 [6]. According to the International Headache Classification Subcommittee of the International Headache Society (2004) reports about 44% of patients suffering from TTH having decreased ability to function and this leads to disability and reduced quality of life [8].

As per the geographical distribution there is higher prevalence of TTH in Europe (80%) than in Asia or America (20-30%) and is estimated 40% globally [9]. Different studies shows that the frequency of TTH is more in women than men [1, 4, 8, 9] and the women to men ratio is 5:4 [1]. Though a person may experience TTH at any point of time in their life but the peak of prevalence occurs at age of 30 to 39 years [9]. The Canadian study [8] reported that TTH have more prevalent in late adolescence or early adulthood.

Tension type headache usually presents as pain (dull, tight or like a pressure or band sensation) which may be constant and generalised but often radiates forward from the occipital region, of varied intensity, duration and frequency along with photophobia or phonophobia, only nausea (no vomiting), pericranial tenderness [10, 11]. However, the exact pathophysiology of  tension type headache is unknown, but many studies shows that there is increased stimulation of myofacial tissue from few triggering factors like stress, caffeine abuse, unhealthy eating habits or sleep deprivation etc., which may cause increased tension in musculoskeletal system of head and neck and causes pericranial tenderness [12]. Another study [13] reported to have involvement of peripheral nociceptive mechanism in episodic tension type headache, and the chronic TTH may be caused by central sensitization. At the same time, many theories evident that there is involvement of brain chemicals or neurotransmitters, genetic factors even environmental factors in pathophysiology of this primary headache disorder. Hence, this most common primary headache disorder remains a challenge to clinicians as the pathophysiology is not clearly understood yet, and there is less scope for pathological investigation in the process of diagnosis [5]. The diagnosis of TTH is mainly dependent on patient’s medical history and the criteria developed in 1988 by Headache Classification Committee of the International Headache Society (IHS) revised in subsequently 2004 and 2013. In my study, ICHD III has been taken as diagnostic criteria [5].

Tension type headache is often caused by over activity, exertion and associated or preceded by various symptoms like stress, physical discomfort, and sleep deprivation. Some life style factors like stress, skipping meal, bad posture, changes in sleep may act as trigger factors [14]. Though time to time many non-pharmacological interventions came into play, such as cognitive behavioral therapy, relaxation training, acupuncture [15], physiotherapy and their combination etc. are proved to have an immediate impact to reducing the frequency and muscle tension but studies indicated that the alternative medicine practice known as Homoeopathy could be effective for relieving headache naturally [16]. Therefore, the holistic approach of homoeopathic treatment including specific medicine Epiphegus virginiana may prove to be beneficial in the treatment of TTH [17].

A systematic review and meta-analysis [18] identified four randomized placebo-controlled trials [19-22] of homoeopathic treatment of headaches and migraine, however, concluded that the pooled overall effect was not significantly superior to placebo. Apart from these, there are few observational trials [23-26] and isolated case reports [27, 28] suggesting homoeopathy as useful therapy in different types of headache. In this study, we intend to examine the comparative effectiveness of EV against IH medicines.

METHODS

Trial design: This open-label, randomized, prospective, exploratory, pilot, pragmatic, clinical trial was conducted at the Homoeopathic Materia Medica out-patient departments of National Institute of Homoeopathy (NIH). Institutional Ethical Committee (IEC) approved the protocol [Ref. No. 5-023/NIH/PG/Ethical Comm. 2009/Vol. III/1974 (A/S); dated March 27, 2017]. The trial protocol (unpublished) and full dissertation was submitted as the postgraduate thesis of the corresponding author to The West Bengal University of Health Sciences.

Participants: Inclusion criteria were the patients suffering from tension-type headache fulfilling the criteria of ICHD-III [10] (ICD 10 code G44.209) for at least last 6 months, of both genders, age 18-50 years, and agree to participate in the trial. On the other hand participants were excluded from the study on the basis of criteria like, unable to read the information sheet, diagnosed cases of unstable psychiatric complaints or other systemic diseases affecting quality of life, currently receiving homoeopathic treatment for any chronic condition(s), pregnant and lactating women, self-reported immune compromised conditions, and substance abuse and/or dependence.

Intervention: Each dose was consisted of 4 cane globules no. 30, moistened adequately with EV 30cH, kept preserved in 90% v/v ethanol. Repetition was dependent upon individual requirement of the cases and as judged appropriate by the homoeopaths. The medicine was obtained from a Good Manufacturing Practice (GMP) certified firm – SBL Pvt. Ltd. The medicine was directed to be taken orally on clean tongue with empty stomach. Such intervention continued for 6 months. The participants were assessed by the two homoeopaths every month in every follow-up. Irrespective of the allocated codes, provision was kept for prescribing “acute medicines” based on “acute totality” to meet adverse or serious adverse events as per homoeopathic principles.

Control: Control was planned as administering individualized homoeopathic medicines in centesimal scale potencies as detailed above and in individualized dosage, as decided appropriate to the case or condition. As in the experimental arm, instructions were given to take each dose orally on clean tongue with empty stomach. Duration of treatment was 6 months. On each occasion, single individualized medicine was prescribed considering symptom totality, clinical history details, constitutional traits, miasmatic features, repertorization as and when required in consultation with Materia Medica, and agreement among the two prescribing homoeopaths. Individualized dose was used based on the two homoeopaths’ judgment of susceptibility and agreement. Subsequent prescriptions were produced in accord with Kent’s observations and Hering’s law. One of the prescribers possessed masters’ degree in homoeopathy and had been practicing ‘classical’ homoeopathy for more than 20 years. The corresponding author was a postgraduate trainee at NIH with 2 years of experience. Both the homoeopaths involved were affiliated with respective state councils.

Outcomes: The score of TSS were measured at baseline and after 6 months. The scale was developed based on ICHD-3 classification of headache disorder. (Tables 1, 2)

Sample size: Formal effect size calculation was not possible on account of absence of any open randomized trial on tension type headache comparing effectiveness of EV with IH. As the designed trial was equivalence or non-inferior in type, and EV was considered as one of the recommended homoeopathic medicines for the said condition, we presumed very small difference and small effect size in favour of either of the therapies and considered both the therapeutic options as equally effective (H0). Hence assuming a small effect size (d) of 0.1, and fixing α at 0.01, power (1 – β) = 80% (minimum recommended) in order to identify a significant difference between two independent means of TSS scores of the two groups by unpaired t test (two tailed), we would have required 3142 patients, i.e. 1571 in each arm. However, keeping in mind the exploratory nature of the trial, feasibility issues, and time constraints, we targeted to achieve 42 patients, i.e. 21 patients in each group. Given β/α ratio of 4, effect size of 0.1 and sample size of 21 in each arm, post hoc analysis revealed a compromised power (1-β) = 21.8%. The final analysis was restricted on the protocol-compliant sample (n=41) only; thus further compromising the study power up to 21.7%. This indicated the need for cautious interpretation while extrapolating the results to general population.

Randomization: Intervention (EV) or comparator (IH) was implemented as per the random number chart created by using the random number generator at StatTrek. The chart was generated using 4 blocks of size restricted to 10 (4 × 10 = 40) plus another block of size 2 to maintain alike allocation between groups and 1:1 ratio easily; thus the same numbers of patients were randomized to either code 1 or 2, either of intervention or control.

Blinding: The prescribing homoeopaths and the patients – both were aware (i.e. open-label) of the generated allocation codes all through the study. Allocated codes were maintained till the end of the trial. This open list of random numbers with allocated codes was made available also with the pharmacist, and he was instructed for dispensing of either EV or IH to the patients according to the chart.

Statistical methods: The protocol-compliant sample was analyzed in the end. Both descriptive and inferential statistics were applied. Baseline comparability of the groups was tested using chi-square (for categorical data) or unpaired t test (for continuous data). Outcome data obtained at baseline and after 6 months were compared by paired t test. Mean group differences after 6 months were compared by unpaired t test. P values for two-tailed tests were set at less than 0.01 as statistically significant. No interim and subgroup analyses were planned.

 

 

RESULTS

Study flow: As per the pre-specified inclusion and exclusion criteria, 45 patients suffering from tension type were screened; 3 were excluded on account of various reasons; 42 met the eligibility criteria and were enrolled into the trial. Following that, baseline socio-demographic and outcome data were obtained and were randomized to either EV (n=21) or IH (n=21). After 6 months of intervention, outcome data were recorded again. During course of treatment, 1 dropped out; 41 completed the trial (EV: 20, IH: 21) and entered into the analysis. (Figure 1)

Table 1: Tension type headache scoring scale (TSS)

Symptoms 0 1 2 3
Intensity
Frequency
Duration
Nausea
Photo- or phonophobia
Pericranial tenderness

Table 2: Scoring instructions of TSS

Intensity 0 No pain
1 Pain barely noticeable and does not interfere with usual activities
2 Pain noticeable, but does not interfere with work/activities
3 Pain distracts from work/activities
Frequency 0 No episodes
1 One episode per month
2 2-15 per month
3 More than 15 episodes per month
Duration 0 No pain
1 Less than 30 minutes
2 30 minutes to 7 days
3 More than 7 days
Nausea 0 Absent
1 Present
Photo- or phonophobia 0 Absent
1 Present
Pericranial tenderness 0 Absent
1 Present
The lowest possible score: 0; The highest possible score: 12

Recruitment: The study continued for 15 months; started in April 2017 and continued up to June 2018.

Baseline data: Distribution of socio-demographics features including age, gender, religion, and employment status, marital status were similar between the EV and IH group (all P > 0.01, Table 3) ensuring comparability of the two groups. Distribution of the outcome measures at baseline was also similar between the two groups with no significant differences (all P > 0.01). It implied that the groups were comparable at baseline.

Numbers analyzed: Outcomes from 20 from IH group and 21 from EV group was complete respectively; rest dropped out of the trial. Only the protocol-compliant patients (n=41) entered into the final analyses.

Outcome and Estimation: Within group changes in outcomes over 6 months showed statistically significant improvement in both groups. In IH group, the TSS score reduced from 10.7 (±0.7) to 2.4 (±3.2), mean change 8.3 (±3.4), 95% confidence interval 6.7 to 9.8, t19=10.800, p < 0.001, paired t test. Similarly, reduction in TSS score was also significant in the EV group, 10.4 (±1.0) to 6.0 (±2.9), mean change 4.4 (±2.9), 95% CI 3.1 to 5.7, t20=7.062, p < 0.001. Group difference of change was significantly higher in IH group than EV [8.3 (±3.4) vs. 4.4 (±2.9), mean difference 3.8, SE 1.0, 95% CI 1.8 to 5.8, t39=3.883, p < 0.001, unpaired t test].

Figure 1: Study flow diagram

 

Medicines used in the IH group: The most frequently indicated medicines in the IH group were Nat. mur, Lachesis, Ignatia, Medorrhinum, Nit. Acid, Pulsatilla, Arnica, Bryonia alb etc.

Adverse events: No harms, unintended effects, serious adverse events, and untoward aggravations were reported from either group during the study period.

 

DISCUSSION

Empirically selected EV seemed to be effective in management of tension type headache, but improvement was significantly higher in the IH group. However, the trial being underpowered, cautious interpretation is warranted. Further exploration is necessary with robust study designs.

One of the major strengths of the study was randomization; i.e. each number had the same chance of being allocated to either of the two arms. It was a “gold standard” for proof of efficacy or effectiveness. The advantages of randomization included equipoise across groups, enhanced internal validity due to homogenous study groups, minimized selection bias, unbiased allocation, generation of two comparable groups, balancing among possible confounders, facilitating simple analysis, and to declare evidently that the difference was because of the treatment. Prospective study design allowed causal inference to be drawn. No placebo control was used; rather all the randomized patients received medicine – either EV or IH. Hence, ethically the study was less vulnerable. In the study design, we kept provision for pair-wise comparisons using parametric t tests. The two trial arms had no significant difference at baseline ensuring comparability.

 

Table 3: Socio-demographic features of the participants at baseline (N=41)

Characteristics EV group (n=21) IH group (n=20) P value*
Age groups (years)

§  11-20

§  21-30

§  31-40

§  41-50

4

5

5

7

3

6

7

4

0.715
Gender

§  Male

§  Female

0

21

2

18

0.232
Religion

§  Hindu

§  Islam

5

16

10

10

0.157
Occupation

§  Professional

§  Skilled worker

§  Semi-skilled

§  Unemployed

0

5

3

13

1

4

3

12

0.951

*Chi square or Fisher exact test applied

The study was the very first of its kind in homoeopathy; hence exploratory in nature. Effect size could not be calculated on account of absence of any study of similar design; hence sample size was based on assumption only. The trial was open; no blinding was used. Thus, patient selection bias, treatment assignment bias, patient evaluation bias, and data analysis bias may have affected the outcomes of the study. Duration of follow-up of 6 months might be considered as insufficient in tension type headache cases. Besides, our analysis was restricted to protocol-compliant sample only. Imputation of missing values using appropriate statistical techniques and an intention-to-treat analysis would have generated more robust results than this. Also the TSS used needs to be tested for validity and reliability in future studies. Further studies are suggested on similar or more rigorous design with validated clinical scoring system and questionnaire focusing on quality of life issues.

CONCLUSION

EV and IH, both the treatment groups revealed significant improvement in tension type headache, although, IH medicines appeared to be superior to EV. Further adequately powered equivalence trials are warranted.


Conflict of interest statement: The authors declare that they have no competing interests. The trial was carried out as the postgraduate thesis of the corresponding author under guidance of AC, who is a permanent teaching faculty of the institute.

Funding: We received no funding for the study. Funding required for the project was borne by the authors themselves.

Authors’ contributions: NG and AC conceived and designed the study and collected data. NG ran the statistical analyses, interpreted the data, and prepared the manuscript. All the authors reviewed and approved the final manuscript.

Acknowledgements: We thank Dr. Subhranil Saha, Independent Researcher for his valuable inputs in statistical analysis and drafting of the manuscript. The authors are grateful to institutional heads, both academic and hospital section for their cooperation. We thank the fellow postgraduate trainees, staff, pharmacists, and the patients for their sincere participation in the study.

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Cite this article as: Ganguly N, Chattopadhyay A. Effectiveness of Epiphegus virginiana 30CH in comparison with individualized homoeopathic medicines in treatment of tension type headache: An open-label, randomized, pragmatic, pilot trial. National Homoeo Recorder 2019;15(1):15-23.

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