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| ORIGINAL ARTICLE |
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| Year : 2016 | Volume
: 10
| Issue : 3 | Page : 172-181 |
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A randomized comparative trial in the management of Alcohol Dependence: Individualized Homoeopathy versus standard Allopathic Treatment
Raj K Manchanda1, KR Janardanan Nair2, Roja Varanasi1, Praveen Oberai1, R Bhuvaneswari2, Rupali Bhalerao1, M Gnnanaprakasham2, Maya Padmanabhan1, VA Siddiqui3
1 Central Council for Research in Homoeopathy, New Delhi, India
2 Central Research Institute (H), Kottayam, Kerala, India
3 Retired, Central Research Institute (H), Noida, Uttar Pradesh, India
| Date of Web Publication | 11-Aug-2016 |
Correspondence Address:
Roja Varanasi
Research Officer (H)/Scientist 2, Central Council for Research in Homoeopathy, 61-65, Institutional area, Opp. D Block, Janakpuri, New Delhi, 110058
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0974-7168.188236
Objectives: This study was undertaken to compare the effects of IH with standard allopathic (SA) treatment. Methods: A randomized controlled, open-label, comparative trial, was conducted, in which alcohol dependents were screened verbally using the CAGE scale. The participants 80 patients fulfilling the inclusion criteria were randomized either IH (n=40) or SA (n=40) and treated cum followed up for 12 months. The primary outcome was more than 50% reduction in the Severity of Alcohol Dependence Questionnaire [SADQ] rating scale at 12 th month. Data analysis was done for both intention-to-treat (ITT) and per-protocol (PP) populations. Results: ITT analysis reflected 80% (n = 32) of the patients in IH and 37.5% (n = 15) of the patients in the SA responding to CI before 2.4 treatment with absolute difference was 42.5% (42.5 [95% confidence interval [CI]: 23.0, 61.6]) and estimated effect: 6.6 (95% C.I: 2.4, 18.2), P = 0.0002. A significant difference favoring IH was also observed in three out of four domains of WHO QOL-BREF. Statistically significant difference was found in the number of drinking days (median difference: −24.00; CI: −39.0-−8.0; P = 0.001) and number of drinks per drinking day (median difference: −6.3 [95% CI: −11.3-−1.9]; P = 0.004), favoring IH. The results showed a similar trend in PP analysis. Medicines found useful were Sulphur, Lycopodium clavatum, Arsenicum album, Nux vomica, Phosphorus, and Lachesis. Conclusion: The results conclude that IH is not inferior to SA in the management of AD patients. More rigorous studies with large sample size are however desirable. Keywords: Alcohol dependence, Allopathic treatment, Individualized Homoeopathy
How to cite this article:
Manchanda RK, Janardanan Nair K R, Varanasi R, Oberai P, Bhuvaneswari R, Bhalerao R, Gnnanaprakasham M, Padmanabhan M, Siddiqui V A. A randomized comparative trial in the management of Alcohol Dependence: Individualized Homoeopathy versus standard Allopathic Treatment. Indian J Res Homoeopathy 2016;10:172-81 |
How to cite this URL:
Manchanda RK, Janardanan Nair K R, Varanasi R, Oberai P, Bhuvaneswari R, Bhalerao R, Gnnanaprakasham M, Padmanabhan M, Siddiqui V A. A randomized comparative trial in the management of Alcohol Dependence: Individualized Homoeopathy versus standard Allopathic Treatment. Indian J Res Homoeopathy [serial online] 2016 [cited 2023 Apr 1];10:172-81. Available from: https://www.ijrh.org/text.asp?2016/10/3/172/188236 |
| Introduction | |  |
Alcohol consumption has numerous health and social consequences. It is an important contributor to death and disability. It is estimated to cause about 20-30% of esophageal cancer, liver cancer and cirrhosis of the liver, homicide, epilepsy, and motor vehicle accidents. Worldwide, about 16.0% of the drinkers aged 15 years or older engage in heavy episodic drinking. The prevalence of alcohol use in India is reported to be 21.4%, and it is among the young people with predominantly male gender (4.5%)who are suffering from alcohol dependence (AD). In the country, deaths attributed to alcohol consumption are 62.9% in males. [1]
The standard allopathic (SA) drugs prescribed for AD are Disulfiram, Naltrexone, Acamprosate, and Baclofen, [2],[3],[4] and SA drugs for alcohol withdrawal are Diazepam and Chlordiazepoxide. [2] However, long-term use of these drugs leads to side effects, thereby poor compliance to medication, which remain as challenges. [3]
Homoeopathy system of medicine, wherein medicines are prescribed tailored to patient, i.e., individualized to patient (individualized homoeopathy [IH]), has been used in various substance use disorders, such as heroin and alcohol with beneficial effects. [5],[6] Homoeopathic treatment has a beneficial role in managing patients with acute alcohol withdrawal symptoms. [7] Observational studies of homoeopathy intervention for AD also direct toward its usefulness in not only breaking the cycle of dependence but also in improving alcohol-related sleep disturbances. [8],[9]
In a pilot study conducted by Gopinadhan and Balachandran [10] homoeopathic medicine "Arsenic album" in alcohol-dependent patients could develop aversion to alcoholic drinks on addition to reduction in the amount and frequency. with this background, this prospective, randomized, controlled, comparative, open-label trial to investigate the effect of IH in managing alcohol-dependent patients compared to SA treatment was undertaken.
| Methods | | |
This was a randomized, controlled, comparative, open-label trial of IH and SA treatment in the management of AD, conducted by the Central Council for Research in Homoeopathy at its Central Research Institute, Kottayam, Kerala, India, during October 2012 to October 2014. The study protocol was in accordance with the latest revision of the Helsinki declaration [11] on human experimentation and Good Clinical Practices in India. [12] Although medicines proposed to be used during the study are known homoeopathic pharmacopoeial preparations, yet necessary clearance of the Ethical Committee and Scientific Advisory Committee was obtained before undertaking the study. The study protocol is published [13] and registered with the Clinical Trial Registry of India, registration number CTRI/2011/12/002213.
A random allocation sequence using statistical software had been generated by a statistician independent of the project prior to the commencement of recruitment. Participant allocation to the groups (1:1 ratio) was done immediately after baseline case recording.
Study Population
From the outpatient department of the institute, patients were screened verbally using the Cutting down, Annoyance by criticism, Guilty feeling, and Eye opener scale (CAGE scale) [14] and referred for detailed screening by the research investigator. Patients who met the inclusion/eligibility criteria as per the ICD-10 diagnostic criteria for research of diseases were invited to participate in the trial. Details of eligibility criteria are published elsewhere. [13] All the participants gave their written informed consent before participation into the study and were randomly divided to receive either group of interventions as per the randomization chart.
Intervention
IH treatment was given by a homoeopath. SA treatment was prescribed by the consultant psychiatrist engaged in the trial as per his/her discretion. After enrolment, patients allocated to SA group were treated with Chlordiazepoxide along with thiamine for 10-14 days for detoxification. Thereafter, the patients were given medication for AD such as Baclofen or Disulfiram. The treatment was decided by the consultant. Rescue medication (conventional) in severe withdrawal symptoms such as seizures and delirium tremens, if required, was kept available for prescription by the psychiatrist for patients in both groups. Homoeopathic medicines were procured from Good Manufacturing Practices-certified pharmacy. Supportive assistance in maintaining follow-ups for the study participants was made by a psychiatric social worker (PSW).
Supportive Counseling
Counseling has been given to patients of both the groups by the psychiatrist involved in the study. PSW helped the investigators in motivating patients during treatment and maintaining follow-up through home visits.
Outcome Measures
Primary outcome measure was more than 50% reduction in symptom score in comparison to baseline as per the Severity of Alcohol Dependence Questionnaire (SADQ) at the exit of 1-year treatment period. Apart from baseline, SADQ score was assessed at every 3 rd month up to 12 months.
Secondary outcome measures comprise changes in the quality of life (QOL), management of detoxification, and changes in alcohol consumption pattern in terms of quantity and frequency. Two variables were defined retrospectively to answer the secondary outcome parameters for changes in alcohol consumption. Total number of drinking days and number of drinks per drinking day over a 12-month period (the total number of drinks reported during the period divided by the number of days on which consumption of one or more drinks was reported) were calculated. An episode of heavy drinking or relapse was defined as five or more drinks per drinking on a single occasion [15] whereas one standard drink is defined as 30 ml which contains 40% alcohol by volume and 31.2 g/100 ml of absolute alcohol. [16]
The WHO-QOL BREF was also assessed at baseline and at 12 months. The revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) was used for the assessment of withdrawal symptoms.
Sample Size
Anticipating the recovery of 90% in SA group and 50% in IH group with noninferiority margin of −10% and to detect this difference with 90% power and one-sided alpha of 2.5%, a total of eighty patients (forty per group) were enrolled.
Statistical Analysis
Statistical analysis was performed in both the per-protocol (PP) and intention-to-treat (ITT) populations using IBM SPSS Statistics version 20. The last observation carried forward method was followed for replacing the missing data. For both ITT and PP groups, comparisons between IH and SA groups were performed at baseline to assess randomization effect using an independent t-test for continuous variable and Wilcoxon rank sum test/Chi-square test for ordinal data as applicable. Odds ratio was also calculated to assess the treatment effects. Resulting treatment effects and estimates/size are given together with 95% confidence interval (CI) and corresponding P values. In all the analyses, P < 0.05 was considered statistically significant.
| Results | | |
A total of 109 AD patients were screened. Twenty-nine patients were excluded for not fulfilling the inclusion criteria. Eighty patients were randomized and allocated to either IH group (n = 40) or SA group (n = 40). Eighty patients were analyzed as per the ITT method, and a total of sixty patients (SA = 27 and IH = 33) on regular follow-ups were analyzed PP. [Figure 1] shows the flow of the patients in the study.
Both set of patients were comparable at baseline [Table 1]. Mean age of all male patients was 39.9 ± 7.5 and 40.9 ± 9.5 years in IH and SA groups, respectively. Most of the patients were laborers by occupation; 33 (82.5%) in IH and 29 (72.5%) in SA groups. There was no difference in the type of drink consumed between the groups, maximum patients were drinking rum; 14 (17.5%) and 16 (20.0%) in IH and SA groups, respectively. Peer group and work pressure were noticed as the main reasons for drinking alcohol in both the groups. Total SADQ score was 30.1 ± 6.5 and 30.2 ± 7.6 in IH and SA groups, respectively, at baseline (P > 0.05).
Efficacy Results: Intention-to-Treat Analysis
AD data for patients who received at least one dose of medication were available for eighty patients (IH: 40; SA: 40). [Table 2] shows the results of outcome parameters considered in the study. The primary outcome of treatment response was achieved by 80% (32/40) of the patients allocated to IH and 37.5% (15/40) of the patients in those allocated to SA; the absolute difference in outcome between the treatment groups was 42.5% (95% CI: 23.0-61.6), with P < 0.0002 [Table 2]. The proportion of patients who maintained complete abstinence over 12 months' treatment period was achieved by 27.5% (11/40) in IH group and 17.5% (7/40) in SA group. There was no significant difference between relapse and abstinence (95% CI: 8.2-28.2), with P = 0.28. A significant difference was found in the total number of drinking days (mean difference −24; 95% CI: −39.0, - 8.0; P = 0.001) and total number of drinks per drinking day (mean difference −6.3; 95% CI: −0.4-3.2; 0.004; P = 0.004) at 12 months of treatment.
The WHO-QOL-BREF score of each patient was calculated at baseline and at 12 months. Statistically significant difference was found in the domains of physical, social, and environment (P = 0.001). No significant difference was obtained in psychological domain (P > 0.05) [Table 2]. Trend line showing changes in SADQ score over a period of 12 months is presented [Figure 2] consistently in favor of IH throughout the treatment period of 12 months. | Figure 2: Trend line showing the changes in the mean Severity of Alcohol Dependence Questionnaire score (intention-to-treat)
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Efficacy Results: Per-protocol Analysis
For protocol-completed and compliant patients, PP analysis was carried out, i.e., IH (n = 33) and SA (n = 27). The primary outcome remained significant: 93.3% (31/33) in IH group and 48.1% (13/27) in SA group; (P = 0.002), similar to ITT analysis. A significant difference was found in the total number of drinking days (mean difference −28; 95% CI: −42.9, - 14; P = 0.0003) and total number of drinks per drinking day (mean difference −7.7; 95% CI: −12.2-−2.9; P = 0.001) at 12 months of treatment.
A significant difference was found in the WHO-QOL BREF domains, i.e environment (P = 0.005), social (P = 0.001), and physical (P = 0.009). There was no significant difference in psychological (P = 0.19) domain [Table 3]. Mean score changes in SADQ score over 12 months showed a positive trend similar to ITT analysis in reduction toward IH as compared to SA from baseline at the exit of treatment period [Figure 3]. | Figure 3: Trend line showing the changes in the mean Severity of Alcohol Dependence Questionnaire score (per-protocol)
Click here to view |
Medicines Used and Symptomatic Improvement
The IH medicine was prescribed in either 30 CH or 200 CH potency in a single dose or two doses in the first prescription. Successive prescriptions were either repetition of the same or change into higher potency up to 1M. There were six different remedies prescribed, namely, Sulphur, Lycopodium clavatum, Arsenic album, Nux vomica, Phosphorus, and Lachesis during the patients' treatment period. The most frequently prescribed medicines were Sulphur:11 (27.5%) and Nux vomica: 10 (25%). Details of prescription and their indications are shown in [Table 4]a and b.
In the SA group, all the patients (n = 40) were given Chlordiazepoxide along with thiamine for managing alcohol withdrawal symptoms. During follow-up, 12 patients continued the same medication. Twelve were dropped out within 3 months. Other 16 patients were prescribed as follows: Baclofen (n = 11), Disulfiram (n = 3), and Risperidone (n = 2). Chlordiazepoxide along with thiamine was given along with the above medicines as and when required. One patient who was on Baclofen was put on disulfiram during the follow-up.
Symptomatic improvement of patients in both groups was analyzed. Apart from improvement in craving for alcohol, other frequently associated symptoms found to be improved are mentioned in [Table 5]. A significant difference was found in symptom irritability and craving for alcohol (P = 0.001) when compared between IH and SA [Table 5]. There was no reporting of severe withdrawal symptoms, thus none of the patients required rescue conventional medication during the study period in both the groups. CIWA-Ar score was assessed in only two patients who were in SA group and treated with the assigned group medication. | Table 5: Outcome status of symptoms presented by patients due to Alcohol dependence
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| Discussion | | |
In this comparative study, IH is noninferior to SA treatment in managing AD. To the best of our knowledge, this is the first and only randomized control trial comparing SA treatment with IH in AD. The primary outcome of treatment response was achieved by 80% of the patients allocated to IH and 37.5% of the patients in SA group. A significant reduction in the number of drinks and drinking days was observed favoring IH compared to SA. Previous studies in homoeopathy are mostly on the management of alcohol withdrawal, but comprehensive management of AD inclusive of alcohol withdrawal was not considered in any of the earlier studies. [4],[5],[6],[7],[8],[9] In this study, patients with alcohol withdrawal symptoms were having mild withdrawal symptoms as per the CIWA-Ar score who did not require IPD admission and treated at OPD as per the group assignment. No patient required rescue conventional medication during the study period.
Psychiatric consultant along with homoeopathic investigator had provided abstinent-oriented, supportive, motivational counseling to patients in both the treated groups. Psychological distress and psychiatric morbidity in the spouses of alcohol-dependent men are high, with marital satisfaction being low. Counseling along with treatment had a positive impact on life of patients as eight couples who were on the verge of divorce because of AD reverted back to normal life. Addressing these issues will be beneficial as spouses are known to play an important role in the treatment of AD. [17] This observation should be taken care of in designing future studies on AD.
A nationwide survey on psychoactive substance use in India has found that around 70% of AD are aged 40 years or less. [18] This finding is in consonance with our study, wherein the patient's mean age was 39.9 years in IH group and 40.9 years in SA group.
In another study of homoeopathy in acute alcohol withdrawal, Arsenicum album, Lycopodium, Nux vomica, Pulsatilla, and Belladonna were useful in the treatment. The quality of life also improved using homoeopathic medicines. [7] In our study also, similar medicines were prescribed for alcohol dependents. Thus, the above group of medicines is found effective in managing not only acute alcohol withdrawal syndrome but also AD.
The SA treatment was given by the consultant psychiatrist engaged in the study as per his discretion. Dosage and regimen were decided by him. The treatment effect in SA group was 3.5, compared to 6.6 [19] in IH group. Disulfiram has been prescribed to only few patients in our study due to established difficulties with compliance and toxicity. [20]
Effect sizes can be used to determine the sample size for follow-up studies or examining effects across studies. [21] Future studies can refer the effect size for sample size calculation which again depends on the research question and the experimental design.
The sample size in our study was small; therefore, a pragmatic study with a large sample size with/without counseling to the patients may be kept in future designs which can be designed to assess the effectiveness. From the experience from this study, it is recommended to develop standard treatment protocols for both the groups, and this needs further exploration in future studies.
| Conclusion | | |
The results conclude that IH is not inferior to SA in the management of AD patients. More rigorous studies are desired to validate these results. The outcome can also be used for future designing of studies and comparing results.
Acknowledgment
The authors acknowledge the contribution of Dr. Suresh Ninan, consultant psychiatrist for standard allopathic prescription in standard care arm and help in the enrollment and assessment of outcome in the followed up patients. The authors would also like to thank Dr. Alok Kumar, Former Director General and Dr. Anil Khurana, Deputy Director General, for their administrative support, Ms. Resmy, Statistical assistant, CRI (H), Kottayam, for input of data into spreadsheet, and Mr. Joji Alex, psychiatry social worker, for follow-up of the patients through home visit and supportive counseling to the patients of both the groups. The acknowledgments are also extended to patients for their support and participation.
Financial Support and Sponsorship
Central Council for Research in Homoeopathy, New Delhi. India.
Conflicts of Interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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