Abstract
Background:
Indian guidelines mention the use of buprenorphine in opioid withdrawal in both outpatient and inpatient setting.
Aim:
This is the first study aiming at assessing the feasibility aspects of outpatient-based buprenorphine-assisted opioid withdrawal treatment for opioid dependence.
Methods:
In this prospective observational study, 30 men with opioid dependence, planned for outpatient-based withdrawal management, were recruited by purposive sampling and were assessed at baseline, 2, 4, and 12 weeks using validated tools. Abstinence was validated by a urine toxicology screen.
Results:
The median age of the sample was 24 (21.75–28.0) years. About 67% retained in treatment with a treatment perception score of 4.1 (4.0–4.4) and a significant reduction of craving and withdrawal scores. More than 80% were abstinent at 12 weeks.
Conclusion:
The study findings suggest that outpatient-based buprenorphine-assisted acute opioid withdrawal management is a feasible and acceptable treatment. Considering the relatively few inpatient addiction treatment settings, the findings are promising.
Keywords: Buprenorphine, opioid withdrawal, outpatient
INTRODUCTION
Opioid dependence is a significant public health issue in India with around 77 lakh people affected.[1] Managing acute opioid withdrawal symptoms is a recommended approach to treat opioid dependence.[2] There is a greater chance of initiation of long-term antagonist treatment with successful withdrawal management.[3] Several pharmacological agents like clonidine, lofexidine, tramadol, methadone, and buprenorphine can be used to treat acute opioid withdrawal in inpatient or outpatient settings.[4,5] Of these, buprenorphine and methadone have the largest evidence and are recommended by treatment guidelines, including one from India[2,6] for both in-patient and out-patient settings. Buprenorphine is recommended due to its longer half-life and slower dissociation from the receptors ceiling effect at higher doses reducing chances of overdose and respiratory depression.[7] Additionally, higher rates of treatment completion have been reported with buprenorphine in comparison with other pharmacological agents.[6,8] Available Indian literature on the management of opioid withdrawal is predominantly confined to inpatient settings.[6,9] There is no reported study from India on outpatient-based opioid withdrawal management with buprenorphine. Considering the huge treatment gap in the field of addiction treatment and the relative lack of inpatient treatment facilities in the country, exploring outpatient-based treatment would enhance the possibility of engaging a larger number in long-term treatment for opioid dependence. Hence, the current study was planned to assess the feasibility aspects of buprenorphine-assisted opioid withdrawal treatment in the outpatient setting among men with opioid dependence.
SUBJECTS AND METHODS
This prospective observational study was conducted at the outpatient setting of a tertiary addiction treatment center in North India. Institutional Ethics Committee approval was obtained. As a routine procedure, all patients visiting the outpatient department of the center are initially evaluated by trained psychiatrists, followed by a detailed evaluation and discussion with senior consultants. The patients are diagnosed based on ICD-10, and a treatment plan is formulated. Patients follow up regularly with the consultant in-charge, and records of all visits are maintained in a clinical file which is retrieved on each follow-up. Patients are initiated on buprenorphine-assisted withdrawal treatment as per case profile and as preferred choice by a patient either in inpatient or outpatient setting as per feasibility, convenience of the recipients, and availability of a family member and subsequently started on long-term opioid antagonist treatment with naltrexone. The buprenorphine tablets are dispensed free of cost for 1–2 weeks to the accompanying family member. Dispensing and follow-up frequency are decided by the consultants based on the clinical profile, availability of family for supervision, and logistic factors.
Newly registered (first-time treatment seekers) opioid dependent (as per ICD-10) men of age group 18–50 years, accompanied by family members (residing in the same house for at least one year and accompanying the patient) who were planned and agreed for buprenorphine-assisted opioid withdrawal treatment as assessed by the treating consultants for outpatient-based buprenorphine-assisted withdrawal treatment and provided informed consent were included in the study. We excluded those with a history of any other substance dependence (excluding tobacco), recent history of inpatient care or outpatient treatment for opioid dependence from any treatment facility within the last 3 months, and a history of psychiatric comorbidity. The sample size (N = 30) was decided as per the feasibility considering the study period was immediately after the COVID pandemic, and the study being a part of the DM Addiction Psychiatry thesis for the first author. The data collection period was from May 2021 to June 2022.
Procedure
Patients initiated on outpatient buprenorphine-assisted withdrawal treatment by treating consultants were recruited from the outpatient clinic after written informed consent and assessed at baseline (within a week of starting buprenorphine-assisted withdrawal treatment by the consultant), 2 weeks, 4 weeks, and 12 weeks. A semi-structured questionnaire, Opiate Treatment Index (OTI)[10] for the severity of opioid dependence, and a treatment perception questionnaire[11] for satisfaction with treatment were applied at the end of 12 weeks. Since this was an observational study, the researcher did not have any control or influence over decisions like dose or duration of dispensing, or change in the long-term treatment plan which were determined by the treating consultants. In the study setting, a flexible dose regime is followed for outpatient buprenorphine-assisted withdrawal management, and a family member is engaged for medication supervision.
Urine specimens (5 mL) were collected under staff supervision from all participants at baseline, and last follow-up for screening of psychoactive drugs (morphine, buprenorphine, cocaine, amphetamines, cannabinoids, and benzodiazepines) by cassette test. Tramadol and antihistaminic (pheniramine) were screened by Gas Liquid Chromatography.
Operational definitions
Retained: Those who were in contact with the treatment center till the end of 12 weeks and received treatment (any).
Completers: Those who completed withdrawal management anytime within the study period (12 weeks).
Drop-out: Those who did not follow up within 2 weeks of a scheduled follow-up visit.
Statistical analysis was carried out using a licensed copy of SPSS version 21.
RESULTS
After screening 73 males of opioid dependence, 30 were found eligible for the study. The demographic and substance use of participants are presented in [Table 1]. The median (IQR) duration of opioid dependence was 3.5 (2.0–7.0) years, and the median (IQR) age of onset of opioid use was 20.5 (17.0–23.0) years in them.
Table 1.
Socio-demographic and substance use details of Sample (n=30)
| Socio-demographic characteristics | Male (n=30) |
|---|---|
| Accompanied by | Parents (83.3%) Spouses (16.7%) |
| Age (years) Median (IQR) | 24.0 (21.75–28.0) |
| Marital status n (%) | |
| Never married | 17 (56.7) |
| Ever married | 13 (43.3) |
| Education n (%) | |
| Below secondary education | 10 (33.3) |
| Secondary education and above | 20 (66.7) |
| Employment status n (%) | |
| Never employed | 6 (20.0) |
| Ever employed | 24 (80.0) |
| Residence n (%) | |
| Urban | 27 (90.0) |
| Rural | 3 (10.0) |
| B. Substance use | |
| Types of opioid use | |
| Heroin Doda Capsule Spasmoproxyvon |
26 (86.7) 2 (6.7) 2 (6.7) |
| Other substance use | |
| Tobacco (dependent) Cannabis (occasional use) Alcohol (occasional use) |
20 (100%) 25 (83.3%) 11 (36.7%) |
There was a significant reduction in OTI scale score at the end of 1 2 weeks from baseline among those retained in treatment (z = 3.921, P ≤ 0.001; Wilcoxon signed rank test). The feasibility of treatment was assessed using the outcome parameters given in [Table 2].
Table 2.
Treatment outcome
| A. Treatment-outcome groups at 12 weeks | |||||
|---|---|---|---|---|---|
| Retained (n=20) |
Drop-out (n=10)## | ||||
| Withdrawal management completers | Withdrawal management ongoing | #Change in treatment plan (shifted to agonist maintenance treatment) | |||
| 12 (60.0) | 5 (25.0) | 3 (15.0) | 10 (33.3) | ||
|
B. Outcome measures among treatment completers and those still ongoing withdrawal management (n=17) | |||||
| Completers, n=12 (%) | Withdrawal management ongoing, n=5 (%) | ||||
|
|
|
||||
| Abstinence | Lapse/s | Abstinence | Lapse/s | ||
|
| |||||
| Abstinence at the end of 12 weeks (treatment completers and those still ongoing withdrawal management, n=17) (by urine toxicology screen) | 12 (100) | 0 | 2 (40) | 3 (60) | |
| Mean number of days taken for completion of withdrawal treatment (n=12) | 44.40±9.6 | ||||
| Treatment acceptability as per treatment perception questionnaire score at 12 weeks (n=17) | 4.12 (4.0–4.45) | ||||
#Patients wished to change to OAT due to intense craving. ##No significant difference between those who were retained (n=20) and those who dropped out (n=10) in socio-demographic variables and clinical parameters like duration of opioid use, and other substance use (Mann-Whitney U Test, P>0.05)
DISCUSSION
To the best of our knowledge, this is the first study from India reporting observations on the feasibility of outpatient-based buprenorphine-assisted opioid withdrawal management through a longitudinal design. Outpatient treatment is often preferred as patients can easily maintain their daily routine, including work and family responsibilities. In the past, a few randomized controlled trials and reviews compared completion rates and relapse risk of the same between inpatient and outpatient settings.[12,13] However, the results were either inconclusive or did not reveal any difference in the outcome. About 66% retention at the end of 12 weeks in the current study could be due to the engagement of family member/s for medication supervision and flexible dosing. Family engagement has been found to be an independent predictor of retention in opioid agonist maintenance treatment.[14] A flexible dosing regimen of buprenorphine has been documented to prevent relapse.[15,16] The flexibility of our study design (it being an observational and not experimental study) allowed a change of treatment plan by the clinician. Thus, a few retained participants (5, 25%) were observed to be on withdrawal treatment beyond 12 weeks, and some (10, 18%) were shifted to agonist maintenance treatment. We regarded those on OAT as “retained” because a successful retention in withdrawal management permitted the treating psychiatrist to consider a change of their treatment to maintenance treatment. Among completers, the mean number of days taken for completion of withdrawal management was 44.39 ± 9.6 days, suggesting that outpatient withdrawal treatment takes longer duration than in an inpatient setting. The optimum duration of taper remains inconclusive with regard to retention and recovery rates and ranges from 2–120 days.[17] Interestingly, the 33% drop-out rate in the current “real world” setting is comparable to previous more controlled studies on the inpatient population (36% [6] and 37% [8]) which might be due to flexible and long duration of tapering in the present study making outpatient withdrawal management as comfortable and acceptable as in inpatient setting. The above all factors possibly contributed to a better abstinence rate at the end compared to previous reports.[5,17]
Fair treatment satisfaction reported by the treatment completers within the study period could be attributed to abstinence and minimal work-hour loss, hence, the absence of financial constraint. While as many as 33% of the patients dropped out of the study after the baseline assessment, this is comparable with the data from a Cochrane review for studies from outpatient settings.[6] Nevertheless, it is important to address the reasons for dropping out for improving retention and thereby the outcome.
Limitations of the study include a small sample size made even more challenging since the study was conducted immediately after the COVID-19 pandemic and lockdown. The limitations notwithstanding, the study is an important addition to the literature on the utility of outpatient treatment of acute opioid withdrawals using buprenorphine, considering the scarcity of inpatient addiction treatment facilities in the country.
CONCLUSION
The study findings indicate that managing opioid withdrawal is feasible in the outpatient setting using sublingual buprenorphine, especially when the family is involved in treatment and a flexible approach is adopted regarding dose and the overall treatment plan. Further studies with larger sample sizes are required to have a better understanding of factors improving outcomes.
Declaration regarding the use of generative AI
The author(s) attest that there was no use of generative artificial intelligence (AI) technology in the generation of text, figures, or other informational content of this manuscript.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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