Opium tincture versus methadone for opioid agonist treatment: a randomized controlled trial

Mohammadali Nikoo; Kiana Kianpoor; Nooshin Nikoo; Sanam Javidanbardan; Alireza Kazemi; Fiona Choi; Marc Vogel; Ali Gholami; Saeed Tavakoli; James S H Wong; Ehsan Moazen-Zadeh; Reza Givaki; Majid Jazani; Fatemeh Mohammadian; Nader Markazi Moghaddam; Christian Schütz; Kerry Jang; Shahin Akhondzadeh; Michael Krausz

doi:10.1111/add.16030

Opium tincture versus methadone for opioid agonist treatment: a randomized controlled trial

Addiction. 2023 Feb;118(2):284-294. doi: 10.1111/add.16030. Epub 2022 Sep 7.

Authors

Mohammadali Nikoo¹, Kiana Kianpoor¹, Nooshin Nikoo², Sanam Javidanbardan², Alireza Kazemi¹, Fiona Choi¹, Marc Vogel^{3

4}, Ali Gholami⁵, Saeed Tavakoli⁶, James S H Wong^{1

7}, Ehsan Moazen-Zadeh⁸, Reza Givaki⁹, Majid Jazani¹⁰, Fatemeh Mohammadian¹⁰, Nader Markazi Moghaddam¹¹, Christian Schütz¹, Kerry Jang¹, Shahin Akhondzadeh¹², Michael Krausz¹³

Affiliations

¹ Institute of Mental Health, Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
² Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
³ Division of Substance Use Disorders, Psychiatric Services of Thurgovia, Münsterlingen, Switzerland.
⁴ Division of Substance Use Disorders, University of Basel Psychiatric Clinics, Basel, Switzerland.
⁵ Kian Methadone Maintenance Treatment Clinic, Private Practice, Sari, Mazandaran, Iran.
⁶ Rooz-e-No, Methadone Maintenance Treatment Clinic (Private Practice), Shiraz, Fars, Iran.
⁷ Complex Pain and Addiction Consult Service, Vancouver General Hospital, Vancouver, BC, Canada.
⁸ Addiction Institute of Mount Sinai, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, NY, USA.
⁹ Psychosomatic Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
¹⁰ Sales, Marketing, Export and Medical Department, Darou Pakhsh Pharmaceutical Manufacturing Company, Tehran, Iran.
¹¹ Department of Health Management and Economics, School of Medicine, AJA University of Medical Sciences, Tehran, Iran.
¹² Psychiatric Research Center, Roozbeh Hospital, Department of Psychiatry, Faculty of Medicine, Tehran University of Medical Sciences, Iran.
¹³ Institute of Mental Health, Centre for Health Evaluation and Outcome Sciences, Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.

PMID: 35971297
DOI: 10.1111/add.16030

Abstract

Aim: To test if opium tincture (OT) was non-inferior to methadone in retaining participants in opioid agonist treatment (OAT).

Design: A Phase III, multi-centre, parallel-group, non-inferiority, double-blind randomized controlled trial with an allocation ratio of 1:1. Participants were provided treatment and followed for a period of 85 days.

Setting: Four OAT clinics in Iran.

Participants: Two hundred and four participants with opioid use disorder [mean age (standard deviation) = 37.4 (9.3); female 11.3%] recruited between July 2017 and January 2018.

Interventions: Participants were assigned to either OT (102) or methadone (102) using a patient-centred flexible dosing strategy.

Measurements: Treatment retention over 85 days was the primary outcome. Self-reported opioid use outside treatment and occurrence of adverse events (AEs) were the secondary outcomes.

Findings: Remaining in treatment at the end of the follow-up were 68.6% in the methadone arm and 59.8% in the OT arm. The relative retention rate of methadone to OT was 1.15 (0.97, 1.36) in both intent-to-treat and per-protocol analyses; non-inferiority was not supported statistically, as the upper bound of the confidence interval exceeded our pre-specified non-inferiority margin (1.25). Opioid use outside treatment was reported by 30.3% of OT (n = 152) and 49.4% of methadone (n = 168) patients, a difference in proportions of -19%: 90% confidence interval (-28%, -10%). The total count of AEs in the OT arm (22 among nine individuals) was significantly higher (P = 0.04) than that in the methadone arm (three among two individuals). Nausea was the most common side effect.

Conclusion: While this study could not conclude the non-inferiority of opium tincture (OT) to methadone for retaining patients in opioid agonist treatment, OT retained 60% of participants to end of follow-up (85 days) and was superior to methadone in reducing self-reported opioid use outside treatment.

Trial registration: ClinicalTrials.gov NCT02502175.

Keywords: Clinical trial; methadone; opioid agonist treatment; opioid substitution treatment; opium; opium tincture; retention.

Publication types

Randomized Controlled Trial
Multicenter Study
Clinical Trial, Phase III
Research Support, Non-U.S. Gov't

MeSH terms

Analgesics, Opioid / therapeutic use
Double-Blind Method
Female
Humans
Methadone* / therapeutic use
Opiate Substitution Treatment / methods
Opioid-Related Disorders* / drug therapy
Opioid-Related Disorders* / rehabilitation
Opium / therapeutic use

Substances

Methadone
Opium
Analgesics, Opioid

Associated data

ClinicalTrials.gov/NCT02502175