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

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2 Scopus citations

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.

Original languageEnglish
Pages (from-to)284-294
Number of pages11
JournalAddiction
Volume118
Issue number2
DOIs
StatePublished - Feb 2023

Keywords

  • Clinical trial
  • methadone
  • opioid agonist treatment
  • opioid substitution treatment
  • opium
  • opium tincture
  • retention

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