Randomized Controlled Trial

. 2024 Apr;69(4):252-263.

doi: 10.1177/07067437231210796. Epub 2023 Oct 30.

Associations Between Buprenorphine\Naloxone and Methadone Treatment and non-Opioid Substance Use in Prescription-Type Opioid Use Disorder: Secondary Analyses From the OPTIMA Study: Associations entre le traitement avec la buprénorphine/naloxone et avec la méthadone et l'utilisation de substances non opioïdes dans le trouble lié à l'usage d'opioïdes de type sur ordonnance : analyses secondaires de l'étude OPTIMA

Hamzah Bakouni^{1

2}, Heidar Sharafi^{1

2}, Sarah Drouin^{1

2}, Raphaelle Fortin^{1

2}, Stéphanie Marsan^{1

3}, Suzanne Brissette^{1

3}, Maria Eugenia Socias^{4

5}, Bernard Le Foll^{6

7

8

9

10

11}, Ron Lim¹², Didier Jutras-Aswad^{1

2}

Affiliations

¹ Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
² Department of Psychiatry and Addictology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
³ Department of Family and Emergency Medicine, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
⁴ British Columbia Centre on Substance Use, Vancouver, British Columbia, Canada.
⁵ Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
⁶ Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁹ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, Ontario, Canada.
¹¹ Waypoint Research Institute, Waypoint Centre for Mental Health Care, Penetanguishene, Ontario, Canada.
¹² Department of Family Medicine and Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

PMID: 37899716
PMCID: PMC10924583
DOI: 10.1177/07067437231210796

Randomized Controlled Trial

Associations Between Buprenorphine\Naloxone and Methadone Treatment and non-Opioid Substance Use in Prescription-Type Opioid Use Disorder: Secondary Analyses From the OPTIMA Study: Associations entre le traitement avec la buprénorphine/naloxone et avec la méthadone et l'utilisation de substances non opioïdes dans le trouble lié à l'usage d'opioïdes de type sur ordonnance : analyses secondaires de l'étude OPTIMA

Hamzah Bakouni et al. Can J Psychiatry. 2024 Apr.

. 2024 Apr;69(4):252-263.

doi: 10.1177/07067437231210796. Epub 2023 Oct 30.

Authors

Affiliations

¹ Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada.
² Department of Psychiatry and Addictology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
³ Department of Family and Emergency Medicine, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
⁴ British Columbia Centre on Substance Use, Vancouver, British Columbia, Canada.
⁵ Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
⁶ Department of Pharmacology and Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁷ Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁹ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Translational Addiction Research Laboratory, Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, Toronto, Ontario, Canada.
¹¹ Waypoint Research Institute, Waypoint Centre for Mental Health Care, Penetanguishene, Ontario, Canada.
¹² Department of Family Medicine and Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

PMID: 37899716
PMCID: PMC10924583
DOI: 10.1177/07067437231210796

Abstract
in English, French

Objectives: There is limited evidence on how opioid agonist treatment (OAT) may affect psychoactive non-opioid substance use in prescription-type opioid use disorder (POUD) and whether this effect might explain OAT outcomes. We aimed to assess the effect of methadone on non-opioid substance use compared to buprenorphine/naloxone (BUP/NX), to explore whether non-opioid substance use is associated with opioid use and retention in treatment, and to test non-opioid use as a moderator of associations between methadone with retention in OAT and opioid use compared to BUP/NX.

Methods: This is a secondary analysis of data from the OPTIMA trial, an open-label, pragmatic, parallel, two-arm, pan-Canadian, multicentre, randomized-controlled trial to compare standard methadone model of care and flexible take-home dosing BUP/NX for POUD treatment. We studied the effect of methadone and BUP/NX on non-opioid substance use evaluated by urine drug screen (UDS) and by classes of non-opioid substances (i.e., tetrahydrocannabinol [THC], benzodiazepines, stimulants) (weeks 2-24) using adjusted generalized estimation equation (GEE). We studied the association between non-opioid substance-positive UDS and opioid-positive UDS and retention in treatment, using adjusted GEE and logistic regressions.

Results: Overall, methadone was not associated with non-opioid substance-positive UDS compared to BUP/NX (OR: 0.78; 95%CI, 0.41 to 1.48). When non-opioid substances were studied separately, methadone was associated with lower odds of benzodiazepine-positive UDS (OR: 0.63; 95% CI: 0.40 to 0.98) and THC-positive UDS (OR: 0.47; 95% CI: 0.28 to 0.77), but not with different odds of stimulant-positive UDS (OR: 1.29; 95% CI: 0.78 to 2.16) compared to BUP/NX. Substance-positive UDS, overall and separate classes, were not associated with opioid-positive UDS or retention in treatment.

Conclusion: Methadone did not show a significant effect on overall non-opioid substance use in POUD compared to BUP/NX treatment but was associated with lower odds of benzodiazepine and THC use in particular. Non-opioid substance use did not predict OAT outcomes. Further research is needed to ascertain whether specific patterns of polysubstance use (quantity and frequency) may affect treatment outcomes.

Objectifs: Les données probantes sont limitées en ce qui concerne la façon dont le traitement agoniste opioïde (TAO) peut influencer l’utilisation de substances psychoactives non opioïdes dans le trouble lié à l'usage d'opioïdes de type sur ordonnance (TUOO) et si cet effet pourrait avoir un impact sur les résultats du TAO. Nous visions à évaluer l’effet de la méthadone sur l’utilisation de substances non-opioïdes comparé à la buprénorphine/naloxone (BUP/NX) et à explorer si l’utilisation de substances non-opioïdes est associée à l’utilisation d’opioïdes et à la rétention en traitement. Nous cherchions à tester l’utilisation de non-opioïdes comme modérateur des associations de la méthadone avec la rétenton et l'usage d'opioïdes comparativement à la BUP/NX.

Méthodes: C’est une analyse secondaire des données de l’essai OPTIMA, un essai ouvert, pragmatique, parallèle, à deux volets, pancanadien, multicentrique, randomisé et contrôlé pour comparer le modèle de soins standard à la méthadone avec le dosage flexible à emporter de BUP/NX pour le traitement du TUOO. Nous avons étudié l’effet de la méthadone et de la BUP/NX sur l’utilisation de substance non-opioïde évaluée par dépistage de drogues dans l’urine (DDU) et par des classes de substances non-opioïdes (c.-à-d., tétrahydrocannabinol [THC], benzodiazépines, stimulants) (semaines 2–24) en utilisant l’équation d'estimation généralisée ajustée (EEGA). Nous avons étudié l’association entre le DDU de substances positives non-opioïdes et le DDU opioïde positif et la rétention en traitement, à l’aide de l’EEGA ajustée et des régressions logistiques.

Résultats: En général, la méthadone n’était pas associée à un DDU de substances non-opioïdes positives comparativement à la BUP/NX (RC : 0,78; IC à 95% 0,41 à 1,48). Quand des substances non-opioïdes ont été étudiées séparément, la méthadone était associée à des probabilités plus faibles de DDU de benzodiazépine positif (RC 0,63; IC à 95% 0,40 à −0,98) et de DDU de THC positif (RC 0.47; IC à 95% 0,28 à 0,77), mais pas avec des probabilités différentes de DDU de stimulants positif, (RC 1,29; IC à 95% 0,78 à 2,16) comparativement à la BUP/NX. Les DDU de substances positifs, en général et les classes séparées n’étaient pas associés au DDU d’opioïde positif ou à la rétention en traitement.

Conclusion: La méthadone n'a pas montré un effet significatif sur l’utilisation générale de substances non opioïdes dans le TAO comparativement au traitement de BUP/NX, mais elle était associée avec des probabilités plus faibles d’utilisation de benzodiazépine et de THC en particulier. L’utilisation de substances non-opioïdes ne prédisait pas les résultats du TAO. Il faut plus de recherche pour confirmer si les profils spécifiques d’utilisation de polysubstances (quantité et fréquence) peuvent affecter les résultats du traitement.

Keywords: buprenorphine; buprénorphine; methadone; méthadone; opioid replacement therapy; opioid use disorder; retention; rétention; thérapie de remplacement d'opioïdes; trouble d'utilisation d'opioïde.

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Conflict of interest statement

Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DJ-A receives study material from Cardiol Therapeutics and Exka for trials funded by public funding bodies. BLF has obtained funding from Pfizer Inc. (GRAND Awards, including salary support) for investigator-initiated projects. He has obtained funding from Indivior for a clinical trial sponsored by Indivior. He has in-kind donations of cannabis products from Aurora Cannabis Enterprises Inc. and study medication donations from Pfizer Inc. (varenicline for smoking cessation) and Bioprojet Pharma. He was also provided a coil for a Transcranial magnetic stimulation (TMS) study from Brainsway. He has obtained industry funding from Canopy Growth Corporation (through research grants handled by the Centre for Addiction and Mental Health and the University of Toronto), Bioprojet Pharma, Alcohol Countermeasure Systems (ACS), Alkermes and Universal Ibogaine. He has received in-kind donations of nabiximols from GW Pharmaceuticals for past studies funded by CIHR and the National Institutes of Health (NIH). He has participated in a session of a National Advisory Board Meeting (Emerging Trends BUP-XR) for Indivior Canada and has been consultant for Shinogi. MES has received partial support from Indivior's Investigator Initiated Study programme for work outside this study. SM has participated in a session of a national advisory board meeting for Indivior Canada as well as for Abbvie Canada.The OPTIMA clinical trial was registered on clinicaltrials.gov before the enrollment of the first participant (NCT03033732).

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Abstract
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Medical

Abstract in English, French

Conflict of interest statement

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Medical

Abstract
in English, French