Call for Study Update: The Flood of Opioids Must be Matched with a Flood of Opioid Treatments

Albert Stuart Reece, MBBS, MD | University of Western Australia and Edith Cowan University

This study compared sublingual buprenorphine with monthly naltrexone injections. For a recent period this was a clinically meaningful comparison.

Buprenorphine may also be given by long acting depot injections which nominally last for one month. In USA these brands include Brixadi and Sublocade, whilst in Australia the brands are Buvidal and Sublocade. Their PI says that they can be active in the treatment of opioid use disorder for one month [1,2]. Sublocade has a very long terminal half life[2] which has many clinical applications including: in many patients injections can be given at intervals much longer than one month; patients experience less fluctuation in their perceived period of opioid instability; the “detox” transition to complete sobriety even from prescribed opioids is often much easier and in practice in many cases is so symptom-free that patients “forget” to dose because they are symptomless. Buprenorphine injections are easy to use for both patients and clinician. Compliance is greatly improve[3]; but even where compliance is suboptimal it can easily be rescued.[4,5] Weekly injections of Buvidal / Brixadi can be given even when patients are actively using short acting narcotics and thus treatment initiation is streamlined and straightforward.[5,6] These and other advantages have inevitably transformed the treatment of opioid dependence.

Groups in several countries have developed long acting naltrexone preparations delivered either by trocar injection or minor surgical procedure lasting several months to up to nine months. An implant developed in Western Australia and trialled by NIH in New York is active for 6-9 months.[7] Protection against mortality comparable to that afforded by methadone has been demonstrated[8] and they have been shown to interrupt the overdose history of high risk patients with recurrent overdoses.[9] Naltrexone seems like an obvious pathway to complete sobriety from all opioids.

Naltrexone and buprenorphine can also be used sequentially and dove tailed in elegant treatment combinations and together readily bring a completely drug free lifestyle easily within the reach of all who may desire it.[10] Psychosocial supports are critically important to attain and secure stability for all substance dependent patients. But such medical techniques mean that the physical detox which was until recently unattainable for many now falls within easy reach for the majority.[10]

Comparative clinical trials may be conducted of these modalities but the real health care imperative is expanding treatment access to desperately vulnerable cohorts.

In our efforts to reign in appalling narcotic statistics we obviously require access to the best treatments available both for our substance dependence and general medical workforces, and for patients currently both in and out of treatment. Wider dissemination of such transformative treatments is urgently required.

References
1. Brixadi Prescribing Information (US FDA) 54 (2025).
2. Sublocade Prescribing Information (US FDA) 47 (2026).
3. Marsden J, Kelleher M, Gilvarry E, et al. Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial. EClinicalMedicine. Dec 2023;66:102311. doi:10.1016/j.eclinm.2023.102311
4. Daglish MRC, Hayllar JS, McDonough M. An Australian retrospective observational cohort comparison of the use of long-acting injectable buprenorphine products. J Subst Use Addict Treat. Jul 2024;162:209348. doi:10.1016/j.josat.2024.209348
5. Naren T, Membrey D, MacCartney P, D’Cunha R, Nielsen S, Garry S. Feasibility of direct induction onto long-acting injectable buprenorphine. J Subst Use Addict Treat. Dec 2025;179:209808. doi:10.1016/j.josat.2025.209808
6. Lee KW, Mead A, Ghauri I, Hollett B, Drolet M, Kozicky JM. Initiation and Dosing of Extended-Release Buprenorphine: A Narrative Review of Emerging Approaches for Patients Who Use Fentanyl. Subst Abuse Rehabil. 2025;16:71-82. doi:10.2147/sar.S516138
7. Comer SD, Sullivan MA, Yu E, et al. Injectable, sustained-release naltrexone for the treatment of opioid dependence: a randomized, placebo-controlled trial. Arch Gen Psychiatry. Feb 2006;63(2):210-8. doi:63/2/210 [pii]
10.1001/archpsyc.63.2.210
8. Tait RJ, Ngo HT, Hulse GK. Mortality in heroin users 3 years after naltrexone implant or methadone maintenance treatment. J Subst Abuse Treat. Sep 2008;35(2):116-24. doi:10.1016/j.jsat.2007.08.014
9. Hulse GK, Tait RJ, Comer SD, Sullivan MA, Jacobs IG, Arnold-Reed D. Reducing hospital presentations for opioid overdose in patients treated with sustained release naltrexone implants. Drug Alcohol Depend. Sep 1 2005;79(3):351-7. doi:10.1016/j.drugalcdep.2005.02.009
10. McLellan AT, Volkow ND. Goals for Opioid Use Disorder Medications – Protection, Remission, and Recovery. N Engl J Med. Oct 2 2025;393(13):1253-1255. doi:10.1056/NEJMp2505377 (Complete Research go to JAMA Network)