Research – EFFECTIVENESS
Treatment for opioid addiction
without medications
may be worse than no treatment at all.
Yale scientists found that those with OUD receiving treatment without methadone or buprenorphine were 75% more likely to die of an opioid-related overdose than those receiving no treatment at all. But treatment with methadone or buprenorphine reduced fatal overdose by over a third.
Heimer R, et. al. Receipt of opioid use disorder treatments prior to fatal overdoses and comparison to no treatment in Connecticut, 2016–17. Drug and Alcohol Dependence. Volume 254, January 2024, 111040.
Medication treatment led to 80%
lower risk of fatal overdose.
In this Retrospective cohort study, subjects experienced 371 opioid overdose deaths overall. During periods in medication treatment, there was a substantially lower risk of opioid overdose death compared with periods in non-medication treatment [adjusted hazard ratio (aHR) = 0.18, 95% confidence interval (CI) = 0.08–0.40].
Krawczyk N, et al. Opioid agonist treatment and fatal overdose risk in a state-wide US population receiving opioid use disorder services. September 2020. Addiction. 115(9):1683-1694
Buprenorphine or methadone were the only
treatments that reduced the risk of overdose.
Among over 40,000 individuals with OUD, only treatment with buprenorphine or methadone reduced the risk of overdose and serious opioid-related acute care use, compared with no treatment, during 3 and 12 months of follow-up. Neither inpatient detoxification, residential services, intensive behavioral health, or naltrexone treatment, without buprenorphine or methadone, resulted in a reduction in overdose deaths.
Wakeman, Sarah E. et al. Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder. Journal of the American Medical Association Network Open. February 2020; 3(2).
A 79% drop in overdose deaths after the widespread introduction of buprenorphine.
Starting in 1995, the French government successfully introduced and encouraged buprenorphine treatment for OUD, reimbursing physicians for this nationwide, so that by 1999 an estimated 80% of individuals with OUD were treated with buprenorphine. From 1995 to 1999, the number of overdose deaths declined by 79%.
Auriacombe M, et al. French field experience with buprenorphine. American Journal of Addiction 2004;13 (suppl 1):S17
"Methadone / Bup treatment without counseling is vastly superior to no treatment."
According to Nora Volkow MD, the Director of NIDA (National Institute for Drug Abuse), “Higher doses of methadone are associated with better retention in treatment, less heroin use during treatment and lower withdrawal symptoms . . . Studies suggest that longer time in treatment is associated with better outcomes and that the risk of relapse greatly increases after medication discontinuation . . .
It is also important to know which patients, when and under what circumstances can safely discontinue MOUD. Current evidence indicates that counseling or psychotherapy do not increase retention in buprenorphine treatment or improve abstinence rates (Timko 2016) (Cushman 1978) (Morgan 2018) (Nosyk 2012) (Sordo 2017) and that methadone treatment (Schwartz 2006) and buprenorphine without counseling is vastly superior to no treatment. (Simon 2017)”
Volkow, ND & Blanco, The Changing Opioid Crisis: development, challenges and opportunities. Molecular Psychiatry. 2021 January; 26(1): 218.
Methadone & buprenorphine:
"Proven life-savers in clinical trial after clinical trial."
According to the Director of the National Institute on Drug Abuse, “methadone … and buprenorphine have proven to be life-savers … enabling [patients] to live healthy and successful lives, and facilitating recovery… The efficacy of MOUD has been supported in clinical trial after clinical trial, and is considered the standard of care in treatment of OUD, whether or not it is accompanied by some form of behavioral therapy.”
Overdose survivors who do not get
methadone or buprenorphine
are more likely to die.
A review of records of over 17,000 adults who had survived on opioid overdose showed that those treated with buprenorphine had 37% fewer opioid-related deaths within 12 months, compared with those who did not receive MOUD. Those treated with methadone had 50% fewer opioid deaths. .
Marc R Larochelle MR, et al. Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study. Annals of Internal Medicine 2018 Aug 7;169(3):137-145.
Up to 33 years of follow-up on and off of MOUD found that longer periods on MOUD are associated
with a greater chance of abstinence.
Overall, death rates, mostly from overdose, were high and increased over time. After ten years, abstinence rates decreased to about 30%.
This review of all 23 published studies with long-term follow-up of OUD patients (3 to 33 years) confirms that OUD is a chronic, relapsing disorder characterized by long-term trajectories of recurring use and treatment episodes.
Most subjects were initially identified in methadone treatment programs. Of those still alive, abstinence rates decreased over time to about 30% or lower after ten years of observation, and remained stable thereafter.
Death rates, mostly from overdose, increased over time and were 6 to 20 times that of the general population.
Hser Y-I et al. Long-Term Course of Opioid Addiction. Harvard Review of Psychiatry. 2015; Volume 23(2)
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13 % of patients who tapered off of methadone had successful outcomes
In a large, population-based retrospective study, 13 percent of patients who tapered from methadone had successful outcomes (no treatment reentry, death, or opioid-related hospitalization within 18 months after taper).
Nosyk B, et al. (2012). Defining dosing pattern characteristics of successful tapers following methadone maintenance treatment: Results from a population-based retrospective cohort study. Addiction, 107(9), 1621–1629.
3-fold reduction in mortality with methadone or buprenorphine in a
review of eligible studies
This review of all available published studies that met inclusion criteria found a 3-fold reduction in mortality from methadone or buprenorphine over 1 – 4.5 years. For methadone treatment, all-cause mortality rates were 36.1 and 11.3 per 1000 person-years while out of, and in methadone treatment, respectively. This is a 3.2-fold higher all-cause death rate while out of methadone treatment vs in treatment (95% confidence interval 2.65 to 3.86). For buprenorphine, all-cause death rates were 2.2-fold higher while out of treatment vs. in treatment.
Overdose mortality results were similar. There were 4.8-fold more overdose deaths while out of methadone treatment vs. in treatment, and 3.3 fold more overdose deaths while out of buprenorphine treatment vs. in treatment.
Sordo, L, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. British Medical Journal 2017 Apr 26:357:j1550.
Editorial: The well conducted systematic review by Sordo and colleagues includes long term follow-up from the highest quality observational cohort studies. . . practitioners might want to discuss their findings with patients. This is in addition to the evidence of lower HIV transmission, improved social functioning, and reduced criminal behavior.
Editorial, British Medical Journal. 2017 Apr 26;357:j1947. Ajay Manhapra, Robert Rosenheck, David A Fiellin
Methadone, buprenorphine, and naltrexone, are the most effective interventions for opioid addiction
Fipps DC, et al. Opioid maintenance therapy: A review of methadone, buprenorphine, and naltrexone treatments for opioid use disorder. Seminars in Neurology, 44 (04) (2024), pp. 441-451, 10.1055/s-0044-1787571
Maintenance medication for opioid addiction is the Foundation of Recovery
“Treatment for opiate addiction requires long-term management. Behavioral interventions alone have extremely poor outcomes, with more than 80% of patients returning to drug use. Similarly poor results are seen with medication assisted tapering . . . Longer periods of tapering (1–6 months) with methadone or buprenorphine are also ineffective in promoting abstinence beyond the initial stabilization period . . . maintenance medication provides the best opportunity for patients to achieve recovery from opiate addiction. Extensive literature and systematic reviews show that maintenance treatment with either methadone or buprenorphine is associated with retention in treatment, reduction in illicit opiate use, decreased craving, and improved social function.”
Bart G, Maintenance medication for opioid addiction: the Foundation of Recovery.Journal of Addictive Diseases. 2012; 31(3):207.
Long-acting injectable naltrexone (Vivitrol) is not a first-line treatment for most individuals with moderate to severe opioid use disorder.
Methadone and buprenorphine are the only treatments for OUD that reduce overdose deaths. Long-acting injectable naltrexone (‘Vivitrol’) is an important option for some, with less evidence of effectiveness.