History of the discovery, development, and FDA-approval of buprenorphine medications for the treatment of opioid use disorder

Heidbreder, Christian; Fudala, Paul J.; Greenwald, Mark K.

doi:10.1016/j.dadr.2023.100133

Cited by 22 publications

(11 citation statements)

References 102 publications

(107 reference statements)

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“…59 Federal regulatory agency concern for buprenorphine diversion dates to the 1990s when the BUP/NX combined product was developed to "minimize the likelihood of diversion." 60 More recently, the same concern for diversion drove development of XR-BUP formulations. 60 An actionable item at the 2014 Buprenorphine Summit convened by SAMHSA and the National Institutes of Health demonstrates the assumed linkage between higher doses and diversion: "Provide guidance to the field about the range of possible effective doses, and the lack of evidence for added benefit of more than 24 mg daily, to reduce habitual overprescribing that may be fueling diversion."…”

Section: Diversionmentioning

confidence: 99%

“…60 More recently, the same concern for diversion drove development of XR-BUP formulations. 60 An actionable item at the 2014 Buprenorphine Summit convened by SAMHSA and the National Institutes of Health demonstrates the assumed linkage between higher doses and diversion: "Provide guidance to the field about the range of possible effective doses, and the lack of evidence for added benefit of more than 24 mg daily, to reduce habitual overprescribing that may be fueling diversion." 61 That specified dose limit references the FDA's inaccurate claim of no clinical advantage greater than 24 mg/d.…”

Section: Diversionmentioning

confidence: 99%

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Evidence on Buprenorphine Dose Limits: A Review

et al. 2023

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Objectives: As overdose deaths from fentanyl continue to increase, optimizing use of medications for opioid use disorder has become increasingly important. Buprenorphine is a highly effective medication for reducing the risk of overdose death, but only if a patient remains in treatment. Shared decision making between prescribers and patients is important to establish a dose that meets each patient's treatment needs. However, patients frequently face a dose limit of 16 or 24 mg/d based on dosing guidelines on the Food and Drug Administration's package label. Methods: This review discusses patient-centered goals and clinical criteria for determining dose adequacy, reviews the history of buprenorphine dose regulation in the United States, examines pharmacological and clinical research results with buprenorphine doses up to 32 mg/d, and evaluates whether diversion concerns justify maintaining a low buprenorphine dose limit. Results: Pharmacological and clinical research results consistently demonstrate buprenorphine's dose-dependent benefits up to at least 32 mg/d, including reductions in withdrawal symptoms, craving, opioid reward, and illicit use while improving retention in care. Diverted buprenorphine is most often used to treat withdrawal symptoms and reduce illicit opioid use when legal access to it is limited. Conclusions: In light of established research and profound harms from fentanyl, the Food and Drug Administration's current recommendations on target dose and dose limit are outdated and causing harm. An update to the buprenorphine package label with recommended dosing up to 32 mg/d and elimination of the 16 mg/d target dose would improve treatment effectiveness and save lives.

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Section: Diversionmentioning

confidence: 99%

Section: Diversionmentioning

confidence: 99%

Evidence on Buprenorphine Dose Limits: A Review

et al. 2023

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“…While this progress is promising, considerable groundwork remains before psychedelics may be safely disseminated in clinical settings to treat SUDs. Prior to obtaining FDA approval in 2002, sublingual buprenorphine, an effective pharmacotherapy for opioid use disorder, was evaluated in 3 phase 3 randomized clinical trials (RCTs), which collectively enrolled 1224 participants . Meanwhile, recently published findings from US psychedelic trials for SUD treatment are limited to a single phase 2 RCT of psilocybin for alcohol use disorder (AUD) (n = 95) and 2 small psilocybin pilot studies for AUD (n = 10) and tobacco use disorder (n = 15) .…”

Section: Expand Public Funding For Psychedelics Researchmentioning

confidence: 99%

“…Prior to obtaining FDA approval in 2002, sublingual buprenorphine, an effective pharmacotherapy for opioid use disorder, was evaluated in 3 phase 3 randomized clinical trials (RCTs), which collectively enrolled 1224 participants. 6 Meanwhile, recently published findings from US psychedelic trials for SUD treatment are limited to a single phase 2 RCT of psilocybin for alcohol use disorder (AUD) (n = 95) and 2 small psilocybin pilot studies for AUD (n = 10) and tobacco use disorder (n = 15). 7 Streamlining regulatory hurdles associated with conducting research with Schedule I substances may reduce administrative burdens among sponsors and expand clinical investigations in this domain.…”

Section: Expand Public Funding For Psychedelics Researchmentioning

confidence: 99%

“…5 Analogously, while the FDA approval of buprenor-phine expanded opioid use disorder treatment access by authorizing office-based prescribing of an opioid-based maintenance medication, considerable racial disparities in buprenorphine use ensued. 2,6 Moreover, all modern US psychedelic clinical trials include components of psychotherapy administered by licensed clinicians, yet high-quality therapy is cost prohibitive for many people with severe addictions. The brief psychotherapy models used in clinical trials are also potentially concerning for treating SUDs, which are considered chronic relapsing disorders and require ongoing supportive care-particularly during abstinence, when return to drug use may pose overdose risks.…”

Section: Avoid Reliance On a Strictly Medical Modelmentioning

confidence: 99%

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Psychedelics in Addiction Treatment—Navigating a Sociopolitical Rift

Mehtani,

Anderson,

Mitchell

2024

JAMA Neurol

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Differential Effects of Prenatal Buprenorphine and Methadone on Postnatal Growth and Gene Expression in the Nucleus Accumbens

Gildawie,

Budge,

Vassoler

et al. 2024

Developmental Psychobiology

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Methadone and buprenorphine are commonly prescribed during pregnancy to maintain recovery and prevent symptoms of withdrawal in women with opioid use disorder. Infants prenatally exposed to medications for opioid use disorder (MOUD), however, commonly show signs of neonatal opioid withdrawal syndrome (NOWS), which can include feeding‐related issues like hyperphagia. To investigate the effects of prenatal MOUD exposure on feeding behavior, female Sprague‐Dawley rats were implanted with osmotic minipumps filled with methadone, buprenorphine, or saline and subsequently mated. On postnatal day (PND) 1, buprenorphine‐ and methadone‐exposed offspring weighed less than saline‐exposed subjects. Throughout early postnatal development (PND2, 7, and 12), this reduction in weight persisted in buprenorphine, but not methadone, offspring. RNAscope in situ hybridization was then used to measure expression of genes in the nucleus accumbens (NAc) previously associated with hyperphagia in NOWS infants, including proopiomelanocortin (Pomc), neuropeptide Y2 receptors (Npy2r), and dopamine type 2 receptors (Drd2). Distinct developmental expression patterns were noted across the postnatal period, with few effects of MOUD; however, significantly lower Pomc expression was observed in methadone‐exposed but not buprenorphine‐exposed offspring. These findings demonstrate differential effects of methadone and buprenorphine on offspring development and gene expression, highlighting differences in offspring outcomes associated with these two MOUDs.

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History of the discovery, development, and FDA-approval of buprenorphine medications for the treatment of opioid use disorder

Cited by 22 publications

References 102 publications

Evidence on Buprenorphine Dose Limits: A Review

Evidence on Buprenorphine Dose Limits: A Review

Psychedelics in Addiction Treatment—Navigating a Sociopolitical Rift

Differential Effects of Prenatal Buprenorphine and Methadone on Postnatal Growth and Gene Expression in the Nucleus Accumbens

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