Sarah E. Wakeman，醫學博士和 Leo Beletsky，法學博士，公共衛生學碩士 /
n engl j med 388;18 / 2023 年 5 月 4 日
根據美國國家衛生統計中心的數據，2021 年是有記錄以來美國藥物過量危機死亡人數最多的一年。 然而，2022 年底出現了期待已久的政策變化，這可能有助於扭轉藥物過量致死人數增加的趨勢。 作為聯合撥款法案的一部分，聯邦政府取消了『X 豁免』，這是一個阻礙臨床醫生為阿片類藥物使用障礙者 (opioid use disorder,OUD) 提供救命丁基原啡因 (buprenorphine) 治療能力的監管障礙。 X 豁免將選擇丁基原啡因的使用權限制在從緝毒局 (DEA) 獲得特別許可並接受無償培訓的處方者上。 這些開處方者除受到隨機審計，他們並面臨可以使用丁基原啡因治療的患者之數量上限。 該政策包含了丁基原啡因治療比其他類型的醫療更複雜、風險更大的錯誤觀念，並助長了對阿片類藥物使用障礙患者的污名化。 這項變更允許任何擁有 DEA 通用許可證（開立任何受管制物質處方所需）的處方者可提供丁基原啡因，使成癮治療與其他健康狀況的治療方法保持一致。終於，X 被“X’ed”（『X 豁免』變成過去式）了。
但這項改革對公共衛生的積極影響並不能保證。聯邦政府已經宣布了一項額外要求，即對開具包括丁基原啡因在內的管制物質處方的處方者進行 8 小時的成癮相關培訓。那些要申請或更新 DEA 註冊的從業者需要接受這種教育，但如具有成癮相關專業的醫生和自 2018 年以來從具有綜合成癮課程的學校畢業的各種從業者除外。
應提供了一些選項來滿足此要求，包括靈活的培訓格式、來源和完成時間。 即便如此，我們認為對不堪重負的勞動力強加任何新的繁重要求都是有問題的。 臨床醫生在開管制藥物時變得越來越猶豫，如果因此開處方者選擇完全不去獲得 DEA 許可，將會有更多患者受到傷害。我們認為，一個更明智的長期替代方案是要求在醫學院、住院醫師計畫和其他培訓計畫中進行成癮治療教育，作為課程的核心組成部分，以便所有未來的從業者在他們的職業生涯中都能滿足這一訓練要求。醫學委員會可能會在現有的執照考試中增加考題，從而推動課程改革；領先的醫學教育組織，如美國醫學院協會，強制要求教授此類內容；或研究生醫學教育認證委員會將成癮醫學教育添加到其核心計畫的要求當中。
除了聯邦要求外，一些州還提議制定超出此新框架的培訓之要求或其他限制。 例如，阿拉巴馬州建議對丁基原啡因治療實施更嚴格的規定，包括強制要求更頻繁的就診次數、不允許服用某些精神科藥物的患者同時接受治療，以及在治療期間要求諮詢。這些干預措施的科學依據尚不清楚；至少在某些司法管轄區，錯誤的信息可能會驅使州之決策者設置新的——而且更繁重的——障礙，即使聯邦障礙正在被拆除。
Covid-19 公共衛生緊急事件即將結束，以及遠程醫療靈活性的潛在恢復——這擴大了丁基原啡因治療的可及性——但也對服務的取得構成了威脅。 儘管緝毒局 (DEA) 提議繼續允許純音頻遠程醫療用於丁基原啡因治療，但新的規則草案還要求在藥物開始後 30 天內進行現場親自就診。 這樣的要求可能會使治療無法獲得，因為醫療保健系統仍在從大流行中恢復，患者有時需要等待數月才能獲得當面預約。
我們認為取消 X 豁免是必要的，但不足以實現預防藥物過量的目標。 根據疾病控制和預防中心的數據，有鑑於種族和族裔差異不斷惡化，採取進一步行動將尤為重要，黑人、美國印第安人和阿拉斯加原住民中服藥過量致死人數的相對增幅最大。有必要進行額外的改革，以促進開處方者能採用阿片類藥物使用障礙之治療並解決其他障礙。 X 豁免是拯救生命的介入措施中繁重和不必要障礙的一個例子，但還有許多其他障礙，包括阻礙獲得減害服務的美沙酮相關法規和政策。
美沙酮的使用與之丁基原啡因的使用一樣，與特定的藥物過量死亡率和全因死亡率的降低有關。美國與其他許多由醫生開處方和藥店配藥的國家不同，一直保持著將美沙酮配藥限制在以下情況的法規：侷限在阿片類藥物治療計畫 (OTP) 下。 該政策將某些形式的阿片類藥物使用障礙之治療從醫療系統中剝離出來，要求患者在接受藥物治療之前每天看診 OTP 數月或數年，並且由於「不要在我家後院」（鄰避效應）的情緒，通常意味著患者必須在位於貧困、公共吸毒和犯罪挑戰的社區的診所排隊等候。
阿片類藥物治療計畫 (OTP) 的提供位置也產生了重要的影響。 首先，它創建了一個種族主義的兩級系統，其中白人和富裕社區更容易獲得丁基原啡因，而美沙酮治療則集中在黑人、拉丁裔和貧困社區。其次，它要求試圖獲得 OUD 治療的人們每天拜訪可能與活躍吸毒有關的區域，從而增加當前再次吸毒的風險。 第三，它在公眾心目中將美沙酮治療與可能在同一地理區域可見的混亂藥物使用混為一談。 例如，在波士頓，一個受露天吸毒和無家可歸影響的地區被貼上了貶義的標籤「美沙酮里」，該地區也是兩個 OTP 的所在地。 最後，在獲得美沙酮方面存在著很大的地區差異，在農村地區擁有廣闊的治療沙漠。最近的一項研究發現，OTP 的數量相對於各州人口亦存在顯著差異，範圍從懷俄明州沒有半個存在到羅德島每 100,000 名居民有 2.1 個。
我們認為，聯邦政府應該透過重新考慮美沙酮有關之法規，在擴大 OUD 藥物可及性方面繼續取得重要進展。更以患者為中心、更便於獲取的美沙酮之治療模式在許多國家已成為常態。反對改變美沙酮法規的批評者將對美沙酮過量服用的擔憂作為維持現狀的理由。儘管使用美沙酮有好處，但在誘導期間過量服用的風險會增加。這種風險增加可能是由於美沙酮劑量緩慢向上調整而持續使用其他鴉片類藥物所致，但美沙酮的藥物代謝動力學也可能意味著在開始階段需要更加謹慎。
自 Covid-19 大流行開始以來收集的數據——在此期間允許擴大和更靈活的帶回家美沙酮劑量——顯示改善了患者體驗和治療的存留，而且沒有明顯證據顯示與美沙酮相關過量服用的增加，這支持潛在的改革。在解決用藥過量問題的同時擴大獲取範圍的第一步可能是允許通過 OTP 治療穩定的患者過渡到由全科醫生提供的辦公室照護，並允許專門從事成癮醫學或成癮精神病學的醫生啟動和提供持續的美沙酮治療。具有聯邦評估合格的健康中心也可以作為美沙酮的關鍵獲取點。
此外，一些政策變化和金融投資可以幫助確保所有有藥物過量風險的人都能得到他們需要的治療和減少傷害的服務。 培訓之計畫置需要持續的聯邦資金，包括成癮醫學和成癮精神病學研究金職位；允許執業護士、心理學家、社會工作者和心理健康諮商師接受成癮專業培訓的計畫；以及支持全科醫生提供毒癮治療的計畫。 通過創造融資機會、實施相關品質措施和增加認證要求來激勵衛生系統提供綜合和低門檻的治療，可以幫助確保採用循證之照護。 最後，支持減害計畫的政策和資金——例如允許聯邦資金用於注射針具獲取計畫的政策； 資助擴大藥物檢查服務，使人們能夠測試藥物的成分以減少過量服用的風險； 藥物過量預防場所的合法化和資助——是必要的。
X 豁免是提供成癮治療服務的巨大障礙，現在已被消除。 我們認為有必要繼續這一進展並推動更多變革以擴大美沙酮的使用範圍，投資成癮治療人員，為衛生系統提供成癮治療的激勵措施，並擴大減少傷害計畫。
作者提供的披露表可在 NEJM.org 獲取。
來自麻薩諸塞州總醫院 (S.E.W.)、哈佛醫學院 (S.E.W.) 以及東北大學 法學院和 Bouvé 健康科學學院的醫學系(L.B.)——都在波士頓； 加州大學聖地亞哥分校醫學院醫學系傳染病和全球公共衛生處（L.B.）。 本文於 2023 年 4 月 29 日發表在 NEJM.org。
Beyond the X — Next Steps in Policy Reforms to Address the Overdose Crisis
Sarah E. Wakeman, M.D., and Leo Beletsky, J.D., M.P.H. / n engl j med 388;18 / May 4, 2023
According to the National Center for Health Statistics, 2021 was the deadliest year on record for the drug-overdose crisis. The end of 2022, however, was marked by a long-awaited policy change that could help reverse the trend of increasing overdose deaths. As part of the Consolidated Appropriations Act, the federal government eliminated the “X waiver,” a regulatory barrier that had impeded clinicians’ ability to offer lifesaving buprenorphine treatment for opioid use disorder (OUD). The X waiver limited buprenorphine privileges to prescribers who opted to get a special license from the Drug Enforcement Administration (DEA) and underwent uncompensated training. Such prescribers were subject to random audits and faced caps on the number of patients they could treat with buprenorphine. This policy enshrined a mistaken notion of buprenorphine treatment as more complicated and riskier than other types of medical care and contributed to stigma against people with OUD. The change allows any prescriber with a general DEA license — which is required to prescribe any controlled substance — to offer buprenorphine, thereby aligning addiction treatment with the approach to other health conditions. At long last, the X has been “X’ed.”
But positive public health effects of this reform aren’t guaranteed. The federal government has already announced an additional requirement of an 8-hour addiction-related training for prescribers of controlled substances, including buprenorphine. This education will be required for practitioners applying for or renewing their DEA registration, with the exception of physicians with addiction-related specializations and various practitioners who graduated since 2018 from schools with comprehensive addiction curricula.
Some options are provided for meeting this requirement, including a flexible training format, source, and time of completion. Even so, we believe imposing any new, onerous requirements on an overstretched workforce is problematic. Clinicians have become increasingly hesitant to prescribe controlled substances, and more patients would be harmed if prescribers opted out of getting a DEA license altogether. We believe a more sensible long-term alternative would be to require education on addiction treatment in medical schools, residency programs, and other training programs as a core component of the curriculum so that all future practitioners will have met this requirement during their training. Curriculum changes could be spurred by medical boards adding questions to existing licensing exams; leading medical-education organizations, such as the Association of American Medical Colleges, mandating the teaching of such content; or the Accreditation Council for Graduate Medical Education adding addiction-medicine education to its core program requirements.
In addition to federal requirements, some states have proposed establishing training requirements or other restrictions that go beyond this new framework. For example, Alabama has suggested imposing stricter rules on buprenorphine treatment, which would involve mandating more frequent visits, not allowing concurrent treatment for patients taking some psychiatric medications, and requiring counseling during treatment. The scientific rationale for these interventions is unclear; at least in some jurisdictions, misinformation may drive state policymakers to erect new — and more onerous — barriers even as federal hurdles are being dismantled.
The impending end of the Covid-19 public health emergency and the potential rollback of telemedicine flexibilities — which have expanded access to buprenorphine treatment — also pose a threat to access. Although the DEA has proposed continuing to allow audio-only telemedicine for buprenorphine treatment, a new draft rule would also require an in-person visit within 30 days after medication initiation. Such a requirement could make treatment inaccessible, since health care systems are still recovering from the pandemic and patients can sometimes wait months to get an in-person appointment.
We believe eliminating the X waiver is necessary but not sufficient to achieve overdose-prevention goals. Further action will be especially critical given worsening racial and ethnic disparities, with the largest relative increases in overdose deaths occurring among Black people and American Indian and Alaska Native people, according to the Centers for Disease Control and Prevention. Additional reforms are necessary to facilitate adoption of OUD treatment by prescribers and to address other barriers. The X waiver was one example of an onerous and unnecessary barrier to a lifesaving intervention, but there are many others, including methadone regulations and policies obstructing access to harmreduction services.
Methadone use, like buprenorphine use, is associated with reduced overdose-specific and allcause mortality. Unlike many other countries, where physicians prescribe and pharmacies dispense methadone, the United States has maintained regulations that limit the dispensing of methadone to opioid-treatment programs (OTPs). This policy carves out some forms of OUD treatment from the medical system, requires patients to visit an OTP daily for months or years before receiving medication to take at home, and because of a “not in my backyard” sentiment, often means that patients must wait in line at clinics located in neighborhoods that are challenged by poverty, public drug use, and crime.
The location of OTPs has had important ramifications. First, it has created a racist, two-tiered system in which buprenorphine is more available to White and affluent communities and methadone treatment is concentrated in Black, Latinx, and impoverished communities.3 Second, it requires people trying to obtain OUD treatment to make daily visits to areas that may be associated with active drug use, thereby increasing the risk of recurrent use. Third, it conflates in the public’s mind methadone treatment with chaotic drug use that may be visible in the same geographic area. For example, in Boston, the derogatory label “methadone mile” has been given to an area affected by openair drug use and homelessness that is also home to two OTPs. Finally, there are profound regional variations in access to methadone, with rural areas often having vast treatment deserts. A recent study found substantial variation in the number of OTPs relative to state populations, ranging from none in Wyoming to 2.1 per 100,000 residents in Rhode Island.4
We believe the federal government should continue its important progress in expanding access to medication for OUD by rethinking methadone regulations. Methadone treatment models that are more patient-centered and better facilitate access are the norm in many countries. Critics of changes to methadone regulations cite concern about methadone overdose as a reason to maintain the status quo. Despite the benefits of methadone use, there is an increased risk of overdose during the induction period. It’s possible that this increased risk is a result of ongoing use of other opioids because of slow upward adjustment of methadone doses, but methadone’s pharmacokinetics may also mean that greater caution is required during the initiation phase.
Data collected since the onset of the Covid-19 pandemic — during which expanded and more flexible take-home methadone dosing was allowed — showed improved patient experience and treatment retention without clear evidence of increased methadonerelated overdose, which supports potential reforms.5 A first step to expand access while addressing concern about overdoses could be to allow patients stabilized by means of treatment at an OTP to transition to office-based care with general practitioners and to permit physicians specializing in addiction medicine or addiction psychiatry to initiate and provide ongoing methadone treatment. Federally qualified health centers could also serve as critical access points for methadone.
In addition, several policy changes and financial investments could help ensure that all people at risk for overdose can receive the treatment and harm-reduction services they need. Sustained federal funding is needed for training programs, including for addiction-medicine and addiction-psychiatry fellowship positions; programs allowing nurse practitioners, psychologists, social workers, and mental health counselors to receive specialty training in addiction; and programs supporting general practitioners in providing addiction care. Giving incentives for health systems to offer integrated and low-barrier treatment by creating funding opportunities, implementing related quality measures, and adding accreditation requirements could help ensure the adoption of evidence-based care. Finally, policies and funding to support harm-reduction programs — such as policies permitting federal funding to be used for syringeaccess programs; funding to expand drug-checking services, which allow people to test the composition of drugs to reduce overdose risk; and legalization of and funding for overdose-prevention sites — are necessary.
The X waiver was a massive hurdle to providing addictiontreatment services that has now been eliminated. We believe it’s necessary to continue this progress and push for additional changes to expand methadone access, invest in the addictiontreatment workforce, provide incentives for health systems to offer addiction treatment, and scale up harm-reduction programs.
Disclosure forms provided by the authors are available at NEJM.org.
From the Department of Medicine, Massachusetts General Hospital (S.E.W.), Harvard Medical School (S.E.W.), and the School of Law and the Bouvé College of Health Sciences, Northeastern University (L.B.) — all in Boston; and the Division of Infectious Diseases and Global Public Health, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla (L.B.). This article was published on April 29, 2023, at NEJM.org.