Jain Lakshit, Meeks Thomas W, Blazes Christopher K
Department of Psychiatry, University of Connecticut, Farmington, CT, United States.
Department of Psychiatry, Oregon Health & Science University, Portland, OR, United States.
Front Psychiatry. 2024 Jul 23;15:1401676. doi: 10.3389/fpsyt.2024.1401676. eCollection 2024.
Buprenorphine has been successfully used for decades in the treatment of opioid use disorder, yet there are complexities to its use that warrant attention to maximize its utility. While the package insert of the combination product buprenorphine\naloxone continues to recommend a maximum dose of 16 mg daily for maintenance, the emergence of fentanyl and synthetic analogs in the current drug supply may be limiting the effectiveness of this standard dose. Many practitioners have embraced and appropriately implemented novel practices to mitigate the sequelae of our current crisis. It has become common clinical practice to stabilize patients with 24 - 32 mg of buprenorphine daily at treatment initiation. Many of these patients, however, are maintained on these high doses (>16 mg/d) indefinitely, even after prolonged stability. Although this may be a necessary strategy in the short term, there is little evidence to support its safety and efficacy, and these high doses may be exposing patients to more complications and side effects than standard doses. Commonly known side effects of buprenorphine that are likely dose-related include hyperhidrosis, sedation, decreased libido, constipation, and hypogonadism. There are also complications related to the active metabolite of buprenorphine (norbuprenorphine) which is a full agonist at the mu opioid receptor and does not have a ceiling on respiratory suppression. Such side effects can lead to medical morbidity as well as decreased medication adherence, and we, therefore, recommend that after a period of stabilization, practitioners consider a trial of decreasing the dose of buprenorphine toward standard dose recommendations. Some patients' path of recovery may never reach this stabilization phase (i.e., several months of adherence to medications, opioid abstinence, and other clinical indicators of stability). Side effects of buprenorphine may not have much salience when patients are struggling for survival and safety, but for those who are fortunate enough to advance in their recovery, the side effects become more problematic and can limit quality of life and adherence.
丁丙诺啡已成功用于治疗阿片类药物使用障碍数十年，但在其使用方面存在一些复杂情况，需要予以关注以使其效用最大化。虽然丁丙诺啡/纳洛酮复方产品的包装说明书仍建议维持治疗的每日最大剂量为16毫克，但当前毒品供应中芬太尼和合成类似物的出现可能正在限制这一标准剂量的有效性。许多从业者采用并适当实施了新的做法来减轻当前危机的后果。在治疗开始时，用每日24 - 32毫克丁丙诺啡使患者病情稳定已成为常见的临床做法。然而，许多这些患者即使在长期病情稳定后仍无限期维持这些高剂量（>16毫克/天）。虽然这在短期内可能是一种必要的策略，但几乎没有证据支持其安全性和有效性，而且这些高剂量可能使患者面临比标准剂量更多的并发症和副作用。丁丙诺啡常见的可能与剂量相关的副作用包括多汗、镇静、性欲减退、便秘和性腺功能减退。还存在与丁丙诺啡的活性代谢物（去甲丁丙诺啡）相关的并发症，该代谢物是μ阿片受体的完全激动剂，对呼吸抑制没有封顶效应。此类副作用可导致医疗发病以及药物依从性降低，因此，我们建议在病情稳定一段时间后，从业者考虑尝试将丁丙诺啡剂量降至标准剂量建议水平。一些患者的康复过程可能永远无法达到这个稳定阶段（即数月坚持用药、戒除阿片类药物以及其他稳定的临床指标）。当患者为生存和安全而挣扎时，丁丙诺啡的副作用可能不太突出，但对于那些有幸在康复过程中取得进展的患者来说，副作用会变得更成问题，并可能限制生活质量和依从性。
