Pathways from Chronic Prescription Opioid Use to New Onset Mood Disorder

我们以前的工作表明，持续30天以上的阿片类止痛剂(非统)的新时期是相关的 新发抑郁症、抑郁症复发和向耐药治疗过渡的风险增加 抑郁与非统组织的1-30天相比。在对包括疼痛在内的混杂行为进行强健控制的多项研究中 严重程度，非统预测中年患者新发抑郁症的时间更长(大大高于年龄 人群中新发抑郁症的风险)没有近期抑郁症病史，没有阿片类药物的证据 对非统组织的滥用和近代史。我们的研究利用了大量电子病历(EMR)数据 退伍军人管理局(VA)和私营部门患者的样本。与停药的患者相比 非统组织在30天内，患者在31-90天非统组织(VA)到33%(私营部门)的可能性更高 新发抑郁症。在90天非统患者中，VA的可能性增加到35%，而VA的可能性增加到105% 私营部门数据。在近期抑郁症和缓解期患者中，启动非统组织与NO相比 非统与退伍军人事务部抑郁症复发有关(HR=2.2，95%CI=2.0-2.3)和私营部门数据 (HR=1.8，95%CI=1.4~2.2)。我们发现，抑郁症患者患抑郁症的可能性要高出22%。 非统组织治疗难治性抑郁症的可能性为31-90天，非统组织90天的可能性比非统组织高49%。这个 结果的一致性，退伍军人和私营部门患者的复制，以及对疼痛的严格控制支持 假设非统组织可能是抑郁症的风险因素，以及抑郁症的复发和严重程度。一位潜在的 需要研究来确认和推进这一研究路线，部分原因是医疗记录数据缺乏生命期 情绪障碍和其他危险因素的病史，如物质使用障碍、创伤暴露以及 良好的功能障碍、睡眠质量和社会支持的衡量标准。此外，电子病历数据不包含 关于疼痛、非统和抑郁症状发展顺序的前瞻性数据。在建议的 在研究中，我们假设非统组织之前的事件，如抑郁史，将增加后抑郁的风险 非统组织新发严重抑郁发作。第二，我们假设非统组织相关的不利后果， 如阿片类药物滥用、睡眠呼吸暂停等，在非统组织长期使用后发生，随后导致新的发病 抑郁症。第三，我们假设非统组织会导致更严重的抑郁，进而导致非统组织程度更高。 而且仍在恶化的抑郁症，不依赖于纵向疼痛措施。 第四，我们关注的是抑郁症 表型(快感缺乏、生命衰竭、心境恶劣、共病物质使用障碍)来阐明新的 发病抑郁表型与慢性非统组织最为密切相关。第五，我们确定哪一个 抑郁表型是阿片类药物滥用和滥用事件的危险因素。数据是在基线上获得的，6 1个月和12个月的随访，每月进行轨迹分析的简要评估。我们的创新研究 在促进对非统组织抑郁症和阿片类药物滥用、滥用/使用障碍的认识方面具有很大潜力。 结果将为慢性非癌症疼痛患者的疼痛管理和安全的阿片类药物处方提供信息。

Our previous work indicates a new period of opioid analgesic use (OAU) lasting beyond 30 days, is associated with increased risk for new onset depression, depression recurrence and transition to treatment resistant depression compared to 1-30 OAU days. In multiple studies with robust control for confounding, including pain severity, longer OAU predicted new onset depression in middle-aged patients (substantially older than the age of risk for new onset depression in the population) with no recent history of depression, no evidence of opioid misuse and no recent history of OAU. Our research utilized electronic medical record (EMR) data from large samples of Veterans Administration (VA) and private sector patients. Compared to patients who discontinued OAU within 30 days, patients with 31-90 day OAU were 18% (VA) to 33% (private sector) more likely to have new onset depression. In patients with >90 day OAU, the likelihood increased to 35% in VA and 105% in private sector data. In patients with recent depression and in remission, initiation of OAU, compared to no OAU, was associated with depression recurrence in VA (HR=2.2, 95% CI = 2.0-2.3) and private sector data (HR=1.8, 95% CI = 1.4-2.2). We found that patients with depression were 22% more likely to develop treatment resistant depression with OAU of 31-90 days and 49% more likely with OAU of >90 days. The consistency of findings, replication in VA and private sector patients, and rigorous control for pain support the hypothesis that OAU is likely a risk factor for depression, as well as its recurrence and severity. A prospective study is needed to confirm and advance this line of research, in part because medical record data lack lifetime histories of mood disorders and other risk factors such as substance use disorder, trauma exposure, as well as good measures of functional impairment, sleep quality and social support. Also, EMR data do not contain prospective data on the sequence of pain, OAU and depression symptom development. In the proposed research, we hypothesize that events prior to OAU, such as history of depression, will increase risk of post- OAU new onset major depressive episode. Second, we hypothesize that OAU-related adverse outcomes, such as opioid misuse, sleep apnea, occur after long term OAU and subsequently contribute to new onset depression. Third, we hypothesize that OAU leads to worse depression that in turn contributes to higher OAU and still worsening depression, independent of longitudinal pain measures. Fourth, we focus on depression phenotypes (anhedonia, vital exhaustion, dysthymia, comorbid substance use disorder) to elucidate the new onset depression phenotypes most strongly associated with chronic OAU. Fifth, we determine which depression phenotypes are risk factors for incident opioid misuse and abuse.Data is obtained at baseline, 6 month and 12 month follow-up with monthly brief assessments for trajectory analysis. Our innovative research has great potential to advance understanding of depression in OAU and opioid misuse, abuse/use disorder. Results will inform pain management and safe opioid prescribing for patients with chronic non-cancer pain.