Pathways from Chronic Prescription Opioid Use to New Onset Mood Disorder

我们以前的工作表明，阿片类镇痛药使用（非统组织）持续超过30天的新时期， 新发抑郁症、抑郁症复发和转变为耐药的风险增加 抑郁症相比，1-30非统组织天。在对混杂因素（包括疼痛）进行稳健控制的多项研究中 严重程度，较长的非统组织预测新发抑郁症的中年患者（大大超过年龄 人群中新发抑郁症的风险），近期无抑郁症史，无阿片类药物证据 滥用和最近没有非统组织的历史。我们的研究利用电子病历（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， 30天内发生非统组织，31-90天非统组织的患者有18%（VA）至33%（私营部门）更有可能发生非统组织。 新发抑郁症在>90天的非统组织患者中，VA的可能性增加到35%， 私营部门数据。在近期抑郁症和缓解期患者中，与未开始治疗相比， 在VA（HR=2.2，95%CI = 2.0-2.3）和私营部门数据中， (HR=1.8，95% CI = 1.4-2.2）。我们发现抑郁症患者比正常人 31-90天的非统组织治疗难治性抑郁症和49%更可能与非统组织>90天。的 研究结果的一致性，在VA和私营部门患者中的重复性，以及对疼痛的严格控制支持了 假设非统组织可能是抑郁症及其复发和严重程度的危险因素。一项前瞻性 需要一项研究来证实和推进这一研究路线，部分原因是医疗记录数据缺乏生命周期 情绪障碍和其他风险因素的历史，如物质使用障碍，创伤暴露，以及 功能障碍、睡眠质量和社会支持的良好指标。此外，EMR数据不包含 疼痛、非统组织和抑郁症状发展顺序的前瞻性数据。拟议 研究中，我们假设在非统组织之前发生的事件，如抑郁症史，会增加非统组织后的风险。 新发重度抑郁发作。其次，我们假设OAU相关的不良结局， 如阿片类药物滥用、睡眠呼吸暂停，在长期OAU后发生，随后导致新发病 萧条第三，我们假设，非统组织导致更严重的抑郁症，反过来又有助于更高的非统组织 并且仍然恶化的抑郁症，独立于纵向疼痛测量。 第四，我们关注抑郁症 表型（快感缺乏，生命衰竭，心境恶劣，共病物质使用障碍），以阐明新的 发病抑郁症表型与慢性非统组织最密切相关。第五，确定哪些 抑郁症表型是阿片类药物误用和滥用的危险因素。 随访1个月和12个月，每月进行简要评估，以进行轨迹分析。我们的创新研究 有很大的潜力，以促进对抑郁症的理解，在非统组织和阿片类药物滥用，滥用/使用障碍。 结果将为慢性非癌症疼痛患者的疼痛管理和安全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.