OBJECTIVE To examine the associations between stopping treatment with opioids, length of treatment, and death from overdose or suicide in the Veterans Health Administration. DESIGN Observational evaluation. SETTING Veterans Health Administration. PARTICIPANTS 1 394 102 patients in the Veterans Health Administration with an outpatient prescription for an opioid analgesic from fiscal year 2013 to the end of fiscal year 2014 (1 October 2012 to 30 September 2014). MAIN OUTCOME MEASURES A multivariable Cox non-proportional hazards regression model examined death from overdose or suicide, with the interaction of time varying opioid cessation by length of treatment (≤30, 31-90, 91-400, and >400 days) as the main covariates. Stopping treatment with opioids was measured as the time when a patient was estimated to have no prescription for opioids, up to the end of the next fiscal year (2014) or the patient's death. RESULTS 2887 deaths from overdose or suicide were found. The incidence of stopping opioid treatment was 57.4% (n=799 668) overall, and based on length of opioid treatment was 32.0% (≤30 days), 8.7% (31-90 days), 22.7% (91-400 days), and 36.6% (>400 days). The interaction between stopping treatment with opioids and length of treatment was significant (P<0.001); stopping treatment was associated with an increased risk of death from overdose or suicide regardless of the length of treatment, with the risk increasing the longer patients were treated. Hazard ratios for patients who stopped opioid treatment (with reference values for all other covariates) were 1.67 (≤30 days), 2.80 (31-90 days), 3.95 (91-400 days), and 6.77 (>400 days). Descriptive life table data suggested that death rates for overdose or suicide increased immediately after starting or stopping treatment with opioids, with the incidence decreasing over about three to 12 months. CONCLUSIONS Patients were at greater risk of death from overdose or suicide after stopping opioid treatment, with an increase in the risk the longer patients had been treated before stopping. Descriptive data suggested that starting treatment with opioids was also a risk period. Strategies to mitigate the risk in these periods are not currently a focus of guidelines for long term use of opioids. The associations observed cannot be assumed to be causal; the context in which opioid prescriptions were started and stopped might contribute to risk and was not investigated. Safer prescribing of opioids should take a broader view on patient safety and mitigate the risk from the patient's perspective. Factors to address are those that place patients at risk for overdose or suicide after beginning and stopping opioid treatment, especially in the first three months.

中文翻译：

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美国退伍军人停止阿片类药物处方、阿片类药物治疗时间长度与过量服用或自杀死亡之间的关联：观察性评估。

目的 研究退伍军人健康管理局停止使用阿片类药物治疗、治疗时间长短与过量服用或自杀导致的死亡之间的关联。设计 观察性评估。设置退伍军人健康管理局。参与者 1 394 102 名退伍军人健康管理局在 2013 财年至 2014 财年结束（2012 年 10 月 1 日至 2014 年 9 月 30 日）期间开具阿片类镇痛药门诊处方的患者。主要结局指标 一个多变量 Cox 非比例风险回归模型检查了过量服用或自杀导致的死亡，以及随治疗时间长短（≤30、31-90、91-400 和 >400 天）的时变阿片类药物戒断的相互作用作为主要协变量。停止阿片类药物治疗的时间是估计患者没有阿片类药物处方的时间，直至下一个财政年度（2014 年）结束或患者死亡。结果 发现有 2887 人死于药物过量或自杀。停止阿片类药物治疗的总体发生率为 57.4% (n=799 668)，基于阿片类药物治疗的时间长度为 32.0%（≤30 天）、8.7%（31-90 天）、22.7%（91-400 天）和 36.6%（>400 天）。停止阿片类药物治疗与治疗时间之间存在显着交互作用（P<0.001）；无论治疗时间长短，停止治疗都与因用药过量或自杀而死亡的风险增加有关，而且患者接受治疗的时间越长，风险就越大。停止阿片类药物治疗的患者的风险比（所有其他协变量的参考值）为 1.67（≤30 天）、2.80（31-90 天）、3.95（91-400 天）和 6.77（>400 天）。描述性生命表数据表明，在开始或停止阿片类药物治疗后，过量服用或自杀的死亡率立即增加，发病率在大约 3 至 12 个月内下降。结论 停止阿片类药物治疗后，患者因过量服用或自杀而死亡的风险更大，停止前患者接受治疗的时间越长，风险就会增加。描述性数据表明，开始使用阿片类药物治疗也是一个风险期。在这些时期减轻风险的策略目前不是长期使用阿片类药物指南的重点。不能假设观察到的关联是因果关系；类阿片处方开始和停止的背景可能会增加风险，因此未进行调查。更安全的阿片类药物处方应该对患者安全有更广泛的看法，并从患者的角度降低风险。需要解决的因素是那些使患者在开始和停止阿片类药物治疗后（尤其是在前三个月）面临用药过量或自杀风险的因素。