Abstract Background and aims Treatment‐resistant depression (TRD), defined as inadequate treatment response after at least two adequate treatment trials, is common among patients initiating antidepressant treatment. Current or previous substance use disorders (SUD) are common among patients with depression and often lead to worse treatment outcomes. However, in clinical studies, SUD have not been found to increase the risk for TRD. The aim of this study was to investigate the association between SUD and TRD. Design Nested case–control study. Setting Nation‐wide governmental health‐care registers in Sweden. Cases and controls Data on prescribed drugs and diagnoses from specialized health care were used to establish a prospectively followed cohort of antidepressant initiators with depression (n = 121 669) from 2006 to 2014. Of these, 15 631 patients (13%) were defined as TRD cases, with at least three treatment trials within a single depressive episode. Each case with TRD was matched on socio‐demographic data with five controls with depression. Measurements Crude and adjusted odds ratios (aOR) with 95% confidence intervals (CI) estimated the association between TRD and SUD diagnosis and/or treatment in five different time intervals until the time for fulfillment of TRD definition for the case. The analysis was adjusted for clinical and socio‐demographic covariates. Findings Having any SUD during, or ≤ 180 days before start of, antidepressant treatment was associated with almost double the risk for TRD [≤ 180 days before: adjusted OR (aOR) = 1.86, CI = 1.70–2.05]. Increased risks for TRD were found ≤ 180 days before treatment start for the subcategories of sedative use (aOR = 2.37; 1.88–2.99), opioids (aOR = 2.02; 1.48–2.75), alcohol (aOR = 1.77; CI = 1.59–1.98) and combined substance use (aOR = 2.31; 1.87–2.99). Conclusions Recent or current substance use disorders is positively associated with treatment resistance among patients initiating treatment for depression.

中文翻译：

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物质使用障碍和难治性抑郁症的风险——基于人群的巢式病例对照研究


摘要 背景和目的 难治性抑郁症 (TRD) 定义为在至少两次充分的治疗试验后治疗反应不足，在开始抗抑郁治疗的患者中很常见。当前或以前的物质使用障碍（SUD）在抑郁症患者中很常见，并且常常导致更糟糕的治疗结果。然而，在临床研究中，尚未发现 SUD 会增加 TRD 的风险。本研究的目的是调查 SUD 和 TRD 之间的关联。设计巢式病例对照研究。在瑞典设立全国政府医疗保健登记册。病例和对照 使用处方药和专业医疗保健诊断的数据建立了 2006 年至 2014 年抗抑郁药物起始者抑郁症队列 (n = 121 669)。其中，15 631 名患者 (13%) 被定义为TRD 病例，在一次抑郁发作期间至少进行了三项治疗试验。每个 TRD 病例都根据社会人口统计数据与 5 名患有抑郁症的对照进行匹配。测量 具有 95% 置信区间 (CI) 的粗略比值比 (aOR) 和调整比值比 (aOR) 估计了五个不同时间间隔内的 TRD 和 SUD 诊断和/或治疗之间的关联，直到满足该病例的 TRD 定义。该分析针对临床和社会人口统计学协变量进行了调整。研究结果 抗抑郁治疗期间或开始前 180 天以内出现任何 SUD 与 TRD 风险几乎加倍相关 [≤ 180 天前：调整后 OR (aOR) = 1.86，CI = 1.70–2.05]。在治疗开始前 180 天以内，发现使用镇静剂 (aOR = 2.37; 1.88–2.99)、阿片类药物 (aOR = 2.02; 1.48–2.75)、酒精 (aOR = 1.77; CI = 1.59–1) 子类别的 TRD 风险增加。98) 和综合物质使用 (aOR = 2.31; 1.87–2.99)。结论 最近或当前的物质使用障碍与开始抑郁症治疗的患者的治疗抵抗呈正相关。