Background Depressive symptoms are common in knee osteoarthritis (OA), exacerbate knee pain severity and may influence outcomes of oral analgesic treatments. The aim was to assess whether oral analgesic effectiveness in knee OA varies by fluctuations in depressive symptoms. Methods The sample included Osteoarthritis Initiative (OAI) participants not treated with oral analgesics at enrolment (n = 1477), with radiographic disease at the first follow-up visit (defined as the index date). Oral analgesic treatment and depressive symptoms, assessed with the Center for Epidemiological Studies Depression [(CES-D) score ≥16] Scale, were measured over three annual visits. Knee pain severity was measured at visits adjacent to treatment and modifier using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (rescaled range = 0–100). Structural nested mean models (SNMMs) estimated causal mean differences in knee pain severity comparing treatment versus no treatment. Results The average causal effects of treated versus not treated for observations without depressive symptoms showed negligible differences in knee pain severity. However, causal mean differences in knee pain severity comparing treatment versus no treatment among observations with depressive symptoms increased over time from −0.10 [95% confidence interval (CI): −9.94, 9.74] to −16.67 (95% CI: −26.33, −7.01). Accordingly, the difference in average causal effects regarding oral analgesic treatment for knee pain severity between person-time with and without depressive symptoms was largest (−16.53; 95% CI: −26.75, −6.31) at the last time point. Cumulative treatment for 2 or 3 years did not yield larger causal mean differences. Conclusions Knee OA patients with persistent depressive symptoms and chronic pain may derive more analgesic treatment benefit than those without depressive symptoms and less pain.

中文翻译：

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膝骨关节炎抑郁症状对口服镇痛效果的时变治疗效果修正：结构嵌套平均模型在前瞻性队列中的应用

背景 抑郁症状在膝骨关节炎 (OA) 中很常见，会加剧膝关节疼痛的严重程度，并可能影响口服镇痛治疗的结果。目的是评估口服镇痛药对膝骨关节炎的疗效是否会因抑郁症状的波动而变化。方法 样本包括入组时未接受口服镇痛药治疗的骨关节炎倡议 (OAI) 参与者 (n = 1477)，在第一次随访时（定义为索引日期）患有放射学疾病。口服镇痛治疗和抑郁症状，通过流行病学研究中心抑郁症 [(CES-D) 评分≥16] 量表进行评估，每年进行 3 次随访。使用西安大略大学和麦克马斯特大学骨关节炎指数 (WOMAC) 疼痛分量表（重新调整范围 = 0-100）在治疗和调节器附近就诊时测量膝关节疼痛严重程度。结构嵌套平均模型 (SNMM) 估计了治疗与不治疗之间膝关节疼痛严重程度的因果平均差异。结果 对于没有抑郁症状的观察，治疗与未治疗的平均因果效应显示，膝关节疼痛严重程度的差异可以忽略不计。然而，在有抑郁症状的观察中，比较治疗与未治疗的膝部疼痛严重程度的因果平均差异随着时间的推移从-0.10 [95%置信区间（CI）：-9.94，9.74]增加到-16.67（95% CI：-26.33， −7.01)。因此，在最后一个时间点，有和没有抑郁症状的人之间口服镇痛治疗对膝盖疼痛严重程度的平均因果效应差异最大（-16.53；95% CI：-26.75，-6.31）。2年或3年的累积治疗并没有产生更大的因果平均差异。结论 具有持续抑郁症状和慢性疼痛的膝关节 OA 患者可能比没有抑郁症状和较少疼痛的患者获得更多的镇痛治疗益处。