Introduction

Pre-existing conditions relevant for adverse events (AE) and the potential for drug–drug interactions (DDIs) may limit safe pharmacotherapeutic augmentation options for patients with major depressive disorder (MDD). This concern may be heightened among patients with treatment-resistant depression (TRD), who often have comorbid medical disorders.

Methods

Adults with MDD and ≥ 1 antidepressant claim within the first observed major depressive episode were identified in the MarketScan® Databases. Those initiating a new regimen after two regimens at adequate dose and duration were considered to have TRD. The index date was defined at TRD onset or on a random antidepressant claim among patients with non-TRD MDD. Pre-existing conditions 12 months pre-index and potential DDIs 3 months pre/post-index associated with specific non-antidepressant augmentation therapies, including atypical antipsychotics (APs), buspirone, psychostimulants, anticonvulsants, thyroid hormone, and lithium were compared between 1:1 matched TRD and non-TRD MDD cohorts.

Results

Overall, 3414 patients with TRD and non-TRD MDD (mean age 39.7 years, 69% female) were matched. Relative to non-TRD MDD, patients with TRD had 33% higher likelihood of ≥ 1 pre-existing condition relevant for AEs listed in product labels of non-antidepressant augmentation therapies (p < 0.001). Patients with TRD vs. non-TRD MDD had 12.9 and 6.4 times higher likelihood of ≥ 2 and ≥ 3 DDIs, respectively, based on their medication regimen (all p < 0.001).

Conclusion

Pre-existing conditions relevant for listed AEs and potential DDIs limit safe augmentation options in MDD, particularly among patients with TRD. Payer prior authorization policies requiring several augmentation therapy trials to access novel treatments may complicate clinical management of this population.

中文翻译：

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难治性抑郁症患者中与不良事件相关的既往疾病患病率以及与增强疗法相关的潜在药物-药物相互作用

介绍

与不良事件 (AE) 相关的预先存在的条件和药物-药物相互作用 (DDI) 的可能性可能会限制重度抑郁症 (MDD) 患者的安全药物治疗增强选择。这种担忧在难治性抑郁症 (TRD) 患者中可能会加剧，他们经常合并有内科疾病。

方法

在 MarketScan® 数据库中确定了在第一次观察到的重度抑郁发作期间患有 MDD 和 ≥ 1 项抗抑郁药声明的成年人。在足够剂量和持续时间的两个方案之后开始新方案的那些被认为具有TRD。索引日期是在 TRD 开始时或在非 TRD MDD 患者中随机抗抑郁药声明时定义的。预先存在的条件 12 个月的指标前和潜在的 DDI 3 个月的指标前/后 3 个月与特定的非抗抑郁药物增强疗法相关，包括非典型抗精神病药 (APs)、丁螺环酮、精神兴奋剂、抗惊厥药、甲状腺激素和锂在 1 之间进行比较:1 匹配的 TRD 和非 TRD MDD 队列。

结果

总体而言，匹配了 3414 名 TRD 和非 TRD MDD 患者（平均年龄 39.7 岁，69% 为女性）。相对于非 TRD MDD，患有 TRD 的患者出现 ≥ 1 种与非抗抑郁增强疗法产品标签中列出的 AE 相关的既往疾病的可能性高出 33%（p  < 0.001）。TRD 与非 TRD MDD 患者的 ≥ 2 和 ≥ 3 DDI 的可能性分别高出 12.9 倍和 6.4 倍（所有p  < 0.001）。

结论

与列出的 AE 和潜在 DDI 相关的预先存在的条件限制了 MDD 的安全增强选择，特别是在 TRD 患者中。付款人事先授权政策要求进行几次增强治疗试验才能获得新的治疗方法，这可能会使该人群的临床管理复杂化。