Prevalence of Pre-existing Conditions for Adverse Events and Potential Drug-Drug Interactions Associated with Augmentation Therapies among Patients with Treatment-Resistant Depression

BACKGROUND: Comorbidities complicate clinicians' efforts to manage major depressive disorder (MDD). Pre-existing conditions and drug-drug interactions (DDI) may limit the array of safe pharmacotherapeutic augmentation options for individual patients. This clinical challenge may be particularly pronounced among patients with treatment-resistant depression (TRD).

METHODS: Adults with MDD and ≥1 antidepressant claim within the first observed major depressive episode were identified in the MarketScan® Databases (10/01/2015-03/04/2019). Those who initiated a new regimen (index date) after no response to two regimens at adequate dose and duration were considered to have TRD. The index date was a random antidepressant claim among patients with non-TRD MDD. Pre-existing conditions in the 12-months pre-index and potential severe/moderate DDIs in the 3-months pre/post-index associated with specific atypical antipsychotics, buspirone, psychostimulants, anticonvulsants, thyroid hormone, and lithium were compared between 1:1 matched TRD and non-TRD MDD cohorts.  

RESULTS: Overall, 3,414 patients with TRD (mean age 40 years, 69% female) were identified and matched to those with non-TRD MDD. Patients with TRD versus non-TRD MDD had 1.33 times higher odds of ≥1 pre-existing condition for AEs, including higher odds of cardiovascular conditions (1.13 times; all p < 0.05). Patients with TRD versus non-TRD MDD had 12.92 and 6.35 times higher odds of ≥2 and ≥3 DDIs, respectively, and 2 more DDIs on average (all p < 0.01).

CONCLUSIONS: Pre-existing conditions for AEs and DDIs limit safe augmentation options in MDD. Patients with TRD pose a greater challenge than patients with non-TRD MDD. Payer prior authorization policies can further limit available options in this population.