CHARACTERISTICS OF DEPRESSION EPISODES TO INFORM REAL-WORLD HEALTH STATES FOR MAJOR DEPRESSIVE DISORDER AND TREATMENT-RESISTANT DEPRESSION

Background

Major depressive disorder (MDD) is a chronic disorder characterized by alternating periods of symptoms and remission. Most claims-based studies, however, treat MDD as a chronic illness without multi-episode dynamics. Treatment-resistant depression (TRD) is defined by a depressive episode that fails to respond to ≥2 antidepressant (AD) trials of adequate dose and duration. To better depict healthcare utilization and health economics of depression, this study sought to evaluate criteria for the start and end of depressive episodes using claims data and characterize the resulting patient depression courses as a series of depressive episodes of varying treatment-responsiveness alternating with periods of stability.

Methods

Adults with MDD aged 18-64 years were identified in the Merative™ MarketScan® Commercial Database (1/1/2019–9/30/2024). Stable periods (treated or untreated) were defined by ≥180 days without any depressive episode events (initiation, augmentation, switch, or dose escalation of an AD; exacerbation (mental health-related emergency department or inpatient visits, suicide attempts, self-harm, psychiatric rehabilitation), or receipt of interventional psychiatry). Following a stable period, the start of a new depressive episode was defined by a depressive episode event following a stable period. An AD was deemed a failure if followed by medication switch/addition, acute exacerbation, or interventional psychiatry treatment. Episodes with ≥2 failed ADs of adequate dose and duration, or receipt of interventional psychiatry were classified as treatment-resistant episodes (TREs). Episodes with ≥ 2 failed ADs but of inadequate dose or duration were classified as inadequate treatment episodes (ITEs). Episodes that did not meet TRE or ITE criteria were classified as non-TREs. Individuals were categorized as having ≥1 TRE (TRD), ≥1 ITE and no TRE (ITD), or only non-TREs (non-TRD).

Results

Among 307,134 individuals (mean age 36.5±12.9 years; 66.3% female), 42% had ≥1 episode, 3.5% had ≥1 TRE, 8.1% had ≥1 ITE, and 88.5% did not experience a TRE. Among patients with an initial non-TRE, 1.2% later developed a TRE during observed follow-up. Anxiety (31.5%) was the most common psychiatric comorbidity. Exacerbations occurred in 17.7% of TRD (6.62 per 100 person-years (PY)), 17.5% of ITD (7.63 per 100 PY), and 4.0% of non-TRD individuals (1.94 per 100 PY). Among TRD individuals, 53.5% met TRD criteria within 180 days of their first episode and 10.1% received interventional treatment. Across all groups there were 11,033 TREs, 26,474 ITEs, and 487,330 non-TREs of which 18,309 included exacerbations. Mean episode duration was longest for TREs (395±229 days), followed by ITEs (271±164 days) and non-TREs (67±100 days). Antipsychotics were observed in 26.7%, 18.4%, and 2.7% and mood stabilizers in 9.7%, 5.7%, and 0.9% of TREs, ITEs, and non-TREs, respectively.

Conclusions

These study results support the feasibility of an episodic framework in real-world claims data. A higher disease burden and exacerbation risk was observed in TRD and ITD patients. The low observed prevalence of TRD may reflect the strict definition applied in this study compared to other real-world studies and the higher prevalence of ITD may suggest suboptimal care in real world. Only half of TRD patients had observed psychiatrist visits and 10% received interventional therapies, highlighting gaps in specialty care. Individuals with TREs and I-TREs warrant further evaluation to reduce subsequent treatment failures and exacerbations.