Frequently Asked Questions

Treatment-resistant depression was estimated in 30.9% of US adults with medication-treated major depressive disorder, equal to 2.76 million adults out of 8.95 million with medication-treated MDD. The authors also estimated that this represented about 1.1% of the overall US adult population.

In the claims-based model, treatment-resistant depression was defined as initiation of a third antidepressant treatment course, including augmentation therapy, after changing 2 antidepressant courses of adequate dose and duration. A treatment gap of up to 180 days was allowed between consecutive antidepressant treatment courses.

The study estimated that adults with medication-treated MDD incurred $92.7 billion in annual incremental costs relative to adults without MDD. This total included $45.5 billion in health care costs, $28.8 billion in productivity costs, and $18.3 billion in unemployment costs.

Adults with treatment-resistant depression accounted for $43.8 billion, or 47.2%, of the total $92.7 billion incremental cost burden of medication-treated MDD. This was disproportionate to their population share, because they represented 30.9% of adults with medication-treated MDD.

The weighted mean annual per-person incremental health care cost across US payers was $9,323 for adults with treatment-resistant depression versus $3,197 for adults with non-treatment-resistant MDD, each compared with adults without MDD. Nationally, this translated to $25.8 billion in incremental health care costs for TRD and $19.8 billion for non-TRD MDD.

The weighted mean annual per-person incremental productivity cost across US payers was $6,727 for employees with treatment-resistant depression compared with adults without MDD. The weighted mean annual incremental unemployment rate for adults with treatment-resistant depression was 8.0 percentage points, and the national incremental unemployment burden of TRD was estimated at $8.7 billion.

Treatment-resistant depression had a somewhat higher work-function burden than non-TRD MDD. The weighted mean annual per-person incremental productivity cost was $6,727 for TRD versus $5,763 for non-TRD MDD, and the weighted mean annual incremental unemployment rate was 8.0 versus 3.9 percentage points, respectively, each relative to adults without MDD.

Yes. In the calculated prevalent samples, the proportion of adults with treatment-resistant depression among those with medication-treated MDD ranged from 21.4% in Medicare to 44.2% in Medicaid. The study then weighted these payer-specific estimates by payer prevalence and adjusted for dual coverage to estimate national prevalence.

The study found that treatment-resistant depression contributed disproportionately because its per-person burden was substantially higher than that of non-TRD MDD. Adults with TRD represented less than one-third of adults with medication-treated MDD but accounted for 56.6% of excess health care costs, 47.7% of unemployment costs, and 47.2% of total incremental costs.

The authors noted several limitations. These included extrapolating mean incremental costs from insured populations to uninsured populations; not capturing quality-of-life burden, caregiver burden, life-years lost, or patients' out-of-pocket costs; using proxy definitions based on treatment patterns because symptom burden was unavailable in claims data; combining inputs from several claims and survey studies with different methodologies; and assuming that the ratio of episode duration in TRD versus non-TRD MDD was consistent across insurance channels.