Coverage Policies for Ketamine-Based Depression Therapies Among Major U.S. Commercial Insurers: Cross-Sectional Analysis of 18 Insurers Covering 85.9 Million Members (August 2025)

We analyzed written coverage policies for Spravato and off-label ketamine (IV/IM/oral) across 18 major U.S. commercial insurers (61.4% of market; 85,884,059 lives). As verified August 31, 2025, coverage was universal for Spravato (100%; 94.4% with prior auth) versus 1.2% for IV and 0% for IM and oral; policy silence affected 35–47% of market share.

Background: Ketamine-based therapies represent a major breakthrough in treatment-resistant depression care, yet insurance coverage patterns across different administration modalities remain poorly characterized. This study examines coverage policies for ketamine therapies among major U.S. commercial health insurers.

Methods: Coverage policies were systematically analyzed across four ketamine modalities—Spravato/esketamine nasal spray (SPR), intravenous ketamine (IVK), intramuscular ketamine (IMK), and oral ketamine (ORK)—among 18 major commercial health insurers representing 61.4% of the market and 85,884,059 covered lives. Coverage determinations were classified as explicit coverage, explicit denial, or policy silence ("Not Stated").

Results: Universal Spravato coverage was documented across all 18 insurers (100% coverage rate, 85.9 million lives), with 94.4% requiring prior authorization. In stark contrast, off-label modalities showed minimal explicit coverage: IV ketamine achieved 1.2% coverage (1 insurer, 1.7 million lives), while intramuscular and oral ketamine received zero explicit coverage. Policy uncertainty was substantial, with 35.2% of market share maintaining unstated IV ketamine policies, rising to 46.6% for oral ketamine. This represents 35-65 million covered lives facing coverage uncertainty for off-label treatments.

Conclusions: FDA approval creates a near-complete coverage divide: 100% coverage for Spravato versus 0-1% coverage for off-label alternatives—a coverage gap approaching 100 percentage points. The extensive policy silence surrounding off-label modalities creates systematic access uncertainty affecting tens of millions of patients. These findings have significant implications for treatment equity, clinical decision-making, and healthcare policy development in psychiatric care.