Esketamine (Spravato) nasal spray — clinical coverage and billing guidance
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Clinical coverage and billing guidance for intranasal esketamine (Spravato) used in adults with treatment-resistant depression or major depressive disorder with acute suicidal ideation, including clinical rationale, trial outcomes, and applicable procedure/drug codes. Affects providers administering esketamine and billing for associated services.
S0013 (Esketamine, nasal spray, 1 mg) cancelled as a code after 12/31/2025; providers should not use this cancelled code for billing beyond that date.
Coverage Criteria and Evidence
Trial efficacy summary
Evidence summary from pivotal trials
Superiority observed at primary endpoint and maintained over 4 weeks but did not increase with longer treatment
Secondary endpoint not superior
Safety profile consistent with prior data
The HCPCS code S0013 (Esketamine, nasal spray, 1 mg) was cancelled effective 12/31/2025. Providers should not use the cancelled S0013 code for billing after that date. For reporting esketamine drug administration beginning 1/1/2026, use the new HCPCS code J0013 (Esketamine, nasal spray, 1 mg) or other applicable unclassified drug/biologic codes (e.g., J3490, J3590) as specified by payer billing guidance.
In the ASPIRE I and II trials, Spravato plus standard-of-care showed statistical superiority to placebo on the primary symptom outcome (MADRS change at 24 hours), but the trials did not demonstrate superiority of Spravato over placebo on the key secondary endpoint measuring severity of suicidal ideation (CGI-SS-r at 24 hours). Use for patients with suicidal ideation should be supported by clinical documentation consistent with the trial populations and concurrent care.
Coding, Billing, and Procedure Codes
| J0013 | Esketamine, nasal spray, 1 mg (effective 1/1/2026) |
| S0013 | Esketamine, nasal spray, 1 mg (cancelled 12/31/25) |
| G2082 | Office or other outpatient visit for the evaluation and management of an established patient that requires the supervision of a physician or other qualified health care professional and provision of up to 56 mg of esketamine nasal self-administration, includes 2 hours post-administration observation |
| G2083 | Office or other outpatient visit for the evaluation and management of an established patient that requires the supervision of a physician or other qualified health care professional and provision of greater than 56 mg esketamine nasal self-administration, includes 2 hours post-administration observation |
Provider Responsibilities and Prior Authorization
Prior authorization must reference J0013 and visit G-codes
Submit prior authorization requests that include the specific HCPCS drug and visit codes for esketamine: use J0013 for esketamine (effective 1/1/2026) when applicable, and include outpatient visit codes G2082 or G2083 for supervised administration with up to 2 hours post-administration observation. Do not bill using S0013 after 12/31/2025.
Record concurrent oral antidepressant use and hospitalization per trial context
Document therapy sequencing consistent with trials: esketamine was administered alongside standard-of-care oral antidepressant therapy and, in the ASPIRE trials, with inpatient psychiatric hospitalization; coverage expectations may require evidence of concurrent oral antidepressant initiation/optimization or documentation of hospitalization when applicable.
- Note concurrent initiation or optimization of an oral antidepressant as used in the trials.
- If treatment follows the ASPIRE context, document inpatient psychiatric hospitalization when clinically warranted.
Document diagnosis, baseline and 24-hour MADRS, and concurrent treatments
Include clinical documentation that demonstrates the covered indication and trial-consistent measures: age and diagnosis (adult with moderate-to-severe MDD, TRD, or MDD with acute suicidal ideation/intent), baseline and follow-up MADRS scores (primary endpoint at 24 hours), and documentation of concurrent standard-of-care treatments (inpatient hospitalization and newly initiated/optimized oral antidepressant) to support medical necessity.
- Record baseline MADRS and 24-hour post-dose MADRS assessments and subsequent scores during the 4-week observation period.
- Document diagnosis (MDD, TRD, or MDD with active suicidal ideation and intent) and patient age (18–64 where applicable).
- Document initiation/optimization of an oral antidepressant and any inpatient psychiatric hospitalization when relevant.
Use current HCPCS/G-codes (J0013, G2082/G2083) to prevent denials
Use the correct HCPCS and G-code combinations and current drug code to avoid claim denials or processing issues: bill the drug with J0013 (effective 1/1/2026) or appropriate unclassified codes (J3490/J3590) only as indicated, and report the supervised visit with G2082 or G2083 per dose thresholds.
- J0013 is the covered HCPCS drug code effective 1/1/2026; S0013 was cancelled 12/31/2025 and must not be used.
- Use G2082 for provision up to 56 mg and G2083 for greater than 56 mg; both include 2 hours post-administration observation.
- Incorrect or outdated codes may result in claim processing issues or denials.
Clinical Background and Indication
Intranasal esketamine (Spravato) was developed and studied as a rapid-acting treatment for adults with moderate-to-severe major depressive disorder, including populations with treatment-resistant depression and adults with active suicidal ideation and intent. Clinical programs evaluated Spravato both as monotherapy (TRD trials such as TRD4005) and as an adjunct to standard-of-care treatments (ASPIRE trials), with trials typically pairing administration with a newly initiated or optimized oral antidepressant and, in ASPIRE, inpatient psychiatric hospitalization. The primary efficacy outcome in key trials was change in MADRS score at 24 hours post-dose, with data collected over a 4-week treatment period; TRD trials also reported higher remission rates at week 4 for Spravato versus placebo (for example, 22.5% vs 7.6% in TRD4005).
Outcome Measures and Definitions
Administration Setting and Supervision
Esketamine Treatment Details
Esketamine nasal spray (Spravato)
Document concurrent oral antidepressant when used adjunctively; follow observation and safety monitoring consistent with trial protocols
Observation and Visit Time Limits
Policy Revision History
Policy current effective date set to December 19, 2025.
Policy reviewed (October 2025).
Policy revised in June 2025 (document indicates a revision in June 2025).
Policy created in July 2019 (original approval/creation of Spravato policy).
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