Medical Necessity Determination: Spravato Continuation for Treatment-Resistant Depression
Recommendation
This continuation of Spravato 84 mg twice weekly is NOT medically necessary based on the available documentation, as the patient does not meet the FDA-approved indication for the dosing regimen being requested.
Critical Issues with This Case
Primary Problem: Wrong Indication for Dosing Protocol
The patient is being treated under the wrong FDA indication. The documentation shows the patient has recurrent major depressive disorder (F33.9) WITHOUT acute suicidal ideation or behavior, yet the dosing protocol (84 mg twice weekly beyond 4 weeks) is only FDA-approved for MDD with acute suicidal ideation or behavior 1.
The FDA label explicitly states that for MDD with acute suicidal ideation or behavior, the recommended dosage is 84 mg twice per week for 4 weeks, and "the use of SPRAVATO, in conjunction with an oral antidepressant, beyond 4 weeks has not been systematically evaluated in the treatment of depressive symptoms in patients with MDD with acute suicidal ideation or behavior" 1.
The mental status exam on page 7 documents "no suicidal or homicidal ideation," which directly contradicts the indication being used to justify this dosing regimen 1.
Correct FDA-Approved Indication Not Being Followed
For treatment-resistant depression (TRD) without acute suicidal ideation, the FDA-approved dosing schedule is different:
- Induction Phase (Weeks 1-4): 56 mg or 84 mg twice per week 1
- Maintenance Phase (Weeks 5-8): 56 mg or 84 mg once weekly 1
- Week 9 and after: 56 mg or 84 mg every 2 weeks or once weekly 1
The patient is at DOS 6/29/2025, which is approximately 6-7 weeks from the start date of 5/14/2025. At this point, the patient should be in the maintenance phase with ONCE WEEKLY dosing, not twice weekly 1.
Documentation Deficiencies
Inadequate Treatment History Documentation
The case summary states the patient has "treatment-resistant depression" and lists prior failures of Cymbalta, Lexapro, Wellbutrin, and Prozac. However, there is insufficient documentation regarding the adequacy of these trials (dose, duration, adherence) to definitively establish TRD 2.
The 2022 VA/DoD guidelines define TRD as failure of at least 2 adequate trials of antidepressants. While the patient appears to meet this criterion, the documentation should explicitly confirm adequate dose and duration for each failed trial 2.
Missing Critical Assessment Data
No documented PHQ-9 or MADRS scores at the current visit (6/29/2025) to objectively assess therapeutic benefit. The initial PHQ-9 was 17, but there is no follow-up measurement 2.
The FDA label requires that "evidence of therapeutic benefit should be evaluated at the end of the induction phase to determine need for continued treatment" 1. This evaluation is not adequately documented.
Subjective improvement is noted ("mood has been stable," "less fluctuant," "significant improvements in mood/symptoms"), but objective measurement tools are absent 2.
Unclear Treatment Timeline
The documentation is contradictory regarding the number of treatments received. Page 6 shows start date 5/14/2025, but references to "Spravato #5" on 5/25/2025 and "Spravato #7" on 6/1/2025 create confusion about the actual treatment schedule 1.
For the DOS 6/29/2025, it is unclear whether this represents treatment session #8, #9, or another number, making it impossible to determine if the patient is still in induction or should have transitioned to maintenance dosing 1.
Evidence-Based Treatment Considerations
Esketamine Efficacy in TRD
The 2022 VA/DoD guidelines suggest ketamine or esketamine as a treatment option in patients who have not responded to several adequate pharmacologic trials, which this patient appears to meet 2.
Meta-analyses demonstrate that esketamine as augmentation to ongoing oral antidepressant use improved depressive symptoms and remission rates in patients with TRD at up to 28 days of follow-up 2.
However, these guidelines emphasize that esketamine is "not recommended as initial treatment but is reserved for patients for whom previous therapies have failed or who have not tolerated previous therapies" 2.
Long-term Use Concerns
The VA/DoD guidelines note that "ketamine lacks long-term efficacy and safety trials in MDD, and the bulk of the evidence on short-term (7-day) efficacy is from studies in patients who have previously not responded to adequate trials of antidepressants" 2.
Although there is evidence to support longer-term maintenance use of esketamine, it has been primarily studied in patients who have previously not responded to trials of antidepressants 2.
A 2025 randomized clinical trial demonstrated efficacy of esketamine monotherapy in TRD, with effect sizes of 0.48 for 56 mg and 0.63 for 84 mg doses 3.
What Would Make This Medically Necessary
To approve continuation, the following would need to be documented:
Correct indication and dosing schedule: If treating TRD without acute suicidal ideation, the patient should be on the TRD maintenance schedule (once weekly or every 2 weeks at this timepoint, not twice weekly) 1.
Objective evidence of therapeutic benefit: Documented improvement in standardized depression rating scales (PHQ-9, MADRS, HAM-D) from baseline to current visit 2, 1.
Clear treatment timeline: Documentation of all treatment sessions with dates to confirm appropriate phase of treatment 1.
Adequate prior treatment failures: Explicit documentation of at least 2 adequate antidepressant trials (specific doses, durations, and reasons for discontinuation) 2.
Ongoing psychiatric oversight: Confirmation that treatment is prescribed by or in consultation with a psychiatrist, which appears to be met 1.
Proper monitoring: Documentation of blood pressure monitoring before and after administration, 2-hour post-administration observation, and assessment for adverse effects 1.
Clinical Pitfalls to Avoid
Do not confuse the two FDA-approved indications for esketamine. The dosing schedules differ significantly between TRD and MDD with acute suicidal ideation 1.
Do not continue twice-weekly dosing beyond the induction phase for TRD patients. The FDA label specifies transition to less frequent dosing after week 4 1.
Do not approve continuation without objective measurement of therapeutic benefit. Subjective reports alone are insufficient 2, 1.
Do not overlook the requirement for concomitant oral antidepressant therapy. The patient is appropriately on duloxetine 60 mg, which meets this requirement 1.
Final Determination
DENY - Medical necessity not established. The patient requires re-evaluation with:
- Clarification of the correct FDA indication (TRD vs. MDD with acute suicidal ideation)
- Adjustment to appropriate dosing frequency based on treatment phase
- Objective measurement of therapeutic benefit using validated depression scales
- Complete documentation of treatment timeline and session numbers