Spravato (Esketamine) for Treatment-Resistant Depression After a Personal Injury

Amar Lunagaria — Co-Founder & Chief Pharmacist, LienScripts | November 21, 2025 | 9 min read

Spravato (esketamine) is a nasal spray administered in a clinical setting for treatment-resistant depression — the most severe form of depression that does not respond to standard antidepressants. For PI patients who develop severe depression after a serious accident and fail multiple antidepressants, Spravato documents a serious, treatment-requiring psychiatric injury consequence.

Spravato (Esketamine) for Treatment-Resistant Depression After a Personal Injury

Spravato (esketamine) is a brand-only FDA-approved nasal spray for treatment-resistant depression (TRD) and major depressive disorder with acute suicidal ideation or behavior (MDSI). Unlike conventional antidepressants, esketamine works within hours — and its use documents a psychiatric injury of exceptional severity and clinical complexity.

For personal injury cases involving serious psychological injury after high-trauma accidents, a Spravato treatment record is among the most powerful psychiatric injury documentation available.

[!KEY] Spravato (esketamine) is only prescribed after at least two antidepressant trials have failed — making its presence in a medication record definitive evidence of treatment-resistant depression. Every dose is administered in a certified clinical setting under REMS monitoring, creating a dense physician-supervised treatment record. The induction phase alone produces 8–12 clinical visits. For PI cases involving serious psychiatric injury after high-trauma accidents, a Spravato prescription is among the strongest psychiatric documentation available.

What Is Treatment-Resistant Depression?

Treatment-resistant depression is defined as major depressive disorder that has failed to respond to at least two adequate trials of antidepressant medications at appropriate doses and durations. It represents the most severe and difficult-to-treat form of clinical depression.

For personal injury patients, the pathway to treatment-resistant depression typically looks like this:

1. High-trauma accident → acute psychological response, PTSD symptoms, sleep disruption
2. First antidepressant trial (e.g., sertraline) → inadequate response after 6-8 weeks
3. Dose adjustment or medication switch (e.g., escitalopram, duloxetine) → still inadequate
4. Augmentation strategies (adding brexpiprazole/Rexulti, bupropion, etc.) → partial response at best
5. Referral to psychiatrist → diagnosis of treatment-resistant depression
6. Spravato → esketamine therapy under REMS monitoring

A patient who has progressed through this pathway has documented, in their medical records, multiple failed treatment attempts for serious depression attributable to the accident. The Spravato prescription is the final documentation of the severity of their psychiatric injury.

The REMS Program: Clinical Administration Requirement

Spravato is a Schedule III controlled substance administered through the FDA's Risk Evaluation and Mitigation Strategy (REMS) program. This means:

Every dose is administered in a certified clinical setting. The patient cannot take Spravato home. They must:

1. Travel to a certified healthcare facility (psychiatrist's office, infusion center, or hospital outpatient department)
2. Administer the nasal spray under direct clinical supervision
3. Remain in the facility for at least 2 hours of mandatory post-dose monitoring
4. Have a driver arranged — patients cannot drive or operate machinery after treatment

Dosing schedule:

• Induction phase: Twice weekly for 4 weeks
• Maintenance phase 1: Once weekly for 4 weeks
• Maintenance phase 2: Once weekly or every 2 weeks, ongoing

This schedule creates 8-12 clinical visits during induction, plus ongoing regular visits for maintenance — a substantial clinical record of psychiatric treatment.

Why Spravato Creates Exceptional Documentation

Volume of Clinical Records

Each Spravato dose requires:

• A clinical visit with physician supervision
• A 2+ hour monitoring session documented in clinical notes
• A separate clinical assessment before each dose
• Transportation documentation (the patient cannot drive)

A patient receiving Spravato twice weekly for 4 weeks has 8 documented clinical treatment sessions in that month alone. Each session creates a clinical record. Months of Spravato therapy create a clinical paper trail of profound depth.

The "Failed Multiple Antidepressants" Finding

The TRD diagnosis requires documented failure of at least two antidepressant trials. This means the psychiatrist's records will contain:

• Prior antidepressant prescriptions with inadequate response documentation
• Dose escalation attempts
• Medication switches
• A documented conclusion that standard antidepressant treatment is insufficient

This history is strong evidence of a serious, persistent psychiatric injury — not a mild depression that resolved with a few weeks of medication.

The Severity That Spravato Implies

[!TIP] When Spravato appears in a client's records, request the complete psychiatric medication history going back to the accident — not just the esketamine prescription. The prior failed antidepressant trials, dose escalations, and augmentation attempts that preceded Spravato are the documentary foundation of a treatment-resistant depression claim. Each failed trial is documented evidence of a serious, persistent psychiatric injury that the accident caused or substantially contributed to.

Spravato is prescribed only for the most severe, treatment-refractory depression cases. A psychiatrist who recommends Spravato has determined that:

• The patient's depression is clinically severe
• Standard treatments have failed
• The clinical urgency is sufficient to justify a twice-weekly clinical procedure with mandatory 2-hour monitoring
• The patient meets FDA criteria for TRD or MDSI

This is not mild situational sadness — this is severe, persistent, treatment-requiring psychiatric injury.

[!KEY] The documented progression from first antidepressant to Spravato — multiple failed trials, dose escalations, medication switches, and augmentation strategies — is itself a powerful chronological narrative of a serious psychiatric injury that resisted every standard treatment attempt; this entire history is in the treating psychiatrist's records and supports a substantial non-economic damages claim.

The Mechanism: Why Esketamine Works When Antidepressants Don't

Conventional antidepressants (SSRIs, SNRIs, TCAs) work primarily through the serotonin and norepinephrine systems — and require weeks to months to achieve therapeutic effect. Treatment-resistant depression suggests these systems are not the primary driver.

Esketamine is an NMDA receptor antagonist — it blocks the same receptor that is dysregulated in central sensitization. The NMDA receptor plays a key role in synaptic plasticity throughout the brain, and its dysregulation underlies the neurological basis of severe treatment-resistant depression.

Esketamine's NMDA blockade:

1. Rapidly restores glutamatergic signaling in the prefrontal cortex and limbic system
2. Stimulates AMPA receptor activity, which triggers BDNF (brain-derived neurotrophic factor) release
3. Promotes synaptogenesis — the formation of new synaptic connections in areas of the brain atrophied by severe depression

This is a fundamentally different mechanism than standard antidepressants, working at the structural level of brain circuitry rather than at the neurotransmitter transport level — which is why it works when other medications have failed.

The connection to accident injury: traumatic stress itself disrupts NMDA receptor function and reduces BDNF levels, creating the neurological substrate in which conventional antidepressants fail to achieve adequate effects. Esketamine directly addresses this trauma-induced neurobiological disruption.

Post-Traumatic Stress Disorder and Spravato

Spravato has an FDA indication for MDD, not PTSD specifically — but PTSD and TRD frequently co-occur in severe trauma cases. A patient with both PTSD and TRD may be on:

• Rexulti (brexpiprazole) — FDA-approved for PTSD as adjunctive treatment
• An SSRI (sertraline, paroxetine) — the FDA-approved PTSD pharmacotherapies
• Spravato — for the co-occurring treatment-resistant depression

This combination documents a psychiatric picture of exceptional severity — PTSD and treatment-resistant depression simultaneously, both requiring advanced pharmacotherapy.

What Attorneys Should Know About Spravato in PI Cases

Spravato is the clinical ceiling of outpatient psychiatric treatment. When a patient reaches Spravato, they have exhausted the standard pharmacological options for depression. The only step beyond Spravato is electroconvulsive therapy (ECT) — a hospital procedure. A patient receiving Spravato is documented at the most severe tier of outpatient psychiatric care.

The REMS documentation is extraordinary. The mandatory clinical visit records, monitoring documentation, and dose records create a treatment record unlike any other medication. Each of the 8 induction visits is individually documented, including clinical assessment, drug administration, monitoring, and clinical response.

Duration is powerful evidence. Ongoing Spravato maintenance (monthly or bimonthly visits) documents persistent, treatment-requiring severe depression for as long as maintenance continues. Monthly Spravato visits for 18 months document 18 months of severe TRD as an unresolved injury consequence.

[!KEY] The REMS-mandated clinical supervision structure means Spravato therapy cannot be fabricated or exaggerated — every dose requires a certified facility visit, physician assessment, and documented monitoring period. This regulatory paper trail is essentially attorney-proof documentation of persistent, severe psychiatric injury at the most advanced tier of outpatient treatment.

LienScripts provides pharmacy lien coverage for Spravato for qualified personal injury patients. Due to the REMS requirements, coverage coordination requires advance planning — contact LienScripts to discuss.

Related Resources

• Rexulti, Quviviq, and Dayvigo: Modern Medications for PTSD and Sleep After PI
• Central Sensitization: Why PI Pain Outlasts the Physical Injury
• Non-Opioid Pain Management in Personal Injury Cases: 2025 Update