Treatment-resistant depression affects an estimated 3 million adults in the United States, representing the subset of major depressive disorder patients who do not achieve adequate symptom relief despite multiple antidepressant trials at therapeutic doses. The 2019 FDA approval of SPRAVATO® (esketamine nasal spray) marked the first new mechanism of action for depression pharmacotherapy in more than three decades — a significant milestone for patients who had exhausted the existing formulary. At Complete Mind Care in Horsham, we administer SPRAVATO® as an FDA-approved treatment for treatment-resistant depression (TRD) and for depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior, serving patients across Montgomery County and the greater Philadelphia area.
Understanding SPRAVATO® and Its FDA Approval
SPRAVATO® is an intranasal formulation of esketamine, the S-enantiomer of ketamine, developed by Janssen Pharmaceuticals and approved by the U.S. Food and Drug Administration in March 2019. It is FDA-approved for two specific indications: treatment-resistant depression in adults, as monotherapy or in conjunction with an oral antidepressant, and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior in conjunction with an oral antidepressant (Janssen Pharmaceuticals, 2025). It is important to state these approvals precisely — SPRAVATO® is not approved for all forms of depression, and its use outside these indications would be considered off-label.
The mechanism of action distinguishes SPRAVATO® categorically from most conventional antidepressants. Conventional antidepressants — SSRIs, SNRIs, TCAs, MAOIs — work primarily through monoamine neurotransmitter systems, increasing available serotonin, norepinephrine, or dopamine in synaptic clefts. SPRAVATO® targets the glutamatergic system, specifically acting as an antagonist at N-methyl-D-aspartate (NMDA) receptors. By blocking NMDA receptors, esketamine triggers downstream pathways involved in synaptic plasticity and neural connectivity in prefrontal circuits affected by chronic depression (Murrough et al., 2013; Zanos & Gould, 2018).
This synaptic restoration mechanism helps explain one of SPRAVATO®’s most clinically distinctive features: relatively rapid onset compared with conventional antidepressant timelines. While conventional antidepressants often require several weeks to produce measurable therapeutic effects, some patients treated with SPRAVATO® report mood improvement within hours or days of early sessions. For patients experiencing acute depressive symptoms, this rapid antidepressant effect can be clinically meaningful. Results vary by individual, and the speed and degree of response differ from patient to patient.
The SPRAVATO® Treatment Protocol
SPRAVATO® is administered exclusively in certified healthcare settings under the FDA’s Risk Evaluation and Mitigation Strategy (REMS) program. At Complete Mind Care in Horsham, patients self-administer the nasal spray under direct supervision in our monitored treatment room. For treatment-resistant depression, the recommended protocol involves 56 mg or 84 mg administered twice weekly for four weeks during the induction phase, followed by once-weekly dosing for four weeks, and then once-weekly or once-every-two-weeks maintenance dosing based on clinical response and tolerability (Janssen Pharmaceuticals, 2025).
Because SPRAVATO® can cause dissociative symptoms, perceptual changes, sedation, respiratory depression, and transient blood pressure elevation, patients are observed for at least two hours following each administration session before being cleared to leave (Janssen Pharmaceuticals, 2025). Patients may not drive themselves home on treatment days — a practical consideration we build into the scheduling process for our Horsham patients commuting from Dresher, North Wales, Fort Washington, and other Montgomery County communities. Arranging a consistent ride is one of the real-world barriers to treatment access that we help patients navigate during intake planning. Another barrier is the perception that SPRAVATO® is simply “ketamine infusions” repackaged — in fact, SPRAVATO® is a distinct compound (the S-enantiomer only, not racemic ketamine), administered via a different route, under a specific regulatory framework, and with an FDA approval that ketamine infusions do not carry.
For TRD, SPRAVATO® may be used as monotherapy or in conjunction with an oral antidepressant; for depressive symptoms in adults with MDD with acute suicidal ideation or behavior, it is used in conjunction with an oral antidepressant (Janssen Pharmaceuticals, 2025). We discuss with each patient whether an oral antidepressant — or whether to adjust an existing regimen — best complements the SPRAVATO® protocol based on their history and current tolerability. Discuss with your provider whether SPRAVATO® and any accompanying antidepressant regimen are appropriate for your individual situation.
Clinical Evidence Supporting SPRAVATO® for TRD
The clinical development program for SPRAVATO® in TRD included several Phase 3 randomized controlled trials. The pivotal TRANSFORM-2 trial, published in the American Journal of Psychiatry, demonstrated that patients receiving esketamine plus a newly initiated oral antidepressant showed significantly greater reduction in depression severity (MADRS score) compared to patients receiving placebo nasal spray plus a new oral antidepressant, with effect observed during the four-week study period (Popova et al., 2019). The SUSTAIN-1 study further demonstrated that patients who achieved stable remission or stable response with esketamine were significantly less likely to relapse when continued on esketamine maintenance compared to those switched to placebo (Daly et al., 2019).
What these trial data mean in practical terms is that SPRAVATO® is not designed only as a short-term crisis intervention — though it may provide rapid relief during acute episodes — but can also function as a maintenance treatment for eligible patients with a history of recurrent TRD. Patients considering their options may also find it helpful to read about treatment-resistant depression breakthrough options beyond medication, which contextualizes where SPRAVATO® fits alongside other emerging approaches. The maintenance phase of the protocol reflects the relapse-prevention evidence: patients who respond well to induction and consolidation may be candidates for continued weekly or every-other-week dosing to preserve response or remission.
How We Evaluate Candidates at Complete Mind Care
At our Horsham clinic, SPRAVATO® candidacy begins with a comprehensive psychiatric evaluation that confirms the TRD diagnosis — specifically, documentation of inadequate response to at least two antidepressant trials. We review prior medication history, current medications, medical history, blood pressure baseline, and any history of psychosis or dissociative disorders, which may affect candidacy.
Patients with aneurysmal vascular disease, arteriovenous malformation, intracerebral hemorrhage, or hypersensitivity to esketamine, ketamine, or formulation excipients should not receive SPRAVATO® (Janssen Pharmaceuticals, 2025). Additional clinical factors, including blood pressure status, substance use history, and dissociative symptoms, are reviewed carefully during evaluation and monitoring. The evaluation also includes a baseline cognitive and functional assessment, which serves as a reference point for monitoring treatment response over time. Our board-certified psychiatrists conduct this evaluation and remain clinically responsible for each patient’s SPRAVATO® program throughout the treatment course.
Our clinical model at Complete Mind Care integrates SPRAVATO® with the broader treatment infrastructure that supports lasting remission — including medication management to optimize any oral antidepressant component and professional psychotherapy services to address the cognitive and behavioral dimensions that pharmacology alone cannot fully resolve. Remission is our mission, and for TRD patients in the Horsham area and across the Philadelphia suburbs, SPRAVATO® represents one of the most powerful tools we have to achieve it.
FAQ
What is SPRAVATO® and is it the same as ketamine infusions?
SPRAVATO® is an FDA-approved nasal spray containing esketamine — the S-enantiomer of ketamine. It is not the same as ketamine infusions: it is a different compound formulation, administered via a different route, regulated under a specific FDA REMS program, and carries FDA approval for TRD and depressive symptoms in adults with MDD with acute suicidal ideation or behavior that racemic ketamine infusions do not. For TRD, SPRAVATO® may be used with or without an oral antidepressant; for depressive symptoms in MDD with acute suicidal ideation or behavior, it is used with an oral antidepressant.
How quickly does SPRAVATO® work for depression?
Some patients treated with SPRAVATO® report measurable mood improvement within hours to days of initial dosing, which is faster than typical conventional antidepressant timelines. The full clinical evaluation of response is typically conducted after the four-week induction phase. Results vary significantly by individual, and not all patients experience rapid response.
Do I need to have tried multiple antidepressants before qualifying for SPRAVATO®?
Yes. The FDA approval for SPRAVATO® in treatment-resistant depression is for adults with TRD, commonly defined in clinical trials and treatment protocols as inadequate response to at least two oral antidepressants of adequate dose and duration. Our team at Complete Mind Care conducts a thorough evaluation of your treatment history to confirm eligibility and discuss the most appropriate treatment path.
Can I drive myself home after a SPRAVATO® session?
No. FDA REMS requirements mandate that patients be monitored for at least two hours after SPRAVATO® administration due to potential dissociative symptoms and sedation. Patients may not drive or operate heavy machinery on treatment days and must arrange transportation. We help Horsham-area patients plan this logistics aspect during the intake process.
Does insurance cover SPRAVATO® treatment?
SPRAVATO® has FDA approval and is covered by many commercial insurance plans and Medicare when TRD criteria are documented. Prior authorization is typically required. Our team handles insurance verification and prior authorization submissions for patients at our Horsham clinic.
Key Takeaways
SPRAVATO® (esketamine nasal spray) is FDA-approved specifically for treatment-resistant depression and for depressive symptoms in adults with MDD with acute suicidal ideation or behavior — not for all forms of depression.
Its NMDA receptor antagonism mechanism works through glutamatergic pathways involved in synaptic plasticity, a fundamentally different action from many conventional antidepressants.
SPRAVATO® is administered exclusively in certified clinical settings with post-dose monitoring; patients cannot drive on treatment days.
At Complete Mind Care in Horsham, SPRAVATO® is integrated with medication management and psychotherapy as part of a comprehensive individualized treatment plan.
Results vary by individual; candidacy requires documentation of treatment-resistant depression criteria and a comprehensive psychiatric evaluation.
Conclusion
For patients in Horsham and across Montgomery County who have not found adequate relief through antidepressant medications, SPRAVATO® offers an FDA-approved treatment option grounded in a fundamentally different neurobiological mechanism. At Complete Mind Care, located at 721 Dresher Rd #1100, Horsham, PA 19044, our team of board-certified psychiatrists provides the comprehensive evaluation, supervised administration, and ongoing clinical management that SPRAVATO® treatment requires. Schedule a consultation by calling 215-607-7250 to learn whether SPRAVATO® is appropriate for your individualized treatment plan.
References
Daly, E. J., Trivedi, M. H., Janik, A., Li, H., Zhang, Y., Li, X., Lane, R., Lim, P., Duca, A. R., Hough, D., Thase, M. E., Zajecka, J., Winokur, A., Divacka, I., Fagiolini, A., Cubala, W. J., Bitter, I., Blier, P., Shelton, R. C., … Singh, J. B. (2019). Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression. JAMA Psychiatry, 76(9), 893–903. https://doi.org/10.1001/jamapsychiatry.2019.1189
Janssen Pharmaceuticals. (2025). SPRAVATO® (esketamine) nasal spray, CIII: Prescribing information. https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf
Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., Iqbal, S., Pillemer, S., Foulkes, A., Shah, A., Charney, D. S., & Mathew, S. J. (2013). Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial. American Journal of Psychiatry, 170(10), 1134–1142. https://doi.org/10.1176/appi.ajp.2013.13030392
Popova, V., Daly, E. J., Trivedi, M., Cooper, K., Lane, R., Lim, P., Mazzucco, C., Hough, D., Thase, M. E., Shelton, R. C., Molero, P., Vieta, E., Bajbouj, M., Manji, H., Drevets, W. C., & Singh, J. B. (2019). Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: A randomized double-blind active-controlled study. American Journal of Psychiatry, 176(6), 428–438. https://doi.org/10.1176/appi.ajp.2019.19020172
Zanos, P., & Gould, T. D. (2018). Mechanisms of ketamine action as an antidepressant. Molecular Psychiatry, 23(4), 801–811. https://doi.org/10.1038/mp.2017.255
Medical Disclaimer
The information provided in this blog is for educational purposes only and does not constitute medical advice. Treatment outcomes vary by individual. Results may vary. Please consult with a qualified healthcare provider before beginning any new treatment. Discuss with your provider whether this treatment is appropriate for you.