For therapists working with clients who have treatment-resistant depression, Spravato represents a meaningful addition to the clinical toolkit — one that keeps the therapeutic relationship at the center of care while opening an FDA-approved, insurance-covered treatment pathway for a population that has historically been managed in highly medicalized settings with little ongoing therapeutic support.
This isn't about choosing between treatment modalities. It's about having more options to meet clients where they are. Some clients are ideal candidates for ketamine-assisted psychotherapy (KAP). Others — particularly those with treatment-resistant depression or acute suicidal ideation — may be better served by an FDA-approved, insurance-covered pathway with a defined protocol and ongoing therapeutic support built in. Spravato makes that possible within a therapy-aligned practice setting.
This post covers what Spravato is, who it's designed for, how it works clinically, and what it looks like when a private practice actually offers it.
What Is Spravato?
Spravato is the brand name for esketamine nasal spray, the S-enantiomer of ketamine. Unlike off-label ketamine treatments — whether sublingual or IV — it is FDA-approved specifically for depression and covered by insurance for its indicated populations.
Spravato currently carries two FDA-approved indications:
- Treatment-Resistant Depression (TRD): for adults who have not responded adequately to at least two antidepressant trials
- Major Depressive Disorder with Acute Suicidal Ideation or Behavior (MDD with SI): for adults in need of rapid symptom reduction
Because it's FDA-approved, Spravato is covered by most commercial insurance plans and Medicare for these indications — making it a financially sustainable long-term treatment pathway for clients who need ongoing support.
How Spravato Works in the Brain
Spravato works through a fundamentally different mechanism than conventional antidepressants. Rather than primarily targeting serotonin pathways, it acts on glutamatergic systems — specifically NMDA receptors — which are associated with neuroplasticity and the brain's capacity to form new synaptic connections.
By modulating glutamate signaling, Spravato may increase synaptic connectivity and create greater cognitive and emotional flexibility. Many clinicians describe this less as symptom suppression and more as increasing flexibility in systems that have become stuck — which may explain why some patients experience relief more rapidly than with conventional antidepressants, particularly when depressive patterns have become rigid or entrenched over time.
This mechanism is also why the patient experience during a session can include dissociation, altered perception, and a temporary loosening of habitual thought patterns — a window that, with skilled therapeutic support, can be clinically meaningful.
Who Is a Good Candidate?
Spravato is FDA-approved for two specific diagnoses only:
- Treatment-Resistant Depression (TRD): adults who have not responded adequately to at least two antidepressant trials
- Major Depressive Disorder with Acute Suicidal Ideation or Behavior (MDD with SI): adults experiencing acute suicidal ideation or behavior who need rapid symptom reduction
Patients must meet criteria for one of these two indications to qualify for Spravato treatment and insurance coverage.
As of 2025, patients no longer need to be on a concurrent antidepressant to receive Spravato — following FDA approval of Spravato as a monotherapy in January 2025, removing a barrier that had previously made the treatment less accessible for certain populations.
What the Treatment Protocol Looks Like
Spravato is administered exclusively in person within REMS-certified settings. Because of risks including dissociation, sedation, and transient blood pressure elevations, it cannot be prescribed for home use.
The standard protocol includes:
- Induction phase: Two sessions per week for the first four weeks
- Maintenance phase: Typically weekly, with some patients eventually spacing to every other week depending on response and stability
- Observation period: Approximately two hours per session for monitoring before the patient is cleared to leave
Each session involves intranasal administration under clinical observation. The patient experience varies — some degree of dissociation or altered perception is common — but the overall experience tends to be more structured and predictable than many other psychedelic modalities. Patients often describe feeling emotionally open, reflective, or temporarily less rigid in their thinking, which creates a meaningful window for therapeutic engagement.
Why Psychotherapy Alongside Spravato Changes the Outcome
This is where the clinical evidence becomes particularly relevant for therapists.
In traditional Spravato settings, many patients do not have ongoing therapists. Treatment is often delivered in highly medicalized environments — infusion-clinic style settings with minimal therapeutic framing or follow-through. The medication is administered. The session ends. The patient goes home.
A 2025 retrospective, multicenter observational study by Gutiérrez-Rojas et al., published in the Journal of Psychopharmacology, found that patients receiving ongoing psychotherapy alongside Spravato showed stronger sustained improvement — particularly beyond the 90-day mark. That finding aligns with what experienced clinicians see in practice: Spravato may create emotional and cognitive flexibility, but therapy is what helps patients actually process, organize, and integrate what emerges. Preparation and integration matter. Continuity of care matters.
The question isn't whether Spravato works. It does, for many people with treatment-resistant depression. The question is whether patients receiving it are supported in making lasting use of the window it opens.
Set and Setting: Why the Environment Is Part of the Treatment
In ketamine-assisted psychotherapy, set and setting are foundational — not incidental — to therapeutic outcomes. "Set" refers to the patient's internal psychological state entering a session: their mindset, intentions, emotional preparation, and expectations. "Setting" refers to the external environment: the physical space, sensory conditions, the presence of a trusted clinician, and the broader therapeutic context surrounding the experience.
Research across psychedelic studies consistently shows that both variables shape not just the subjective experience, but the clinical outcomes that follow. A supportive environment reduces anxiety during altered states. Psychological preparation helps patients enter the experience with intention rather than fear. Integration after the session is what converts insight into lasting change.
Spravato sessions involve a meaningful altered state — dissociation, emotional openness, a temporary loosening of habitual thought patterns. That window is clinically significant, and what surrounds it matters as much as what happens inside it. A patient receiving Spravato in a sterile, impersonal infusion-clinic environment is having a fundamentally different experience than one treated in a calming, intentional therapeutic space with a familiar clinician present and an ongoing therapy relationship on either side of the session.
The five core components of set and setting in psychedelic-assisted psychotherapy map directly onto what makes Spravato in a therapy-aligned setting different from standard delivery:
Preparation helps patients arrive with psychological readiness, clear intentions, and a grounded relationship with their treating clinician — reducing the likelihood of disorienting or destabilizing experiences during the session.
Therapeutic environment shapes the quality of the altered state. Comfortable seating or reclining setups, soft lighting, quiet — these are not aesthetic preferences. They are clinical variables that influence whether a patient feels safe enough to move through the experience openly.
Supportive presence during the session — even in a monitoring role — matters. Knowing that a trained, trusted clinician is present changes how patients navigate the experience.
Integration is what makes the work stick. The emotional and cognitive flexibility Spravato may create is most therapeutically useful when patients have space afterward — in ongoing psychotherapy — to process what emerged, connect it to their broader patterns, and translate it into behavioral and psychological change.
Continuity of care across preparation, dosing, and integration is what distinguishes a therapy-aligned Spravato model from a purely medicalized one. It is also, the evidence suggests, what drives better sustained outcomes.
What It Looks Like in Private Practice
Bringing Spravato into a private practice setting has historically required navigating a significant operational burden: REMS certification, DEA compliance, staffing for clinical monitoring, secure medication storage, inventory tracking, and coordination with specialty pharmacies. Most therapy practices aren't set up for this — and shouldn't have to rebuild themselves as medical clinics to participate in this model.
The emerging alternative is a decentralized, therapy-aligned model in which medical providers come on-site to certified practice settings to handle clinical monitoring, while the practice provides the space, operational coordination, and — critically — ongoing therapeutic support.
One example of this in practice is Casa Wellness, a therapy and healing space in Long Island City, New York. Casa isn't a traditional medical clinic. It hosts workshops, community events, and integrative healing work — and that's precisely what makes it a meaningful environment for Spravato treatment. Patients receive sessions in a calming, intentional setting: reclining setups, soft lighting, eye masks, quiet. Journey Clinical's medical providers handle monitoring and REMS compliance on-site, while referring therapists continue preparation, integration, and ongoing psychotherapy with their clients.
"It ends up feeling much closer to a supportive healing environment than what people might imagine when they hear 'monitored medical treatment,'" said Erica Sandoval, LCSW, founder of Casa Wellness.
This collaborative model keeps the therapeutic relationship intact. The medical side is handled. The therapist's role — preparation, integration, continuity of care — doesn't disappear.
The Accessibility Argument
One of the most important things about Spravato is what it doesn't cost the patient. The table below shows how it compares across the broader ketamine treatment landscape:
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At Journey Clinical, the Spravato model is structured differently — we recommend that every patient has a therapist involved in preparation, integration, and ongoing psychotherapy throughout the course of treatment.
Through the Spravato WithMe patient assistance program, some commercially insured patients may qualify for treatments at approximately $10 per session — and in some cases, depending on coverage and eligibility, at no cost.
That creates a meaningfully more sustainable long-term treatment pathway for patients who need ongoing support rather than a single acute intervention.
Why REMS Infrastructure Matters for the Future of Psychedelic Care
Spravato is not just a treatment. It's a proof of concept.
REMS (Risk Evaluation and Mitigation Strategy) infrastructure — the framework that governs where and how Spravato can be administered — is likely to become increasingly relevant across the psychedelic treatment landscape. Compass Pathways' COMP360 psilocybin has now completed two positive Phase 3 trials for treatment-resistant depression, with a rolling NDA submission targeted for Q4 2026 and a potential FDA approval decision as early as late 2026 or early 2027. Future psychedelic medicines may involve similar REMS-like structures requiring certified delivery settings, clinical monitoring, and operational compliance infrastructure.
Practices and networks investing in REMS-capable infrastructure now are building the operational foundation for the next generation of psychedelic care delivery — not just for esketamine, but for whatever comes after it.
Frequently Asked Questions
What is the difference between Spravato and off-label ketamine treatments? Spravato is an FDA-approved intranasal esketamine product specifically indicated for treatment-resistant depression and MDD with acute suicidal ideation. Off-label ketamine treatments — including sublingual and IV formulations — are not FDA-approved for psychiatric indications and are typically not covered by insurance for mental health use. Spravato is delivered in REMS-certified settings with standardized dosing and monitoring protocols, and is covered by most commercial insurance plans and Medicare for its indicated populations.
Does a patient need to be on an antidepressant to receive Spravato? As of 2025, concurrent antidepressant use is no longer required for Spravato treatment, expanding access for patients who are not currently on or tolerating antidepressant medications.
Can outside therapists continue working with their clients during Spravato treatment? Yes. In a therapy-aligned model, referring therapists are strongly encouraged to continue preparation, integration, and ongoing psychotherapy with their clients throughout the course of Spravato treatment. The medical monitoring side of care is handled separately.
How long do patients typically stay in treatment? After the initial four-week induction phase, most patients transition to weekly maintenance sessions. Over time, some patients may space to every other week depending on their response and stability. Treatment duration varies by individual clinical presentation and response.
What does REMS certification require? REMS certification involves training and compliance requirements for settings where Spravato is administered, including protocols for medication storage, inventory tracking, patient monitoring, and adverse event reporting. The operational requirements are significant — which is why Journey Clinical handles the REMS compliance infrastructure on behalf of member practices, making it operationally viable for therapists to offer Spravato without rebuilding their practice around medical clinic workflows.
The Takeaway for Therapists
If you work with clients who have treatment-resistant depression, Spravato is worth understanding — not as a replacement for your therapeutic relationship, but as a potential complement to it. The evidence suggests that the combination of Spravato and ongoing psychotherapy produces better sustained outcomes than Spravato alone. That means the therapist's role isn't marginal in this model. It's central.
The question isn't whether to refer clients to highly medicalized treatment settings. The question is whether you can find - or help build - a setting where the medical and therapeutic sides of care are integrated from the start.
That's the model worth building.
Journey Clinical is a platform supporting licensed mental health professionals in delivering ketamine-assisted psychotherapy and Spravato treatment in their own practices. To learn more about the Journey Clinical network or explore whether your practice could offer Spravato, visit journeyclinical.com or find a therapist in the directory at my.journeyclinical.com/directory.