What SPRAVATO® Is and Why It Is Different

SPRAVATO® (esketamine) is an FDA-approved nasal spray containing esketamine, the S-enantiomer of ketamine, formulated specifically for clinical administration. It was approved by the FDA in 2019 for two indications: treatment-resistant depression (TRD) in adults who have not responded adequately to at least two antidepressants of adequate dose and duration, and major depressive disorder with acute suicidal ideation or behavior (MDSI). These are distinct indications with different clinical protocols; this overview focuses primarily on the TRD indication.

What makes SPRAVATO® different from all other FDA-approved antidepressants is its mechanism of action. Every standard antidepressant currently available — SSRIs, SNRIs, TCAs, MAOIs, bupropion, mirtazapine — works through the monoamine neurotransmitter system: serotonin, norepinephrine, or dopamine. These medications enhance monoaminergic neurotransmission through various mechanisms, and while they are effective for many patients, approximately one-third of people with depression do not achieve remission after adequate trials of multiple monoamine-based treatments. SPRAVATO® works through the glutamate system, specifically as an NMDA receptor modulator. Glutamate is the principal excitatory neurotransmitter in the central nervous system, and glutamate receptor modulation triggers a cascade of neuroplastic effects including AMPA receptor potentiation and BDNF (brain-derived neurotrophic factor) release that restore synaptic connectivity in circuits disrupted by depression. This is an entirely different neurobiological target, which is why SPRAVATO® can work in patients who have not responded to monoamine-based treatments.

The speed of SPRAVATO®’s antidepressant effect is also different from standard antidepressants. While SSRIs and SNRIs require 2–6 weeks to produce meaningful therapeutic effects, many patients on SPRAVATO® notice improvement within the first one to two weeks of the induction phase. For patients with severe TRD who have been waiting years for an effective treatment, this faster onset is clinically meaningful. For the MDSI indication, the rapid reduction of suicidal ideation — within hours to days of the first session in some patients — is the primary therapeutic target.

SPRAVATO® is not a monotherapy and is not a replacement for an oral antidepressant. FDA approval requires that it be used alongside a standard oral antidepressant. The combination of SPRAVATO® and an oral antidepressant consistently outperforms SPRAVATO® alone in clinical trials. The oral antidepressant provides steady-state antidepressant coverage between SPRAVATO® sessions and during the maintenance phase.

Who Qualifies and the Eligibility Process

The primary criterion for SPRAVATO® eligibility for TRD is inadequate response to at least two antidepressants of adequate dose and duration during the current depressive episode. “Adequate” means reaching at least the minimum therapeutic dose and maintaining it for at least 4–8 weeks — not brief trials at subtherapeutic doses. If you have tried multiple antidepressants but several were stopped within days or weeks due to side effects before reaching therapeutic doses, your medication history may need review to determine how many of those constitute qualifying inadequate responses.

Contraindications that preclude SPRAVATO® include: aneurysmal vascular disease, arteriovenous malformation, history of intracerebral hemorrhage, hypersensitivity to esketamine or ketamine, and (for the MDSI indication) certain clinical presentations where the risk-benefit calculation differs. Active psychosis or a history of a primary psychotic disorder is evaluated carefully, as esketamine can worsen psychotic symptoms. A personal or family history of certain substance use disorders requires individualized risk assessment. Cardiovascular conditions are monitored through blood pressure checks at each session and may require cardiology clearance in some cases.

The eligibility evaluation at East Texas Psychiatry includes a comprehensive psychiatric assessment to confirm TRD and review contraindications, a review of your complete medication history, and initiation of the insurance prior authorization process. Most major insurers cover SPRAVATO® for appropriate candidates, though the prior authorization process typically takes one to two weeks to complete. Our team manages the prior authorization process and works with your insurance to maximize the chance of approval.

The Treatment Process From Induction to Maintenance

The SPRAVATO® treatment process follows a structured protocol established by the FDA and the manufacturer as part of the REMS (Risk Evaluation and Mitigation Strategy) program, which requires in-clinic administration and monitored observation for every session.

The induction phase consists of twice-weekly sessions for four weeks (eight sessions total). Each session involves arriving at the clinic, completing a brief pre-session assessment, self-administering the esketamine nasal spray under provider supervision (in two doses separated by five minutes), and then remaining in the clinic for the mandatory two-hour observation period during which vital signs are checked at regular intervals. Common in-session effects include dissociation (altered sense of time, space, and self; feeling detached from surroundings), dizziness, nausea, and sedation. These effects are expected, are monitored, and typically resolve completely by the end of the two-hour observation period. Patients are discharged once vital signs are stable and the observation period is complete. Transportation must be arranged for treatment days — patients may not drive for the remainder of any treatment day.

Following the four-week induction, the treatment transitions to a maintenance phase. The initial maintenance phase involves weekly sessions for four weeks. Subsequently, sessions are typically scheduled every one to two weeks depending on clinical response and the specific maintenance protocol determined by the provider. As patients achieve and maintain stable remission, the session interval may be extended further, with the goal of using the lowest frequency that maintains the therapeutic benefit. Long-term SPRAVATO® patients continue regular medication management appointments alongside their treatment sessions to monitor overall psychiatric status and maintain the oral antidepressant component.

How to Start at East Texas Psychiatry

East Texas Psychiatry administers SPRAVATO® at our Tyler clinic (100 Independence Pl, Suite 405, Tyler, TX 75703). The process begins with a comprehensive psychiatric evaluation to confirm TRD, review your medication history, and assess eligibility. This evaluation can be conducted by telepsychiatry; SPRAVATO® sessions themselves require in-person attendance at the Tyler clinic. Once eligibility is confirmed, our team initiates the insurance prior authorization process. Following authorization, the induction phase is scheduled and you are oriented to the session protocol. We accept Medicare, Aetna, Blue Cross Blue Shield, Cigna/Evernorth, Optum, UnitedHealthcare, UMR, and Ambetter for SPRAVATO®. To discuss eligibility and schedule your evaluation, Call (430) 288-5800schedule online.