SPRAVATO® Treatment in Minnesota: Understanding Esketamine Nasal Spray for Depression

The FDA’s 2019 approval of SPRAVATO® represented a watershed moment—the first truly novel antidepressant mechanism in decades. Esketamine is the only pharmacological agent with glutamatergic neuromodulatory properties approved by both the US FDA and European Medicines Agency to enhance effects of SSRI or SNRI antidepressants (Vasiliu, 2023). This nasal spray formulation makes the treatment more accessible than IV ketamine while maintaining the rapid antidepressant effects ketamine is known for.

What Makes SPRAVATO® Different From Other Antidepressants

SPRAVATO® works through an entirely different biological mechanism than the medications most people have tried for depression. Understanding this distinction helps explain why it might work when other treatments haven’t.

Traditional antidepressants—SSRIs like sertraline or escitalopram, SNRIs like duloxetine or venlafaxine—work by increasing levels of serotonin or norepinephrine in your brain. These monoaminergic medications take weeks to months to show effects because they work indirectly, gradually shifting neurotransmitter balance over time. When you’ve tried multiple medications from these classes without adequate response, trying yet another SSRI or SNRI is unlikely to provide dramatically different results.

Esketamine acts on glutamate, your brain’s most abundant neurotransmitter. Specifically, it blocks NMDA receptors, triggering a cascade of molecular events that increase mammalian target of rapamycin (mTOR). This pathway promotes synaptogenesis—the formation of new connections between brain cells—and enhances neuroplasticity. Think of esketamine as creating conditions where your brain can form new neural pathways rather than just adjusting the activity of existing ones.

The speed of response distinguishes SPRAVATO® from conventional antidepressants. Research shows that esketamine nasal spray significantly improved depression scores within 24 hours following the first dose in many patients (Vasiliu, 2023). While not everyone experiences such rapid effects, this timeline differs dramatically from the four to eight weeks typically required to assess whether a traditional antidepressant is working.

SPRAVATO® is derived from ketamine but isn’t identical to it. Esketamine represents the S-enantiomer of the ketamine molecule—essentially a more potent, specific version. It has approximately four times higher affinity for NMDA receptors compared to the R-enantiomer, allowing effective doses to be lower than racemic ketamine while theoretically producing fewer side effects.

At Aurora Mental Health & Wellness in Waite Park, Emily Luitjens brings specialized expertise in esketamine treatment from her years at VA medical centers treating veterans with severe, treatment-resistant depression. Her experience helps optimize dosing and manage the unique aspects of SPRAVATO® administration. Learn more about her background on our About Us page.

Understanding the FDA Approval and REMS Requirements

SPRAVATO®’s FDA approval came with specific requirements that shape how the medication is administered. These regulations exist because esketamine has abuse potential and causes temporary side effects requiring supervision.

The Risk Evaluation and Mitigation Strategy (REMS) program mandates that SPRAVATO® can only be administered in certified healthcare settings under direct medical supervision. You cannot take esketamine home—every dose must be self-administered at the clinic under a healthcare provider’s observation. This requirement adds logistical complexity but ensures your safety during treatment.

The FDA approved SPRAVATO® specifically for treatment-resistant depression in adults. This means you must have tried at least two different antidepressant medications at adequate doses for sufficient duration without achieving adequate improvement. You can’t access SPRAVATO® as a first-line treatment—it’s reserved for cases where standard treatments haven’t worked.

SPRAVATO® must be used in conjunction with an oral antidepressant. You don’t stop your existing antidepressant to start esketamine—you add SPRAVATO® to enhance the effects of ongoing treatment. This combination approach reflects how the medication was studied in clinical trials and how it received FDA approval.

Blood pressure monitoring is required before and after each dose. Esketamine temporarily increases blood pressure, sometimes significantly. If your blood pressure is already elevated when you arrive for treatment, your provider may need to reconsider whether to administer that day’s dose. Anyone with unstable or poorly controlled cardiovascular disease faces additional risks requiring careful evaluation.

The two-hour observation period following each dose addresses dissociation, sedation, and perceptual changes esketamine causes. These effects peak around 40 minutes after administration and gradually resolve over the next hour or two. You’ll be monitored throughout this period and can’t leave until symptoms resolve adequately for safe departure. You cannot drive for the rest of the day after SPRAVATO® treatment.

What the Treatment Process Actually Involves

Understanding SPRAVATO® treatment logistics helps you decide whether this fits your life circumstances and prepare for what’s involved. The process differs substantially from simply taking daily pills.

Initial evaluation determines if you’re an appropriate candidate. Your provider reviews your depression history, previous medication trials, current health status, and contraindications. Certain conditions—active substance use disorder, history of psychosis, aneurysmal vascular disease—may preclude SPRAVATO® use. Pregnancy requires careful risk-benefit assessment since effects on fetal development aren’t fully known.

Treatment begins with an induction phase involving twice-weekly sessions for the first four weeks. This intensive initial period establishes therapeutic effects before transitioning to less frequent maintenance dosing. The twice-weekly requirement represents a significant time commitment, particularly given the hours each session requires with travel, administration, and mandatory observation.

Each treatment session follows a standardized protocol. You’ll refrain from eating for at least two hours before treatment and avoid drinking liquids for 30 minutes prior to reduce nausea risk. If you use nasal decongestants or corticosteroid sprays, these should be administered at least one hour before esketamine to avoid interference with absorption.

The self-administration process involves three nasal spray devices for a full 84 mg dose—the most commonly used dose for treatment-resistant depression. Each device delivers 28 mg through two sprays (one per nostril). You administer the first device under supervision, wait five minutes, use the second device, wait another five minutes, then use the third device. This staggered timing allows absorption from each dose before administering the next.

During and immediately following administration, you’ll likely experience dissociation—a sense of detachment from your surroundings or yourself. Some people describe feeling like they’re observing themselves from outside, or that their environment seems unreal. These perceptual changes can feel strange or unsettling initially, though most people find them tolerable and they diminish with repeated treatments. Sedation, dizziness, and altered sense of time are also common during this period.

The mandatory two-hour observation ensures side effects have resolved sufficiently before you leave. Blood pressure is checked periodically during this time. Once dissociation, sedation, and blood pressure have returned to baseline, you’re cleared to leave with your pre-arranged driver. Planning for this substantial time commitment—typically three hours total including travel—is essential before starting treatment.

Research Evidence Supporting SPRAVATO® Efficacy

Multiple large clinical trials established SPRAVATO®’s effectiveness for treatment-resistant depression before FDA approval. Understanding this evidence base helps set realistic expectations about outcomes.

The TRANSFORM-2 trial demonstrated significant improvement in depression scores for esketamine plus antidepressant compared to placebo plus antidepressant. This multicenter, randomized study of 227 patients with treatment-resistant depression showed that those receiving esketamine experienced greater symptom reduction, with effects appearing earlier than the placebo group (Vasiliu, 2023).

Response rates vary across studies but generally show that roughly half to two-thirds of people with treatment-resistant depression achieve meaningful symptom reduction with SPRAVATO®. The ESCAPE-TRD trial compared esketamine nasal spray to extended-release quetiapine (another augmentation strategy for treatment-resistant depression), both added to ongoing SSRI or SNRI treatment. This head-to-head comparison evaluated efficacy in real-world treatment settings across 171 sites in 24 countries (Sanacora et al., 2024).

Long-term safety data from the SUSTAIN-3 study demonstrated that esketamine can be used safely over extended periods with individualized maintenance dosing. Patients who participated in initial trials could continue treatment with flexible dosing adjusted to their depression severity. This research addressed concerns about long-term effects and sustainability of benefits (Wilkinson et al., 2023).

Results vary by individual—not everyone responds to SPRAVATO®, and among responders, the degree of improvement differs. Factors predicting response aren’t fully understood, though severity of depression, presence of anxiety symptoms, and previous treatment history all appear to play roles. There’s currently no way to definitively predict whether you’ll respond before trying the treatment.

Insurance Coverage and Cost Considerations

SPRAVATO®’s FDA approval status generally makes insurance coverage more accessible than off-label IV ketamine, though significant variations exist between plans. Understanding financial aspects upfront prevents surprises.

Many major insurance carriers cover SPRAVATO® for treatment-resistant depression with prior authorization. Aurora accepts 13 major insurance carriers for SPRAVATO® services, including Medicare, major commercial plans, and some regional carriers. However, each plan has specific requirements about what constitutes “treatment-resistant” depression and what documentation is needed.

Prior authorization typically requires detailed documentation of your antidepressant trials—which medications, at what doses, for how long, and why they were inadequate. Your provider submits this information demonstrating you meet FDA criteria for treatment-resistant depression. Authorization processes take days to weeks, delaying treatment start.

Copays and coinsurance vary dramatically between plans. Some people pay modest copays per session, while others face significant out-of-pocket costs despite having coverage. The twice-weekly induction phase means these costs accumulate quickly—eight sessions over four weeks before transitioning to maintenance dosing. Clarifying expected costs before starting prevents financial strain.

For those without adequate insurance coverage or whose plans don’t cover SPRAVATO®, self-pay costs are substantial. Aurora offers financing options including CareCredit and AdvanceCare Card to make treatment more accessible when paying out of pocket.

Maintenance phase costs continue indefinitely for most people. While treatment frequency decreases after the initial four weeks—often to weekly, then bi-weekly, then monthly—SPRAVATO® typically requires ongoing treatments to sustain benefits rather than representing a one-time intervention. Factoring long-term costs into decisions about starting treatment ensures you can sustain the approach if it works.

Comparing SPRAVATO® to IV Ketamine and Other Options

When considering advanced treatments for treatment-resistant depression, understanding how SPRAVATO® compares to alternatives helps guide decision-making. Each option has distinct advantages and limitations.

SPRAVATO® versus IV ketamine involves the same basic mechanism—both affect glutamate neurotransmission through NMDA receptor antagonism. However, the delivery method, FDA approval status, and insurance coverage differ substantially. SPRAVATO®’s nasal spray administration is generally more convenient than IV infusion. Its FDA approval for treatment-resistant depression means better insurance coverage in most cases. The REMS requirements and mandatory observation apply to both, though protocols differ slightly.

Some people who don’t respond adequately to SPRAVATO® nasal spray do respond to IV ketamine, or vice versa. The pharmacokinetics differ—how quickly the drug enters your bloodstream and reaches your brain varies between routes of administration. If one form hasn’t worked, the other might still be worth trying. Results vary by individual.

Compared to TMS therapy, SPRAVATO® offers faster initial response but requires ongoing treatments to maintain benefits. TMS involves daily sessions for weeks initially but may provide longer-lasting effects after completing a course. TMS doesn’t involve medication or cause dissociation, which some people prefer. However, TMS requires considerably more frequent visits during the treatment course—daily versus twice weekly.

Relative to oral medication augmentation strategies, SPRAVATO® works faster but requires clinic visits and medical supervision. Adding lithium, thyroid hormone, or atypical antipsychotics to your existing antidepressant involves taking additional pills at home but doesn’t require clinic time. Oral augmentation typically costs less but works more slowly and may not be effective when multiple medication trials have failed.

The choice between these options depends on multiple factors including insurance coverage, your ability to commit time for clinic visits, previous treatment responses, side effect tolerability, and personal preferences regarding medication versus non-medication approaches.

FAQ Section

Q: Can I take SPRAVATO® at home?
A: No. FDA regulations require SPRAVATO® be administered only in certified healthcare settings under direct medical supervision due to side effects like dissociation and blood pressure increases. Every dose must be self-administered at the clinic, and you must be observed for two hours afterward before leaving. This requirement cannot be waived.

Q: How quickly does SPRAVATO® work?
A: Some people notice improvement within hours to days after the first dose, though this varies considerably. Clinical trials showed significant depression score improvements within 24 hours for some patients. However, many people require multiple treatments before experiencing noticeable benefits. Full therapeutic effects typically emerge over the four-week induction phase rather than after a single dose.

Q: Will SPRAVATO® cure my depression permanently?
A: SPRAVATO® is not a cure—it’s a treatment that requires ongoing maintenance for most people. After the initial induction phase, most patients transition to less frequent maintenance dosing. Discontinuing treatment often leads to symptom return. Results vary by individual, but SPRAVATO® typically represents ongoing management rather than a one-time fix.

Q: What are the most common side effects?
A: The most common side effects are dissociation, dizziness, nausea, sedation, increased blood pressure, and perceptual disturbances. These effects peak around 40 minutes after administration and resolve within about two hours. Most people find side effects tolerable and they often diminish with repeated treatments. Serious side effects are rare but can include significant blood pressure elevation.

Q: Does insurance typically cover SPRAVATO®?
A: Many insurance plans cover SPRAVATO® for FDA-approved treatment-resistant depression, but coverage varies significantly between plans. Most require prior authorization demonstrating you’ve failed at least two antidepressant trials at adequate doses and duration. Even with coverage, copays and coinsurance can be substantial. Checking specific coverage with your insurance before starting treatment prevents financial surprises.

Moving Forward with SPRAVATO® Treatment

SPRAVATO® represents a genuinely novel approach to depression that might work when previous treatments haven’t. The glutamatergic mechanism differs fundamentally from what you’ve likely tried before, offering hope through a different biological pathway.

The practical requirements—twice-weekly clinic visits with hours of observation, mandatory supervision, driving restrictions, ongoing maintenance—demand significant commitment. These aren’t trivial inconveniences but rather essential aspects of accessing this treatment safely. Weighing these requirements against the potential for rapid symptom relief helps you make informed decisions.

If you’re struggling with treatment-resistant depression in Central Minnesota, Aurora Mental Health & Wellness offers comprehensive SPRAVATO® evaluation and treatment. We accept 13 major insurance carriers for SPRAVATO® services and can help you understand coverage specifics. Contact us to learn if SPRAVATO® treatment is right for you and discuss insurance coverage for this FDA-approved therapy in St. Cloud.