Spravato vs Ketamine Infusion: Which Is Right for You?

You've been told ketamine might help your depression, and now you're looking at two very different options: a nasal spray called Spravato or an intravenous (IV) infusion at a clinic. They're both ketamine-based, but the cost, logistics, and insurance picture look nothing alike. It's hard to know which one actually makes sense for your situation.

If you've already been through rounds of antidepressants that didn't work, the last thing you need is more confusion about what to try next. Here's how these two options actually differ, so you can make a clearer decision.

The bottom line: Spravato and IV ketamine infusion can both help treatment-resistant depression, but they differ meaningfully in cost, insurance coverage, and speed of relief. IV ketamine often produces faster initial improvement, while Spravato's FDA approval makes insurance coverage more straightforward. Your best choice depends on your insurance situation, how quickly you need relief, and how much flexibility you want in your treatment.

What Is Spravato?

Spravato is the brand name for esketamine, an FDA-approved nasal spray for treatment-resistant depression and major depressive disorder (MDD) with acute suicidal ideation or behavior. As of January 2025, it can also be used as a standalone treatment without requiring an additional oral antidepressant.

What matters most for your decision: Spravato is FDA-approved, which means there's a clearer path to insurance coverage. But every dose must be administered in a certified healthcare setting under a Risk Evaluation and Mitigation Strategy (REMS) program. You can't take it home.

What Is IV Ketamine Infusion?

IV ketamine infusion delivers racemic ketamine, the original form of the medication, directly into your bloodstream through an IV line. Clinics administer it at much lower doses than its original use as an anesthetic.

Many clinics use protocols involving six to eight infusions over two to three weeks during the initial phase, with each session lasting about 40 minutes. After that, maintenance sessions typically continue on a weekly or biweekly basis.

The key distinction: IV ketamine is not FDA-approved for depression. It's used off-label, meaning providers prescribe it based on clinical evidence rather than formal regulatory approval. No standardized REMS requirements apply, so clinics have more flexibility in how they structure protocols, but consistency across providers can vary.

How Both Treatments Work in the Brain

Both treatments work through a fundamentally different pathway than traditional antidepressants. They block N-methyl-D-aspartate (NMDA) receptors. This blockade triggers a rapid surge of glutamate, your brain's primary excitatory signal. That glutamate surge prompts the release of Brain-Derived Neurotrophic Factor (BDNF), which acts like fertilizer for brain cells. Neurons then grow new connections in regions affected by depression. This process, called neuroplasticity, may explain why ketamine can produce results in hours rather than the weeks that traditional antidepressants require.

The molecular difference between the two is subtle but relevant. IV ketamine delivers racemic ketamine, which contains equal parts of two mirror-image molecules: S- and R-ketamine. Spravato delivers only the S-enantiomer, which binds NMDA receptors more potently. Whether that potency translates to better clinical outcomes is still an open question. A 2025 meta-analysis found no statistically significant difference in response or remission rates between the two by the end of acute treatment.

How Efficacy Compares

Both treatments help many people with treatment-resistant depression. In real-world studies, IV ketamine produces response rates around 50–70% during the acute treatment phase. In some observational and trial datasets, intranasal esketamine shows response rates in the high-40% to 60% range in the first month, with some studies reporting around two-thirds responding by three months.

What those numbers often look like in practice: the constant background noise of dread or emptiness doesn't vanish, but it quiets enough to function. You might notice you can get out of bed without the usual negotiation, or that a conversation with a friend doesn't feel like performing. For people who've waited months for medications to kick in, that kind of shift can feel significant.

Where the two treatments differ most is speed. IV ketamine often produces noticeable improvement after a single infusion or within the first few sessions. Spravato typically takes a bit longer, with many people improving within the first week or two. Both work faster than traditional antidepressants, where relief can take four to six weeks. That speed difference matters not just emotionally but practically: it affects how quickly you can tell whether treatment is working and whether the financial commitment is paying off.

Durability is harder to generalize because maintenance schedules vary by clinic and by person. Some people receiving IV ketamine can space maintenance infusions further apart over time, while Spravato commonly follows a structured schedule that starts twice weekly and tapers to weekly or every-other-week dosing.

What Treatment Sessions Feel Like

The day-to-day experience of these treatments differs more than the clinical data suggests.

How Do I Receive Treatment?

A Spravato session starts at a certified clinic. You self-administer the nasal spray under supervision, then sit in a monitored room for at least two hours while staff check your blood pressure periodically. Dissociation is common during this window, ranging from mild detachment to a more noticeable altered state. Once cleared, you'll need someone to drive you home, and you can't drive until the following day. Plan for roughly a half-day commitment per session, plus travel.

IV ketamine infusion also happens in a clinic, but the setup is different. A nurse places an IV line, and the infusion runs for about 40 minutes at a controlled rate. The experience during infusion can include dissociation, visual changes, and a feeling of emotional distance from your usual thought patterns. Monitoring during and after varies by clinic. Most keep you for 30 to 60 minutes post-infusion before clearing you to leave with a driver.

Do Spravato and Ketamine Infusion Feel Different?

The dissociative experience itself tends to differ between the two. Spravato's intranasal route generally produces milder, shorter-lasting dissociation. IV delivery, because it reaches the brain faster and at more precisely controlled doses, often produces a more pronounced altered state. Neither is dangerous in a supervised setting, but the intensity difference matters if you're feeling nervous.

Both treatments require you to block out a significant portion of your day and arrange a ride home. For some people, the structured clinical environment feels reassuring. For others, it makes treatment feel unsustainable over months of maintenance sessions.

Cost and Insurance

Cost is where these two options diverge most sharply, and the gap has less to do with the medication itself than with insurance coverage.

Spravato's FDA approval creates a coverage pathway that IV ketamine doesn't have. Many large commercial insurers and some Medicare and Medicaid plans cover Spravato when prior authorization criteria are met. Your out-of-pocket cost with insurance may range from $0 to $250 per session, but on some high-deductible plans, early sessions could cost over $1,800 until your deductible is met. Without insurance, clinics typically charge $1,000 to $1,500 per session.

IV ketamine is rarely covered by insurance. You're typically looking at $400 to $650 per session out of pocket, with significant regional variation (from $250 to $1,300 depending on location). Depending on protocol and frequency, a first year of infusions can reach tens of thousands of dollars. Many people can use Health Savings Account (HSA) or Flexible Spending Account (FSA) funds for IV ketamine, which reduces the effective cost by your marginal tax rate.

Getting Spravato covered often requires documentation: a treatment-resistant depression diagnosis, evidence of at least two adequate antidepressant trials (commonly six to eight weeks each), use of validated depression scales, and oversight by a qualified mental health prescriber. The prior authorization process can take weeks.

Side Effects and Safety

Both treatments share a similar side effect profile. The most common effects include dissociation, sedation, dizziness, nausea, and temporary blood pressure elevation. These typically resolve within 30 minutes to two hours after treatment. Some people may need blood pressure management during their session.

The practical safety difference comes down to monitoring. Spravato has federally mandated protocols under its REMS program: blood pressure checks and a mandatory two-hour observation period after every session. IV ketamine monitoring varies by provider. Some clinics follow rigorous protocols comparable to Spravato's standards, while others are less standardized.

These treatments are generally not recommended if you have uncontrolled high blood pressure, certain active substance use disorders, or are pregnant, unless a specialist team determines that potential benefits clearly outweigh risks. Both carry abuse potential, though the risk is low when treatment happens in supervised medical settings. If you're unsure whether you'd be a good fit, you can check common eligibility criteria or take Innerwell's free assessment for a personalized evaluation.

Which Option Fits Your Situation

If you've made it this far, you're probably weighing practical tradeoffs. Here's how to think about them.

Spravato may make more sense if you have insurance that covers it and can navigate the prior authorization process, if you prefer a noninvasive nasal spray over an IV, or if you have MDD with acute suicidal ideation or behavior (Spravato has a specific FDA approval for this indication).

IV ketamine infusion may be better if you prioritize the fastest possible initial response, if you don't have insurance coverage for Spravato, or if your depression comes with comorbidities like anxiety, PTSD, OCD, or chronic pain. Spravato is FDA-approved only for MDD, while providers can use IV ketamine off-label across a broader range of conditions, though evidence strength varies.

Neither clinic-based option is ideal if logistics are your primary barrier. Both require regular in-person visits, monitoring periods, and a ride home. For someone managing depression while working full-time or providing care for others, that time commitment can compound the stress treatment is supposed to relieve.

How Innerwell's At-Home Ketamine Therapy Works

If the clinic schedule is what's standing between you and treatment, a third option is worth knowing about. Innerwell pairs sublingual ketamine tablets with licensed therapeutic support, all from home.

This isn't ketamine dropped off with minimal supervision. Innerwell's clinical team includes Master's and Doctoral level licensed therapists, not unlicensed guides. Ketamine promotes neuroplasticity, which makes your brain more capable of forming new patterns. But that window is most valuable when you use it intentionally. The medication opens a door; integration therapy helps you walk through it.

The process:

1. Evaluation: A psychiatric provider reviews your history, current medications, and treatment goals to design a personalized protocol.
2. Delivery: Sublingual ketamine tablets are prescribed and shipped to your home through a licensed pharmacy. No IV lines, no clinic visits.
3. Preparation and integration: Licensed therapists guide intention-setting before sessions and help process insights afterward. This is what translates short-term relief into lasting change.
4. Ongoing monitoring: Your care team tracks mood, symptoms, and progress, adjusting dosage and frequency as needed.

Innerwell sessions cost $54–$75 per session with insurance or $83–$125 for self-pay. HSA and FSA funds are also accepted.

In Innerwell's clinical data, 69% of people experience a 50% or greater reduction in depression symptoms after 10 weeks. 60% see a comparable reduction in anxiety symptoms in the same period. 87% report improvement within four weeks, and the average patient satisfaction rating is 4.7 out of 5.

Take the free assessment to see if at-home ketamine therapy might work for you.

Frequently Asked Questions

Can you switch between Spravato and IV ketamine?

Yes, and a nonresponse to one form doesn't necessarily mean the other won't work. A small retrospective case series found that many people who switched from IV ketamine to Spravato maintained or showed continued improvement. If one format isn't working, switching is a reasonable next step.

How long do antidepressant effects last after a session?

Effects from a single session can last days to weeks, which is why both treatments require ongoing maintenance rather than a fixed course. How long benefits last varies from person to person and depends on your dosing schedule and whether you're combining treatment with therapy.

Does the type of ketamine affect side effects differently?

The side effects are similar, but intensity differs. IV ketamine tends to produce stronger dissociation because it reaches the brain faster, while Spravato's intranasal delivery generally produces milder effects. Both can cause sedation, dizziness, and temporary blood pressure changes. The two-hour REMS monitoring requirement for Spravato means side effects are closely tracked at every session; IV ketamine monitoring varies by clinic.

What happens if neither Spravato nor IV ketamine works?

Other evidence-based options exist, including transcranial magnetic stimulation (TMS), medication adjustments, and structured psychotherapy approaches like eye movement desensitization and reprocessing (EMDR). At-home sublingual ketamine is also worth exploring if the clinic-based format itself was the barrier. Support organizations like the National Alliance on Mental Illness (NAMI) and the Depression and Bipolar Support Alliance offer education and community while you explore next steps.

Do you need to stop other antidepressants before starting ketamine treatment?

Not necessarily. Spravato was originally approved for use alongside an oral antidepressant, though as of January 2025, it can also be used as a standalone treatment. Many providers continue other medications during IV ketamine as well. Innerwell's clinical team evaluates potential interactions based on your full medication history as part of the initial assessment.