What’s More Effective At Ending Depression–IV Ketamine or Spravato?

Comparing IV ketamine to Spravato nasal spray? We’ll walk you through the evidence for how well each treatment works, how fast they act, how many sessions you’ll need, and what it’s likely to cost. Everything here is grounded in real-world data—not hype—so you can make a confident decision about what’s more likely to help you feel better, faster.

Let Me Walk You Through Everything I’ve Put Together on This Page

• Which Treatment Works Best for Depression—IV Ketamine or Spravato?
• How Long Does Ketamine or Spravato Take to Work?
• How Much Ketamine Reaches Your Brain—and How Long Does It Stay?
• How Molecular Differences Between IV Ketamine and Esketamine Affect Treatment Outcomes
• Can Your Ketamine Dose Be Adjusted for Your Body and Symptoms?
• Which Ketamine Treatment Disrupts Your Life Less?
• How Much Does Ketamine Treatment Cost—and Will Insurance Help?
• Why Has IV Ketamine Been Studied Longer Than Spravato?
• FAQs About IV Ketamine vs Spravato

Which Treatment Works Best for Depression—IV Ketamine or Spravato?

If you’re deciding between IV ketamine and the Spravato nasal spray, there’s really only one question that matters: Which one is more likely to actually end your depression?

So let’s start with the clearest summary we can give, based on 33 systematic reviews and evidence-based modeling:

When combined with therapy, IV ketamine is estimated to lead to remission in up to 72% of patients. Spravato (nasal esketamine) reaches up to 49%.

These aren’t numbers pulled from one hand-picked trial. They’re modeled estimates based on all available placebo-controlled studies, with psychotherapy effects added conservatively. Here’s how the comparison holds up when you unpack the full data:

My Personal Take

Nobody Could Tell Me the Success Rate for Ketamine Treatment—So I Figured It Out Myself

One of the most frustrating parts of trying to get better is just figuring out the odds. Not hopes. Not theories. Actual numbers. When I started researching ketamine therapy, I just wanted to know: What are my chances of this actually working?

You’d think that would be easy to find. It’s not.

Search for remission rates—how often people actually get better—and you’ll find everything from 25% to 80%. The numbers bounce all over the place depending on the study, the drug company, the sample size, or just the agenda behind it. It’s a mess. And the language? It’s all “promising” and “potential.” No one wants to commit to anything.

But when you’re in the middle of a depression you can’t get out of, vague answers don’t help. You need something solid. Something that says, “Here’s what this treatment can actually do.”

That’s why I spent months gathering every systematic review and meta-analysis published in the last five years on ketamine treatment—33 in total. Not blog posts. Not testimonials. Real data.

From there, I built a model to estimate what remission looks like for both IV infusions and the nasal spray. It wasn’t easy—almost all of the Spravato studies looked at outcomes over months, while IV ketamine studies usually stopped after just a week or two. But we adjusted for that. Carefully. Transparently.

So now there’s one number you can hold onto. Not a guarantee. But a meaningful estimate of your chances—based on the best available evidence—of whether ketamine treatment could actually end your depression or at least pull you out of the worst of it.

I’m proud of that. Because I know how hard it is to find anything real when you’re drowning.

See How We Got The Numbers

Why We Used Meta-Analyses to Compare Ketamine vs Spravato

We didn’t cherry-pick miracle stories from clinic websites. We used meta-analyses—the highest level of evidence available. They average outcomes across dozens of trials, cut through the noise, and show you what’s real.

And what’s real is this: IV ketamine delivers stronger, faster results in more people.

Is There a Head-to-Head Study Comparing IV Ketamine and Spravato?

So far, no large trial has directly compared IV ketamine and Spravato in the same population. Almost all data comes from separate placebo-controlled trials—which makes modeling necessary.

But that’s about to change. A major head-to-head study at Yale is underway. 400 patients. Randomized. One group gets IV. The other gets Spravato. The results will tell us what the meta-analyses strongly suggest: that IV ketamine is the more powerful treatment.

Key Takeaways About Ketamine Remission Rates

• IV ketamine leads to remission in more patients, especially with therapy
• Modeling puts IV ketamine at up to 72% remission—Spravato tops out at 49%
• Every data point comes from high-quality systematic reviews
• Yale’s direct comparison study will either confirm or challenge this—but the early signs are clear

Key Takeaway: Which Treatment Works Best for Depression

How Long Does Ketamine or Spravato Take to Work?

IV ketamine doesn’t just work better—it works faster. About one in three patients hits remission after just one or two infusions. That’s not wishful thinking. That’s what the data says.

Spravato takes more time. For most people, it’s several weeks before any serious relief kicks in. That delay can be brutal—especially if you’re barely holding it together. When you’re in crisis, every extra day hurts.

So how long does each one actually take?

How Many Ketamine Sessions Will You Need in 6 Months?

Most people either get better, stabilize, or stop treatment entirely within the first six months. Here’s the difference:

Why Fewer Sessions Make Ketamine Easier to Stick With

Every single session costs something. Time off work. Gas. Childcare. Mental bandwidth. Fewer sessions means fewer disruptions—and that’s not a small thing.

It also means people are more likely to stick with it. One major review found that dropout rates were 24% lower for IV ketamine than for Spravato. That’s not just a scheduling issue. It’s a signal: IV ketamine works faster, feels more worth it, and is easier to follow through.

With IV ketamine, you’ll likely spend significantly less time in treatment than with Spravato (up to 10 sessions). What does this mean for you in practical terms?

Key Takeaway: How Long Ketamine and Spravato Take to Work

How Much Ketamine Reaches Your Brain—and How Long Does It Stay?

If the treatment can’t reach your brain, it can’t do its job. That’s what makes IV ketamine so different from the Spravato nasal spray. It gets 100% of the drug directly into your bloodstream. Nothing is lost. Nothing is filtered out. That full-strength dose moves fast—and hits hard.

In contrast, Spravato (esketamine) nasal spray has a bioavailability of about 48%. This means that if you’re prescribed an 84mg dose, around 40mg of the medication will actually be absorbed.

Spravato’s High Dose Makes Up for Low Absorption – But There’s a Catch

Let’s be fair – the makers of Spravato aren’t ignoring the fact that less medicine gets absorbed through your nose. They handle this by giving you a higher dose (84mg) knowing that only about half will make it into your bloodstream. On paper, this seems like a perfect solution.

But here’s the real issue: nasal absorption isn’t reliable or consistent. Think about the last time you had a cold or allergies. Your nose wasn’t working quite right, was it? The same problem affects how well Spravato gets absorbed. The expected 48% absorption rate can drop even lower due to:

• A stuffy or runny nose
• Seasonal allergies
• Sinus problems
• Post-nasal drip (when mucus runs down the back of your throat)
• Not using the nasal spray correctly (it’s trickier than it sounds)

This means that even though you’re getting the same dose each time, your body might absorb different amounts from one treatment to the next. One day you might get the full 48% absorption, but the next time it could be much less if you’re congested or not feeling well.

IV ketamine doesn’t have this problem. When it goes directly into your vein, you get 100% of the medicine every single time – no guesswork, no variation, no wondering if your stuffy nose is getting in the way of your treatment.

Why IV Infusions Provide the Full Impact

IV ketamine infusions eliminate any guesswork. Every molecule of medication is delivered directly into your bloodstream, ensuring consistency and predictability with each treatment. Think of it as having a direct line from the medication to the areas of your brain that need it most. This precision allows your doctor to tailor the dosage exactly to your needs, giving you maximum control over your treatment outcomes.

Spravato, on the other hand, relies on nasal absorption, which can vary from person to person. Factors like nasal congestion or how well the spray is administered can influence how much of the medication actually gets absorbed. Even though Spravato works for many people, this variability can sometimes make the results feel inconsistent.

Can Your Ketamine Dose Be Adjusted for Your Body and Symptoms?

Think of depression as a lock and ketamine as the key—if the key doesn’t fit perfectly, it won’t unlock the relief you need. IV ketamine therapy excels in this regard by delivering weight-based dosing, tailored specifically to each patient’s body size and needs.

Why Weight-Based Dosing Matters

Spravato offers only two fixed doses—56 mg or 84 mg—regardless of body weight or individual needs. This means someone like me, a 186 lb male, receives the same dosage as a 120 lb female. It’s a one-size-fits-all approach that doesn’t account for the significant differences in body size or how individuals metabolize the drug.

In contrast, IV ketamine uses weight-based dosing, ensuring the treatment is tailored specifically to you. The standard dosage for depression is 0.5 mg per kilogram of body weight. For example:

• A person weighing 120 lbs (approximately 54.5 kg) would receive 27.25 mg.
• A person weighing 186 lbs (approximately 84.5 kg) would receive 42.25 mg.

This personalized approach ensures each patient gets the dose their body needs, maximizing effectiveness and minimizing the risk of underdosing or overdosing. It’s the difference between getting a custom-tailored suit and picking one off the rack—it simply fits better.

A Note on Dosing Comparisons

It’s important to recognize that you can’t make a direct, apples-to-apples comparison between IV ketamine and Spravato doses. Here’s why:

• Administration method matters. With IV ketamine, 100% of the dose goes directly into your bloodstream, while with Spravato’s nasal spray, only 25-50% of the dose is absorbed. The rest is lost in the nasal passages or during metabolism.
• Different compounds. Spravato contains only the S-ketamine molecule, while IV ketamine includes both R- and S-ketamine, which may affect how the drug works and how much is needed to achieve the desired effect.

This means that while the esketamine nasal spray Spravato’s doses seem higher on paper, the actual amount of ketamine reaching your system may be significantly lower than an equivalent IV ketamine dose. It’s another reason why IV ketamine often provides more predictable and consistent results.

Ketamine infusion’s individualized approach ensures the treatment fits the patient, like adjusting the tension on a stringed instrument to produce the perfect note. By contrast, Spravato’s one-size-fits-all approach can leave some patients underdosed or overdosed.

Adjustable if Patient Gains or Loses Weight

Depression treatment isn’t static—neither is your body. Weight fluctuations are common due to changes in appetite, activity levels, or even the depression itself. Unlike Spravato, IV ketamine doses can take into account changes in body weight. For example:

• A patient weighing 180 lbs (81.5 kg) would receive a starting dose of 40.75 mg.
• If the patient’s weight decreases to 170 lbs (77.1 kg), their dose can be adjusted to 38.55 mg.

This ensures the treatment remains as effective as possible while minimizing the risk of side effects from over- or underdosing. Fixed-dose treatments like Spravato simply don’t have this kind of flexibility—they offer the same dose regardless of weight changes, which can impact efficacy.

Fine-Tuned Based on Individual Response

No two people experience depression or respond to ketamine therapy in exactly the same way. With IV ketamine, providers can fine-tune the dose throughout the course of treatment, adjusting for how each patient responds.

For instance:

• If a patient reports feeling dissociated for too long after a session, the provider might slightly decrease the dose to reduce this side effect.
• Conversely, if the antidepressant effect isn’t as strong as expected, the dose might be increased by small increments to enhance results.

This ability to adjust in real-time helps optimize the therapeutic effect and ensures the treatment evolves with the patient’s needs.

Precise Adjustments by Tiny Amounts

IV ketamine offers unparalleled precision, allowing providers to make dose adjustments as small as 0.1 mg/kg. This level of control is crucial for finding the “sweet spot” where the medication is most effective without causing unnecessary side effects.

Imagine a patient starting at the standard 0.5 mg/kg dose:

• If the response is too mild, the dose might be increased to 0.6 mg/kg, offering a more robust effect.
• If the dose feels too intense, it might be decreased to 0.4 mg/kg, reducing side effects like dissociation or nausea.

This incremental approach is like tuning a radio dial to find the clearest signal—it allows providers to fine-tune the treatment until it’s just right for the individual.

Why This Matters

With ketamine IV infusion, every detail of the treatment is designed to fit the patient, not the other way around. This precision ensures the medication works as effectively as possible, reducing trial-and-error frustration and providing a smoother path to remission.

In comparison, the esketamine nasal spray’s fixed doses (56 mg or 84 mg) lack this adaptability. Patients must either accept the dose as-is or stop treatment altogether if it isn’t working for them.

Which Ketamine Treatment Disrupts Your Life Less?

Spravato requires more sessions. That’s just a fact. Over the first six months, most people attend 21 appointments. IV ketamine typically takes 11 to 18. That difference might not seem huge on paper—but it hits hard when you’re trying to plan your life around it.

IV Ketamine Saves You Up to 18 Hours of Clinic Time Compared to Spravato

With IV ketamine sessions averaging 1 hour and 43 minutes compared to Spravato’s 2 hours and 15 minutes, you’ll spend about 32 minutes less at the clinic per visit. While half an hour might not seem dramatic, let’s look at what this means over the course of your full treatment (continues below the chart).

Time Spent At Ketamine Clinic: IV Infusion vs Spravato Nasal Spray

Each Spravato visit lasts at least two hours—often longer with check-in, waiting, and post-dose monitoring. That’s a half-day off work, every time. And you can’t drive home afterward, which means arranging a ride or paying for one. If you’re parenting, caregiving, or working a rigid schedule, those extra hours pile up fast.

IV ketamine sessions are shorter. You’re usually in and out in 60–90 minutes. Fewer appointments, shorter stays, and less need to rearrange your week. That difference adds up when you’re trying to hold your life together while getting help.

It’s also about fatigue. Twenty-one appointments in six months means showing up again and again, even if you’re drained or barely functional. Burnout is real. And it’s one reason dropout rates for Spravato are higher. The treatment becomes the burden.

For many people, the best therapy is the one you can actually stick with. IV ketamine keeps that door open by demanding less from your schedule, your support system, and your already-thin capacity to cope.

How Much Does Ketamine Treatment Cost—and Will Insurance Help?

Spravato is FDA-approved. IV ketamine isn’t. That one distinction shapes nearly every part of how these treatments are billed, coded, and covered.

If you have commercial insurance and meet strict criteria, Spravato may be covered under your plan. But “covered” doesn’t mean free. You’re still responsible for coinsurance, deductibles, and clinic fees. Some patients end up paying $75–$150 per session. Others pay much more depending on when in the year they start, how high their deductible is, and whether the provider bills as a hospital or office setting.

IV ketamine is almost never covered. It’s considered off-label, even though the medication itself is generic. That means most people pay out-of-pocket—anywhere from $350 to $600 per infusion, depending on where you live and how many sessions are included in the protocol.

Spravato has more billing codes. IV has more freedom. One lets you chase reimbursement. The other lets you plan. Neither is cheap, but one is more predictable: with IV, you know exactly what you’re paying. With Spravato, it often depends on how many hoops you can clear.

If you’re relying on insurance to afford treatment, Spravato might be your only option. If you can self-pay—or if you’re tired of fighting denials—IV might actually cost less over time, especially if you reach remission faster and need fewer sessions overall.

How Molecular Differences Between IV Ketamine and Esketamine Affect Treatment Outcomes

Think of IV ketamine as a symphony, where every instrument contributes to a rich and complex performance, while Spravato is more like a solo act—impressive, but missing the depth of the full orchestra. The reason lies in the molecular composition of these treatments.

The ketamine in IV is made up of two mirror-image molecules, known as R-ketamine and S-ketamine. These enantiomers interact differently with receptors in the brain, producing distinct effects:

R-ketamine

Emerging research suggests this molecule may have longer-lasting and more potent antidepressant effects. It appears to exert its impact through mechanisms beyond just NMDA receptor antagonism, including promoting neuroplasticity—the brain’s ability to form and reorganize connections. R-ketamine also has a weaker dissociative effect compared to S-ketamine, potentially reducing some of the side effects associated with treatment.

S-ketamine

Known for its quick-acting properties, S-ketamine works primarily through NMDA receptor antagonism, increasing glutamate activity. While it can rapidly reduce symptoms of depression, particularly suicidal ideation, its effects may not last as long as those of R-ketamine.

Why IV Ketamine is a Symphony

IV ketamine contains both R- and S-ketamine, combining the rapid relief of S-ketamine with the sustained benefits of R-ketamine. This dual-action approach not only provides faster symptom relief but also promotes longer-term mood stabilization and brain repair. The inclusion of R-ketamine is like adding harmonies to the melody—it brings depth and balance, creating a more comprehensive treatment effect.

For example, studies have shown that R-ketamine’s ability to enhance neuroplasticity may lead to more durable antidepressant effects, potentially reducing the frequency of maintenance treatments. This could be a key factor in why patients treated with IV ketamine often report greater overall improvement compared to those using Spravato.

Spravato: A Solo Performance

Spravato, on the other hand, contains only S-ketamine, leaving out the potentially critical contributions of R-ketamine. While S-ketamine’s quick action can be life-changing for those in acute crises, such as experiencing suicidal thoughts, it doesn’t address the broader spectrum of ketamine’s potential benefits.

This limitation is like hearing only the melody without the harmonies—it can still be beautiful and impactful, but it lacks the richness and complexity that make the experience truly transformative. By excluding R-ketamine, Spravato may require more frequent dosing or additional therapies to achieve the same long-term benefits as IV ketamine.

The Full Orchestra vs. the Soloist

Both R- and S-ketamine have unique and valuable properties, and IV ketamine leverages the strengths of both molecules to deliver a balanced, robust treatment. In contrast, Spravato’s singular focus on S-ketamine limits its range, potentially leaving out key benefits.

Key Takeaway: How Molecular Differences Impact Outcomes