Which Treatment is Likelier To End Your Depression?

Nasal Esketamine Works, But IV Ketamine Works Best

Although racemic ketamine outperformed esketamine in this study, it’s important to highlight that esketamine still showed significant benefits compared to a placebo. In other words, it works—it just doesn’t work as effectively as racemic ketamine.

Picture it this way: if racemic ketamine is a full-fledged firehose extinguishing the flames of depression, esketamine might be more like a garden hose. It’s effective, but not as powerful, and it may take longer to achieve similar results. For people with treatment-resistant depression, esketamine can still be a lifeline, especially since it’s currently the only FDA-approved ketamine treatment for depression.

The study showed that esketamine improved depressive symptoms better than placebo, which means it can make a real difference for some patients. However, its effects were less pronounced, and it often took longer to work compared to racemic ketamine. For patients in crisis—those who need rapid relief to prevent further suffering or even harm—this slower response time could be a critical downside.

Another challenge with esketamine is its rigid treatment protocol. Administered as a nasal spray under strict clinical supervision, it’s not as adaptable as racemic ketamine. There’s less room to adjust the dose based on how a patient is responding, which can limit its effectiveness for some people.

That said, esketamine is still a valuable tool in the fight against depression. It’s proven to work better than doing nothing, and for patients who have no other options, it’s a step in the right direction. But when you compare it to racemic ketamine, it’s clear which treatment has the upper hand in terms of speed, flexibility, and overall impact.

Nasal Esketamine’s Strict Protocols Create a Lot of Barriers 

As the only FDA-approved form of ketamine for depression, esketamine’s nasal spray must be given in a certified healthcare facility.

Not all ketamine clinics are certified to offer esketamine, which can limit your options. Additionally, the FDA requires longer monitoring for esketamine patients compared to IV ketamine. On average, an esketamine session takes about 32 minutes longer than it does for IV ketamine.

Racemic ketamine (IV or injection), by contrast, is administered intravenously in settings that are less standardized. This allows for greater adaptability. Providers can adjust the dose, the frequency of treatments, and even the duration of the infusion to suit the individual needs of each patient. This flexibility makes racemic ketamine feel more tailored—like a treatment designed specifically for you.

The takeaway? Esketamine’s highly controlled process gives it a structured, one-size-fits-all approach. But for patients who need more adaptability and personalization, racemic ketamine’s less rigid framework offers a significant advantage. 

In the end, the right choice depends on what matters most to the individual patient—consistency in process or flexibility in care.

IV Ketamine Gets 100% of the Ketamine to Your Brain, Spravato Only 48% 

When it comes to treating depression with ketamine, one of the most important factors is how much of the medication your body actually uses. This is called bioavailability, which measures how much of a drug enters your bloodstream and can take effect. With IV ketamine infusions, the bioavailability is 100%—every bit of the medication reaches your system exactly as intended. It’s like filling up a glass of water straight from the faucet: nothing is lost.

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.

With IV Ketamine, You Need Fewer Sessions—Saving Time, Money, and Effort Compared to Spravato

 

Fewer Sessions

IV ketamine generally requires fewer sessions, particularly during the maintenance phase. For patients juggling work, family, and other responsibilities, this difference can have a big impact on how easily treatment fits into their lives.

It’s important to note, however, that every patient is unique. The number of sessions needed varies widely depending on factors such as how quickly remission is achieved, the severity of symptoms, individual response to treatment, and even personal preferences. No two journeys are the same, so these numbers provide a general framework rather than a rigid schedule.

To make a fair comparison, let’s restrict our analysis to a three-month (12-week) period.

 

How Many Ketamine Sessions Will You Need?

Click here for even more detailed tables on how many ketamine therapy sessions you need. 

 

The Benefits of Fewer Treatments

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

 

Faster Return to Normal Life

You could achieve full remission or a dramatic reduction in symptoms with up to 57% less treatments.  Think about what this means for your daily life:

• Less time asking your boss for medical leave or using up precious vacation days
• Fewer times asking family or friends to drive you to appointments and wait around
• Not having to arrange childcare as often
• Reduced transportation costs and less money spent on gas
• Fewer disruptions to your weekly routine and family commitments
• More predictable scheduling for your work and personal life
• Less explaining to coworkers about your frequent medical appointments

 

Cost Savings

Fewer sessions often means lower overall treatment costs. If you need only, say,  8 IV sessions instead of 14 Spravato sessions, that’s a 43% reduction in the number of treatments you’re paying for.

But let’s break this down realistically. While many patients achieve relief with fewer IV sessions, everyone’s journey is different. Some people will need only 8 IV sessions, while others may need 10, 12 or the full 14 treatments – similar to Spravato’s schedule.

IV ketamine infusion sessions typically range from $400-$800 per treatment depending on individual clinics, while Spravato costs $800-$1,600 per session depending on whether you need the lower (56mg) or higher (84mg) dose. Spravato is partially covered by insurance since it’s FDA-approved, while IV ketamine usually requires 100% out-of-pocket payment. 

So what does this mean for your wallet? If you’re someone who responds quickly and needs only 8 IV sessions at $600 each, your total cost would be $4,800. With Spravato’s required 14 sessions, even with insurance coverage, your out-of-pocket costs (including copays and deductibles) could still be substantial (click here for my guide on getting insurance approval for Spravato). For example, with a typical 20% coinsurance after meeting your deductible, you might pay about $500 per Spravato session, totaling $7,000 for all 14 sessions. 

IMPORTANT: The manufacturer of Spravato, Johnson & Johnson, offers significant financial assistance that can substantially reduce out-of-pocket costs for patients with commercial insurance, and also provides some savings programs for Medicare and Medicaid beneficiaries. Find out how you can qualify here. 

The key takeaway is that fewer sessions doesn’t just save money – it saves time, reduces work disruption, and minimizes the burden on your support system. But treatment decisions should be based on what works best for your depression, not just costs.

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

If, in a 3-month period, you need only 8 IV sessions (compared to Spravato’s required 14), you’d spend:

• Ketamine infusion therapy: About 13.5 hours total in the clinic
• Spravato: About 31.5 hours total in the clinic

This means you could save up to 18 hours of clinic time over your treatment course. That’s like getting more than two full workdays back in your life. Even if you need all 14 sessions with IV ketamine, you’d still save about 7.5 hours compared to Spravato (because nasal spray sessions take about 32 minutes longer).

What could you do with those extra hours?

Remember, when you’re dealing with depression, every bit of extra stress matters. Less time in the clinic means more time and energy for your recovery and the people and activities that matter most to you.

Ketamine Infusion Therapy Tailors Your Dose to Your Body

Personalized, Weight-Based Dosing Delivers More Effective and Precise Treatment

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.

IV Ketamine’s Molecular Makeup Delivers Faster, Longer-Lasting Relief Than Spravato’s Esketamine

 

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.

Therapy With Ketamine IV Offers More Treatment Locations and Shorter Travel Times Compared to Spravato

If you live in a rural area or far from major healthcare centers, IV ketamine offers a critical advantage: it’s simply easier to find and access than Spravato. While both treatments have their challenges, IV ketamine can be administered in a variety of settings, including dedicated ketamine clinics, psychiatric offices, and even hospitals. This flexibility means patients have more options and often shorter travel times to receive care.

Spravato, on the other hand, is only available at REMS-certified facilities—specialized treatment centers that meet strict FDA safety requirements. These facilities are often concentrated in larger cities or healthcare hubs, making it far less accessible for patients in underserved areas. For many, accessing a Spravato-certified clinic involves long commutes or, worse, no access at all.

With IV ketamine, the setup may require specialized equipment and trained staff, but it’s adaptable to different types of medical facilities, broadening its reach to more communities. Whether you live near a psychiatric practice, a ketamine clinic, or even a hospital, you’re more likely to find an IV ketamine provider than a Spravato-certified location.

For patients battling depression, accessibility matters. IV ketamine’s flexibility ensures more people can access the treatment they need without the extra burden of extensive travel or limited availability. It’s a solution designed to meet you where you are, not the other way around.