Choosing the Best Ketamine Treatment: IV vs Injection vs Spravato

Ketamine therapy can be life-changing, but figuring out the best way to take it? That’s where things get tricky. IV infusions, injections, or the esketamine nasal spray—each comes with its own benefits, downsides, and logistical hurdles. And if you’re already struggling, sorting through all the fine print can feel like just one more obstacle between you and relief.

That’s why I put together a straightforward, no-nonsense table that lays it all out for you. These aren’t my recommendations; they’re a framework to help you weigh competing priorities and make the best decision for your situation.

Whether your top priority is maximum effectiveness, avoiding needles, or keeping costs down, this table lays it all out clearly. It isn’t a debate about what’s good or bad—it’s about figuring out what’s good, better, or best for you.

Ketamine Treatment Comparison Table: IV Infusions, Injections and Spravato

See Which Ketamine Method Works Best for Your Needs, Costs, and Treatment Goals

How IV Ketamine Infusion Therapy Works

Ketamine is delivered directly into your bloodstream via an IV line, allowing for precise dosing and controlled delivery over a set period of time (usually 40 minutes to an hour). This method ensures rapid absorption and consistent blood levels of the medication throughout the infusion.

Pros:

1. IV Ketamine Has Proven To Be The Most Effective Method 

IV infusion is the most researched and widely studied method for ketamine treatment, with systematic reviews and meta-analyses showing it’s three to five times more effective than the esketamine nasal spray, Spravato.

2. With IV Ketamine You Need Fewer Treatments Than The Nasal Spray Spravato

Because IV infusion is so much more effective, you don’t need as many treatments to reach remission or substantially improve your symptoms.

3. High Bioavailability Ensures Stronger Effects

Because the ketamine goes straight into your bloodstream, almost 100% of the dose is available for use by your body. This ensures the most potent and predictable effects.

4. Of All The Ketamine Treatments IV Has The Lowest Dropout Rates

You’re less likely to quit IV ketamine because it works faster and feels more effective. The rapid relief and noticeable improvements make it easier for people to stick with treatment compared to the slower and less predictable results of the Spravato nasal spray.

5. IV Ketamine Has Fewer and Milder Side Effects Than Spravato

IV ketamine has fewer and less intense side effects than the nasal spray. That said, side effects for all administration methods are generally mild and temporary.

6. IV Ketamine Dosing Can Be Adjusted During Treatment

A clinician can adjust the dosage during the session to tailor the treatment to your needs. For example, if side effects occur or your response suggests you need more or less, the infusion can be modified immediately.

7. IV Infusions Offer The Fastest Relief of Any Ketamine Treatment

The effects of IV ketamine are usually noticeable during or immediately after the session, making it ideal for those seeking quick relief.

8. Flexible Protocols

Ketamine clinics use infusions like a dimmer switch, allowing clinicians to adjust your treatment frequency based on how you actually respond. This flexibility means your treatment can evolve with your healing, rather than forcing your healing to conform to an arbitrary timeline. 

9. IV Ketamine Requires Fewer Sessions Than Spravato

Over 6 months, IV ketamine needs just 11-18 sessions compared to Spravato’s 21 sessions. Spravato demands nearly twice the time of IV ketamine—about 42 clinic hours, 21 rides, and 52 childcare hours over six months—creating a much heavier real-world burden on work, family, and schedules.

Cons of IV Ketamine Infusions

1. IV Ketamine Requires an Invasive Procedure

Requires the placement of an IV line, which can be uncomfortable for people with needle phobias or hard-to-access veins. This can also increase anxiety for some patients.

2. IV Ketamine Costs More Than Injections

That’s due to the need for specialized equipment and trained staff (including a clinician or anesthesiologist).

3. IV Ketamine Is Not Covered by Commercial Insurance

You’ll have to pay 100% of the costs.

4. IV Ketamine Is Not Covered by Medicare or Medicaid

You’ll have to pay 100% of the costs.

5. IV Ketamine Costs A Lot More Than Spravato If You Have Insurance & Qualify for the Manufacturer’s Subsidy.

Spravato’s manufacturer subsidy of up to $8,150 eliminates most out-of-pocket costs, making IV infusions significantly more expensive.

How Intramuscular Ketamine Injections Work

Ketamine is injected into a large muscle, such as the upper arm, thigh, or buttocks. This injection uses a small-to-medium gauge needle, similar to what’s used for a flu shot or a B12 injection, and goes deep into the muscle rather than just under the skin. It’s typically quick, with minimal equipment needed beyond the syringe and medication.

Pros Of Injection Ketamine

1. Intramuscular Ketamine Provides High Bioavailability Compared to Oral Methods

Slightly less than IV but still far more than oral or nasal options.

2. Ketamine Injections Offer Fast and Simple Administration Process

The injection process is quick and simple—it doesn’t involve setting up an IV line or the delays of the nasal spray, which requires three separate doses with a 5-minute wait between each.

3. Intramuscular Ketamine Costs Less Than IV Infusion Treatment

Generally less expensive than IV infusion because it doesn’t require as much equipment.

4. Ketamine Injections Have Fewer Side Effects Than Spravato Nasal Spray

Ketamine injections have fewer and less intense side effects than the nasal spray. Again, side effects for all administration methods are generally mild and temporary.

5. Intramuscular Ketamine Requires Minimal Medical Equipment

IM injections only require a syringe, needle, and the ketamine solution. Unlike IV infusions, they do not need IV lines, infusion pumps, or other specialized equipment.

6. Ketamine Injections Need No Continuous Patient Monitoring

IV infusions require real-time monitoring of vitals (e.g., heart rate, oxygen levels, blood pressure) during the infusion process to adjust dosing and manage potential side effects. IM injections, being a single shot, do not require this level of monitoring.

Intramuscular Ketamine Injection Disadvantages:

1. Ketamine Injection Dosing Cannot Be Adjusted During Treatment

Once injected, the dose cannot be adjusted mid-treatment.

2. Intramuscular Ketamine Injections Require Needle Insertion

While quicker than an IV, it’s still not ideal for those uncomfortable with needles.

3. Ketamine Injections Can Cause Injection Site Soreness

Injections into muscles can cause soreness at the site, particularly with repeated use.

4. Intramuscular Ketamine Has No Commercial Insurance Coverage

You’ll have to pay 100% of the costs.

5. Ketamine Injections Not Covered by Medicare or Medicaid

You’ll have to pay 100% of the costs.

6. Intramuscular Ketamine Costs More Than Spravato With Manufacturer Subsidy

Again, Spravato’s manufacturer subsidy of up to $8,150 (if you qualify) eliminates most out-of-pocket costs, making injections more expensive.

Despite simplicity and speed, intramuscular ketamine can cost more than Spravato and carries needle-related drawbacks without the benefit of insurance coverage.

How Spravato Esketamine Nasal Spray Works

A clinically supervised, self-administered nasal spray containing esketamine (a form of ketamine). The process requires three separate doses, with a 5-minute wait between each, all under medical supervision. Find out how esketamine is different than ketamine.

Spravato Nasal Spray Treatment Advantages:

1. Spravato Requires No Needles or IV Lines for Treatment

No needles or IV lines are required, making it a great option for needle-averse patients.

2. Spravato Has FDA Approval for Treatment-Resistant Depression

Backed by rigorous research, ensuring safety and effectiveness.

3. Spravato Nasal Spray Offers Simple Self-Administration Process

Straightforward process with minimal discomfort.

4. Spravato Covered by Most Commercial Health Insurance Plans

Average insurance coverage for Spravato is about 50-60%, leaving you with over $8,000 in out-of-pocket costs unless you qualify for the manufacturer’s $8,150 subsidy. Without both insurance coverage and the subsidy, Spravato is absolutely the most expensive ketamine administration method of all.

5. Spravato Treatment Covered by Medicare Part B

Medicare Part B covers the esketamine nasal spray cost as it is a physician-administered treatment requiring medical supervision. Out-of-pocket costs depends on your plan. Note: Many clinics won’t take Medicare. Check out my guide on how to get Spravato approved by Medicare.

6. Spravato Available Through Medicaid in Most States

Medicaid generally covers Spravato, but coverage varies significantly by state – some states fully cover it while others don’t cover it at all. Note: Many clinics won’t take Medicaid. Check out my guide on how to get Spravato approved by Medicaid.

Spravato Nasal Spray Treatment Disadvantages:

1. Spravato Has Lower Effectiveness Than IV Ketamine and Injections

Spravato is much less effective than IV or injections, but make no mistake—it’s still a powerful treatment that delivers significant relief.

2. Spravato Nasal Spray Has Lower Bioavailability Than Other Methods

Only about 40-50% of the medication is absorbed through the nasal tissues, making it less efficient than IV or injection.

3. Spravato Uses Only Esketamine Instead of Full-Spectrum Ketamine

Only esketamine is available in this method, not full-spectrum (racemic) ketamine, which is more effective.

4. Spravato Nasal Spray Can Cause Nasal Irritation and Discomfort

Some users report nasal discomfort or irritation after use.

5. Spravato Has Higher Treatment Dropout Rates Than IV Ketamine

That’s because it works slower and feels less effective compared to IV ketamine. The delayed relief and less noticeable improvements can make it harder for some people to stay committed. HOWEVER. It’s important to note that Spravato is a VERY effective treatment with clinical trials showing significant benefits for those who stick with it.

6. Spravato Treatment Centers Are Limited Due to FDA Requirements

Spravato is subject to a Risk Evaluation and Mitigation Strategies (REMS) program established by the FDA to ensure that the benefits of certain medications outweigh their risks. This means having safety protocols in place, such as certified treatment centers and requiring patients to be monitored for at least two hours after receiving the first spray of Spravato (there are three in total).

This means you shouldn’t assume that every ketamine clinic offers Spravato (though many do). Click here to find the nearest certified Spravato clinic to you.

I don’t provide information on oral forms of ketamine–tablets, capsules, sublingual troches, lozenges, or liquid solutions because they’re less safe, less effective, and far less researched than IV infusions, injections or Spravato.

Oral ketamine shows some early promise as an antidepressant, but the evidence behind it is shaky. While meta-analyses report statistically significant symptom reductions, the improvements often don’t reach meaningful clinical impact for most patients. The results are based on small, inconsistent studies, with remission and response rates hovering just above the margin of statistical significance—raising doubts about how reliable or repeatable these effects really are.

Unlike IV ketamine or esketamine nasal spray, which can deliver rapid relief within hours or days, oral ketamine takes much longer—usually 2 to 6 weeks—to show results, putting it on the same delayed timeline as standard antidepressants. This slower response limits its usefulness for patients needing fast-acting solutions, especially in severe or treatment-resistant depression cases.

Overall, the research on oral ketamine is riddled with problems: small sample sizes, high bias risk, short follow-up periods, and poor tracking of side effects. Until larger, better-designed trials are done, oral ketamine remains an uncertain option—not ready for widespread clinical use, no matter how intriguing the early findings appear.