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Which is Better: Spravato vs Ketamine Infusion for Depression?

Depression is the most common mental health disorder around the world, affecting around 10% of adults today. Depression can have a significant impact on mental health, leading to the co-occurrence of many other mental health disorders, including anxiety. Those who struggle with depression will face significant issues with their quality of life and physical well-being as a result.

Major depressive disorder can manifest with suicidal ideations, and for many, major depressive disorder turns into treatment-resistant depression when several forms of traditional antidepressants don’t provide relief. 

Today, the use of ketamine in different forms offers an adjunct therapy with significant potential for all of these circumstances. This article will review many facets of Spravato and Ketamine Infusion so you can make an informed choice as to what method works best for major depressive disorder and treatment-resistant depression.  

Understanding Ketamine and Its Uses in Depression

Ketamine has been used since the 1970s, originally as an anesthetic for surgery. It derives from PCP or angel dust. As an anesthetic, it offered fast relief for anxiety and depression symptoms. For that reason, in the 1990s, Yale researchers started to investigate the use of ketamine as a treatment for depression and found that low doses of IV ketamine infusion could offer immediate relief from symptoms, especially for those with treatment-resistant depression. 

For Spravato, Phase 2 data was published in 2018, with new studies continuing throughout the year on the efficacy of rapid improvement in suicidal ideations and treatment-resistant depression. 

Long-term studies were completed regarding the use of the nasal spray plus an oral antidepressant later that year, and applications were submitted to the FDA for approval near the end of 2018. Spravato was approved in 2019 for use in treatment-resistant depression and in 2020 for major depressive disorder in adults who had acute suicidal ideations.

ketamine infusion vs spravato

Introduction to Ketamine Infusion

Ketamine infusion is a form of treatment for major depressive disorder with suicidal ideations and for treatment-resistant depression. It is best for those who have tried traditional depression treatments with no symptom relief. It works by way of an intravenous infusion that is administered in a clinical setting over the span of 40 to 60 minutes. 

How ketamine infusion works for depression

Ketamine works by interacting with different subsets of your neurotransmitters. The IV ketamine infusion focuses on the NMDA (N-methyl-D-aspartate) receptors. Those who struggle with severe depression typically lose essential connections that handle communication in the brain. These synapses start to die off, but ketamine causes them to regrow, re-establishing communication.

Many neurons in the brain rely on a neurotransmitter called glutamate to effectively send messages to one another, but with depression, the nerve cells that normally have glutamate receptors on either end to catch the messages get deactivated or weakened. 

Ketamine grows new glutamate receptors at the ends of these nerve cells, which means that messages can be more effectively sent and received in the brain. This improves brain circuit function, boosts mood, and eliminates depression and anxiety symptoms.

Current status of ketamine infusions in medical practice

As of right now, ketamine infusions are used throughout medical practices, under supervision, although they are not yet FDA-approved. When you look at Spravato vs. ketamine infusion in terms of common practices and approval, there are some key differences.

IV ketamine vs Spravato FDA approval

As of right now, Spravato has FDA approval as a treatment for major depressive disorder or treatment-resistant depression. The FDA has approved Sparvato nasal spray, but only when used with an oral antidepressant. FDA approval is pending for IV ketamine and has not yet been approved.

Ketamine infusion vs. Spravato common practice

Both options can be received as treatment, but they must be done at a clinic that is part of a certified government program. After each administration, you must remain under supervision for a short time frame so that a qualified physician can check for any negative side effects.

Spravato and ketamine administration

Spravato is administered as a nasal spray, and you get to use the spray yourself. A qualified physician will explain exactly how to do it and watch you as you do it so that you get the right dosage. Then, you’ll take an oral antidepressant. With ketamine IV infusions, the doctor will put a needle in a vein in the inside of your elbow and monitor the infusion process.

Introduction to Spravato (Esketamine)

Spravato (esketamine) is a derivative of ketamine used in the treatment of major depressive disorder (MDD) and treatment-resistant disorder (TRD). It is used as a nasal spray, approved by the FDA, and offers promising results for those who have not found treatment elsewhere. 

ketamine infusion vs spravato

Development of Spravato as a derivative of ketamine

Ketamine has been explored for a while as a depression treatment, but the new nasal spray was developed over the last several years. 

Ketamine (or RS-ketamine) is a racemic mixture. It has equal levels of:

  1. R-ketamine and 
  2. S-ketamine (or esketamine)

Esketamine is the generic name of the new medication provided as an intranasal esketamine. The chemical name is (S)-2-(o-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride. 

The esketamine hydrochloride is a water-soluble powder, so it gets mixed into the liquid of the nasal spray for administration as Spravato. 

FDA approval

Spravato has FDA approval specifically for treatment-resistant depression. It must be used at a certified clinic, under supervision, and taken with an oral antidepressant. 

Administration method and treatment protocol for Spravato

Spravato is only available through restricted programs called Spravato REMS. These facilities provide treatment in an outpatient setting. You will arrive and be seated in a comfortable chair.

Your treatment plan will typically include six doses administered over two or three weeks. When you arrive at your treatment center, your blood pressure will be taken, and a doctor will explain how to use the nasal spray. They will watch as you use the nasal spray and then monitor your changes over the next two hours. You must remain at the clinic under observation for any potential side effects.

It’s not uncommon to feel dissociation, lightness in your body, warmth, or slight tingling. Once you are allowed to leave, someone else will have to drive you home. You are not supposed to use heavy machinery, drive, or do anything that requires your alertness until after you have slept well. 

Comparison of Spravato vs Ketamine Infusion

Let’s look at how these two compare in several ways.

How each drug works in the brain

When you look at esketamine (Spravato) in the brain of someone with TRD or MDD, science shows us that long-term depression can cause shrinkage in the hippocampus by up to 20%. This area of the brain is responsible for learning and memory, which causes long-term brain damage and increases the risk of neurological conditions as you age.

Esketamine has been shown to improve the connections broken by chronic stress and depression by regrowing glutamate receptors on the ends of nerve cells.

IV ketamine does the same because it is a mixture of S-ketamine and R-ketamine. This means it improves communication in the brain in much the same way by improving synapses and glutamate receptors along the nerve ends of the brain. This improves the brain circuitry function and communication between brain cells. It actually helps to regrow the areas of the brain that have been damaged by depression.

Is Spravato the same as ketamine?

Is Spravato the same as ketamine? Not quite. It is ketamine administered through a nasal spray, but the administration comes with an oral antidepressant.

Additionally, generic ketamine IV is comprised of equal parts esketamine and arketamine. The nasal spray is only esketamine. 

Efficacy of IV ketamine vs Spravato

Recent studies have found no discernible difference in efficacy between IV ketamine vs Spravato. Cambridge researchers have published data confirming that both IV ketamine and Spravato have similar response rates and remission levels for those with treatment-resistant depression.

With both options, patients notice a change almost immediately, with depression symptoms diminishing or going away entirely within 24 hours.

The key difference is that ketamine infusions provide relief faster compared to Spravato. In fact, the number of treatments required is also diminished, which means that relief is enjoyed faster, and it doesn’t take as long for a treatment plan.

This is important when you consider the cost, especially if you are paying out of pocket.

Which is better: Spravato vs ketamine infusion for side effects?

When you look at ketamine infusion vs. Spravato, they both have potential side effects. 

Research regarding Spravato and ketamine infusions has not found any significant difference in terms of side effects.

The physical side effects that are a risk are the same across both, including:

  • Headaches
  • Nausea
  • Vomiting
  • Panic attacks

However, the administration method can cause differences in Spravato vs. ketamine infusion side effects. One of the key differences between Spravato and ketamine is that the injection itself can cause a subset of potential side effects such as:

  • Pain at the injection site
  • Temporary blurred vision
  • Allergic reaction
  • Swelling

Spravato, being a nasal spray, can also cause issues with:

  • Runny nose
  • Nasal discomfort

Sometimes, patients describe the effects of IV ketamine as more of an immediate and aggressive journey, with Spravato being a slightly less immediate and gentler journey.

Safety and Administration

With a ketamine infusion vs. Spravato, the spray is better for anyone who has a fear of needles and is much more convenient. Many people who struggle with depression are already anxious, and for them, having to undergo an IV treatment might cause additional anxiety. 

In this case, the administration method of a nasal spray is going to be a much better option.

Safety is always a concern, especially where ketamine is concerned. In terms of the risk of abuse, Spravato being FDA-approved and under a federal program is much more heavily monitored. Clinics and treatment centers that provide this form of treatment have to be approved as part of the FDA Risk Evaluation and Mitigation Strategies (REMS) program. 

This means that they have to be registered with the program and they have to adhere to certain precautions such as keeping patients at the treatment center for up to 2 hours after each treatment in order to monitor for any potential side effects. Patients also have to sign waivers and forms adhering to this need and acknowledging that they will do so.

Given that an IV ketamine treatment is not as heavily monitored, there are slightly higher risks where safety is concerned simply because there could be more abuse or neglect. This can, of course, be mitigated by choosing reputable facilities that undergo strict safety measures even without an FDA requirement. 

Time required

Administration for both methods, Spravato and Ketamine, take the same amount of time in total because you have to remain at the facility after your treatment for observation. The Spravato is faster and does not take nearly as long as an IV, but since you have to remain for observation, it can take just as long. 

However, given how much faster Ketamine infusions work, compared to Spravato, in terms of alleviating symptoms, those who struggle with suicidal ideations may benefit more from the faster-acting responses that IV ketamine offers over Spravato. 

Long-term safety data and any known risks

As of right now, the only approved drug therapy that involves Spravato is a combination of antipsychotic or antidepressant medication with the nasal spray, and this can have long-term effects, including:

  • Blood pressure problems
  • Weight gain
  • Metabolic changes

Unfortunately, all of the negative side effects associated with oral antidepressants are a risk if you choose the nasal spray because it’s a government requirement that the two be combined. 

which is better spravato vs ketamine infusion

Impact of each treatment on patients

Studies indicate that patients receive significant improvement from either option. Both Spravato and IV ketamine can, in 30% of cases, provide complete remission.

Studies also indicate that either option can reduce anxiety symptoms in addition to depression symptoms, which improves several areas of daily life and helps with mental health recovery. 


  • Between 35.6% and 46.1% of participants with Spravato go into remission.
  • 70% of patients have at least a 50% reduction in symptoms with Spravato.
  • Studies show 62% of patients have better social functioning, 53% of patients have a better quality of life, 41% of patients have a better ability to work, 30% of patients are better equipped to meet their own basic needs, and 34% of patients saw general improvements in their overall health with Spravato. 

IV ketamine:

  • 63% of patients with MDD or TRD with suicidal ideations no longer experience suicidal thoughts after just three days of ketamine IV treatment.  
  • An IV ketamine infusion offers a 70% success rate for both TRD and MDD. 
  • Nearly 90% of patients in clinical trials for IV ketamine infusions saw a reduction in their symptoms after two weeks of care. 
  • IV treatments offer fast improvement, with many patients noting changes after their first or second session. 
  • Studies show that 35% of those who use IV ketamine treatment have complete remission after their full treatment. 

Costs and availability

In terms of cost, Spravato can be more affordable. The biggest reason is that it’s covered by most insurance companies, including:

  • Medicaid
  • United Healthcare
  • Anthem /BCBS
  • Aetna
  • Cigna
  • Medicare 

There are savings opportunities through things like the Spravato Savings Card Program, which offers more affordable visits for Spravato treatment sessions.

By comparison, ketamine IV infusions are not covered by insurance nor will they be until such time as they receive complete FDA approval. As such they can cost several hundred dollars per session depending on where the treatment is received and this is typically something that has to be paid out of pocket.

There are some exceptions, though:

Insurance coverage

It is important to note, however, that the costs between the two have a significant difference because esketamine is sold under an established brand name, Spravato, and is heavily regulated. 

The cost, for example, with Medicare, is $951 for a standard starting dose of 56 milligrams of Spravato but goes up to $1,353 for the maximum dose of 84 milligrams. The majority of patients with treatment-resistant depression need the maximum dose.

With an IV ketamine treatment, the starting dose is 0.5 mg/kg with a maximum of 1 mg/kg, and this cost can be partially covered by Medicare as well at an average of $187 per treatment in many places. 

With Medicare, 80% of the costs are handled by the insurance company, and patients are responsible for only the remaining 20%. This makes the overall cost of an IV infusion significantly less for many people, given what they end up paying out-of-pocket.

Now, if you have private insurance, the cost of Spravato is typically covered almost entirely, which means there is next to no out-of-pocket cost.

Number of sessions

It is worth noting, however, that fewer sessions are required to achieve results with IV ketamine treatments compared to the nasal spray and if you have a deductible you have to meet before your insurance covers the costs, the difference may be negligible but that’s something to compare with your individual insurance provider.

When you look at availability, Spravato is more widely available because it is an approved treatment option from Janssen Pharmaceuticals. In order to get the IV infusions you need to work with a specialized treatment center and options may be limited depending on where you live. 

Which is better, Spravato vs ketamine infusion?

When you look at ketamine infusion vs Spravato, you’ll have to decide which one might work better for you based on things like efficacy, side effects, cost, and availability. Both can be used to treat major depressive disorder and treatment-resistant disorder, offering significant relief for those who might not be able to find it anywhere else.

Summing Up

Deciding between the two treatment options is something that you need to consider personally and with the help of your healthcare provider. Are you in need of help right away? Do you want something that is easier to take, without needles? 

You will also need to consider the time and resources you have. The length of time the treatment takes, how easy the administration is, and other facets should inform your decision. 

Ketamine has a long-standing history of effectively treating depression immediately. However, Spravato is a little bit easier to administer and has a lower risk of abuse, which means it might be a better option for anyone who is worried about addiction. Moreover, there are certain healthcare programs that make Spravato a slightly more affordable option depending on your insurance coverage.

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