IV ketamine vs. Spravato—what’s the difference, and which one is right for you? These two treatments are both being used to relieve symptoms of depression, especially when traditional therapies have failed. While they share similarities, understanding the distinctions in how they’re administered, how quickly they work, and how they’re covered by insurance is key to making an informed decision.
What Is Ketamine?
Ketamine is a compound made up of two mirror-image molecules: R-ketamine and S-ketamine. Ketamine was initially developed as an anesthetic but has since become widely recognized for its powerful mental health benefits, especially in cases where other treatments have not been effective.
Research shows that ketamine can deliver fast and lasting relief for various conditions, including depression, anxiety, post-traumatic stress disorder (PTSD), and addiction. Ketamine is also an analgesic, providing significant benefits for people with chronic pain conditions.
Ketamine can be administered in several formats, including:
- IV (Intravenous): Delivered directly into the bloodstream through a vein for fast absorption and immediate effect.
- IM (Intramuscular): Injected into muscle tissue, slower absorption, and used when IV isn’t available or preferred.
- Oral: Capsules or lozengesare typically used in remote or at-home therapy programs. These have a slower-acting and more subtle effect.
- Nasal Spray: Sometimes compounded by pharmacies, but less common. Quicker absorption compared to oral administration, but less intense effects compared to IV or IM.
What Is Spravato?
Spravato is the brand name for esketamine, which is the S-enantiomer of the ketamine molecule. Spravato was specifically designed for depression and has received FDA approval for two indications: treatment-resistant depression (TRD) and major depressive disorder with suicidal ideation (MDSI). In contrast, ketamine is used “off-label,” meaning it hasn’t been approved for mental health conditions, but there’s strong evidence to support its use.
Whereas ketamine can be administered in various forms, Spravato is only available as a nasal spray and must be provided under a strict FDA-approved protocol.
Mechanism of Action: How They Work
Ketamine and Spravato both block NMDA receptors, which are proteins in the brain involved in learning and memory. This interaction results in a cascade of neurochemical effects that help overcome depression. Some of these mechanisms include:
- Increased levels of brain-derived neurotrophic factor (BDNF)—a protein that supports the growth and repair of brain cells. This can help restore damaged neural pathways associated with mood regulation and resilience.
- Increased activity in the prefrontal cortex, an area involved in mood and emotional regulation.
- Increased synaptic plasticity, which describes the connectivity between nerve cells. This helps strengthen neurological pathways and increases the capacity for learning.
- At higher doses, ketamine can also induce a dissociative or psychedelic-like experience, which some patients find therapeutic when paired with psychotherapy (often referred to as ketamine-assisted psychotherapy or KAP).
Spravato has a stronger binding affinity at NMDA receptors compared to ketamine, meaning it works effectively at lower doses. This also results in a milder psychoactive experience, and the therapeutic effect is thought to rely more on biochemical changes than on the psychological experience itself.
Administration: What to Expect
Ketamine Therapy
At Emerge Wellness, we provide ketamine as an IV infusion, as this is the most well-studied method and provides rapid results. During a treatment, you’ll have a small catheter inserted into a vein in the arm. The medication is infused over about 40 minutes, and you’ll be monitored throughout the treatment and for a short period afterward.
There’s no strict protocol for ketamine therapy, but for severe depression, two treatments a week for six weeks is typically recommended. Our team will work closely with you to develop a treatment plan according to your unique needs and response to ketamine.
Spravato Therapy
Emerge Wellness is a certified Spravato provider, administering the medication with strict adherence to the FDA’s Risk and Evaluation Mitigation Strategy (REMS). If you undergo treatment at our clinic, you’ll self-administer Spravato under supervision. You’ll be closely monitored for two hours afterwards to ensure that side effects have fully worn off.
The initial treatment phase involves twice-weekly visits for four weeks, then shifts to weekly or biweekly sessions depending on your response.
Effectiveness: How Do They Compare?
When comparing IV ketamine vs. Spravato, it’s important to consider how quickly each works and how patients respond. Head-to-head comparisons show mixed results when it comes to treating depression. Some research, including a Cambridge study, suggests IV ketamine may be more effective than Spravato in terms of symptom relief and remission rates. However, most trials report similar outcomes between the two.
In general, ketamine’s infusions have a faster onset compared to Spravato and so may be more useful for patients in an acute crisis. Yet, this benefit may be outweighed by other factors, such as cost (discussed below) and ease of administration.
Safety and Side Effects
Both treatments share common short-term side effects, including:
- Dizziness
- Nausea
- Dissociation – feeling from one’s body and normal sense of reality
- Temporary elevation in blood pressure or heart rate
Spravato’s lower dosage typically results in less intense side effects, making it more tolerable for some people. In contrast, ketamine’s psychoactive effects can vary widely. At Emerge, we use a therapeutic dose of ketamine, which has mild side effects without inducing a full psychedelic experience. However, high doses can cause out-of-body experiences, hallucinations, and sometimes, an emotional release.
There are also differences in side effects between Spravato and ketamine based on differences in administration methods. IV ketamine can cause pain and bruising at the site of injection, whereas Spravato can cause nasal discomfort and irritation.
Cost and Insurance Coverage
One of the major deciding factors when choosing IV ketamine vs. Spravato is whether your insurance will cover it. Spravato is FDA-approved, so it’s typically covered by insurance, especially for patients who meet criteria for TRD or MDSI. Patients often only pay a copay or deductible portion of the cost.
Ketamine, being an off-label medication, is less commonly covered by insurance. However, some insurance companies cover costs, and our clinic will provide you with a “super bill” that you can send to your insurer for reimbursement. We’re also one of the most affordable clinics operating in the Boston area.
Our team at Emerge is here to help you navigate costs and insurance options.
Ketamine or Spravato: Which One Is Right for Me?
Choosing between ketamine and Spravato often comes down to your specific needs, preferences, and medical circumstances. While both treatments can be highly effective for depression and related conditions, one may be a better fit depending on a few key factors:
Diagnosis
Spravato is only approved for people with TRD and MDSI. If you don’t have a formal diagnosis for either of these conditions, then you won’t be eligible for Spravato treatment.
Insurance Coverage
If cost is a major consideration and you have insurance, Spravato may be the more accessible option. Since it’s FDA-approved for depression, many insurance providers cover the treatment if you qualify for TRD or MDSI. Ketamine, while often more affordable per session out-of-pocket, is not usually covered by insurance or has only partial coverage.
Treatment Goals
If you’re looking for a more flexible and potentially deeper therapeutic experience, IV ketamine may be more appropriate. Its more pronounced psychoactive effects could help you gain insight and have an emotional release. On the other hand, if you prefer a more medically structured and less psychoactive approach, Spravato may be the better fit.
Response Time and Flexibility
IV ketamine generally has a faster onset of action, with some patients noticing improvements within hours. The dosing protocol can also be more tailored to individual needs. However, Spravato, while slightly slower to act for some, offers a more standardized and predictable treatment process.
Sensitivity to Side Effects
If you are concerned about dissociative effects or anything related to IV injections, Spravato may be easier to tolerate. Its lower dose and slower absorption typically result in milder side effects compared to IV or IM ketamine.
Key Takeaways
Both ketamine and Spravato are effective options for treatment-resistant depression, but they differ in how they’re administered, regulated, and experienced by patients.
Ketamine is a versatile, off-label treatment available in multiple forms (IV, IM, oral, nasal) and is known for its rapid antidepressant effects, especially when delivered intravenously.
Spravato (esketamine) is FDA-approved specifically for TRD and MDSI and must be administered in a certified clinic under strict medical supervision as a nasal spray.
Side effects and efficacy are generally the same, although IV ketamine tends to work faster and has more pronounced psychoactive effects.
Insurance coverage is a major differentiator—Spravato is often covered by insurance, whereas ketamine treatment is typically out-of-pocket, although some clinics offer support for reimbursement.
Still unsure about IV ketamine vs. Spravato? Book a consultation with our expert team to discuss which treatment is best for your needs. Emerge Wellness is a leading provider of IV ketamine and Spravato in Boston. If you’re interested in either of these options but are still unsure which is best, be sure to book a consultation with one of our expert staff members, and we can help you make the best decision.