The reputation of ketamine and esketamine is evolving. Once known mainly as anesthetics, these drugs are now making headlines, showing up in celebrity interviews, and even tied to tragic news stories.
From Elon Musk discussing ketamine for depression to the heartbreaking overdose of Matthew Perry, ketamine and esketamine have entered the public spotlight in a big way. With all this buzz, it’s easy to confuse fact with fiction. If you or someone you care about is exploring new treatment options for depression, this guide will help clear up myths, lay out the facts, and explain what you need to know.
What is ketamine and esketamine?
Researchers first developed ketamine in the 1960s as a general anesthetic. Today, doctors continue to use it in hospitals and emergency rooms. It provides pain relief, sedation, and anesthesia during surgeries.
Over the past two decades, researchers and clinicians discovered something new. At low doses, ketamine can have powerful antidepressant effects. This breakthrough treatment has been especially helpful for people with treatment-resistant depression (TRD). That means their depression hasn’t improved with standard medications like SSRIs or therapy.
Ketamine is usually given as a racemic mixture, meaning it contains two mirror-image forms of the molecule: R-ketamine and S-ketamine. When both are combined (as in traditional ketamine), the drug affects several brain receptors, including the NMDA receptor, which plays a role in mood, memory, and thought patterns.
Esketamine is the S-enantiomer of ketamine — just the S-form, not the mix of R and S. It was developed and patented as a separate drug by a pharmaceutical company and approved by the FDA in 2019 under the brand name Spravato®.
Unlike ketamine, which is often delivered off-label by IV or intramuscular injection at clinics, esketamine is FDA-approved specifically for use in adults with treatment-resistant depression and major depressive disorder with suicidal thoughts or behavior. It comes as a nasal spray that must be administered in a certified medical office under supervision.
What’s the difference between ketamine and esketamine?
Here’s a side-by-side comparison to help you understand how these medications differ:
| Feature | Ketamine | Spravato (esketamine) |
| FDA approval | No (used off-label) | Yes (FDA-approved) |
| Route of administration | IV infusion, IM injection | Nasal spray |
| Conditions treated | TRD, chronic pain (off-label) | TRD, depression with suicidal ideation |
| Insurance coverage | Often NOT covered | Often covered by insurance |
| Monitoring required | Clinic-dependent | Two-hour observation post-dose (FDA required) |
Is ketamine safe?
When Matthew Perry died in 2023, toxicology reports showed high levels of ketamine in his system. Many people were shocked and began asking: Is ketamine therapy safe? It’s an understandable question and one that deserves a clear, evidence-based answer.
Therapeutic ketamine use is completely different from recreational or unsupervised use. In a medical setting, providers administer ketamine in carefully controlled doses and follow strict safety protocols. Patients are closely monitored for vital signs, mental and physical reactions, and any potential side effects throughout the process.
What happened in Perry’s case was tragic, but it does not reflect how ketamine is used clinically. According to coroner reports, the amount of ketamine in his body was far higher than what would be used in depression treatment, and he was not in a clinic or receiving supervised care at the time.
Elon Musk and ketamine use — let’s talk about it
When Musk mentioned he uses ketamine for depression, it sparked another wave of public interest. While it’s encouraging to see mental health openly discussed, it’s important to remember that not everyone is a good candidate for ketamine treatment, and it’s not a one-size-fits-all solution.
Also, ketamine should not be self-administered or taken casually. While Musk may have access to private physicians and elite care, most people should only consider ketamine therapy after consulting with a psychiatrist or mental health provider, especially if other depression treatments haven’t worked.
5 myths about esketamine (Spravato®)
Let’s clear up some common myths and replace them with facts based on current clinical knowledge.
Myth: Esketamine is just legal ketamine.
Fact: Esketamine is not simply “legal ketamine.” It’s a separate, FDA-approved medication developed specifically for depression and is delivered as a nasal spray in medical offices.
Myth: You’ll get addicted to esketamine.
Fact: When used as prescribed and under medical supervision, esketamine carries a low risk of addiction. Patients are carefully screened before starting treatment to ensure safety.
Myth: It’s a last resort only.
Fact: Although often used for treatment-resistant depression, esketamine isn’t just a last resort. It’s part of a broader set of evidence-based options for individuals who haven’t responded well to traditional treatments.
Myth: You can take it at home.
Fact: Esketamine must be administered in a certified clinic or hospital. After each dose, patients are monitored for at least two hours to ensure safety.
Myth: It works instantly.
Fact: While some people may experience relief within hours or days, full therapeutic effects typically require multiple sessions over several weeks.
Clinical safety and monitoring
Both ketamine and esketamine are generally safe when used appropriately. That said, they are powerful drugs that affect brain chemistry and require clinical oversight.
Patients receiving esketamine are monitored for:
- Blood pressure changes
- Dissociation or hallucinations
- Nausea or dizziness
- Sedation or confusion
- Any signs of misuse or dependency
For ketamine infusions, similar precautions are taken, though there’s more variation across clinics.
Who should avoid ketamine or esketamine?
These treatments are not right for everyone. People with a history of psychosis, active substance use disorders, or uncontrolled high blood pressure may not be good candidates. Pregnant individuals, people with unstable medical conditions, or those with certain heart issues should also be cautious.
A psychiatric evaluation is always recommended before starting either medication.
Conclusion: two options, one goal — renewed hope
Ketamine and esketamine are two related, but distinct, tools in the treatment of depression and other mental health challenges. While public figures may draw attention to their use, it’s important to view these treatments through the lens of science and safety — not celebrity.
For those struggling with depression that hasn’t responded to traditional treatments, esketamine offers a promising, FDA-approved path forward. Ketamine, when delivered by trained professionals in clinical settings, can also be effective and life-changing for many.
If you or someone you care about is considering ketamine or esketamine therapy, talk to a licensed mental health provider. Ask about qualifications, protocols, and follow-up care. The right treatment, delivered the right way, can make all the difference.
Key takeaways
- Ketamine’s role in mental health is expanding. Once just an anesthetic, ketamine now shows promise for treatment-resistant depression (TRD), offering rapid relief when standard meds don’t work.
- Esketamine (Spravato®) isn’t just “legal ketamine.” Esketamine is FDA-approved as a nasal spray for TRD and must be given under medical supervision — unlike off-label ketamine infusions.
- Media buzz blurs safe use vs. misuse. Celebrity stories and tragic overdoses can mislead. Clinical ketamine therapy involves careful screening, dosing, and monitoring — very different from recreational use.
- Safe under expert care, but not for everyone. Both treatments require close supervision. They’re not suitable for people with certain medical conditions, making psychiatric evaluation essential.
Looking for Spravato® treatment near you?
Pacific Mind Health offers Spravato® (esketamine) therapy for treatment-resistant depression and major depressive disorder at our Long Beach and Irvine locations. Our experienced clinicians provide compassionate, evidence-based care to help you feel better.
Ready to take the next step? Schedule a consultation today to see if Spravato is right for you.
