SPRAVATO® (Esketamine) vs. Ketamine for Treatment-Resistant Depression: What’s the Difference?

Esketamine and ketamine are two therapies that have recently emerged as promising options for individuals struggling with treatment-resistant depression. And while they share similarities, there are many important distinctions in how they’re formulated, administered, and regulated.

What Is Treatment-Resistant Depression?

Treatment-resistant depression (TRD) is typically defined as major depressive disorder that does not respond adequately to at least two different antidepressant treatments. For some people, this resistance becomes apparent early, but for others it may develop gradually after years of partial or diminishing levels of symptom improvement.

If you have tried at least two different antidepressants and your symptoms persist, you may be considering one of these innovative treatments.

What Is Ketamine?

Ketamine is a medication originally developed in the 1960s as an anesthetic. It has been widely used in medical and veterinary settings for decades because of its fast-acting effects. More recently, researchers and clinicians have discovered that ketamine, particularly when given at low doses, can rapidly alleviate symptoms of depression. However, its use as a depression treatment is considered off-label, so practices can vary between providers.

What Is Esketamine?

Esketamine is a derivative of ketamine. It works by acting on glutamate receptor systems in the brain, often alleviating symptoms of depression within hours after the first treatment. Esketamine’s side effects are often milder than those of ketamine, and it is generally considered a safer treatment because its dosing, screening, and safety protocols are standardized.

Key Differences Between Esketamine and Ketamine

FDA Approval and Regulation

Esketamine is FDA-approved for treatment-resistant depression when administered in a certified health care setting. Ketamine, while FDA-approved as an anesthetic, is used off-label for depression and is not regulated in the same way for mental health treatment.

Chemical Composition

Ketamine is made of two slightly different versions of the same molecule (R and S), while esketamine is just the S version on its own. Both work by blocking NMDA receptors in the brain, which affects how brain cells communicate and helps rebuild connections involved with mood, giving them antidepressant effects. Because esketamine is the more targeted S form, it may work more precisely and can be more potent for depression, and it tends to cause fewer intense dissociative effects than regular ketamine.

Administration Method

Ketamine is typically administered as an intravenous (IV) infusion in clinical settings that usually lasts over 40 minutes. Patients will generally receive multiple doses spaced out over a few weeks. Unlike ketamine, esketamine is a nasal spray that patients self-administer in a comfortable, clinical setting, making it a convenient alternative to ketamine. Overall treatment time lasts approximately 8 to 10 weeks, but there is no limit on how long you can continue treatment.

Cost and Accessibility

Ketamine therapy for TRD isn’t covered by insurance, so you’d have to pay for the treatment out of pocket. Esketamine, however, is covered by most insurance providers, including Medicare, because it is an FDA-approved treatment backed by extensive research demonstrating [AM1] its safety and effectiveness. However, for your insurance to cover your esketamine treatment, you must have already tried two traditional antidepressants without success in alleviating your symptoms.

Onset and Side Effects

Both ketamine and esketamine treatments are known for rapid results, sometimes within hours of the first treatment. Both can cause side effects, such as dizziness, disorientation, confusion, or anxiety. However, ketamine often has more intense side effects, sometimes described as a deeper, more intense dissociative experience, because of the higher, sustained concentration in the bloodstream.

Which One Is Right for You?

The choice between esketamine and ketamine may depend on several factors:

• Diagnosis and severity of symptoms
• Treatment history
• Insurance coverage
• Access to certified providers
• Personal preference regarding administration method

Overall, esketamine is a more targeted, evidence-backed therapy that is FDA-approved specifically for treatment-resistant depression, which means its safety and effectiveness have been thoroughly tested in a more structured way.

SPRAVATO® Treatment at LiveWell Counseling

Christian Health offers SPRAVATO[AM2] ® (esketamine therapy) in our comfortable, calming lounge, where clients can self-administer the nasal spray under the supervision of our board-certified psychiatrists and nurses.

To learn more, please call (201) 848-5800 or visit SPRAVATO®. This innovative treatment is covered by most insurance providers.