Advancements in mental health care are offering new avenues of hope for people with hard-to-treat depression. Among these are esketamine and ketamine, two powerful tools in the fight against severe depression. While they target a similar chemical in the brain, they have chemical differences and therefore vary in side effects, FDA approval, and how they’re administered.

What Is Ketamine?

Ketamine was originally developed as an anesthetic, used in medical settings for decades. It works to boost the NMDA receptors in the brain, boosting overall activity and mood. It has a reputation for its hallucinogenic effects, though in clinical settings these impacts are monitored closely.

What Is Esketamine?

Esketamine is derived from ketamine, but it has a more selective influence on NMDA receptors and doesn’t produce the same hallucinogenic effects. Esketamine, under the brand name Spravato®, is approved by the FDA as a solution for hard-to-treat depression.

Esketamine vs. Ketamine: Key Differences

While both esketamine and ketamine are used to treat severe depression, there are several key differences between the two, including their actual chemical makeup, current FDA approval, and how they’re administered. Additionally, ketamine treatments will likely not qualify for insurance coverage, while esketamine (Spravato®) is likely to get approved for those with difficult-to-treat depression.

Here are the key differences between ketamine and esketamine:

Chemical Composition

Ketamine is a racemic mixture containing two mirror-image molecules: R-ketamine and S-ketamine. Esketamine is a purified version containing only the S-ketamine molecule. This version of the chemical is more potent for targeting depression-related symptoms, and also comes with fewer side effects.¹

FDA Approval & Regulation

Ketamine has been used off-label for depression treatment, meaning it is not FDA-approved specifically for this use but has shown effectiveness. Esketamine, marketed as Spravato®, is FDA approved for difficult-to-treat depression, providing a regulated and monitored treatment option.

Clinical Use & Administration

Ketamine is typically administered intravenously (IV) or through intramuscular (IM) injections in a clinical setting. Esketamine is given as a nasal spray, making it a more convenient and less invasive option for patients.

Ketamine infusions are typically administered 2-3 times weekly for a total of 6-8 sessions, while Spravato® doses are given twice weekly for the first four weeks, weekly for the next four weeks, then weekly or biweekly over the course of several months depending on the needs of the client.

Side Effects & Efficacy

Both ketamine and esketamine act on the brain’s NMDA receptors. However, esketamine is believed to have a more selective action, potentially leading to fewer side effects and improved efficacy in treating depression.

Ketamine and esketamine have similar side effects, which can include dissociation, drowsiness, dizziness, and short-term increased blood pressure. However, the impacts of ketamine can be somewhat more severe, and can also include hallucination. Plus, it’s at a greater risk for being misused outside of clinical settings.

Cost & Insurance Coverage

Ketamine treatments can be expensive and are not covered by insurance, as they are considered off-label for treating depression. Esketamine (Spravato®) is covered by many insurance plans, reducing the out-of-pocket cost for people seeking this treatment.

Which Is More Effective, Ketamine or Esketamine?

From the studies currently published, ketamine and esketamine appear to be similarly effective in alleviating symptoms related to difficult-to-treat depression. However, some studies show that the selective nature of esketamine makes it more targeted for treating depression.¹

Since esketamine is FDA approved for this approach while ketamine is not, more research is needed directly comparing the two drugs for this purpose.

The Benefits of Spravato® for Hard-to-Treat Depression

Spravato® nasal spray is designed to work differently than traditional antidepressants, targeting specific pathways in the brain to provide rapid relief from depressive symptoms.

Here are some of the benefits of Spravato® for difficult-to-treat depression:

• It works much quickly than other medications for depression, with many clients experiencing relief from symptoms within a few hours or days
• Especially when combined with other medications and talk therapy, Spravato® can significantly improve daily functioning for those with depression
• Spravato® is much more convenient and accessible compared to IV ketamine

 

Start Spravato® Treatment Services in Massachusetts at NEHS

At Northeast Health Services, we are committed to offering cutting-edge treatments for our clients in Boston, Springfield, and across Massachusetts. Our Spravato® treatment services utilize esketamine, a promising option for those struggling with difficult-to-treat depression.

If you’re ready to take the next step in your mental health journey, schedule an appointment or call us at 508.794.8711 to learn more. For existing clients, find your office location to contact them directly and learn more about whether Spravato® could be right for you.