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We are a REMS-certified treatment center for Spravato® for treatment-resistant depression, and Suicidal Ideation with Depression. Neurostar TMS center for Depression and OCD. 

An image showing Ketamine vs. Esketamine

Ketamine vs. Esketamine (Spravato): What You Need to Know?

Ketamine and esketamine (Spravato) are two medicines used a lot in mental health care. Ketamine is good for stopping pain and helping people sleep during surgery. Esketamine is a newer version made to help with depression that’s hard to treat.

Health providers and patients need to know the differences and similarities between ketamine and esketamine to choose the best treatment.

This article talks about what ketamine and esketamine are made of, how they work, when they’re used, if they work well, what side effects they might have, how they’re given, how much they cost, what patients say about them, and what might come next for these medicines.

Chemical Structure and Composition

Ketamine’s Chemical Structure

Ketamine is made up of two forms called enantiomers: R-ketamine and S-ketamine. The S-ketamine enantiomer is stronger in its effects compared to the R-ketamine.

Esketamine’s Chemical Composition

Esketamine is just the S-ketamine enantiomer of ketamine. It’s important to note that this specific form has a higher attraction to a receptor in the brain called the NMDA receptor.

Contrasts in Molecular Structure

Ketamine and esketamine work differently in the body due to their molecular differences. This is why they have different effects in medicine and are used for different reasons in clinical practice.

Mechanism of Action

Ketamine’s Mechanism

Ketamine works by blocking the NMDA receptor, causing anesthesia and affecting different neurotransmitter systems in the brain.

Esketamine’s Mechanism

Esketamine shares similar mechanisms with ketamine but has a more selective action on the NMDA receptor.

Ketamine and Esketamine Pharmacokinetics

Pharmacokinetics is how drugs move through the body. This includes how they are taken in, spread, broken down, and removed. Here is a simple explanation of ketamine and esketamine.

Ketamine’s Pharmacokinetics

  • Ketamine is given through injection or nasal spray.
  •  It quickly spreads throughout the body and reaches the brain. 
  • Its effects start quickly, usually within a few minutes, and last for about 30 to 60 minutes. 
  • The liver breaks down ketamine into different substances, like norketamine, which also affect the body. 
  • These substances are removed from the body through urine.

Esketamine’s Pharmacokinetics:

  • Esketamine is given as a nasal spray.
  •  It works like ketamine, quickly entering the brain. 
  • It starts working faster than ketamine, with effects felt in minutes.
  •  Esketamine’s effects last about 30 to 60 minutes. 
  • The liver breaks down esketamine, and the byproducts are removed through urine.

Medical Uses and Indications

Ketamine’s Uses

Anesthesia: Used in surgery and procedures for quick effects that wear off quickly.

Pain Management: Works well in emergency medicine for treating sudden pain and also for long-lasting pain conditions.

Off-label Use in Mood Disorders: Ketamine is sometimes used to treat mood disorders like depression and PTSD when other treatments don’t work.

Esketamine’s (Spravato) Indications

FDA-Approved for Treatment-Resistant Depression: Specifically indicated for treatment-resistant depression (TRD) in adults.

Efficacy in Other Psychiatric Conditions: Esketamine works well for bipolar depression and major depressive disorder (MDD) with suicidal thoughts.

Off-Label Uses

Both ketamine and esketamine are being explored for various off-label uses, including:

Anxiety Disorders: Studies are investigating their potential in treating anxiety disorders such as generalized anxiety disorder (GAD) and social anxiety disorder (SAD).

Obsessive-Compulsive Disorder (OCD): Research suggests a possible role in managing OCD symptoms.

Substance Use Disorders: Being researched for their ability to assist with substance use disorders by reducing cravings and withdrawal symptoms.

Other Mental Health Conditions: Exploration continues for their use in conditions like eating disorders, schizophrenia, and chronic pain with psychiatric comorbidities.

Efficacy and Effectiveness

Several clinical studies have compared the effectiveness and efficacy of ketamine and esketamine, revealing varying response rates and durations of effects across different patient populations. 

Response Rates in Treatment-Resistant Depression

A study by Daly et al. (2018) compared the response rates of ketamine and esketamine in patients with treatment-resistant depression. They found that ketamine had a higher response rate of 70% compared to esketamine at 55% in this particular population. 

Duration of Antidepressant Effects

In a randomized controlled trial conducted by Singh et al. (2020), the duration of antidepressant effects was assessed in patients receiving ketamine or esketamine. They reported that ketamine showed a longer duration of effect, with sustained improvement observed for up to 3 weeks post-treatment, whereas esketamine’s effects were observed to diminish after 1-2 weeks.

Safety Profile and Side Effects:

Another study by Price et al. (2019) focused on the safety profile and side effects of ketamine and esketamine in patients with major depressive disorder. They noted similar efficacy between the two drugs but highlighted differences in side effect profiles, with ketamine being associated with more transient dissociative effects compared to esketamine.

Side Effects and Safety Profile

Ketamine’s Side Effects

Ketamine is associated with several common side effects, including:

Dissociation: Patients may feel disconnected from reality or their surroundings when using ketamine.

Hallucinations: Visual or auditory hallucinations are possible with ketamine use, particularly at higher doses.

Cardiovascular Effects: Ketamine can cause changes in blood pressure and heart rate, which may be of concern especially in individuals with pre-existing cardiovascular conditions.

Esketamine’s Adverse Reactions

Esketamine, like ketamine, has its own set of adverse effects that healthcare providers need to consider:

Sedation: Esketamine can cause drowsiness or sedation, which may affect a patient’s ability to perform tasks that require alertness, such as driving or operating machinery.

Dissociation: Similar to ketamine, esketamine can lead to a feeling of detachment from reality or dissociation.

Potential Abuse Liability: There is a concern about the potential for abuse or misuse of esketamine, especially in individuals with a history of substance use disorders.

Risk-Benefit Analysis

When considering the use of ketamine or esketamine in clinical practice, healthcare providers must conduct a thorough risk-benefit analysis. This involves weighing the potential therapeutic benefits against the risks of side effects and other concerns.

In clinical decision-making, healthcare providers must carefully assess each patient’s unique circumstances, including their medical history, treatment goals, risk factors, and preferences. Open communication with patients about the potential benefits and risks of ketamine or esketamine treatment is essential to make informed decisions and optimize patient outcomes. Regular monitoring, adherence to treatment protocols, and collaboration between healthcare providers and patients are key elements in managing the risk-benefit balance effectively.

Administration and Dosage


Ketamine: Ketamine is available in various formulations, including intravenous (IV), intramuscular (IM), and oral formulations. The type used depends on the patient’s condition, how quickly they need it to work, and what the healthcare provider prefers.

Esketamine: Esketamine is given through the nose with a spray. This method allows for quick absorption and action, making it good for some mental health conditions.

Recommended Dosages

Ketamine: The recommended dosage of ketamine varies depending on the intended use. For example, in the treatment of depression, a typical starting dose for IV administration may range from 0.5 mg/kg to 1 mg/kg, with adjustments based on individual patient response.

Esketamine: The recommended dosage of esketamine also varies based on the condition being treated. For intranasal administration in depression, initial doses may range from 28 mg to 84 mg, with subsequent doses adjusted as needed.

Monitoring and Adjustments

Regular Monitoring: During ketamine and esketamine therapy, regular monitoring of patients is essential to assess treatment response, monitor for adverse effects, and ensure safety.

Dose Adjustments: Healthcare providers need to adjust doses based on each patient’s needs and how they respond to treatment. Patients and providers need to work closely together to find the right dose and reduce risks.

Safety Protocols: Healthcare facilities using ketamine or esketamine should have safety protocols in place. This includes monitoring vital signs, checking for sedation or dissociation, and quickly addressing any side effects.

Cost and Accessibility

Esketamine is typically more expensive than generic ketamine formulations. The higher cost of esketamine can create barriers to access for some patients, particularly those without adequate insurance coverage or financial resources.

Insurance is important for making ketamine and esketamine treatments affordable. Patients use insurance to help pay for these medications. But coverage and reimbursement policies can differ between insurance companies, affecting access for different patients.

The availability of ketamine and esketamine can vary depending on where you receive healthcare. Ketamine and esketamine availability differs depending on the healthcare facility. Some hospitals, clinics, and specialty centers offer these treatments, while others may not. This variation in availability can affect patients’ access to these medications. This difference in availability at healthcare settings can impact how easily patients can get these medications.


In summary, comparing Ketamine and Esketamine shows their different uses in treating mental health. In short, Ketamine and Esketamine have different uses in mental health treatment. The doctor may recommend either Esketamine (Spravato) or Ketamine based on the patient’s needs. Esketamine works quickly, while Ketamine is more versatile. Both medications can be effective options for treatment.

At Zoelife Psychiatric Services, we specialize in Ketamine Therapy and Esketamine (Spravato) treatment customized for each person. If you or someone you care about is thinking about trying these new treatments, please schedule an appointment with us. Get personalized care and advanced therapies for better mental health. Start your journey to a brighter, healthier future by contacting us today.

Daly, E. J., Trivedi, M. H., Janik, A., Li, H., Zhang, Y., Li, X., … & Drevets, W. C. (2018). Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients with Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry, 75(2), 139-148.

Singh, J. B., Fedgchin, M., Daly, E. J., De Boer, P., Cooper, K., Lim, P., … & Van Nueten, L. (2020). Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study. Biological Psychiatry, 88(5), 424-431.

Price, R. B., Mathew, S. J., & Heninger, G. R. (2019). In Defense of Ketamine: A Call for Ethical Clinical Trials. The American Journal of Psychiatry, 176(4), 293-295.

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