Ketamine Nasal Spray: What Exactly Is It?

Ketamine nasal spray is a pharmaceutical preparation of ketamine, formulated for intranasal delivery, primarily used to treat certain mental health conditions. It is designed to rapidly absorb through the nasal mucosa into the bloodstream, providing fast-acting effects compared to oral or injectable forms.

One notable variant is Esketamine (Spravato), an FDA-approved nasal spray derived from ketamine’s S-enantiomer, specifically for treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation.

Core Features of Ketamine Nasal Spray

1. Active Ingredient:
   • The active substance can be either racemic ketamine (used off-label) or esketamine (a more potent S-enantiomer).
2. Delivery System:
   • Administered intranasally, allowing rapid absorption and bypassing the digestive system for quicker onset.
3. Purpose:
   • Used primarily for psychiatric disorders (TRD, MDD) and being investigated for other conditions like PTSD and chronic pain.

Ketamine nasal spray is a medical formulation designed for intranasal delivery of ketamine, primarily used in the treatment of mental health conditions such as treatment-resistant depression (TRD) and major depressive disorder (MDD). This route of administration offers rapid absorption into the bloodstream through the nasal mucosa, providing a faster onset of effects compared to oral or injectable routes.

The most notable form of ketamine nasal spray is esketamine (a derivative of ketamine), marketed under the brand name Spravato, which has received FDA and EMA approval for depression treatment.

Medical Uses of Ketamine Nasal Spray

1. Treatment-Resistant Depression (TRD)

• Approved for patients who have not responded to at least two other antidepressant treatments.
• Administered under medical supervision as part of a comprehensive treatment plan that includes oral antidepressants.

2. Major Depressive Disorder (MDD) with Suicidal Ideation

• Used to rapidly alleviate acute depressive symptoms and reduce the risk of suicide.

3. Chronic Pain Management (Investigational)

• Ketamine nasal spray is being explored for managing chronic pain conditions like neuropathic pain or migraine.

How It Works

Ketamine and its derivative esketamine act primarily as NMDA receptor antagonists, modulating the activity of glutamate, an excitatory neurotransmitter in the brain. This mechanism:

• Promotes neuroplasticity (the brain’s ability to form and reorganize connections).
• Provides a rapid antidepressant effect within hours, compared to weeks for traditional antidepressants.

Administration and Dosage

• Route: Intranasal (sprayed directly into the nostrils).
• Setting: Administered in a clinical environment due to potential side effects.
• Dosage: Typically measured in milligrams per spray. Esketamine is dosed based on the patient’s weight and clinical condition.

A typical treatment regimen involves:

• Induction Phase: Twice-weekly doses for the first 4 weeks.
• Maintenance Phase: Weekly or biweekly doses thereafter.

Advantages of Nasal Spray Over Other Forms

1. Rapid Onset:
   • Effects are often noticeable within 1–2 hours, making it ideal for acute situations.
2. Convenience:
   • Easier to administer compared to intravenous or intramuscular injections.
3. Minimized Risk of Recreational Use:
   • Medically formulated nasal sprays, like esketamine, are less prone to abuse than powdered ketamine.

Side Effects of Ketamine Nasal Spray

Common Side Effects:

• Drowsiness or dizziness
• Nausea and vomiting
• Increased blood pressure
• Dissociation or feeling “spaced out”
• Headache

Serious Risks:

• Dissociation: Temporary feelings of detachment from reality.
• Addiction Potential: Although rare under medical supervision, ketamine’s psychoactive properties can lead to dependency.
• Cardiovascular Concerns: Increased heart rate and blood pressure require monitoring, especially in patients with pre-existing conditions.

Esketamine (Spravato) vs. Regular Ketamine

Legal Status

• Esketamine (spravato): Approved by the FDA (USA), EMA (Europe), and other health authorities for medical use under strict regulation.
• Ketamine Nasal Spray (Compounded): May be used off-label for depression or pain but is not formally approved for this route.

Future Directions and Research

Research into ketamine nasal sprays is ongoing to:

• Optimize formulations for more consistent absorption.
• Expand applications to other conditions, such as PTSD and chronic pain.
• Minimize side effects and abuse potential.

Summary

Ketamine nasal spray represents a groundbreaking advance in the treatment of mental health disorders, offering rapid relief for conditions like treatment-resistant depression. With its fast onset of action and convenient administration, it provides an alternative to traditional antidepressants and injectable ketamine. However, due to its psychoactive properties and potential for misuse, it is primarily used in controlled clinical settings. Its evolving role in psychiatry and chronic pain management underscores its significance as a modern therapeutic option.