S-ketamine, also known as esketamine, is a specific form of ketamine recognized for its unique properties and therapeutic applications.
Distinguishing S-Ketamine
Ketamine is a chiral molecule, existing in two mirror-image forms called enantiomers: S-ketamine (esketamine) and R-ketamine (arketamine). Standard ketamine production yields a racemic mixture, containing equal parts of both.
S-ketamine has a significantly higher binding affinity for N-methyl-D-aspartate (NMDA) receptors, a type of brain protein, compared to R-ketamine. This makes S-ketamine more potent for certain effects, including its anesthetic and analgesic properties.
How S-Ketamine Affects the Body
S-ketamine primarily functions as an N-methyl-D-aspartate (NMDA) receptor antagonist. These receptors are activated by glutamate, a key neurotransmitter involved in excitatory signaling, learning, and memory. By blocking NMDA receptors, S-ketamine disrupts normal glutamate signaling.
This blockade can lead to a surge of glutamate in brain regions like the prefrontal cortex. This glutamate surge activates AMPA receptors, triggering molecular events that include the production of brain-derived neurotrophic factor (BDNF) and activation of the mTOR pathway. These processes are involved in forming new connections between brain cells, known as synaptogenesis or neuroplasticity. This enhancement of neuroplasticity contributes to S-ketamine’s rapid antidepressant effects.
Medical Uses of S-Ketamine
S-ketamine has established medical applications, primarily in mental health. Its main use is treating severe or treatment-resistant depression (TRD) in adults who have not responded to at least two conventional antidepressant treatments. It is also approved for adults with major depressive disorder (MDD) experiencing acute suicidal ideation or behavior.
Historically, ketamine, including its S-enantiomer, has been used as a general anesthetic. It induces a trance-like state while preserving breathing and airway reflexes, and stimulating heart function. This makes it useful in emergency and trauma situations, especially for patients at risk of low blood pressure. The specific S-ketamine formulation for depression, Spravato, is distinct from the racemic ketamine commonly used for anesthesia.
What to Expect with S-Ketamine Treatment
S-ketamine treatment for depression uses a specific nasal spray formulation, sold as Spravato. This nasal spray received FDA approval for treatment-resistant depression in 2019. Patients receive treatment in a supervised clinical setting, such as a doctor’s office or clinic, because potential side effects require monitoring.
During a session, patients self-administer the nasal spray, typically with a few doses spaced minutes apart, under direct supervision. After administration, patients are monitored for at least two hours for side effects like dissociation, dizziness, sedation, increased blood pressure, nausea, or vomiting. Dissociation, a feeling of being disconnected from oneself or surroundings, is a common temporary effect. Patients are advised not to eat for at least two hours or drink liquids for 30 minutes before treatment to reduce nausea and vomiting. A caregiver must drive the patient home after the observation period.