S-ketamine, known by its brand name Spravato, is a prescription medication derived from ketamine, a substance historically used as an anesthetic. Specifically, esketamine is used to manage severe depressive symptoms in adults who have not responded to conventional treatments.
Medical Applications of S-Ketamine
S-ketamine is approved for adults experiencing specific, difficult-to-treat forms of depression. One primary indication is Treatment-Resistant Depression (TRD), which refers to major depressive disorder where individuals have not responded adequately to at least two different oral antidepressant medications taken at appropriate doses and for sufficient durations in their current depressive episode. For these patients, esketamine is typically used alongside a new oral antidepressant.
The medication is also approved for adults with Major Depressive Disorder (MDD) who are experiencing acute suicidal ideation or behavior. In these cases, esketamine is administered in conjunction with an oral antidepressant. This application addresses a particularly urgent need, as esketamine has shown evidence of reducing depressive symptoms within 24 hours of use.
Mechanism of Action
S-ketamine functions differently from traditional antidepressants, which typically target neurotransmitters like serotonin, norepinephrine, or dopamine. Instead, esketamine primarily acts as a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, a type of glutamate receptor in the brain. Glutamate is the brain’s most abundant excitatory neurotransmitter, playing a role in learning, memory, and mood regulation. By blocking NMDA receptors, esketamine is thought to lead to a temporary increase in glutamate release.
This surge in glutamate then activates other receptors, particularly alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The activation of AMPA receptors can promote the growth of new synaptic connections, a process known as synaptogenesis, in brain regions associated with mood regulation, such as the prefrontal cortex. This rapid re-establishment of neural pathways is believed to contribute to the medication’s quick antidepressant effects, offering a novel approach compared to the slower onset of conventional antidepressants.
The S-Ketamine Treatment Process
The administration of esketamine, typically through a nasal spray, requires specific protocols. Patients self-administer the nasal spray under the direct observation of a healthcare provider in a certified medical setting. This ensures proper dosage and immediate supervision for any transient effects. Before each session, patients are often advised to avoid food for at least two hours and liquids for 30 minutes to minimize potential nausea or vomiting.
Following administration, patients must remain at the healthcare setting for a mandatory observation period of at least two hours. During this time, medical staff monitor for any potential immediate effects, such as changes in blood pressure or feelings of dissociation. Patients cannot drive or operate machinery until the day after treatment, following a full night’s sleep, due to the potential for impaired alertness and coordination.
Potential Side Effects and Safety Protocols
Patients receiving S-ketamine may experience acute side effects, which are monitored and typically resolve within the two-hour observation period. Common effects include dissociation, described as an “out-of-body” experience or feeling disconnected from oneself, along with dizziness, nausea, and sedation. Temporary increases in blood pressure are also observed, often peaking around 40 minutes after administration and generally resolving within approximately four hours. Less common but notable effects can include vomiting, anxiety, and a feeling of being drunk.
To manage these potential risks, esketamine is available only through a restricted distribution program mandated by the U.S. Food and Drug Administration (FDA), known as the SPRAVATO® Risk Evaluation and Mitigation Strategy (REMS). This program requires esketamine be dispensed and administered only in certified healthcare settings under direct medical supervision. The REMS program also prohibits patients from taking the medication home. These safety measures, including patient enrollment and facility certification, mitigate risks like sedation, dissociation, and misuse.