Labyrinth Psychiatry Group · Published
Depression casts an impenetrable gloom over everything in life, sapping all the joy and energy from your existence. The CDC reports that 4.5% of American adults have regular feelings of depression, and research estimates that about 30% of adults taking medication for major depression have treatment-resistant depression (TRD).
TRD is particularly frustrating because you’ll have already tried medication, therapy, or both without relief. Spravato® offers a different biological approach. Rather than concentrating mainly on the brain’s monoamine neurotransmitters (chemicals that relay information), it acts on the glutamate system, which plays a major role in communication between nerve cells.
At Labyrinth Psychiatry Group, we use Spravato as one of our targeted treatments for adults whose depression hasn’t responded adequately to standard antidepressants and/or therapy. Here’s a closer look at the science behind this treatment and what researchers have learned about its effects.
Why treatment-resistant depression is different
Doctors commonly use the term TRD when depression hasn’t improved adequately after at least two appropriate antidepressant trials. That doesn’t necessarily mean the medications had no effect — some people experience partial improvement but continue to have significant symptoms.
Traditional antidepressants usually influence brain chemicals such as serotonin, norepinephrine, dopamine, or combinations of these neurotransmitters. Antidepressant medicines remain valuable treatments, but depression involves more than a single chemical pathway.
Research increasingly points to changes in various aspects of brain function, including:
- Neural circuits
- Stress responses
- Synaptic function
- Neuroplasticity (the brain’s ability to adapt and reorganize)
These findings helped scientists investigate treatments that work through different signaling systems.
How Spravato works: it targets the glutamate system
Spravato contains esketamine, a form of the anesthetic medication ketamine. Unlike most traditional antidepressants, esketamine mainly affects a brain chemical called glutamate, which helps nerve cells communicate with each other. Glutamate plays an important role in learning, memory, mood, and the brain’s ability to form and strengthen connections.
Spravato blocks certain glutamate receptors, or receiving sites, called N-methyl-D-aspartate (NMDA) receptors. Researchers believe this sets off a chain reaction that changes how glutamate signals travel between brain cells.
One part of this process appears to increase activity at another type of glutamate receptor called the AMPA receptor. In simpler terms, blocking one signaling route may encourage activity through another route that helps brain cells communicate and adapt.
Researchers also believe these changes may stimulate substances and processes that support the growth and strengthening of connections between nerve cells. One of these substances is brain-derived neurotrophic factor (BDNF), a protein that helps brain cells survive, develop, and form new connections.
This may be particularly relevant in depression because long-term stress and depression can disrupt communication within brain networks involved in mood, thinking, and emotional responses.
Spravato works relatively quickly
Most traditional antidepressants take several weeks, often longer, to produce their full clinical effects. Esketamine can produce measurable changes much sooner in many patients.
That doesn’t mean everyone feels dramatically better the next day. Response varies, and some people need several treatments before they notice a meaningful change. Still, the possibility of earlier improvement makes Spravato scientifically and clinically distinctive. (For more on timing, read How Long Does It Take Spravato® to Work?)
Spravato isn’t a one-time treatment. Patients who respond usually continue treatment on a structured schedule, with frequency reducing after the initial phase. We assess progress individually and adjust treatment according to your response, side effects, and clinical needs.
Why Spravato requires in-office monitoring
Spravato treatment takes place in a certified health care setting rather than at home because esketamine acts rapidly on the central nervous system. It can cause temporary effects including:
- Dissociation
- Sedation
- Dizziness
- Nausea
- Altered perception
- Increases in blood pressure
The FDA also warns about respiratory depression and the potential for abuse and misuse.
We check relevant health factors before treatment and monitor you afterward until you’re clinically stable.
After Spravato is administered in the form of a nasal spray, you stay with us for at least two hours. You can’t drive yourself home after a session, and you shouldn’t drive or operate machinery until the next day after a restful sleep.
A different route through depression
Treatment resistance doesn’t mean every antidepressant pathway has failed, but it may mean we need to approach depression treatment through a different biological system.
Spravato gives us a way to target glutamate signaling and neural plasticity rather than relying solely on traditional monoamine pathways. Since January 2025, the FDA has approved Spravato for TRD either as a standalone treatment or alongside an oral antidepressant, giving us more flexibility when developing treatment plans.
If depression continues despite trying several antidepressants, contact Labyrinth Psychiatry Group to learn whether Spravato therapy could help you. Call our Cranford or Edison, New Jersey, office today at 908-336-1187, or learn more by completing our online form.