As someone with TRD who recently tried ketamine therapy for herself, trust me when I say there’s a lot of info to digest and consider before you dive into treatment. Ahead, discover what experts want you to know about using ketamine for depression—including what it can and can’t do, and how to discern if it could be right for you.
5 important FYIs about ketamine for depression
1. It works differently from common treatments for depression
Ketamine is still in its relative infancy as a treatment for depression, and the precise biochemical mechanism leading to its efficacy has yet to be confirmed. One hypothesis is that ketamine may enhance neuroplasticity, or the brain’s ability to change and adapt, which could mediate or even reverse depression. Another is that it increases the availability of glutamate, a key neurotransmitter, says Steve Yun, MD, an anesthesiologist and the medical director of Kure Medical Group, a ketamine infusion clinic in Santa Monica, California. This “master neurotransmitter” is important for cognition, memory, and mood regulation, and mounting evidence shows that getting a sudden surge of it in the brain is likely associated with rapid relief from depressive symptoms.
“In contrast, traditional antidepressants work by increasing the supply of a different neurotransmitter: serotonin,” Dr. Yun says. Consistent intake of antidepressant SSRIs are necessary for them to work—and it can take weeks or months to feel their effects. In contrast, ketamine can provide discernible relief upon the first administration and doesn’t require long-term, daily use.
Electroconvulsive therapy (ECT), another treatment for severe depression and bipolar disorder, works by inducing seizures that may “‘reset’ the brain and relieve depressive symptoms,” Dr. Yun explains. Yet a 2023 study found that subanesthetic intravenous ketamine was at least as effective as ECT, while avoiding ECT’s potential risks like memory loss and pain.
2. Different forms of ketamine treatment are available
Medicinal ketamine can be administered in different forms, including via nasal spray, infusion (IV), intramuscular (IM) shot, and ingestibles. The “S” form of ketamine via nasal spray—known as esketamine, or by the brand name Spravato—is the only FDA-approved form of ketamine administration for TRD, though the other forms are permitted for off-label use. Dr. Yun, whose clinic administers ketamine via infusion, believes infusion to be the most reliable method of ketamine administration, and says it has the most robust evidence behind it to date.
“A nasal ketamine spray should work in theory because there usually is good absorption of the drug via the nasal mucosa,” he says, “but it is very dependent on the practitioner’s technique, [and the] patient’s ability to cooperate. And the nasal spray is prohibitively expensive.” (Though Spravato is covered by some insurances.)
At-home, self-administered ketamine treatments are also available, but they’re not recommended by the American Psychiatric Association Council of Research Task Force on Novel Biomarkers and Treatments, since the drug could raise someone’s heart rate and blood pressure to concerning levels, and potentially cause psychoactive effects for up to two hours. Ketamine also has a history of being a drug people abuse (known as “special K”).
3. It’s most suitable for specific mental health conditions
Ketamine therapy is ideal for people with TRD, meaning they’ve been unable to respond well or achieve remission after being treated with two or more medications. “There is growing scientific evidence that ketamine therapy can effectively relieve symptoms in these severe cases,” Dr. Yun says. In addition to its promise to treat major depressive disorder, ketamine infusion can elicit positive outcomes for anxiety and obsessive-compulsive disorder (OCD). It may also be beneficial for those with treatment-resistant bipolar disorder, though more evidence via stronger studies is needed.
However, Dr. Yun warns that people with a history of psychosis should avoid ketamine therapy, since the treatment may exacerbate symptoms given its dissociative effects. (In people without psychosis, these same effects can actually be beneficial—altering consciousness and perceptions of themselves and their environment can yield antidepressant effects.)
4. It’ll likely require an investment of time and money
Most ketamine treatments for depression are for off-label use, and in many cases, insurance won’t cover the treatment. Even FDA-approved esketamine may not be covered, depending on the insurance you have.
Of course, it doesn’t hurt to consult potential providers and your insurance company to see what options are available, but know that treatments can be costly. (Per my own handful of consultations for ketamine infusions in Los Angeles, prices ranged from $350 to $750 a session, with six sessions often recommended based on clinical trials.) Moreover, you may wish to work alongside a therapist who specializes in ketamine integration—i.e., unpacking any visions or breakthroughs you experience during treatment and learning how to apply them going forward—which can take a bigger hit on your wallet.
If you do decide to undergo treatment, it’s also important to get in the right headspace before and after treatment. While you technically can work your normal 9-to-5 before and potentially after a ketamine session, providers typically advise avoiding stimulation and prioritizing calming activities—like meditating, journaling, and spending time in nature—the evening before and the day of treatment. It may be in your best interest to take time off work and hit pause on other obligations, so be sure to factor that into your plans accordingly.
5. Ketamine isn’t a cure-all
While ketamine continues to show promise to alleviate TRD both immediately and in the long run, it’s important to manage expectations. “Patient response is highly variable and it is difficult to make generalizations,” Dr. Yun says. “Broadly speaking, the majority of patients will experience significant relief from their symptoms in the short term, [but] long-term efficacy is more unpredictable.”
During a single ketamine treatment, you may experience things like less rumination, positive visualizations, pain relief, and a sense of calm or even euphoria. (At the same time, less favorable experiences can include nausea, dizziness, and fear—though most of these side effects are typically mild.) In the best case scenario, continued treatment may yield complete remission from depression, but this is far from guaranteed.
“At Kure, we do not make any false promises that ketamine therapy will be a miracle cure and completely and permanently eliminate all depressive symptoms,” Dr. Yun says. He recommends that patients still keep up with their current therapies—whether medicinal, psychological, or both—under the guidance of a trusted healthcare professional. “But for those patients who have failed traditional antidepressant therapy, ketamine is a viable alternative that can provide significant relief.”