Medically reviewed by Peter Scheid, MD
Medical Director, SILC Health
Clinically reviewed by Christina Kayanan, LMFT, LPCC
Clinical Director, Mental Health Services — SILC Health
Last reviewed: June 16, 2026
If you've tried antidepressant after antidepressant and still wake up feeling like you're moving through concrete, you're not broken and you haven't failed. Depression is one of the most complex conditions medicine knows, and the truth is that the treatments we've relied on for decades simply don't work for everyone. Ketamine therapy has emerged as one of the most significant shifts in depression care in a generation — and if you're here because you're wondering whether it might help you or someone you love, that curiosity is worth following. This post will explain, in plain language, how ketamine works in the brain, who tends to benefit most, what a treatment session actually looks like, and what questions to ask before you start.
Why Ketamine Is Different From Every Antidepressant You've Tried
Almost every traditional antidepressant — SSRIs (selective serotonin reuptake inhibitors, meaning medications that help more serotonin stay active between nerve cells), SNRIs, MAOIs — works by adjusting the serotonin or norepinephrine systems in your brain. That's not a small thing, and for many people those medications are life-changing. But they share one significant limitation: they take weeks to kick in and they don't help everyone. Ketamine works on an entirely different system. It targets glutamate (the brain's main 'go' signal, its most abundant excitatory chemical), specifically blocking a receptor called NMDA (N-methyl-D-aspartate, a switch on nerve cells that controls learning and mood). By temporarily blocking that switch, ketamine triggers a rapid surge of glutamate activity, which in turn stimulates the growth of new synaptic connections — the tiny bridges between nerve cells that depression literally erodes over time. That regrowth, researchers believe, is what produces the fast relief many patients report, sometimes within hours of a single infusion.
What Is Treatment-Resistant Depression, and Who Qualifies?
Ketamine therapy is most often discussed in the context of treatment-resistant depression, or TRD (depression that has not responded to at least two adequate trials of different antidepressant medications at the right dose for the right amount of time). TRD affects roughly one-third of people diagnosed with major depressive disorder, according to data cited by the National Institute of Mental Health. That is not a small number — that's millions of people in the United States who have done everything their doctors asked and still can't find consistent relief. Ketamine has also shown promise for bipolar depression, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and severe suicidal ideation (active, urgent thoughts of ending one's life) when rapid intervention is critical. A psychiatrist or licensed prescriber will evaluate your full history before recommending ketamine — including prior medications, any substance use history, cardiovascular health, and current medications.
The Two FDA-Cleared Forms of Ketamine for Depression
There are currently two forms of ketamine used clinically for depression in the United States, and they are meaningfully different from each other. The FDA (the U.S. Food and Drug Administration, the federal agency that approves medications for safety and effectiveness) approved esketamine (brand name Spravato) as a nasal spray in 2019 — the first truly new class of antidepressant the FDA had approved in decades. Spravato is administered in a certified healthcare setting, where you stay for at least two hours of monitoring after each dose. It is approved specifically for treatment-resistant depression and for major depressive disorder with acute suicidal ideation. IV ketamine infusions, by contrast, use racemic ketamine (a form of the drug that has been used safely in medicine as an anesthetic since the 1970s) and are considered an off-label use — meaning a prescriber can legally offer it, but the FDA has not formally evaluated it for this specific purpose the way it has Spravato. Both forms are real, used widely, and supported by a growing body of clinical research.
What Actually Happens During a Ketamine Session
Knowing what to expect reduces a lot of anxiety around starting something new. Here is what a typical IV ketamine infusion experience looks like in most clinical settings.
- Intake and medical screening: A prescriber reviews your health history, current medications, and mental health diagnosis. You'll discuss goals, risks, and what the dissociative effect — a temporary feeling of being detached from your body or surroundings — may feel like.
- IV placement: A nurse places a small intravenous line, usually in the arm. The medication is delivered slowly over 40 to 60 minutes at a carefully calculated dose — far lower than the anesthetic doses used in surgery.
- The infusion experience: Many people describe a dreamlike, floaty state. Perceptions of time and space may shift. Music, an eye mask, and a reclining chair are common features in ketamine clinics designed to support a calm, inward experience. A provider is present throughout.
- Recovery period: The dissociative effects resolve within 15 to 30 minutes after the infusion ends. You'll rest in the clinic until staff confirm you're stable. You cannot drive yourself home — plan for a trusted person to pick you up.
- Post-session integration: Many clinics offer psychotherapy alongside infusions. Integration therapy (the process of making meaning from the ketamine experience to support lasting change) is increasingly recognized as an important part of sustained benefit.
How Many Sessions Does It Take?
The most common IV ketamine protocol for depression is a series of six infusions delivered over two to three weeks. Most people who respond to ketamine begin noticing a shift somewhere between the second and fourth infusions. After the initial series, maintenance infusions (ongoing periodic treatments, often monthly, to sustain the effect) may be recommended depending on how long the relief lasts. Spravato (esketamine nasal spray) follows a different schedule: twice weekly for four weeks, then weekly for four weeks, then every one to two weeks after that. Neither path is a lifetime commitment that's set in stone — your provider adjusts the plan based on how you're responding. The honest reality is that some people experience dramatic, lasting relief; others notice a partial improvement; and a portion of people do not respond. A good provider will walk you through the realistic range of outcomes before you begin.
Does Ketamine Therapy Interact With Other Treatments?
Ketamine therapy is typically used as part of a broader mental health treatment plan — not as a standalone cure. Evidence strongly supports combining ketamine with psychotherapy, particularly CBT (cognitive behavioral therapy, a skills-based approach to reshaping unhelpful thought patterns), DBT (dialectical behavior therapy, a skills-based approach combining acceptance and change strategies), or trauma-focused modalities like EMDR (Eye Movement Desensitization and Reprocessing, a structured therapy that helps the brain reprocess distressing memories). The window of neuroplasticity (heightened brain flexibility and openness to change) that ketamine opens in the days after an infusion may make psychotherapy more effective during that period — which is a compelling reason to have both running at the same time. At SILC Health and through our network of trusted partners, our clinical teams can help coordinate care that makes sense for the full picture of where you are right now.
Understanding the Risks: What Ketamine Therapy Is Not
Ketamine has a legitimate recreational misuse history, and it would be dishonest to skip past that. At clinical doses used in controlled settings, the risk profile is very different from recreational use — but it is not zero, and a responsible provider will be transparent about that. Known risks and considerations include: temporary increases in blood pressure and heart rate during infusion, which is why cardiovascular screening matters; psychological distress during the dissociative phase, which is why a supportive setting and screened providers matter; and the potential for psychological dependence (a pattern of craving the experience or the relief it brings) in people with certain histories. This is one reason ketamine therapy requires a careful evaluation of any substance use history. If you or someone you love has a history of substance use disorder, that doesn't automatically disqualify you — but it is a critical piece of information your provider needs. SAMHSA (the Substance Abuse and Mental Health Services Administration, the federal agency overseeing behavioral health) recognizes the importance of integrated care that addresses both mental health and substance use simultaneously.
- Ketamine is not a long-term standalone medication — maintenance planning is part of good care.
- It is not appropriate for people with certain conditions, including uncontrolled hypertension, active psychosis, or a history of ketamine or PCP misuse without careful evaluation.
- It is not a replacement for psychotherapy — the evidence supports combining both.
- It is not covered by all insurance plans, and out-of-pocket cost can be significant; our admissions team can help you understand your coverage options.
- It is not available without a formal psychiatric evaluation and prescriber oversight.
Ketamine Therapy and Co-Occurring Conditions
Depression rarely travels alone. It frequently co-occurs with anxiety disorders, PTSD, substance use disorders, chronic pain conditions, and eating disorders. The presence of co-occurring conditions (two or more diagnoses happening at the same time, also called a dual diagnosis) doesn't make ketamine off the table — but it does make comprehensive assessment more important, not less. ASAM (the American Society of Addiction Medicine, a national professional organization that sets clinical standards for addiction and co-occurring care) emphasizes that co-occurring mental health and substance use conditions should be treated together, not sequentially. At the ASAM levels of care (a national clinical scale that matches treatment intensity to need), from outpatient to residential, an integrated approach yields better outcomes than treating one condition while ignoring the other. Our clinical team can help you figure out what level of care actually fits your situation — whether that's an outpatient program, intensive outpatient (IOP, a structured program of 9+ hours of treatment per week), or a higher level of residential support through programs like One Path Mental Health or others in our network.
How to Have the Conversation With Your Doctor — Or With Us
Not every primary care doctor or general psychiatrist is familiar with the details of ketamine therapy, and some are cautious about it — which is fair given how new the formal evidence base is. If you want to bring it up with your current provider, a few things help: come with the name of the FDA-approved treatment (Spravato/esketamine) as a starting point, ask specifically about treatment-resistant depression criteria, and ask for a referral to a psychiatrist who has experience with ketamine or esketamine. If navigating that feels overwhelming, or if you don't have an existing provider, that's where we come in. SILC Health's admissions team can help you understand your options, verify your insurance coverage, and connect you with the right level of care — whether that's a ketamine consultation, a comprehensive mental health program, or both. You don't have to have it all figured out before you call.
Your Next Step Doesn't Have to Be a Big One
You've probably spent a lot of energy managing depression — tracking symptoms, trying medications, pushing through days that didn't feel livable. The idea of starting something new can feel exhausting on top of exhausted. We understand that. The only step we're asking you to consider right now is a conversation. Call (844) 422-8640 and talk to someone who can listen without judgment, answer your questions about ketamine therapy and other treatment options, and help you figure out what makes sense for your life. If you'd rather start online, our admissions and insurance pages are there for you. Bring a family member or trusted friend to that first call if it helps — that's not a sign of weakness, it's just good sense. Whatever depression has been telling you about your chances of feeling better, we'd like the opportunity to tell you a different story — one backed by science, and by the people we've had the privilege of walking alongside.