Can ketamine infusion therapy help with depression, trauma, and pain?
For some patients, yes, and the honest answer has more conditions attached to it than most ketamine clinic websites will tell you. Ketamine is an anesthetic that, at doses well below those used for surgery, can lift depression quickly in people for whom several antidepressants have not worked. It can also quiet certain kinds of chronic pain.
Much of the practical side of what follows comes from my interview with anesthesiologist Steven Reichbach, M.D., of the Reichbach Center, on The Rehab Podcast. He had worked with ketamine for three decades by the time we spoke, in the operating room and then for complex regional pain syndrome and depression. The rest comes from the two U.S. Food and Drug Administration (FDA) labels that govern the drug.
So, how good is ketamine, really, for the depression and pain that trauma leaves behind and that have outlasted every pill? Which form is safe to take at home? Will your insurance pay for any of it? And, what should you ask before you let anyone put it in your arm or under your tongue?
Ketamine is an anesthetic first, and everything else is off-label.
The FDA label for Ketalar, the brand name for ketamine injection, lists exactly one job: anesthesia for surgery and diagnostic procedures. Nothing on that label says depression, pain, or post-traumatic stress disorder (PTSD). Every infusion clinic in the country is using the drug off-label, which is legal and common, but worth knowing.
There is one exception. Spravato, or esketamine, is one of the two mirror-image forms of the ketamine molecule made into a nasal spray. Its label covers treatment-resistant depression in adults, on its own or with an oral antidepressant, and depressive symptoms in adults with major depression and acute suicidal thinking or behavior. That is the whole list.
Is PTSD on either label? No. While clinics advertise ketamine for PTSD, and some patients with PTSD do improve, the evidence is early and mixed, and in my opinion it belongs in the investigational column rather than the established one.
Of course, off-label does not mean wrong. It means the burden of judgment sits with your doctor, and with you.
How does ketamine work on the brain?
Nearly every antidepressant you have heard of works on serotonin, norepinephrine, or dopamine. Ketamine does not. It blocks the N-methyl-D-aspartate receptor, or NMDA receptor, a receptor for glutamate, the brain’s main excitatory messenger.
What happens after that is where the certainty ends. In fact, the Spravato label states plainly that the mechanism by which esketamine treats depression is unknown. One theory is that the sudden change in glutamate signaling sets off a burst of growth in dendrites, the branches that neurons use to connect with each other, and in the synapses between them.
That is neuroplasticity, or new wiring between existing brain cells, and not neurogenesis, the word some ketamine pages use, including older ones on this site, because neurogenesis means new cells. Ketamine replaces nothing, and it may help the brain reconnect.
Dr. Reichbach made the point that stuck with me most. Patients come in expecting a psychedelic trip, and the dissociation of an infusion has some of that flavor, yet the experience is not the treatment. The treatment is what happens on a microscopic level in the days after, when the dendrites grow.
Is ketamine addictive? Does ketamine cause physical dependence?
An earlier version of this article said that ketamine is not addictive and does not cause dependence. That was wrong, and it is corrected here. The Ketalar label lists ketamine as a Schedule III controlled substance and reports tolerance and physical dependence with prolonged use, with withdrawal symptoms after stopping frequent, large doses.
Physical dependence is not addiction. Dependence is the body adapting to a drug so that stopping it produces symptoms, and it can happen to anyone who takes a regular dose of a drug that does this.
Addiction is a pattern of compulsive use despite harm. A monitored clinic dose a few times a month rarely leads there, yet the label warns that a person with a history of addiction may be at greater risk.
Unfortunately, the bigger risk is quieter. The same label ties long-term use to bladder damage, including cystitis and reduced bladder capacity, and reports liver and bile duct injury with recurrent use, where it names “medically supervised unapproved indications” alongside misuse. That phrase is about ketamine clinics, and it belongs in any first conversation with one.
Chronic pain and depression seem to travel together.
Pain doctors like to say that pain is in the brain, and they do not mean it dismissively. Chronic pain is a maladaptive response of the central nervous system to an injury that may have healed years ago. The alarm keeps ringing after the fire is out.
Interestingly, Dr. Reichbach pointed out that the patients who respond to ketamine for pain often carry a chronic depression, and the two seem to improve together. He has watched chronic pain patients reduce their opioid pain medication, or stop it, after a series of infusions, and that is a real benefit.
Yet, a drug that is safer than the one it replaces is not the same as a drug that is safe. No drug that produces tolerance should be started without a plan for how it ends.
Is that one disease or two that share a mechanism? I do not know, and neither does anyone else yet. A person with both should not expect an infusion to sort out which one it is treating.
Can patients take ketamine at home?
Not the infusion. Dr. Reichbach is an anesthesiologist, and while the doses delivered through an intravenous line, or IV, at a clinic are below a surgical dose, they are an anesthetic drug given the way an anesthetic is given. They are not safe for unsupervised home use, and the Ketalar label tells patients not to drive, operate machinery, or do anything hazardous for 24 hours after the drug.
That is why a ketamine clinic will insist that someone drive you home and that you take the rest of the day off. The instructions are the ones you get after a colonoscopy, because you have had an anesthetic drug.
Fortunately, there is a form of ketamine that can be used at home. A compounding pharmacy can prepare a troche, or lozenge, that dissolves under the tongue at a small fraction of an infusion dose. The dose is set by the prescriber for the individual patient, and a number on a website is not a prescription, so none appears here.
Dr. Reichbach does prescribe troches for some patients, because he sees benefit from small daily doses in the right person. Still, daily use of any ketamine product is the pattern that produces tolerance and, over years, bladder trouble. Home use needs a prescriber who is watching for both.
What should you expect after a ketamine session?
Expect to feel strange for an hour or two. Dissociation, the sense of being detached from your body or the room, is the most common effect, and the Spravato label reports it in most patients. Blood pressure rises during a session, which is why clinics check it before and after, and why the same label requires at least two hours of monitoring.
The rest of the day is a loss. No driving until the next day after a full night’s sleep, some nausea, some fatigue, and a wobbly, dreamy feeling that fades by evening. While some patients notice a lift in mood within a day or two, others notice nothing until several sessions in, and some never do.
Expect the effect to wear off. Patients commonly describe the benefit of a series of infusions fading over weeks to months, and clinics offer boosters for that reason.
Spravato’s own label builds this in, with twice-weekly sessions for the first month, weekly for the second, and then weekly or every other week for as long as the benefit holds. So, plan on a course of treatment rather than a cure.
Ketamine without psychotherapy has no direction.
The most important thing Dr. Reichbach said in our interview was about therapy, not ketamine. He is an anesthesiologist, not a psychiatrist or a psychologist, and he tells his patients to be in psychotherapy during the weeks they are receiving infusions.
The analogy I used with him was a computer, and while it is not a perfect analogy, it holds up well. Ketamine works on the hardware, on the wiring between the cells. Therapy works on the software, on what the patient does with the new connections.
New wiring with no new program runs the old program faster. A clinic that infuses you six times and hands you a receipt has done half of a treatment.
So, ask, before you start, who is doing the other half. Integration therapy, or talking through what came up during a session with a trained therapist, is the usual name for it. It is not an extra. It is the treatment.
Does ketamine help borderline personality disorder?
This question gets searched often, and it deserves a careful answer. Borderline personality disorder, or BPD, comes with a great deal of depression, unstable mood, and, for many patients, persistent suicidal thinking. In my experience, antidepressants alone do little for it, and while the psychotherapies that help BPD do help, they take years.
Because ketamine acts quickly on depressive symptoms, some clinicians have tried it in patients with BPD who also have major depression or acute suicidality. The evidence for this is early and small. No ketamine product is approved for BPD, and any page that calls it proven, and some have, is ahead of the evidence.
The Spravato label is careful here too. It is approved for depressive symptoms in patients with acute suicidal thinking, and in the same section it says that its effectiveness in preventing suicide or in reducing suicidal thinking itself has not been demonstrated. Ketamine may lift the depression that feeds the suicidal thinking. It is not, by itself, suicide prevention.
If you have BPD and depression and are considering ketamine, the honest framing is an adjunct to dialectical behavior therapy or another established therapy, in a clinic that monitors you closely, with a therapist who already knows you. It is not a replacement for any of that.
If you are having thoughts of suicide right now, call or text 988, the Suicide & Crisis Lifeline, at any hour. Call 911 or go to the nearest emergency room if:
- you have a plan to end your life, or have already taken steps toward one
- you have taken more of any drug than prescribed, or mixed drugs, and feel unwell
- you cannot keep yourself safe until you can reach your doctor or therapist
Is ketamine covered by health insurance?
Yes and no, and the split follows the FDA label rather than the evidence. Insurers generally cover treatments for the conditions a drug is approved for. Spravato is approved for treatment-resistant depression, meaning depression that has not responded adequately to previous antidepressants, so many plans cover it once that history is documented.
Racemic ketamine, the mixture of both forms of the molecule that is given by IV, is approved only for anesthesia. So, its use for depression is off-label, and most insurance plans do not pay for the infusions. Ask the clinic what it bills and what you will owe before your first appointment, not after.
Should coverage decide your treatment for you? No. While Spravato is given on a fixed schedule in a certified clinic with two hours of monitoring each time, and IV ketamine lets the doctor adjust the dose more finely, both require a driver, both cause dissociation, and both need psychotherapy alongside them.
Insurance follows the label. Your doctor should follow you.
Which questions should you ask before your first session?
Ask who is prescribing, who is monitoring, and whether a physician is in the building during your infusion, and then ask what the plan is for psychotherapy, how many sessions are planned, what happens if the benefit fades, and how the clinic screens for bladder symptoms in patients who continue for months.
Above all, ask what the exit looks like, because a good ketamine doctor can tell you when you will stop and what the plan is if the depression returns. A clinic that answers every one of those questions with another package price is a store, not a practice.
Fortunately, the drug itself has been in operating rooms for more than fifty years, is legal, and is given every day under clear protocols, which is more than can be said for most of what gets called psychedelic medicine.
With the right doctor, the right therapist, and a realistic expectation, ketamine can move a depression that nothing else has moved. The questions above are how you find out, before you pay, whether you have found them.
I do not run an infusion clinic. My practice is a telemedicine deprescribing practice in Florida, built around helping patients taper off of benzodiazepines, Z-drugs, and psychiatric medications, and I approach ketamine the way I approach every medication: as a tool with a purpose, a dose set for the individual, and a plan for how it ends.
For patients who want an independent opinion on whether a clinic infusion or low-dose ketamine at home fits their situation, I offer a ketamine consultation that is separate from any clinic selling the treatment.
If you would like to talk it through, contact Dr. Leeds through the contact form to ask whether a consultation makes sense for you.
This article is educational. It is not medical advice, and reading it does not create a doctor-patient relationship. Decisions about starting, continuing, or tapering any medication should be made with your own physician.
