Anesthesiologist-Led Ketamine Infusion Therapy

RESTORE ketamine infusion therapy

RESTORE is a structured course of ketamine infusion therapy for depression and bipolar depression, anxiety, post-traumatic stress disorder, and chronic nerve pain that has not responded to other treatment. We also treat fibromyalgia, complex regional pain syndrome, and burnout syndrome. It was developed at this institute over many years of treating these conditions, and it is deliberately not the way ketamine is usually given.

Ketamine is approved by the FDA as an anesthetic. Using it for depression or chronic pain is off-label, which means the FDA has not evaluated it for those uses. That is true of every ketamine clinic in the country, and it is worth knowing before you begin.

Two reinforcement infusions follow at two to three months, and then we reassess you formally. Most people who are still doing well need one infusion once or twice a year after that.

Why patients travel here

There are well over a thousand places in this country offering ketamine infusions. Four things separate what happens here.

If there is a good program near you, use it. These are the reasons people fly to Sarasota instead.

Ketamine is an anesthetic, and an anesthesiologist gives it

Most ketamine clinics are run by psychiatrists, emergency physicians or nurse practitioners — all capable clinicians. Anesthesiology is the specialty that has been giving this drug since 1970, and whose daily work is managing breathing, sedation and blood pressure while someone is under. The physician who treats you here spent his career in it. That difference is invisible on a good day. It is the whole difference on a bad one.

Your dose is worked out from your blood, not from the scale

Nearly every clinic gives half a milligram of ketamine for each kilogram you weigh. But ketamine dissolves into body fat rather than staying in the bloodstream, so two people who weigh the same and are built differently end up with different amounts reaching the brain from an identical dose. We calculate the concentration your blood should reach, and deliver the infusion in a way that gets there and holds it.

We test you first, and we correct what we find

A full metabolic and hormonal work-up before we accept you — thyroid, hormones, vitamins, magnesium, carnitine. Low levels of some of these are associated in the literature with a poor response to antidepressant treatment. Where yours are low we correct them first, rather than treating you and hoping. Where that step is skipped, a course of treatment can fail for a reason that was knowable in advance.

We will tell you if this is not right for you

Every condition that rules someone out is listed openly on this site, and you will hear about any that apply to you on the first call — before you travel, and before you pay anything. We do not treat anyone without reviewing their records first, and we do not prescribe take-home ketamine in any form. If we do not believe you are likely to benefit, we will tell you so and explain why.

Why nobody else does this

The dose almost every clinic uses was never designed to treat depression.

That ketamine relieves depression is not in dispute. It has been shown repeatedly over twenty-five years, and for people who have not responded to anything else it is one of the more important findings in modern psychiatry. None of what follows questions any of that.

What almost nobody examines is the dose. Nearly every clinic in the country gives the same one — half a milligram of ketamine for each kilogram you weigh, infused over forty minutes — and treats it as settled. It is worth knowing where that number actually came from, because it explains a great deal about why results in the real world are so uneven.

It comes from a 1994 study at Yale by Krystal and colleagues — a study of glutamate and schizophrenia, not of mood. They needed a particular concentration of ketamine in the blood, and measuring it in every subject was expensive and technically difficult. So they used a practical shortcut: half a milligram per kilogram of body weight, over forty minutes.

Six years later Berman took that same dose and that same timing and showed, in Biological Psychiatry, that it relieved depression. Zarate replicated it in 2006. Neither study revisited the dose — there was no reason to. It was the dose that had worked in the paper before.

Then in 2013 Murrough showed the effect had to be repeated to hold: six infusions over two weeks, on a schedule lifted from electroconvulsive therapy. That became the default, and it is still what most clinics do today.

Clinics are aware of this. A survey found that most begin at half a milligram per kilogram, but the great majority change the dose during a course of treatment, across a range running to six times the starting figure [4]. The number was meant to be a place to start. It is not always treated as one.

I was a faculty member in the department of anesthesiology at Yale that the psychiatrists came to for that infusion protocol. It was a sound approximation for a research question in 1994. Thirty years later it is still being used as a treatment plan.

So the standard of practice traces back through four papers to a number chosen because measuring the real one was inconvenient. Nobody went back to ask what would happen if you modeled the concentration and held it there instead, and corrected the things that change it. Answering that took seven years.

Krystal JH et al. Arch Gen Psychiatry 1994;51(3):199–214 · Berman RM et al. Biol Psychiatry 2000;47(4):351–354 · Zarate CA Jr et al. Arch Gen Psychiatry 2006;63(8):856–864 · Murrough JW et al. Biol Psychiatry 2013;74(4):250–256.

1962

Ketamine is developed by Parke-Davis as an anesthetic. FDA-approved for children and adults in 1970.

1994

Krystal, Yale. A study of glutamate and schizophrenia needs a specific blood concentration of ketamine. Measuring it in every subject is expensive, so half a milligram per kilogram over forty minutes is adopted as a practical stand-in.

2000

Berman, Biological Psychiatry. The same dose and the same timing are given to patients with treatment-resistant depression. Their symptoms lift within hours.

2006

Zarate replicates it. The dose is not revisited — it is the dose that worked in the paper before.

2013

Murrough. The effect has to be repeated to hold: six infusions over two weeks, on a schedule borrowed from electroconvulsive therapy. This becomes the default.

Since

Seven years of clinical investigation into what concentration, held for how long, and which metabolic and genetic factors change the answer. That work became RESTORE.

Five things decide whether a ketamine infusion works for you. Your weight is the weakest of them.

If a course of ketamine has already failed you somewhere else, the reason is usually on this list. It is worth knowing which of them were checked.

How fast you break it down

Livers clear ketamine at rates that differ several times over from one person to the next. If you clear it quickly, a standard dose may never reach the level in your blood where it does anything at all. Nobody would find out, because nobody measured. You would simply be told that ketamine does not work for you.

Whether your brain can use it

A handful of inherited variations change the response, and one of them — a gene called BDNF — is associated with not responding at all. A simple test can show it. We would rather learn that before you spend three days here than after.

Where the drug actually goes

Ketamine dissolves into body fat rather than staying in the blood. Two people of the same weight, built differently, given the identical dose: one may get more than they needed and have a hard afternoon, the other may get too little and feel almost nothing. Same prescription, opposite experiences.

What you are already taking

Some common psychiatric medications blunt the effect. Lamotrigine is the one we see most often, and higher-dose benzodiazepines reduce it too [6]. If nobody reviews your medication list beforehand, a course of treatment can fail for a reason that was knowable in advance.

Who is in the room with you

Ketamine produces a real psychological experience, not only a chemical one, and how that hour goes affects what you take away from it. Published surveys of community ketamine practice report wide variation in how these treatments are dosed and supervised. Whether the person beside you can tell an ordinary reaction from one that needs attention changes both how the session feels and how safe it is.

The difference, in one picture

A weight-based dose overshoots, then leaves you short.

Your weight is not what decides how much ketamine ends up in your bloodstream. Ketamine dissolves readily into body fat, so of two people who weigh the same, the one carrying more fat has more of the drug pulled out of circulation and less of it reaching the brain. Livers then clear it at speeds that differ several times over from one person to the next.

So the same prescription lands differently in different people. Overshoot and the concentration climbs above the useful range — which is where the experience turns unpleasant, and where blood pressure and heart rate rise. Undershoot and it never arrives there at all: the session passes uneventfully and very little changes afterward. Both are the same error in opposite directions, and neither is visible to anyone who is not aiming at a number.

How this is done

Seven stages. Four of them happen before you are anywhere near an IV.

This is the part that takes the time, and it is the part that decides the result. A standard infusion has one stage: give the drug.

Evaluation

We read everything before we decide anything

The complete record comes first — every medication trial, every prior treatment, what the side effects were and why things were stopped. If a course of ketamine has already failed you somewhere, we want its details. This is not a formality. A great deal of what will determine your response is already in that history.

Selection

We decide whether to treat you at all

Some conditions make ketamine unsafe, and one genetic variant makes it unlikely to work. Both are settled before you book travel or pay anything. Declining people we do not think we can help is the least commercial thing we do and the most important.

Optimization

We correct what the bloodwork finds, then treat

A full metabolic and hormonal work-up before treatment: complete blood count and metabolic profile, hsCRP, thyroid, estradiol and FSH/LH or testosterone by LC/MS, vitamin D, B12 and folate with homocysteine and methylmalonic acid, RBC magnesium and acetyl-L-carnitine. Where something on that list comes back low, we correct it first and then treat, rather than treating around it.

Target concentration

We work out the number the infusion is built to reach

Rather than calculating a milligram dose from your weight, we model the concentration your blood should reach and hold — from your body composition, how fast you clear the drug, and what else you are taking. That number, not your weight, is what the infusion aims at. In complex cases a pharmacogenomic panel informs it, but only where the result would change what we do.

Delivery and observation

One patient, one physician, the whole infusion

The infusion runs in three stages at variable rates rather than one constant rate, which reaches the target sooner and holds it there. One patient at a time. The physician who set your dose gives it and stays for the whole of it, watching heart rate and heart rate variability, blood pressure, ECG and oxygen saturation — an anesthesiologist doing what anesthesiologists do.

Adjustment and refinement

Each day is set from the day before

The infusion is adjusted while it runs, in response to what is actually happening rather than to a preset. And each day is set from the one before: Thursday informs Friday, Friday informs Saturday. Three infusions given to an identical plan would be three separate appointments. Refining each one from the last is what makes them a course of treatment.

Follow-up and measurement

What happens afterward is measured, not remembered

You continue with the RESTORE supplement after the course, which is included in your fee, and complete the same symptom scales you filled in beforehand — so the result is measured rather than recalled. We send those results to your psychiatrist or prescriber, which we would generally prefer to do.

Our results

We publish the number that makes us look worse. It is the one we would want to be judged on.

Eighty-seven patients treated here for treatment-resistant depression between 2017 and 2022, scored on the Beck Depression Inventory-II. Nine of them did not finish the course. Whether you count those nine changes the figures a great deal, so here are both.

Counting everyone who started — all 87

79%responded — 69 of 87

51%reached remission — 44 of 87

This is the pair to judge us on.

Counting only those who finished — 78 of 87

88.4%responded

56.3%reached remission

The figure most clinics would quote.

The average time between finishing the course and needing a further infusion was 245 days — about eight months. What this is not: a retrospective review of one practice — ours. No control group, no blinding, no independent adjudication, and patients were selected by us for treatment. It has been presented at medical meetings, which is a considerably lower bar than peer review, and it has not been replicated by anyone else. Read it as a description of what happened to our patients, not as a prediction of what will happen to you. How to read these numbers →

Before you spend anything

Not everyone should have this treatment.

Some conditions make ketamine unsafe, and one genetic variant makes it unlikely to work. Every one of them is listed openly on this site, and you will hear about any that apply to you on the first call — before you travel, and before you pay anything.

See the full list →

Conditions that rule someone out entirely

Heart and circulation. Rapidly worsening or uncontrolled high blood pressure, or unstable angina. A recent heart attack or stroke. An aneurysm or abnormal blood-vessel formation in the brain. Fibromuscular dysplasia. Narrowing of the aortic valve. Hypertrophic cardiomyopathy. Pulmonary hypertension.
Inherited conditions. Polycystic kidney disease or vascular Ehlers-Danlos syndrome. Multiple endocrine neoplasia type 2. The BDNF met/met variant, which is associated with not responding to ketamine.
Mental health. Psychosis or schizophrenia. Delusional disorder or depersonalization disorder. A substance use disorder that is not in remission.
Pregnancy, IVF treatment, or breastfeeding.
A known allergy to ketamine.

And four things we will not do

We will not treat you if we do not think you are likely to benefit.
We will not treat you without reviewing your records first.
We do not prescribe take-home ketamine in any form — no lozenges, no nasal spray, no oral formulation.
We will not advise you to stop or reduce a psychiatric medication. That is your prescriber’s decision, and we will speak to them directly.

A separate and longer list — blood pressure, thyroid, liver and kidney disease, anticoagulants, benzodiazepines, lamotrigine — does not rule you out. Those change how treatment is planned, and we deal with them before the first infusion rather than during it.

About the Ketamine Research Institute

We do one thing. The Ketamine Research Institute in Sarasota, Florida provides ketamine based infusion therapy and trains clinicians to deliver it. We do not offer other services, and we do not plan to.

Gerald W. Grass, MD, Founder and Medical Director

An anesthesiologist by training, with a career spanning anesthesiology, neurosurgery, pain medicine and emergency medicine. He held a faculty appointment at Yale School of Medicine in anesthesiology and pain medicine and directed the Yale Pain Medicine Fellowship Program — at the institution where the first controlled trial of ketamine for depression was run.

He first used ketamine clinically in 1989, in his neurosurgical residency, and has worked with it ever since. He began treating private patients in 2006 and has given thousands of ketamine infusions, personally present for the whole of every one.

Before that, in 2005, holding a joint appointment at the Yale Department of Anesthesiology and Pain Medicine and at the VA, where he served as Chief of Pain Management, he began treating veterans returning from Iraq and Afghanistan — people carrying chronic pain, depression and post-traumatic stress at the same time. That work is where RESTORE began.

That range is visible in how the program is built. Aiming at a target blood concentration is a technique from anesthesiology. The concentration targets used for nerve pain come from pain medicine. The airway assessment and sedation monitoring that make it appropriate to give an anesthetic outside an operating room come from the same training.

He has also served as principal investigator on a multicenter randomized controlled trial of a new treatment for postpartum depression. Full background, academic history and publications →

Other physicians come here to learn this approach. Since 2016 the Institute has run an intensive training program in which licensed clinicians travel to Sarasota for classroom instruction and supervised clinical training in a working infusion suite. RESTORE itself is proprietary to this practice and is given only here. What clinicians take away is the KRI Precision Ketamine Infusion — the same principles of measured, individualized dosing, applied in their own practices. About the training program

Research and teaching

Dr. Grass is a published author and lecturer whose work includes peer reviewed articles, abstracts, book chapters, and educational presentations. He has presented his research at regional and national conferences and meetings, and to government agencies including the Veterans Administration and the Department of Defense. In 2016 he founded the Institute’s intensive training program for clinicians, which teaches the precision medicine and targeted infusion methods used here through classroom instruction and supervised clinical training in a working infusion suite.

Working with the physicians who already care for you

Ketamine therapy is one part of your care, not a replacement for it. You keep your psychiatrist, your primary care physician, and any specialist treating your pain. We are not asking you to choose between us and them.

We work with them directly. Before we treat you, we go over your history and every medicine you take with the clinician who prescribes it, because several common medicines change the way ketamine behaves in the body, and that has to be settled before an infusion rather than discovered during one [6] [22]. Through your course of treatment and afterward, your own physicians get what they need from us to make their decisions well: what you were given, how you responded, and what we recommend next. We stay available to them for as long as you are our patient.

This coordination is part of the treatment, not a formality. Ketamine can change how a patient is doing within days rather than months, and the decisions that follow, about your other medicines, your therapy, and how closely you are watched, are made better by physicians who are working from the same information we are.

We do treat patients with active suicidal thinking, but only on the recommendation of their psychiatrist, and only with that psychiatrist continuing to co-manage their care.

Learn more about Dr. Grass For referring clinicians

References

Every clinical statement on this page is referenced below. Where a number appears in the text, it points to the source listed here.

1. Krystal JH, Karper LP, Seibyl JP, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Arch Gen Psychiatry. 1994;51(3):199-214. PMID 8122957.

2. Andrade C. Ketamine for depression, 4: In what dose, at what rate, by what route, for how long, and at what frequency? J Clin Psychiatry. 2017;78(7):e852-e857. PMID 28749092.

3. Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351-354. PMID 10686270.

4. Wilkinson ST, et al. An Update on Community Ketamine Practices. Am J Psychiatry. 2022. PMID 35491568.

5. Abuhelwa AY, Somogyi AA, Loo CK, et al. Population Pharmacokinetics and Pharmacodynamics of the Therapeutic and Adverse Effects of Ketamine in Patients With Treatment-Refractory Depression. Clin Pharmacol Ther. 2022;112(3):720-729. PMID 35560226.

6. Veraart JKE, Smith-Apeldoorn SY, Bakker IM, et al. Pharmacodynamic Interactions Between Ketamine and Psychiatric Medications Used in the Treatment of Depression: A Systematic Review. Int J Neuropsychopharmacol. 2021;24(10):808-831. PMID 34170315.

7. Frye MA, Blier P, Tye SJ. Concomitant benzodiazepine use attenuates ketamine response. J Clin Psychopharmacol. 2015. PMID 25928701.

8. Albott CS, Shiroma PR, Cullen KR, et al. The Antidepressant Effect of Repeat Dose Intravenous Ketamine Is Delayed by Concurrent Benzodiazepine Use. J Clin Psychiatry. 2017;78(3):e308-e309. PMID 28394513.

9. Andrashko V, Novak T, Brunovsky M, et al. The Antidepressant Effect of Ketamine Is Dampened by Concomitant Benzodiazepine Medication. Front Psychiatry. 2020;11:844. PMID 33005153.

10. Williams NR, Heifets BD, Blasey C, et al. Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism. Am J Psychiatry. 2018;175(12):1205-1215. PMID 30153752.

11. Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clin Pharmacokinet. 2016;55(9):1059-1077. PMID 27028535.

12. Hijazi Y, Boulieu R. Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Drug Metab Dispos. 2002;30(7):853-858. PMID 12065445.

13. Li N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329(5994):959-964. PMID 20724638.

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17. Zarate CA Jr, Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63(8):856-864. PMID 16894061.

18. Murrough JW, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. PMID 23982301.

19. KETALAR (ketamine hydrochloride) injection, prescribing information. NDA 016812, initial US approval 1970. US Food and Drug Administration.

20. Anand A, Charney DS, Oren DA, et al. Attenuation of the neuropsychiatric effects of ketamine with lamotrigine. Arch Gen Psychiatry. 2000;57(3):270-276. PMID 10711913.

21. Target-controlled infusion, past, present, and future. J Anaesthesiol Clin Pharmacol. 2024. PMID 39391641.

22. Kornhall D, Nielsen EW. Failure of ketamine anesthesia in a patient with lamotrigine overdose. Case Rep Crit Care. 2014;2014:916360. PMID 25114807.

23. Wilkowska A, Wiglusz MS, Jakuszkowiak-Wojten K, Cubala WJ. Ketamine and Lamotrigine Combination in Psychopharmacology: Systematic Review. Cells. 2022;11(4):645. PMID 35203296.

24. Cunningham MO, Jones RSG. The anticonvulsant lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vitro. Neuropharmacology. 2000;39(11):2139-2146. PMID 10963757.

25. Kim TK. Obesity and anesthetic pharmacology: simulation of target-controlled infusion models of propofol and remifentanil. Korean J Anesthesiol. 2021;74(6):478-487. PMID 34407372.

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800 850 6979

RESTORE — ketamine therapy,
done precisely.

One patient at a time

A physician stays with you

Dosing built around you

Insurance does not cover this