Physician-led ketamine infusion therapy
Are you a candidate for RESTORE?
Not everyone is. Here is how we decide — before you spend anything.
Ketamine is FDA-approved as an anesthetic. It is not FDA-approved for depression, anxiety, PTSD, or chronic pain, and its use for those conditions is off-label. Individual results vary and cannot be predicted in advance.
Who this is for
You may be a candidate if
- You have depression, bipolar depression, anxiety, or PTSD that has not responded adequately to at least two medication trials, or to psychotherapy, rTMS, ECT, or esketamine
- You have chronic neuropathic or nociplastic pain — fibromyalgia, peripheral neuropathy, complex regional pain syndrome — that has not responded to conventional management
- You are under the care of a psychiatrist or prescriber, or are willing to be. We work alongside that person; we do not replace them
- You can arrange three consecutive days, and someone to drive you home after each session
The decision is made in conversation, with your records in front of us.
Absolute
We will not treat you if you have
We will tell you on the phone, before you travel and before you pay anything.
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 — thickened heart muscle
- Pulmonary hypertension
Inherited conditions
- Polycystic kidney disease, or vascular Ehlers-Danlos syndrome (type IV) — both carry a high risk of aneurysm
- Multiple endocrine neoplasia type 2
Mental health and medication
- Psychosis or schizophrenia
- Delusional disorder or depersonalization disorder
- A substance use disorder that is not in remission
Pregnancy
- Pregnancy, IVF treatment, or breastfeeding
Allergy
- A known allergy to ketamine. This is genuinely rare — six cases have been reported and one confirmed
Not disqualifying
Things we work through with you first
These do not rule you out. They change how we plan treatment, and we deal with them before your first infusion rather than discovering them afterward.
Heart and circulation
- High blood pressure that is not well controlled
- A heart attack or stroke further in the past
- Previous surgery inside the skull
- A pituitary tumor, or SIADH
Liver, kidney and blood
- Significant liver disease
- Significant kidney disease
- Taking anticoagulants, or a bleeding disorder
Hormones and metabolism
- Thyroid over- or under-activity that is not well controlled
- Diabetes that is not well controlled
Mental health and medication
- Borderline personality disorder, antisocial personality disorder, or intermittent explosive disorder
- Kratom use (mitragynine)
- A substance use disorder in remission
- Higher-dose benzodiazepines, which reduce the response — timing can sometimes be adjusted, but only with your prescriber
- Current treatment with lamotrigine
Genetics
- A variant of the BDNF gene — val/met or met/met — may change how much ketamine a person needs. Laboratory work shows it blunts the synapse growth ketamine produces; in patients the findings are mixed, and at least one study found the difference narrowed at a higher dose. We test for it where it may matter, and account for it when setting your target concentration
The role of lamotrigine remains a topic of controversy, and the evidence that it blunts the response to ketamine is mixed rather than settled. Our preference is that patients we accept for treatment are not taking lamotrigine at the time of their infusions. That is a decision for the clinician who prescribes it, and we are happy to work with them on it.
The medicine list
Medicines that change how ketamine works
A patient finishes a course of infusions, reports very little benefit, and goes into the record as a non-responder. Sometimes that is the right conclusion. Sometimes the medicine list was not reviewed.
Benzodiazepines are the best documented. The class includes diazepam, lorazepam, clonazepam and alprazolam, and the effect is dose-related.
A systematic review concluded that higher doses can delay the time it takes to respond and can shorten how long the benefit lasts.1 Individual studies point the same way. Benzodiazepine doses were significantly lower in responders than in non-responders in one series.2 Concurrent use lengthened the time to response and shortened the time to relapse in another.3 In a third, a dose above the equivalent of eight milligrams of diazepam predicted a poorer result.4
Lamotrigine is a more complicated case, and worth understanding if you take it. Lamotrigine reduces the release of glutamate, the signaling chemical whose surge follows ketamine’s action at the NMDA receptor.9 There is a striking clinical observation that fits. A patient admitted after a lamotrigine overdose was given 250 milligrams of intravenous ketamine, several times an anesthetic dose, and developed no dissociative effect at all.7
What nobody knows is where the threshold sits. Every human study of the combination has used the same single 300 milligram dose of lamotrigine. No dose-ranging study has ever been done, and no figure has been published for the amount at which interference begins.8 Even at that one dose the studies disagree with each other, and the most careful volunteer study found that lamotrigine reduced ketamine’s dissociative and cognitive effects while increasing its effect on mood.6 So we treat lamotrigine as something to discuss with your prescriber before treatment, not as a reason to turn you away.
Naltrexone raises a different question. There is early evidence that blocking opioid receptors interferes with ketamine’s antidepressant action. A small crossover trial found that pretreatment with naltrexone prevented the antidepressant effect while leaving the dissociative effects intact.5 Twelve patients completed that study and it was stopped early, so the finding is provisional rather than settled. We take it into account anyway, because the cost of being wrong is a wasted course of treatment.
Other medications. These three are the best studied, not the whole list. Other drugs may affect how ketamine is metabolized, act at the same receptors, or change the downstream effects that follow an infusion. Your full list is reviewed before we accept you — prescriptions, anything you take over the counter, and supplements — and we will talk through anything on it that matters for your treatment.
Going through your medicine list is a required step before we accept you. Where something you take may interfere, we talk to your prescriber before your first infusion rather than after your last.
If you are in crisis
If you are having thoughts of suicide
Tell us. We do treat patients with active suicidal thinking — but only on the recommendation of, and in ongoing co-management with, your psychiatrist. We will not take this on alone, and we would not be doing you a service if we did.
If you need help today, call or text 988 to reach the Suicide and Crisis Lifeline, or go to your nearest emergency department. Ketamine therapy is scheduled care and is not a substitute for emergency treatment.
Our limits
What 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 records. If a provider is willing to give you ketamine without reviewing your history, that is worth knowing about them
- 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 psychiatric medication. That is your prescriber’s decision
Do not stop or change the dose of any prescribed medication on your own. We will speak to the physician who prescribes it directly if that would help.
References
1. 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.
2. Frye MA, Blier P, Tye SJ. Concomitant benzodiazepine use attenuates ketamine response. J Clin Psychopharmacol. 2015. PMID 25928701.
3. 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.
4. 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.
5. 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.
6. 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.
7. Kornhall D, Nielsen EW. Failure of ketamine anesthesia in a patient with lamotrigine overdose. Case Rep Crit Care. 2014;2014:916360. PMID 25114807.
8. Wilkowska A, Wiglusz MS, Jakuszkowiak-Wojten K, Cubala WJ. Ketamine and lamotrigine combination in psychopharmacology: systematic review. Cells. 2022;11(4):645. PMID 35203296.
9. Cunningham MO, Jones RSG. The anticonvulsant lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vitro. Neuropharmacology.
Related pages
The RESTORE Method Conditions We Treat Safety, Risks and Limits Fees Our Results
Talk to us
Not sure? Call us and we will tell you honestly.
We would rather tell you on the phone that this is not for you than take your money and find out afterward.
RESTORE — ketamine therapy, done precisely.