Breakthroughs in Treatment Resistance

Since I like to be successful in helping my patients get excellent results, I have gone out looking for better cutting edge treatments. Accordingly, a few years ago I joined forces with a team of researchers testing a new treatment protocol for chronic, treatment-resistant post-traumatic stress disorder (TR-PTSD), another difficult clinical challenge. The novel paradigm we are studying combines psychotherapy with a medication, MDMA, that works in the body only for several hours, taken only 3 times, to help people open up, explore traumatic memories, and resolve the imprint of trauma. This model is now in phase 3 clinical trials, after performing in phase 2 at a response rate of 75 to 80%. You can read more about this research at MDMA is not the same thing as “ecstasy.” The street drug “ecstasy” taken recreationally and without psychotherapy obviously has significant risks and doesn’t produce therapeutic results, although it can make people feel more open and connected to others, for a few hours.

Its off-label use for treatment-resistant depression has been studied extensively for the past several years, at the National Institutes for Mental Health (NIMH) and elsewhere, following Carlos Zarate’s 2006 randomized trial (Zarate et al. Arch Gen Psychiatry. 2006 Aug;63(8):856-64) which reported a 71% response rate. Ketamine dosing in psychiatry is lower dose than anesthetic dosing, and does not require the same level of monitoring that anesthesia requires. Many ketamine studies report upwards of 75 or even 80% treatment response to intravenous ketamine treatment, results about 2 to 3x better than results from traditional antidepressants. Almost all of the ketamine research to date has been based on a treatment model in which 0.5mg per kg body weight of ketamine is infused intravenously (IV) over 40 minutes. Today, this protocol is being provided to people with treatment resistant depression in a rapidly-growing number of “ketamine clinics,” settings where several people get ketamine infusions in a room with dimmed lights and no psychotherapy provided. This model often (75-80% of the time) produces robust and rapid treatment responses. But the problem with IV ketamine responses is that often they do not last very long. The big research question remains: why doesn’t the ketamine response stay with a person beyond a few days or weeks??

Ketamine Assisted Psychotherapy

Due to my ongoing experiences in clinical research witnessing rapid and long-lastingresolution of chronic treatment resistant PTSD using a medication-assisted psychotherapy model, I got very interested in ketamine when I heard that some trailblazing doctors are providing ketamine with psychotherapy essentially the same way we have been using MDMA in phase 2 clinical research to treat TR-PTSD: to facilitate deeper psychotherapeutic work to resolve stubborn symptoms.

Most ketamine treatment clinics are following the NIMH protocol, as delineated above. But there are a growing number of clinics, including IPHC, delivering brief intensive ketamine with psychotherapy with the intention of getting longer-lasting results. Many of us are collecting data in the form of symptom rating scales, in order to build a database to share outcomes in the future, hopefully contributing toward directing the field toward what kinds of ketamine protocols make the effect last.

Steven J. Hyde MD (Ketamine for Depression, 2015) pioneered the approach of combining psychotherapy with ketamine treatment, and using alternative routes of administration (intranasal, oral, sublingual, and intramuscular). Phil Wolfson MD edited The Ketamine Papers, 2016, is a collection of chapters authored by leaders in this burgeoning field of exploration of what works best with ketamine for treatment resistant depression.

IPHC ketamine psychotherapy protocol

Ketamine for TRD is an off-label treatment, which means that FDA has not evaluated phase 3 clinical data. Only smaller trials exist at this point, and these trials consistently show that ketamine, when delivered in a clinical environment, is a safe and effective treatment for TRD. Low dose ketamine brings on mild dissociation for about 40 minutes, immediately after which significant gains in psychotherapeutic process can be achieved. Ketamine can cause side effects such as nausea and dissociation, during the drug effect. These effects are transient and generally resolve as the drug wears off.

I have designed the IPHC ketamine-assisted protocol based on the work of Steven J. Hyde MD and other pioneers such as Phil Wolfson MD, Richard Yensen PhD, and Cole Marta MD. We offer a package of 6 to 8 ketamine psychotherapy sessions at a frequency designed to maximize effectiveness, twice weekly for 4 weeks. The sessions are two hours long. After each ketamine psychotherapy session, you will need a ride home from the clinic.


Ketamine-assisted psychotherapy is not for everyone. There are some people who should not take ketamine, and our clinical staff can discuss these details with you. Transient nausea, mildly elevated blood pressure, and dissociation are the most common side effects, and these risks can be mitigated with proper screening and vital sign monitoring. Also, there is the concern about ulcerative cystitis. Amongst people who abuse ketamine as a street drug, who often take a mixture of multiple illegal drugs on frequent occasions, there have been case reports of a serious adverse effect of ketamine called ulcerative cystitis, or, an ulceration of the lining of the bladder. Such side effects have never been reported in brief, low dose ketamine clinical trials the protocols of which match closely the amounts of ketamine prescribed at IPHC. Thus ulcerative cystitis is a known risk of high dose chronic ketamine abuse, and it is considered a very low risk for low dose brief ketamine treatment. Your clinician at IPHC will provide you with more detailed information so that you can make a very well informed decision about ketamine psychotherapy at your intake appointment.

More information

Please contact us at IPHC if you are interested in discussing with our clinical staff whether ketamine assisted psychotherapy would be an appropriate treatment for you.