Ketamine-Based Treatments

Ketamine has a long history of use in depression, chronic pain, and substance abuse disorders. It appears to help about ⅔’s of all patients with those conditions.  In general, ketamine is used for “rescue” treatment and is focused on quick but short-lived relief from suffering.  There are some ways to predict who will respond to ketamine for short-term relief: both neurophysiological (EEG) and cognitive (neuropsychological) testing indicate that dysfunction in a network that connects the frontal & temporal lobes can predict which patients will respond to ketamine-based treatment.

We discovered a method to target drug delivery and heighten the pharmacologic effect of ketamine - by stimulating the brain with non-invasive methods (TMS, tES) during the administration of ketamine.  we’ve been able to increase response from ⅔’s of all patients to over 85% of patients, and to take response from the very short window of relief (4 - 7 days) to semi-permanent.  a very large percentage of our patients have enjoyed ongoing relief (as long as 5 years) from previously treatment refractory illness like depression or neuropathic pain.

Ketamine Infusion Facilitated by TMS

For treatment of long-standing dysphoric depression with co-morbid anxiety, or with chronic phantom pain.

by Steve Best, M.D.

For many years I have provided TMS/rTMS in a private setting with great success. Nevertheless I have been ever more dissatisfied with the heavy human-burden on patients & their families/occupation. This clinic specializes in evaluating and treating patients who have already failed to achieve adequate recovery in spite of many attempts and multiple modalities. The patients are typically debilitated from occupation, and emotional recovery is their primary focus. An important impediment to an acceptable level of recovery had become apparent – the patient spends too much time here (daily treatment regimens that might consume most of each day). So I remained hopeful for a more resource-efficient method of treating.

I now believe I have happened upon a particularly effective treatment for long-standing & intensely dysphoric depression. Recently, I became aware of the likely synergistic effect of ketamine (on CNS perfusion) and Transcranial Magnetic Stimulation (on focal CNS perfusion). After discussion with a number of scientific advisors I moved forward with the project and began the treatment process on 28 patients. Of these patients, 85% have developed highly significant relief from otherwise un-remitting misery. 2 patients dropped out of the program – one was diagnosed with a horrible illness and the other for personal reasons unrelated to the treatment.

It is my belief that brain metabolism is a better way to approach neurophysiologically relevant diagnosis & thereby guide the treatment of disabling neuropsychiatric disorders like depression, OCD, bipolar depression or chronic pain. Each of these patients had already undergone lengthy psychopharmacologic intervention (before and sometimes during treatment in this clinic). Many had already undergone para-medical treatments including long-term psychotherapy, hospital-based treatment or even unusual treatments such as nutrient-based or hyperbaric oxygen treatment.
Uncomfortable experiences such as fear or disorientation/dissociation of experience occurred in 40% patients. One of the patients – with a mixed connective tissue disease did receive “nice” relief of musculoskeletal pain but unfortunately suffered with clinically relevant nausea. None of the remaining adverse effects foretold a good or bad outcome, and none persisted for more than a few minutes. Most patients were able to walk/talk/jest within a few minutes after the 30-minute procedure ended. All of the patients were treated using conventional pre-anesthesia guidelines like not eating, and all were able to eat without consequence here in the clinic within an hour after the ketamine infusion.

In short, this treatment both highlights the similarity of the painful emotional illnesses and chronic “phantom” pain. It also underlines the clinical utility of improving neuropsychiatric status by directly intervening to improve cerebral blood flow. I believe it holds great promise as both a research tool and in the compassionate treatment of otherwise treatment-resistant patients.