A different approach to ketamine infusion therapy
The RESTORE Infusion Program Difference
Our Clinical Findings Have Been Presented Internationally
The RESTORE Infusion Program is uniquely different from the "standard ketamine infusion" developed years ago. It is built around a measured target serum concentration rather than a dose calculated from body weight alone. The first full course is three infusions over three days rather than six over about two weeks. In a retrospective review of our own patients, the mean interval before a further infusion was needed was about eight months. That review was retrospective, had no control group and was not peer reviewed, and it is not a prediction of your result.
If you’ve suffered for years and given up hope of ever finding relief, then the RESTORE Infusion Program is not the way ketamine is usually given. The number of patients receiving it is growing rapidly. Today, almost 20 years after the breakthrough discovery at Yale, Ketamine infusion therapy, dosed to a measured target - the RESTORE Infusion Program - is finally starting to reach the patients who need it most.
We understand that living with Chronic Neuropathic Pain, Migraines, Fibromyalgia, and Depression can be difficult, but considering RESTORE Infusion Therapy is a step in the right direction. Choosing RESTORE is a decision you and your doctor make together. And you’re not alone. RESTORE Infusion Program therapy has been used to treat hundreds of patients all across the country and internationally.
Why RESTORE Is So Effective
There Is A Reason Why Current Medications Don't Work Well.
If your current prescription medications are falling short, recent discoveries in brain imaging studies reveal a new treatment and why it might help.
Medications are a standard and sometimes an effective treatment for depression, migraines, and Fibromyalgia, but they are far from perfect. In fact, in some cases, our current medications have proven to be no better than a sugar pill or placebo, and some patients don't respond to any of the drug options currently available.
I've Tried Everything And... Nothing Works!
Even after over 50 years of medical research, prescription medications have not been very effective in treating most people suffering from depression, migraines, Fibromyalgia, and other forms of chronic pain. These limited treatment options represent a vast clinical challenge, and many people continue to struggle.
From the time drugs were first developed back in the 1950s to today, they have all worked through similar biochemical actions. The most commonly known and prescribed class of drugs is the selective serotonin reuptake inhibitor, or "SSRI." These drugs, including the brands Prozac, Zoloft, Paxil, and Lexapro, attempt to regulate the amount of serotonin, a brain chemical called a neurotransmitter that carries signals between neurons and thought to control mood. The assumption is that if you could increase the amount of serotonin (or dopamine or norepinephrine) available, your symptoms would improve.
Unfortunately, they have not been as helpful as we had hoped for many people. And the rate of response to them is not as high as we need it to be. Studies have shown that only 1 in 3 patients respond to any single SSRI. And if they do respond, it can take several weeks or months before experiencing improvement. Even more aggressive new treatments to combat mood disorders such as transcranial magnetic stimulation (rTMS) are only about 38% effective, and electroconvulsive therapy (ECT), long established in psychiatry, is reported to be effective for about 50 percent of patients.
Why Haven't We Been Able To Do Better?
Until now, treatments for depression with antidepressants assumed that low levels of brain neurotransmitters like serotonin and dopamine were the cause of depression. But what if we were wrong? The answer to that question may be becoming apparent with new current research and brain imaging studies showing how the brain works.
Significant findings emerged in the late 1990s with the observation by researchers that brain tissue in critical areas of the brain was reduced in people who had been under prolonged stress and in combat veterans who had developed depression and PTSD.
Investigators at Stanford University suggested that stress might cause the "death" of neurons, suggesting that the critical brain size reductions seen in patients under stress and those with depression and PTSD might reflect the loss of nerve cells.
These new findings suggest that the old theory about low serotonin causing these illnesses may be incorrect. But why were these vital areas of the brain "shrinking" and getting smaller and smaller?
The "Disconnected" Brain
The answer to that question was found with the development of a type of MRI study called Diffusion Tensor Imaging or "DTI." Using DTI techniques, researchers could examine these areas and the "neural network connections" around them in much greater detail.
With this new way of looking at the brain's inner workings, it became apparent that these critical neural circuits, which play an essential role in the development of major depressive disorders, Fibromyalgia, and even migraine headaches, were becoming "disconnected" and isolated in some way.
They saw microscopic changes occurring between the white matter (wiring-neural circuit pathways) of the higher and deeper layer of the brain known as the cortical-subcortical circuits, leading to a type of "disconnection syndrome" between those regions. This decrease in "connectivity" linking the various critical areas of the brain appears to be directly involved in developing multiple disorders, including depression, anxiety, and PTSD.
The loss of these connections means that various areas of the brain may no longer communicate information effectively and become stuck in a sort of continuous "loop." Almost like a computer program that freezes and won't work correctly. It now appears that this "disconnection" in the brain's wiring network and loss of communication is responsible for low neurotransmitter levels.
The repetitive circuits may only communicate limited signals, like continuous thoughts and feelings of depression, anxiety, or pain, by losing those connections. We now suspect that as these critical connections are lost or "disconnected," people may feel depressed, and anxious, or start to experience pain, increased sensitivity, and headaches. Often, they also report having difficulty concentrating or remembering important information. The result is that everyday life can become challenging and less meaningful. Friends, family, and things they used to enjoy no longer seem to please them.
It can seem almost as if someone has slowly and methodically "turned off" all the light switches in a big house, and now the house becomes cold, uncomfortable, dark, and gloomy.
If that is the case, the question then becomes: can you restore those lost connections?
New Options to "Reboot and Reconnect" the Brain
New research shows additional evidence supporting the "disconnection syndrome" theory and suggests that the connections can be "restored or rebooted."
Part of that research was the discovery that a 50-year-old medication commonly used for anesthesia can have some very remarkable "side effects." Researchers were astonished when they discovered that following the intravenous administration of ketamine, they saw a rapid "reconnection" of the brain network. More than that, they found that following the treatment, brand new nerve connections began to develop almost immediately.
Ketamine was found to have this unusual effect by stimulating a brain "nerve growth" factor known as BDNF, which could reverse some of the disconnections in minutes. That small study conducted at Yale also established an arbitrary "standard" for ketamine infusions in the treatment of mood disorders. The standard was, and is, to this day - "administer 0.5mg/kg of ketamine over 40 minutes" based on body weight.
While the effects of ketamine were astounding, and it was truly remarkable that the brain could be "reconnected" so quickly, there was a catch. After a single infusion, the "rebooting" only lasted 3-7 days before the connections were lost and symptoms returned.
How could it be made to last longer?
The Standard Medical Model -
How Others Tried To Make Ketamine Last Longer
The Old ECT Model
To study this, one group in Minnesota and another in New York thought that ketamine might work like another older and more aggressive form of therapy known as electroconvulsive therapy or "ECT." They knew that it usually requires six or more ECT sessions before a person improves, so perhaps ketamine needed to be given more than once, just like ECT.
To test this hypothesis, they began to administer six ketamine infusions, one every other day for two weeks, just like they would for ECT. What they found by doing that was that the improvement seen could be extended to 1 month before the patients needed another infusion. That was better than 3-7 days, but patients continued to need ongoing "booster infusions" every four weeks after that to make it last.
While six infusions given every other day for two weeks did improve the benefits of ketamine substantially, many patients found it challenging to return each month for "boosters." We set out to see whether the schedule could be shortened and the interval between infusions lengthened.
That schedule has been carried forward in the literature ever since, although it was not originally derived for the treatment of depression and was not built around a target serum concentration. Published surveys of community ketamine practice report wide variation in how these treatments are dosed and monitored. The schedule most often described uses a fixed dose in milligrams per kilogram of body weight given over about 40 minutes. That is a description of the published literature and not of any particular clinic.
Using that approach, published outcomes have changed little over the past twenty years. Controlled trials report improvement in roughly 70 percent of participants, while reports from community practice describe a lower figure, in the range of 40 to 50 percent achieving a 50 percent or greater reduction in symptoms, typically for about a month before a further infusion is given.
Although I was initially impressed with the results, it was also clear that many other factors could influence how well the infusion worked. After all, we all have taken either over-the-counter or prescription medications at one time or another, and most medications come in various strengths for different conditions. For example, Prozac, an older and very common antidepressant, is supplied in 10mg, 20mg, 40mg, 90mg strengths. It is available that way because each person will metabolize the drug differently, some more slowly and others very rapidly, leading to different amounts of the medication in their system. Some conditions may be more challenging to treat and require more medicine to be effective. Also, there may be potential drug interactions to consider. Whenever we start a new medication, our practitioner or pharmacist will also warn us about taking other medicines simultaneously and how they might negatively interact. The same is also true for ketamine.
So, just based on common sense and logic, there was room for improvement with ketamine infusions utilizing the same approach. The first step was to determine if other doses or specific serum concentrations of ketamine would be more effective or last longer. Once that was determined, the next step was to determine the time necessary to maintain that concentration for each person to have a maximal effect. Finally, what other metabolic or medication issues affect how well someone would respond or how long the improvements would last?
We took a different approach...
Precision Medicine -
New Solutions Require New Ways Of Thinking
The New RESTORE Approach
We knew we had to look at this in a new way to get the best results, so we took a different approach. Some people have the impression that all people with an illness like depression, Fibromyalgia, or migraines are alike. With that thinking, you give the same medication, in the same amount, to everyone in the same way and hope they improve. Unfortunately, as we all know, it doesn't always work well that way.
But we knew that each person is unique and different, so it was apparent that the treatment must be individually tailored to match the patient. Rather than use an old model like ECT, we used a new integrated and systems model. Using the same old methods and expecting different results never leads to breakthroughs.
There were many factors to consider. First, the medication needed from patient to patient can vary greatly. Based on our experience, we knew that it was critically important to achieve a certain "blood level" or effective serum concentration, also known as the effective dose for 95% of patients or (ED95), to achieve optimal results. Reaching and holding that concentration reliably is technically demanding, and the published literature on the concentrations associated with response remains limited.
But there was even more than that to consider. Precision Medicine and innovative clinical research have shown a wide variation in the way people metabolize medications, which is often due to liver enzymes known as Cytochrome P450. More than that, some individuals may lack acetyl-L-carnitine (LAC) or have a BDNF variant, which may affect optimal treatment response. It is also vital to account for other factors such as current medications, metabolism, body composition, ancestral heritage, and genetic factors, which all play a critical role in treatment response. All of these factors need to be considered to have the best result.
And then, we found that it was not only essential to optimize the amount of medication given, but we had to change the way it was administered. It had to be carefully adjusted to each patient, minute-by-minute, while adding synergistic agents, all of it carried out under continuous monitoring. Following this approach the first full course was shortened to three infusions over three days.
Over a 7-year period, I was able to identify and determine what those optimal levels were, the time necessary to maintain them, and what effect body metabolism and other medications had on the infusion. For example, to have predictable and consistent results, body mass composition, not total body weight, directly affects the serum concentration of ketamine achieved during an infusion. Also, I found that a person's basic metabolic rate for drugs, current medications, hormones, and carnitine levels all affect the response to ketamine. So, before we consider beginning an infusion, we spend a great deal of time determining if each patient is in an optimal state to have an infusion or requires specific additional lab tests or supplementation before beginning infusion therapy to have the best results.
In addition to metabolic optimization before therapy, the RESTORE infusion itself differs in several respects. RESTORE combines ketamine with magnesium. Magnesium acts as a synergistic agent, or cofactor, which works at the same NMDA receptor sites as ketamine does and is necessary for an optimal response. Timing and ratio matter, and both are set for each patient.
We also use additional neuromodulators alongside ketamine. Specific well-known molecules can augment the binding affinity of ketamine for its receptor targets. At the same time, others can enhance the downstream effects of BDNF and mTOR activation, which promote neurogenesis and synaptic plasticity. These mechanisms are described in the laboratory literature. How far each contributes to clinical benefit in any individual patient is not established.
The infusion itself is given as a three-stage, variable-rate infusion rather than a single fixed rate. The stages are designed to reach the target serum concentration and then hold it for a defined period. By optimizing serum concentrations in this way, the RESTORE infusion program achieves higher effective serum concentrations of the parent molecule ketamine and higher concentrations of the critical secondary metabolites of ketamine known as HNK (Hydroxynorketamine) and DHNK (Dehydronorketamine). This is important because it is the secondary metabolites of ketamine that promote the long-term benefit by increasing BDNF (brain-derived neurotrophic factor) levels over a more prolonged time. Increased levels of BDNF have been found to contribute to the enhanced neuroplasticity and synaptic connectively seen with ketamine.
Supplementation with the same and additional cofactors is continued after the infusion. All of this, of course, does not speak to the possible therapeutic benefits that can occur from the psychological experience achieved during an infusion. Some patients describe personal insights or a change in perspective during an infusion, and for some this forms part of the recovery process.
The RESTORE infusion program is more involved than a fixed weight-based infusion. It requires a metabolic assessment before treatment, a three-stage variable-rate infusion, and continued monitoring afterward. The course is three infusions over three days rather than six over about two weeks.
The RESTORE Infusion Program has been used in patients who had not responded to medication, psychotherapy, transcranial magnetic stimulation, electroconvulsive therapy, or to ketamine given on the conventional schedule. Individual results vary and no course of treatment can be guaranteed to work.
The Ketamine Research Institute and the RESTORE Infusion Center
If you suffer from chronic pain or depression and have not had relief with prescription medication or other traditional treatment modalities, then the RESTORE Infusion Program therapy program may be an option for you. We will be happy to provide you with an initial consultation to see if infusion therapy is right for you.
Just call us today:
800.850.6979
