in ketamine-based Therapy...
How We Developed
RESTORE Ultra-Rapid Infusion
The RESTORE Ultra-Rapid Infusions are uniquely different from the "standard ketamine infusion" developed years ago. It is the most advanced formulation of therapy available and is not only more effective than the "standard" ketamine infusion; but when enhanced through the use of Precision Medicine and our unique protocol it can last 3-6 times longer and need fewer "booster" infusions than standard ketamine infusions do. In addition to metabolic and genetic optimization of each patient we see, the RESTORE infusion process is a unique combination of ketamine and magnesium additives to make it more effective, that it is then administered by our physicians using a proprietary 3-stage variable rate infusion protocol to provide the optimal blood levels for a longer period of time. That is why RESTORE is faster acting, more effective and longer lasting than a regular ketamine infusion. And the beneficial results can begin in just minutes to hours after the first infusion.
Why RESTORE Ultra-Rapid Is So Effective
It's All About The "Disconnected" Brain
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 common and sometimes 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 huge clinical challenge, and many people continue to struggle.
From the time these drugs were first developed back in the 1950’s 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, which include 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 is thought to regulate mood. The assumption being 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 improvement is seen. Even more aggressive new treatments to combat mood disorders such as transcranial magnetic stimulation (rTMS) is only about 38% effective and even the older “gold standard” treatment of psychiatry, electroconvulsive shock treatment (ECT) is not much better. It is only effective for about 50% of patients.
Why Haven't We Been Able To Do Better?
The answer to that question may be becoming apparent with new cutting edge research and brain imaging studies showing how the brain works. 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?
Important findings emerged in the late 1990’s 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 finding began to 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 new way type of MRI study called Diffusion Tensor Imaging or “DTI”. Using DTI techniques researchers have could examine these areas and the “neural network connections” around in much greater detail.
With this new way to look at the inner workings of the brain, it became apparent that these critical neural circuits which play an important role in the development of major depressive disorders, fibromyalgia and even migraine headaches were becoming “disconnected” and isolated in some way.
What they saw were microscopic changes occurring between the white matter (wiring-neural circuit pathways) of 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 the development of various disorders including depression, anxiety and PTSD.
The loss of these connections means that various areas of the brain may no longer be able to 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 what was responsible for low neurotransmitters levels.
By losing those connections, the repetitive circuits may then only communicate limited signals; like continuous thoughts and feelings of depression, anxiety or pain. We now suspect that as these important connections are lost or “disconnected” , people may begin to feel depressed, 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 difficult and less meaningful. Friends, family and things they used to enjoy no longer seems to bring them pleasure.
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 is showing additional evidence supporting the “disconnection syndrome” theory and suggesting 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 was been found to have some very remarkable “side effects”. Researchers were astonished when they found that following the intravenous administration of ketamine, they saw a rapid “reconnection” of the brain network. More than that, they discovered 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 served to establish 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 minute" 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 seemed to last for 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 may work like another older and more aggressive form of therapy known as electroconvulsive therapy or "ECT". They knew that is usually requires 6 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 6 ketamine infusions, one every other day for 2 weeks, just like they would for ECT. What they found by doing that was that beneficial effect could be extended to 1 month before another infusion had to be given. Obviously, that was better than 3-7 days, but patients then needed ongoing “booster infusions” every 4 weeks after that to make it last.
While 6 infusions given every other day for 2 weeks did improve the benefits of ketamine substantially, many patients found it difficult to return each month for "boosters". We thought it could be better and it was always a little surprising that few have had the imagination, experience or expertise administering ketamine infusions to improve on it. They either seem content with the way it works now or have not been able to move beyond those minor improvements.
Since that time, others have adopted that same protocol without realizing or understanding that it was not intended to treat depression nor was it ever optimized to achieve the most effective serum concentrations necessary. So, today the only factor that many physicians and “ketamine clinics” consider when determining your infusion is your body weight. They rely upon a very simple formula of “so many milligrams” of ketamine per kilogram of your weight and administer the infusion over 40 minutes.
Using that approach, the results today are about the same as they were almost 15 years ago. Approximately 70% of patients will have a 50% or better reduction in their symptoms for about one month before they require another infusion to maintain the benefits. Still, even with the need for 6 infusions to have the effects last one month, the effectiveness of this approach is far better than those obtained for many with conventional antidepressant therapy.
Although I was initially impressed with the results as well, it was also clear to me that there were many other factors that 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 which is an older and very common antidepressant is supplied in 10mg, 20mg, 40mg, 90mg strengths. The reason for this is 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; and some conditions may be more difficult to treat and require more medication 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 medication at the same time and how they might negatively interact with each other, 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 various 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 length of time necessary to maintain that concentration for each person to have maximal effect. Finally, were there were metabolic or medication issues that could affect how well someone would respond or how long the improvements would last?
We thought it could be better and it was always a little surprising that few have had the imagination, experience or expertise administering ketamine infusions to improve on it.
We took a different approach...
Precision Medicine -
New Solutions Require New Ways Of Thinking
The New RESTORE Ultra-Rapid 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 obvious 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 new breakthroughs.
There were many factors to consider. To begin, the amount of 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. This can be challenging and many physicians are unaware of the optimal serum concentrations needed.
But there was even more than that to consider. It is also vitally important 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. Precision Medicine and innovative clinical research has shown that there is a wide variation in the way people metabolize medications and this 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 effect optimal treatment response. All of these factors need to be considered to have the best response.
And then, we found that it was not only important 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 constantly monitoring them and by adding synergistic agents; if all of that was done very carefully then, ketamine worked remarkably better and lasted much longer. Following this approach, we discovered the we could achieve better results with only 3 infusions and that they would last for 3-6 months.
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 effects the serum concentration of ketamine achieved during an infusion. Also, I found that a person’s basic metabolic rate for drugs, current medications, hormone and carnitine levels all effected 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 certain additional lab tests or supplementation prior to beginning infusion therapy to have best results.
In addition to metabolic optimization prior to therapy, the RESTORE infusion itself is unique in important ways. RESTORE utilizes combination of ketamine combined with magnesium additives to make it more effective than ketamine alone. Magnesium acts as a synergistic agent, or cofactor, which also works at the same NMDA receptors sites as ketamine does and are necessary for an optimal response. However, it must be given at the correct time and in the correct ratio to have maximal effect. When provided in this way it has been found to increase the responsiveness of NMDA receptor to ketamine by 2-3 times.
Beyond that, the older infusion protocol has also been updated to a more sophisticated 3-stage variable rate infusion. Utilizing this approach RESTORE achieves optimal blood levels much faster and maintains them for a longer period of time. By optimizing serum concentrations in this way, the RESTORE infusion program not only achieves higher effective serum concentrations of the parent molecule ketamine, but it also achieves 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 which promote the long-term benefit by increasing BDNF (brain derived neurotrophic factor) levels over a more prolonged time period. It is increased levels of BDNF that have been found to contribute to the enhanced neuroplasticity and synaptic connectively seen with ketamine.
We have also found that post infusion supplementation with those same and additional cofactors in a specific ratio, continues to promote and enhance the infusion benefits and increase how long it lasts. All of this, of course, does not speak to the possible therapeutic benefits that can occur from the psychological experience achieved during an infusion. By optimizing the serum concentrations in the way that we do, each person has the best opportunity to gain personal insights, understanding and a new perspective that can sometimes greatly aide in the recovery process.
Although the RESTORE infusion program is much more involved and complex than a conventional ketamine infusion, the results, at least in our opinion, are worth it. RESTORE has a broader range of disorders that can be treat successfully, and it is more effective (85% vs 70%), more efficient (3 treatments vs 6 infusions) and longer lasting (3-6 months vs 1 month) than conventional ketamine infusions. Lastly, it is also less expensive and more cost-effective compared to a ketamine infusion.
Using this new “RESTORE” model and treatment protocol we have had outstanding results in people who didn’t respond to any medication, therapy, magnetic stimulation, ECT or the even the “old ECT model of ketamine administration”. The RESTORE Ultra-Rapid Infusion is the result of years of hard work. It is an advanced treatment which has been shown to enhance and restore brain connectivity, capable of establishing new neuronal connections within minutes of treatment.
You Can See The Results...
See The RESTORE Difference For Yourself
Neuropathic Pain - Including CRPS/RSD
What The Future May Hold...
The future of drug treatment for migraines, fibromyalgia and depression, as with for many other diseases, lies in the genetic code and a better understanding of how the disorder occurs. Realizing the tremendous potential of ketamine therapy, numerous pharmaceutical companies are working to develop other versions of ketamine that can be administered in other ways, including as an oral medication or a nasal mist.
Major drug companies, including Johnson & Johnson, Janssen and Allergan are stopping research into older antidepressants and rushing into the development of new drugs that they hope will come close to duplicating the rapid and remarkable benefits of the ketamine infusion.
There is little wonder why this is happening when you consider the dramatic improvements that can occur in just 24 hours after just a single infusion. No current medications or treatment that can match the seen with ketamine. While the pharmaceutical companies are trying to make something almost as good as ketamine, the results have been disappointing.
We have taken another path...
Rather than changing what we already know works well…we made it even better and longer lasting!
It may be a few years before any of these other ketamine-like treatments or other drugs are FDA-approved; but because the drug is already approved for other uses, some physicians are recommending RESTORE Ultra-Rapid Infusion therapy for their patients with migraines, fibromyalgia or treatment resistant depression now.
That is the RESTORE Ultra-Rapid Infusion Difference.
If you suffer from chronic pain or depression and have not had relief with prescription medication or other traditional treatment modalities, then the RESTORE Ultra-Rapid Infusion 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:
“The most important breakthrough in antidepressant treatment in decades”....
Thomas Insel, MD - Director, National Institute of Mental Health