Why Restore is better than Ketamine for mood disorders and chronic pain
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Why is RESTORE better than ketamine for rapidly improving depression, anxiety, and PTSD as well as chronic pain from neuropathy, migraine, and fibromyalgia?
It seems like a simple and straight forward question, but it must be put into a broader context to fully appreciate the unique advantages of the new RESTORE® Infusion program over typical ketamine. There are at least five major factors that can limit the effectiveness of a ketamine infusion and we will need to review a little history of the origin of the ketamine infusion, how it is administered and who is administering it to better understand why RESTORE is significantly faster, longer lasting and less expensive than ketamine.
First… a little history about ketamine
It surprises many to learn that the standard ketamine infusion currently used around the country today was not originally intended to treat depression but was actually developed as part of a research protocol at Yale University in the late 1990’s to study another psychiatric condition – schizophrenia. At that time research was underway to determine if a specific neurotransmitter known as “glutamate” was involved in causing or contributing to the symptoms experienced by patients suffering from schizophrenia. The Psychiatry Department at Yale was aware of earlier research studies in animal models that suggested glutamate may play a crucial role in this condition, but it was very difficult to study because there were very few available drugs that could safely alter glutamate release in humans. The one medication that would block glutamate release in clinical use at that time was a common anesthetic agent – ketamine. Ketamine was formulated in 1962 by Parke-Davis and had been used as an FDA approved anesthetic agent for children and adults since 1970. It had a well-known safety profile in the field of Anesthesiology for over 25 years by that time – a perfect choice.
The Yale Psychiatrists being unfamiliar with the use and administration of this type of medication, approached my department (Anesthesiology) to collaborate with them in the study by formulating and administering a safe “ultra-low” dose of ketamine. The goal of the study was to determine if it would produce symptoms in normal volunteer research subjects that would seem to mimic the behavior seen in schizophrenia. If it did, then the underlying cause of this serious psychiatric condition could be studied further with the aim to find a more effective treatment.
They determined that the lowest possible blood level (serum concentration) of ketamine that might produce such an effect in about 75% of normal subjects was approximately 175 ng/ml. Because it was technically difficult and expensive to directly measure blood levels in each person undergoing an infusion, the Anesthesiology Department developed a simplified infusion protocol of giving each person 0.5mg of ketamine per kilogram of general body weight, that when administered slowly over a period of 40 minutes, would achieve peak blood levels of approximately 150-185 ng/ml by the end of the infusion in most individuals.
Although the initial results of the study were successful in terms of achieving the intended blood levels, they were not successful in reproducing the negative symptoms associated with schizophrenia. Instead, research subjects in the study reported feeling good! They reported the experience as giddy, mildly euphoric, and feeling slightly “intoxicated”. Although this was certainly an unexpected and unintended outcome, nevertheless perhaps they “were on to something” here.
Disappointed with the failure of ketamine to produce a model in which to study schizophrenia, several years later a new question came to mind. Would ketamine produce these same types of positive effects in people with depression?
Ketamine as a possible treatment for depression
So, in 1999-2000 the Yale researchers decided to give a small group of nine patients with severe, treatment-resistance depression a single ketamine infusion and see what would happen. Remarkably, not only did they also experience mild euphoria and feeling a little intoxicated, many of the patients also reported a rapid and dramatic improvement of their depression in just a matter of hours following the infusion session. More surprisingly, the improvement continued to last for about a week, far longer than the 2-4 hours that ketamine would typically remain in their system.
No one knew at time how this was possible, but it happened. This dramatic response to a common anesthetic became the first published study in the Journal of Biological Psychiatry suggesting that ketamine, a glutamate/NMDA receptor blocking agent, could rapidly reverse depression and improve overall mood.
The medical community’s initial response to the publication of this early study was unimpressive to say the least. Few researchers or clinicians saw the future implications of this new rapidly acting antidepressant agent. It was not until about 6 years later, in 2006, when Dr. Carlos Zarate, Director of Pharmacology and Therapeutics Division of the National Institute of Mental Health, and his team published a larger study using the same infusion protocol that once again showed the remarkable benefits of ketamine that the medical community took note.
His research study and subsequent detailed investigation into the mechanism of ketamine’s action for alleviating depression ignited a growing interest in ketamine. Soon many other prestigious medical and scientific institutions around the world began to look more closely at it. But there was a problem. Although patients responded very quickly, usually within a matter of hours, the positive effect only lasted a few days to one week following a single infusion. Clearly, it would not be practical or cost-effective for people with depression to undergo ketamine infusions every week.
It wasn’t until four years later in 2010 that psychiatrists, attempting to prolong the benefits of ketamine, used a model to extend the benefits of ketamine that they were familiar with – electroshock therapy (ECT). It was well known that patients undergoing ECT needed to have multiple sessions before the improvement lasted. Typically, patients would have one session of shock therapy every other day for two weeks before longer term improvement occurred. Would the same model work for ketamine?
Fortunately, it did – at least to some degree. Studies found that if ketamine was administered with the same scheduled that was used for ECT, every other day for two weeks, the improvement would last about 28 days before another infusion was needed. Satisfied with the results that six infusions provided, at least one month of symptom improvement, the simple infusion protocol of 0.5mg of ketamine administered intravenously over 40 minutes became the “de facto” standard ketamine infusion protocol.
Since that time, almost everyone – major universities, researchers, hospitals, and practitioners – have adopted that same simple protocol without significant modification or improvement. It seems as if the drive to explore the full potential of the remarkable medication stopped right there. Surprisingly few physicians or researchers have attempted to determine if there may be other underlying metabolic, genetic, or infusion related factors which may increase or inhibit the response to ketamine. Today the only factor that many physicians and “ketamine clinics” consider when administering your infusion is adjusting the dose based upon your individual overall body weight.
While this approach can be beneficial, many believe that it falls short of providing more than a “band-aid” type of short-term relief requiring “monthly” booster infusions to maintain the benefit. Not surprisingly, using that same simple infusion protocol, the results seen today are about the same as they were almost 15 years ago. Approximately 70% of patients will have a 50% or greater 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 and monthly “boosters”, the effectiveness of this approach is often far better than that obtained for many with conventional antidepressant therapy.
But… Could ketamine be made to work even better?
Although I was initially impressed with the results as well, it was also very clear to me that there were many other factors that could influence how well the infusion worked. After all, most of us have taken over-the-counter or prescription medications at one time or another and we know that most medications come in various strengths for different conditions.
Prozac for example, is an older and very commonly prescribed antidepressant that supplied in various strengths including 10mg, 20mg, 40mg, 90mg capsules. The reason for this is because each person will metabolize the drug differently, some more slowly and others very rapidly leading to very different levels of Prozac in their blood stream. Also, some conditions may be more difficult to treat and therefore require more medication or higher blood levels to be effective.
In addition to basic metabolism, it is also important to consider each person’s unique genetic traits. Some individuals may have variations in receptor sites where the drug works or lack critical neurotrophins (small proteins that effect nerve cell growth and development) that play a role in how they will respond to ketamine.
Another factor that needs to be considered is potential drug-drug interactions. 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.
Clearly, many other factors beyond just overall body weight (or a “one-size-fits-all” approach) need to be considered and accounted for to achieve the best results with any ketamine-based treatment. So, just based on common sense and logic, there was room for improvement with ketamine infusions utilizing the same approach.
How we improved the ketamine infusion
The first step in our investigation was to determine if various other doses or specific blood levels 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, there were genetic, metabolic, or medication issues that could affect how well someone would respond or how long the improvements would last?
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 genetic, metabolic rate for drugs, current medications, hormone, and carnitine levels all effected the response to ketamine.
RESTORE is the advanced and improved version of ketamine
To unleash the full potential of ketamine – to make it better, faster acting, longer-lasting and less expensive – we used the results of our long clinical investigation of ketamine to develop RESTORE. The RESTORE® Infusion Program utilizes an individualized and unique methodology that includes optimal blood levels of ketamine, improved administration technique, synergistic supplements, and a metabolic optimization protocol to achieve the best results. So, before we consider beginning an infusion, we spend a great deal of time determining if each person is a good candidate for the RESTORE program and in an optimal state to obtain maximal improvement.
1. Metabolic Optimization
We have found, for example, that some of our patients may benefit from a more detailed laboratory evaluation and metabolic optimization prior to the infusion series. Often these critical tests have not been performed by their doctor but are very important for many of our patients with depression, anxiety, and PTSD. They are specific for various underlying metabolic or hormonal factors that can contribute to the development of the mood disorder and once identified and corrected greatly improve and enhance your responsiveness to the RESTORE infusion.
In some challenging or very complex cases, we also find it advisable to obtain a highly specialized genetic profile which looks at serotonin, dopamine, and norepinephrine receptors, as well as MTHFR, BDNF, and COMT genotype variants which can provide very important additional information improving the outcome of an infusion.
2. Synergistic Agents
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.
3. Improved Infusion Administration
Beyond that, the older, simple weight based 40-minute 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 than a standard ketamine infusion. By optimizing serum concentrations in this way, the RESTORE 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. This is important because increased levels of BDNF are critical and ave been found to contribute to the enhanced neuroplasticity and synaptic connectively seen with ketamine.
4. RESTORE Supplements
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. Utilizing our advanced program combined with the RESTORE supplement continues to promote and enhance the infusion benefits and increase its durability at least 300% over ketamine alone.
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. And that brings us to the last important factor…
5. Who is administering the infusion and in what setting?
Unlike any other program in the world — we only see one person at a time — so you have our full and undivided attention while you are with us.
Many physicians providing ketamine infusion therapy today have relatively little clinical or research experience with the pharmacology of the medication and lack detailed insight to its actual mechanism of action (i.e., pharmacokinetics and pharmacodynamics). While some ketamine providers are more knowledgeable about ketamine than others, most of those administering ketamine have never experienced a ketamine infusion themselves and so do not fully understand the shift in perception that occurs during an infusion.
We do. Not only have we have performed thousands of infusions over the years, being right by each person’s side during the entire session, but we have also personally experienced what it feels like to have an infusion. Many of our patients have told us that the experience they have during a RESTORE session was one of the most important life changing events in their lives.
So, we understand better than most what the experience is like, and we are there with you, during each infusion, personally adjusting, assisting, and guiding you during the entire session. You are never left alone, with a friend, or with a nurse just “checking in on you” from time-to-time.
So, How RESTORE is better than ketamine?
• More Effective:
85% improve with RESTORE vs 70% improve with ketamine
• Faster Acting:
Only 3 RESTORE sessions over 3 days vs 6 infusions over 2 weeks
• Longer Lasting:
Up to 1-3 years with RESTORE vs Only 1 month with ketamine
• Less Expensive and More Convenient
Although the RESTORE® infusion program is much more sophisticated than a conventional ketamine infusion, the results — at least in our opinion — are well worth it.
We are committed to what we do. We will use all our knowledge, experience, and expertise to help you. And while we cannot promise success in every case, we can promise and guarantee that we will make every possible effort and take every step necessary to ensure that you have the best possible chances of recovery with RESTORE.
RESTORE is the new “Gold Standard” in ketamine-based therapy
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The RESTORE® infusion program is an advanced program that unlocks the full benefit of ketamine. It is the most rapidly acting, effective, and longest-lasting ketamine-based infusion available today.
If you would like to learn more about the RESTORE program, please feel free to visit our website and clinical research center (ketamineinstitute.com). We are also available to assist you with a free private consultation, please feel free to call us at 800-850-6979, we want to help.
We don’t treat patients, we treat people – one person at a time.
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