NEW YORK—Physicians have been largely shooting in the dark when prescribing drug therapies for depression, anxiety, insomnia, attention deficit disorder and other psychiatric diagnoses. While drug therapies, guided by symptom assessment and history, do help some people, they often fall short of optimal outcomes.
Gottfried Kellermann, PhD, has spent the better part of the last 20 years developing validated methods for assessing neurotransmitter imbalances, in the hope of bringing some much-needed light to the management of mental illness. The good news is many common psychiatric problems can be effectively managed through targeted amino acid supplementation, once the physician obtains a clear picture of what is going on in terms of a patient’s neurotransmitter profile.
“Physicians all use selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). But despite widespread use of these medications, few people know how they actually work. When I see the lab results on these patients, and I see the medications they are on, I’m consistently amazed. People are taking medications that make no sense for them,” said Dr. Kellermann, at a presentation during the first international Complementary and Alternative Medicine Expo.
Dr. Kellermann, a population geneticist by training, became interested in the neurochemical basis of common mental illnesses when he was studying genetic variations and familial clustering of psychiatric disorders. He sought a link, in the realm of neurotransmitter chemistry, to explain how genetic predispositions translate into clinical manifestations. This led to years of work to establish reference standards for all the key neurotransmitters.
“I believe in numbers, and in things that can be measured,” said Dr. Kellermann. Six years ago, he established a company called NeuroScience, which offers clinicians a set of well-validated tools for comprehensive neurotransmitter assessment, as well as carefully formulated amino acid supplements to rectify neurotransmitter imbalances.
“Neurotransmitters are about much more than the central nervous system. They are signaling molecules that affect mood, behavior, social function, cognitive function, sleep, digestion, weight regulation, and many other processes.” He stressed that many common disorders including irritable bowel, migraines, hypertension, premenstrual problems, and various metabolic disorders are linked to neurotransmitter imbalances. “Incidence is rising for most of them.”
Excitatory and Inhibitory Neurotransmitters
Neurotransmitters don’t act alone; they work in concert with one another. While Dr. Kellermann and his colleagues have established norms for each individual neurotransmitter, one can only understand the meaning of one neurotransmitter level when viewing it in the context of the others.
“It is very rare to see only one abnormal value,” he explained. “If a patient has abnormal serotonin levels, they’re likely to also have abnormal levels of several other neurotransmitters as well. For example, depression is almost always the result of deficiencies in both serotonin and norepinephrine.”
Generally, one can classify neurotransmitters as excitatory, in the sense that they rev up various physiologic functions, or inhibitory, in that they put the brake on the excitatory stimuli. The primary excitatory neurotransmitters are: glutamate, aspartate, epinephrine, norepinephrine, and phenylethlylamine (PEA). The key inhibitory neurotransmitters are gamma aminobutyric acid (GABA), glycine and serotonin.
NeuroScience’s assessment protocols, which measure levels of neurotransmitters in urine, focus on these key neurochemical signals, but also measure glutamine, an amino acid precursor for glutamate and GABA; histamine, a key regulator of sleep and wakefulness as well as pituitary hormone release; and other neuromodulators such as taurine, and aspartic acid. Depending on the patient’s specific symptoms and history, it is also useful to look at levels of sex hormones, insulin, and other key hormones.
The primary objective of the NeuroScience approach is to bring all of the neurotransmitters back into a dynamic balance by correcting deficiencies through carefully guided supplementation with amino acids.
Urine Testing for Neurotransmitters
There are a number of methods for assessing neurotransmitters, including measurement in saliva, serum, cerebrospinal fluid, and urine. According to Dr. Kellermann, urine testing is the most practical and also shows the best clinical correlations. “Neurotransmitter levels flux a lot over the course of the day. They’re all going up and down constantly. Single point urine collection gives you a better picture of what’s going on in the last 2–3 hours, so you really need integrated measurements over several voiding intervals.”
NeuroScience obtains neurotransmitter and hormone measurements from a fully-licensed, CLIA certified independent contract lab. The baseline test panel provides data on 11 key neurotransmitters and precursors (glutamate, epinephrine, norepinephrine, dopamine, PEA, GABA, serotonin, glutamine, histamine, glycine and taurine), indicating for each one whether a patient is above, below or within normal ranges. The report includes recommendations for targeted amino acid supplementation to correct existing imbalances.
NeuroScience’s reference ranges are based on analysis of several hundred men and women in the 25–35 year age range who are healthy, with no clinical complaints, and not taking any medications. Dr. Kellermann stressed that under healthy conditions, there is little change in neurotransmitters with age. Ideally, there’s no difference between newborns and elderly people. The balance should be roughly the same. Of course few people match those ideals.
In general, management of a complex condition like depression is a three-phase process. The first phase, lasting 1–2 weeks, is focused on correcting deficiencies in the inhibitory neurotransmitters. The second phase, which usually lasts between 3 and 6 months, focuses on restoring optimal balance between excitatory and inhibitory neurotransmitters. NeuroScience recommends retesting every 4–6 weeks, to track changes in neurotransmitter levels.
Once a patient reaches a healthy neurotransmitter balance, which should be accompanied by improvement in mood, cognitive function, and energy, he or she enters a maintenance phase, in which the daily amino acid doses are reduced.
As with any lab test, the neurotransmitters need to be interpreted in the context of history and symptoms. “Never try to diagnose anything in isolation,” Dr. Kellermann reminded.
The same “chief complaint” can emerge from several different neurotransmitter imbalances, which is why it is important to look comprehensively at the key neurotransmitters and hormones before planning an intervention.
To illustrate the point, Dr. Kellermann compared baseline neurotransmitter profiles of several patients suffering from insomnia. One patient showed high epinephrine levels and low serotonin. “In this case, there’s no compensation for the excitatory side. This patient can’t relax and slow down enough to fall asleep.” A second patient showed normal epinephrine and serotonin levels, but high PEA. “In this case, the patient experiences obsessive, racing thoughts, which makes it difficult to sleep.” This patient needs a different amino acid protocol.
In a similar way, chronic fatigue can result from very different neurotransmitter patterns. “The couch vegetables tend to have very low epinephrine and very low serotonin. If you test their cortisol over the day, they may be okay in the morning, but they drop like a rock after noon.”
Some fatigue patients have normal epinephrine but low norepinephrine. Others have really low glutamic acid and histamine levels. While not technically a neurotransmitter, histamine is a neuromodulator that induces release of epinephrine, norepinephrine, and dopamine. People in a state of sympathetic overdrive have high histamine, typically accompanied by low serotonin, while those who are fatigued have really low histamine.
When using amino acids to correct neurotransmitter imbalances, Dr. Kellermann has found it best to begin by building up inhibitory neurotransmitters. “We always start with the inhibitory side. If you try to raise dopamine or norepinephrine right off the bat, you will fail, and you could trigger hypertension, tachycardia or other excitatory neurotransmitter effects. So our recommendations always start out with precursors for serotonin and GABA.” These include glycine, 5-HTP, taurine, beta-alanine, theanine and glutamine.
Limitations of Conventional Drug Therapies
Dr. Kellermann takes a neutral stance on the issue of psychiatric drugs. While they can be useful, particularly for short-term therapy, they have limitations. “Medications do not add any new neurotransmitters to the system or help to build them. They basically help you make do with what’s there.” This is often necessary to stabilize patients. In the long term, though, drugs tend to facilitate neurotransmitter depletion.
“Medications like SSRIs require a minimal amount of the neurotransmitter to be present in order to be effective. So the effect of these drugs tends to decline as the level of the neurotransmitter in question declines below certain thresholds. This is why for patients with severe depletions of serotonin, an SSRI is unlikely to work, and also why the drug effect tends to drop off over time.” Unless one rebuilds serotonin stores, continued serotonin depletion simply gives the drug less substrate to work with.
It is also difficult to discontinue the drug unless you’ve corrected deficiencies. In the case of SSRIs, cessation often results in a precipitous serotonin crash.
Targeted amino acid therapy can be done in conjunction with conventional drug therapy, and Dr. Kellermann believes this approach makes sense. “In patients with low serotonin, you can give the SSRI to prevent reuptake at the same time give 5HTP as a precursor to increase serotonin.” Later, when serotonin levels rise, it is easier to withdraw the drug.
A better understanding of neurotransmitter balance helps explain phenomena like suicidal ideation in children and teens on SSRIs. Unlike depressed adults, many depressed kids have high norepinephrine levels. In effect, they’re in sympathetic nervous system overdrive, and they deplete serotonin very quickly.
“A doctor will give a kid a medication to raise their serotonin, which is right in principle, but in some of these patients it induces a drastic drop in norepinephrine. This is the point where you start to see suicidal ideation.”
The situation can be avoided by giving 5HTP as a serotonin precursor while also giving norepinephrine precursors like tyrosine and phenylalanine to keep norepinephrine up and prevent the crash. “This is a real art,” he said.
NeuroScience in Clinical Practice
Dr. Kellermann and his colleagues believe neurobiological assessment should be a central component of primary care. Over the last 6 years, the company has slowly built a strong and growing network of physicians who share this view.
Donielle Wilson, ND, a naturopathic physician practicing in the New York City area, and president of the New York Association of Naturopathic Physicians, told Holistic Primary Care that the NeuroScience protocols have made a big difference for many patients. “It has become part of my fundamental approach. As an ND, I routinely take a comprehensive look at a patient’s digestive, endocrine, and immune function. Now I can also look at their neurochemistry. We’ve always wanted to do this, but before we didn’t have the tools.”
Dr. Wilson, who has no financial relationship with NeuroScience, said she’s had good results applying the protocols to patients with anxiety, PMS, depression, insomnia, and also for kids with ADHD. “I do the testing on a good number of my patients. There’s such a sense of drive here in NYC, and people can’t turn off, they can’t sleep. Some of my patients have asked me why no other doctors have ever tested them for this stuff.”
NeuroScience offers a range of test panels, from the basic 11-neurotransmitter profile, to condition-specific panels for insomnia, menopause, and andropause. The tests range in cost from $125 to $373, and they are covered by some insurance plans. The company also provides a range of amino acid supplement products designed to address common neurotransmitter deficiencies.
Dr. Kellermann explained that, “Amino acid therapy supplies precursors for neurotransmitters, to increase the levels. So you want to do it in a targeted way. Don’t just throw amino acid cocktails at a patient. You have to target based on actual neurotransmitter levels.”
“I’ve come to really trust the NeuroScience formulations,” said Dr. Wilson. “The company also provides great technical support. Their technical staff really helps me understand what’s going on in a case.”
For more information on the NeuroScience approach, visit: www.neuroscienceinc.com or call 888-342-7272.
For information on nutrition and neurotransmitters visit www.holisticprimarycare.net and download the story “Nutritional Causes of Neurotransmitter Deficits.”
Causes of Neurotransmitter Deficits
Neurotransmitter deficiencies have multifactorial origins. Genetic predispositions do play a role. For example, some people inherently produce less serotonin than others. Other people inherently have weaker production of epinephrine or other excitatory signals. But by far the most common factor is stress.
Sympathetic nervous system overdrive, widely prevalent in our society, exhausts multiple neurotransmitter systems. Long periods of chronic stress gradually deplete serotonin, as the body tries to downregulate excitatory signals. Once serotonin is depleted, the excitatory arm of the nervous system has free rein, creating prolonged states of anxiety and agitation. “Many people just cannot relax any more. The inhibitory neurotransmitters are totally burned out,” explained Dr. Gottfried Kellermann, founder of NeuroScience, a laboratory that offers well-validated tests of neurotransmitter function.
Eventually, excitatory neurotransmitters are also depleted. Many adults with depression and chronic fatigue have low serotonin, GABA and also epinephrine and norepinephrine.
The problem is exacerbated by poor diet. “Carbohydrates cannot be made into neurotransmitters. They’re made out of amino acids, so you need to have good protein in the diet,” said Dr. Kellermann. A diet high in refined carbs provides plenty of glucose for the overdriven sympathetic nervous system to burn, but nothing to replenish exhausted neurotransmitter supplies. However, carbs do stimulate endorphin release, which is why people like carb-rich “comfort” foods.
Coffee, being a strong adrenal stimulant, contributes to the depletion of epinephrine. Chronic coffee drinking is detrimental to neurotransmitter balance. On the other side, alcohol adversely affects GABA production. While moderate drinking helps people relax, it promotes long-term neurotransmitter imbalance.
Exercise can induce large increases in neurotransmitter levels, but the effect is transient. The problem is that a lot of patients are so depleted it is difficult to get them to exercise at all. Over-exercise can be depleting. Triatheletes are often extremely low in key neurotransmitters. “This can be very dangerous.”
Dr. Kellermann has a strong interest in the role of parental nurturing on the ability to produce serotonin. It seems that in young children, nurturing strengthens serotonin production. Children who lack adequate nurturing tend to have lower serotonin levels. “I am trying to find the equivalent of nurture in chemistry. When we’re really balanced and happy, there is a particular neuro-chemical balance, and I’m trying to understand that.”