Naturopathic and Natural Mood Stabilization
Alternatives to Prescription Psych Meds do Exist. In many cases both can be used together.
Psychiatric conditions that respond well to neurotransmitter therapy include: anxiety, depression, insomnia, ADD, ADHD, addiction, dysthymia and some bipolar disorders. We have been treating patients in Boulder for over 12 years using neurotransmitter testing.
Neurotransmitters are recognized as the primary biochemical messengers of the central and peripheral nervous systems. Studies have demonstrated that urinary neurotransmitter measures are reflective of circulating levels as evidenced by renal neurotransmitter clearance mechanisms. Laboratory methodology for the accurate assessment of urinary neurotransmitter levels has been established. Urinary measures are not recognized as a direct reflection of central activity, however definite associations exist. The ability to measure neurotransmitters has led to the generation of scientific literature that demonstrates urinary neurotransmitter measurements have clinical value as representative biomarkers of various neurological, immunological, and endocrinological conditions. Urinary neurotransmitter assessment carries a long history as a means to assess nervous system activity.
Early investigations date back to the 1950s when von Euler, et al, first described the measurement of urinary catecholamines as biomarkers for pheochromocytoma, a rare tumor of the adrenal gland. Since then, many studies have been published regarding neurotransmitter excretion and its relevance to neurological, endocrinological, and immunological function. While urinary neurotransmitter measures are not considered direct reflections of central nervous system activity, various disease states stemming from central nervous system imbalances have been associated with urinary neurotransmitter alterations. There is a definite association between urinary and central neurotransmitter concentrations and many studies have examined that association through various neuro-endoimmune communication mechanisms.
A biomarker is a measurement used as an indicator of biological actions. A neurotransmitter test is a biomarker test. Currently, there are no biomarkers available for psychiatric disorders; therefore, diagnostic tools and treatment decisions are restricted to the evaluation of clinical signs and symptoms that lack objectivity. That said, treatments for managing psychiatric symptoms are relatively effective. However, no single treatment works for everyone with a given disorder, and selection of the best treatment in mainstream psychiatry remains a challenge. Neurotransmitter testing provided a novel method for treating the unique attributes of an individual patient, its personalized medicine.
As in any other disease state, a primary goal in natural psychiatry is the identification of specific biomarkers that would permit a more precise definition of specific disorders and, in turn, enhance the ability to develop targeted patient treatments. In fact, research has highlighted a need for biomarkers in psychiatry to enhance patient management and ensure treatment success.
In a recent article by Cook (2008), an outline of desirable characteristics of biomarkers in psychiatry was described. Cook (2008) stated that certain criteria must be met for a biomarker to be considered for psychiatric management. First, the biomarker must be timely, clinically useful, and cost-effective. Second, the technology needed to assess the biomarker must be well tolerated by the target patient population. Third, methods that can be easily integrated into the practitioner’s current practice patterns are more likely to be accepted than those that require a major change in the delivery of care.
Urinary neurotransmitter analysis has a breadth of data to support its usefulness in clinical practice. In the late 1950s, publications revealed correlations of urinary catecholamine measures to various psychiatric symptoms. Since then, research on urinary neurotransmitter analysis has expanded to encompass methodological improvements and further development on clinical utility for psychiatric disorders.
Specifically, research has focused on categorizing subsets of depression and anxiety through urinary neurotransmitter analysis, as well as determining biochemical changes with pharmaceutical intervention.
Roy and colleagues (1986) examined subsets of unipolar depressed patients and compared these subjects to non-depressed controls. Overall, depressed patients had high urinary norepinephrine and its metabolite normetanephrine, but lower urinary output of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) compared to controls. Subjects that met DSM-III criteria for a major depressive episode with melancholia, characterized by irrational fears, guilt, and apathy, exhibited significantly higher urinary outputs of normetanephrine than controls. Subjects with a major depressive episode but without melancholia or subjects with dysthymic disorder had levels comparable with controls. It was concluded that high urinary output of norepinephrine and its metabolite, normetanephrine, reflected abnormal sympathetic nervous system activity and thus, may be helpful in determining subsets of depression.
Later studies confirmed these findings, which reported elevations in urinary norepinephrine output in depressed and anxious individuals.
Although research shows significant correlations between depression and urinary neurotransmitter levels, its clinical application is not validated unless changes in urinary values and symptoms can be observed with treatment.
Mooney and colleagues (1988) conducted a study in which depressed patients who had favorable antidepressant responses to alprazolam, a benzodiazepine, had significantly higher pretreatment urinary catecholamine levels than control subjects. In addition, non-responders to alprazolam did not have significant elevations in urinary neurotransmitters output compared to control subjects. After only eight days of treatment with alprazolam, urinary catecholamine levels declined significantly, which contributed to the improvement in depressive symptoms.
Additionally, a double-blind, placebo-controlled, block-randomized, two-way crossover study revealed that after administration of 20 mg/d of paroxetine, urinary serotonin excretion significantly increased when compared to placebo, and correlated with an improved symptom profile. Lastly, fear and anxiety were analyzed in patients who underwent outpatient surgery, by examination of urinary catecholamines. Duggan and colleagues (2002) examined the effect of the benzodiazepine diazepam on the stress response in patients after outpatient anesthesia and surgery, by the measurement of urinary catecholamines. The study showed significant reductions in urinary norepinephrine levels in the group that received diazepam compared to placebo. These findings, along with earlier studies, illustrate the importance of urinary neurotransmitter measurements in the determination of treatment effectiveness.
Attention-Deficit-Hyperactivity Disorder (ADHD) has also been a primary target for the utilization of urinary neurotransmitter analysis. Research has shown that subjects with ADHD tend to have decreased urinary beta-phenylethylamine (PEA) levels. Beta- PEA is a monoamine neurotransmitter that has amphetamine-like functions that can alter mood and attention, and decreased beta-PEA levels may contribute to symptoms of inattentiveness.
After treatment with methylphenidate (ritalin), those that responded to medication had significantly elevated urinary beta-PEA levels. Other studies have reported decreased urinary epinephrine levels in ADHD children compared to controls. These findings are consistent with prior studies that demonstrated an inverse relationship between epinephrine excretion and inattentive, restless behavior.
Urinary norepinephrine levels were found to be positively correlated with the degree of hyperactivity in ADHD children. The same study showed that after one month of Pycnogenol treatment, a bioflavonoid extract from pine bark, norepinephrine levels decreased significantly and correlated with improvement in ADHD symptoms.
Overall, urinary neurotransmitter analysis can be a useful tool when dealing with psychiatric disorders. In addition, other neurotransmitters such as glutamate, gamma-aminobutyric acid (GABA), histamine, glycine, and taurine are being measured with high specificity and selectivity. Urinary neurotransmitter analysis is cost-effective, timely, non-invasive. Objectivity is essential to treating patients with psychiatric disorders. Medical history and DSM-IV criteria may suffice for the diagnosis of psychiatric disorders, however, the wide differences in patient biochemistry can decrease successful treatment outcome with conventional drugs. Neuropsychiatric biomarkers may aid in determining successful treatment regimens based on patient biochemistry rather than simply relying on standard diagnostic protocols.
Typical treatments that we use with brief mechanism of action:
4-amino-3-phenylbutyric acid is a GABA derivative. It easily crosses the blood-brain barrier, binds to GABA receptors, and may increase GABA levels. Additionally, it appears to inhibit the excitatory neurotransmitter phenylethylamine (PEA).
5-hydroxytryptophan (5-HTP) is the amino acid intermediary in the synthesis of serotonin. Taken orally, 5-HTP is easily absorbed from the GI, readily crosses the blood-brain barrier and is converted to serotonin by the actions of the enzyme amino acid decarboxylase.
acetyl-11-keto-beta-boswellic acid (AKBA) inhibits the production of leukotrienes via inhibition of the enzyme 5-lipoxygenase.
Acetyl-L-carnitine is neuroprotective and promotes mitochondrial health.
Alpha-glyceryl phosphoryl choline (Alpha-GPC) has been found to support nervous system function by increasing the availability of the neurotransmitters choline and acetylcholine.
Alpha-lipoic acid is an antioxidant that may have benefits in memory enhancement.
Boswellia serrata extract includes compounds that block the production of leukotrienes by inhibiting the enzyme 5-lipoxygenase (5-LOX).
Calcium stimulates cellular processes that lead to catecholamine release and an increase in tyrosine hydroxylase gene expression.
Chromium is a required factor in carbohydrate and fat metabolism and is generally lacking in the normal diet.
Coenzyme Q10 is a cofactor in the production of cellular energy and acts as an antioxidant for cellular and mitochondrial membranes. It also helps in the regulation of glutamate.
Epigallocatechin galate (EGCG) is a natural component of green tea and is an antioxidant. EGCG has also been studied for its ability to stimulate metabolism.
Folic acid is a necessary cofactor to the enzyme, tyrosine hydroxylase, which converts tyrosine to L-DOPA. Folic acid also serves as a methyl donor in a number of neurotransmitter pathways, including the conversion of norepinephrine to epinephrine.
Forskolin is a natural component of the plant Coleus forskohlii. It activates the enzyme adenylate cyclase resulting in an increase in cyclic adenosine monophosphate (cAMP) levels. cAMP is an intracellular messenger that activates protein kinase A.
Glutamine is a conditionally essential amino acid that serves as the precursor to the neurotransmitters GABA and glutamate. It also supports immune and gastrointestinal function.
Glycine serves as a calming neurotransmitter.
Histidine is a semi-essential amino acid that serves as the precursor to histamine. Histidine is an important component of many enzymes that affect neurotransmitter function.
Huperzine serrata is an acetylcholinesterase inhibitor, which blocks the breakdown of acetylcholine, an important neurotransmitter involved in immune system regulation and cognitive and motor function.
L-tryptophan is an essential amino acid and a precursor to serotonin. The conversion of L-tryptophan to serotonin is a two-step process with the intermediary synthesis of 5-HTP being a rate-limiting step.
Magnesium is a GABA receptor agonist and a glutamate receptor (NMDA) antagonist. It has been shown to reduce brain excitability.
Methionine is the amino acid precursor to S-adenosylmethionine (SAMe), which is a required cofactor in the conversion of norepinephrine to epinephrine as well as the conversion of L-DOPA to dopamine.
Mucuna cochinchinensis is a natural source of 3,4-dihydroxyphenylalanine (L-DOPA), the amino acid intermediary in dopamine synthesis. NeuroScience's M. cochinchinensis extract is standardized to contain 99% L-DOPA.
N-acetylcysteine (NAC) supports sulfur-containing pathways. NAC is a more soluble and less hydroscopic form of cysteine, making it very stable. NAC is converted to cysteine within the body by the actions of deacylase, an enzyme found ubiquitously in the intestines.
Cysteine is a key component of glutathione, the body's toxin-neutralizing powerhouse.
Niacin is a B-vitamin that supports adrenal function and the production of adrenal hormones.
Pantothenic acid is a B-vitamin that supports adrenal function and the production of adrenal hormones.
Phenylalanine is converted to the catecholamines in a multi-step enzymatic process. Phenylalanine can also be converted to phenylethylamine (PEA) by amino acid decarboxylase. The D-isoform of phenylalanine may enhance endorphin activity by inhibiting enkephalinase, the enzyme responsible for endorphin degradation. L-phenylalanine stimulates the production of the appetite-suppressing peptide, cholecystokinin (CCK).
Phosphatidylserine is a major phospholipid in the brain and is involved in many aspects of cellular membrane function. Phosphatidylserine also resensitizes cortisol receptors.
Rhodiola rosea is a natural product that has been found to decrease the effects of stress and fatigue on mental performance. These effects have been attributed to the ability of R. rosea extract to influence the levels and activity of monoamine neurotransmitters. NeuroScience, Inc.'s R. rosea extract is standardized to contains 15% rosavins.
Riboflavin serves as a precursor to the flavin adenine dinucleotide, a coenzyme involved in the energy-producing mitochondrial electron-transport chain. It has been postulated that headaches could be due to a deficiency in neuronal energy systems.
Selenium is involved in a number of detoxification pathways. Selenocysteine is a component of glutathione peroxidase, an enzyme that may behave as an antioxidant to protect tissues against oxidative stress.
Taurine is a GABAB agonist and may increase GABA levels by increasing GABA synthesis, preventing GABA breakdown, and blocking GABA reuptake.
Theanine is an amino acid naturally found in green tea and has been widely studied for its calming effects. The ability of theanine to reduce over-stimulation is thought to be due to its function as a glutamate receptor (NMDA) antagonist. Theanine has been found to prevent the death of neurons exposed to oxidative stress or glutamate over-stimulation.
Vicia faba is a natural source of 3,4-dihydroxyphenylalanine (L-DOPA), the amino acid intermediary in dopamine synthesis. NeuroScience's Vicia faba extract is standardized to contain 50% L-DOPA.
Vitamin B6 is a required enzymatic cofactor in numerous metabolic processes, including the synthesis of neurotransmitters such as serotonin and dopamine.
Vitamin B12 supports methylation pathways including the formation of S-adenosyl-homocysteine (SAMe) and the elimination of the neurotoxic compound homocysteine.
Vitamin C is a necessary cofactor in the conversion of dopamine to norepinephrine by the enzyme dopamine monooxygenase. It is also required for the conversion of 5-hydroxytryptophan to serotonin; however, it inhibits peripheral conversion of the monoamines in the GI tract.
Zinc is a mineral required for the function of numerous enzymatic pathways.