Depression, Melancholia, and Bipolar Depressive Disorders

Paul Reller, L.Ac.

Depression is a term that is widely used and misunderstood medically and socially. There are various medical conditions that we term depression, depressive disorders that are secondary to other heath conditions, common emotional depressions that may not be part of a significant physiological disorder, and depression that is cyclical and tied to a predominant anxiety disorder. Bipolar disorder is also now a familiar term, signifying alternating periods of depression and mania, which is an abnormal state of increased activity and elevated mood, characterized by various combinations of the following symptoms: abnormally increased energy and activity level, inappropriate elation, increased irritability, insomnia, grandiose notions, disconnected and racing thoughts, increased sexual desire, poor judgment, and/or inappropriate social behavior. Depression may be characterized by feelings of worthlessness and self-loathing, difficulty concentrating, restlessness, problems with decision making, fatique, low energy, weight changes, poor sleep patterns, with both insomnia and somnolence, body aches, and thoughts of suicide or death. Often, the term depression is used to describe all of these diseases and syndromes, and the treatment is often standardized for not only all individuals with these problems, but for subsets of patient with various depressive disorders. Such disorders are serious and should always be treated with a thorough integrated approach, utilizing various specialties to achieve a cure, not just a medicated state.

Traditional Chinese Medicine, and Complementary and Integrative Medicine, offers the patient an individualized proactive approach to regaining a healthy control of mood and correcting underlying imbalances in one's health that contribute to the diseases of depressive disorders. Treatments don't just block chemicals activities, but actually restore the patient's health, and a variety of treatment protocols are tailored to each individual disorder. Acupuncture, herbal/nutrient medicine, and patient counseling are now recognized as important adjunct therapies in an integrated multifaceted treatment of a variety of depressive disorders and related underlying health problems.

There is still a stigma attached to the diagnosis of Depression despite the recognition that this is a widespread societal health problem. It is possible that 100% of the population suffers from some sort of depressive episodes at some time in their life. The degree of dysfunction that results from these depressive episodes and their chronicity is what determines the need for treatment. The failure of society to accept the prevalence of depression and to deal with it in an open and healthy manner may be key to the prevalence of clinical disorders and dysfunctional states. The failure of patients to treat depressive episodes and discover the underlying health problems related to these episodes leads to the development of clinical dysfunctional disorders. Looking at your condition objectively, and not giving in to a purely subjective emotional response to depressive disorders, is an important step in treating these health problems early and effectively. Early treatment with Complementary Medicine holds much promise in preventing depressive episodes from becoming severe enough to require medication.

The World Health Organization (WHO) has determined from study that treatment for depressive disorders is so prevalent now that it consumes more than 1% of gross domestic product in Europe. The WHO is looking to find more effective treatment strategies to curb the rising costs of clinical depression, both to individuals and to society as a whole. An example of such treatment focus is the area of dysfunctional neurogenesis, which is a term applied to deficiency of brain function and physiology brought about by chronic stress and emotional depression, or constraint. Areas of the brain affected by problems with dysfunctional neurogenesis include the prefrontal cortex, amygdala, hippocampus and neocortex. Physiological problems objectively measured with fMRI study include reductions in neuronal volume, size and density, changes in blood flow, changes in glucose metabolism, and reduction in glial cell support. These various physiological problems are not addressed in standard pharmaceutical therapy. New approaches in medicine are needed as new research unveils the physiological aspects of depressive disorders.

The WHO has found a number of novel treatment strategies proven helpful in neurogenesis stimulation, or the formation of new healthy nerve and nerve support cells. Standard medicine, until recently, insisted that nerve cells in the brain could not be regenerated. This has been found to be patently untrue. The motivations for perpetuation of the myth that brain cells could not be regenerated are being explored, and many believe that this prevalent theory was promoted by profit motives in the pharmaceutical industry. Helpful tools in the stimulation of neurogenesis include increased daily exercise, new learning activities, hormonal balancing, resolution of metabolic dysfunctions, stress reduction, treatment of accelerated aging mechanisms, and neurotransmitter bioavailability promoted by natural precursors to neurotransmitters. The WHO studies found that both acute and chronic stress inhibits neurogenesis and gliogenesis, predominantly in the hippocampus, as well as the prefrontal cortex. Since there are 100 times as many glial (support) cells in the brain than actual neurons, reduced gliogenesis may be the key to reduced neurogenesis. Glial cells have been found to possess cellular receptors that are stimulated by both neurotransmitters and hormones. This type of research points to the explanation of how a complex strategy with Complementary and Integrative Medicine could have a profound effect over time on the success of treatment of Depressive Disorders.

Differentiating Depressive Disorders to individualize therapy

Standard medicine terms the most prevalent depression diagnosis clinically as Major Depressive Disorder, which is also sometimes called unipolar depression, and defines this type of depression as a mood disorder characterized by the occurence of one or more major depressive episodes and the abscence of any history of manic, mixed, or hypomanic episodes. Minor Depressive Disorder is a term signifying a mood disorder closely resembling major depressive disorder and dysrhythmic disorder but intermediate in severity between the two. Disrhythmic Disorder is defined as a mood disorder characterized by depressed feeling, loss of interest or pleasure in one's activities, and other symptoms typical of depression but tending to be longer in duration and less severe than the episodes in Major Depressive Disorder. Mood Disorder is defined as a group of mental disorders characterized by disturbances of mood manifested as one or more episodes of mania, hypomania (mild mania), depression, or some combination, the two main categories being bipolar disorders and depressive disorders. Hypomania is characterized by episodes of unusually excitable, energetic and productive behavior, with hyperactivity and talkativeness, increased sexual interest, quick anger, irritability, and a decreased need for sleep. All of these disorders contain a key aspect, which is an abnormality or derangement of function, and a morbid (pathological) mental or physical state. If one is becoming dysfunctional, and this may be due to a physical and/or mental disease mechanism or mechanisms, treatment is recommended, and the modern physician is looking past the standardized one-size-fits-all approach and designing individualized and integrated treatment protocols, addressing both the symptoms and the related health imbalances.

The underlying pathophysiology of Major Depressive Disorder is still not clearly defined in standard medical theory. Theories identify imbalances of key neurotransmitters, such as serotonin (i.e. 5-HT, hydroxytryptophan), dopamine and norepinephrine (adrenaline). The links between these neurotransmitters and the disorder are still largely defined by the fact that drugs that block receptor activity for the neurotransmitters seem to alleviate symptoms for a percentage of patients. The most common drugs used to treat Major Depressive Disorder work by either inhbiting reuptake of 5-HT at the synapse, antagonizing 5-HT or norepinephrine receptor activity and enhancing neurotransmitter release, or inhibiting the enzyme monoamine oxidase (MAO) and reducing neurotransmitter breakdown. Due to the poor control of depressive symptoms in long term therapy, other classes of drugs have now been approved to also treat various types of depressive disorder, or to add to these first order drugs to increase effectiveness. Expanded research is finally linking a variety of other chemical imbalances to depressive disorders, such as adiponectin dysregulation in obesity and metabolic syndrome, and the realization that we must address a complex host of chemical imbalances to really treat these disorders is finally taking hold. Many medical experts, as well as more informed and proactive patients, are also exploring the reasons why these neurotransmitter imbalances occur, and are looking for more treatment aimed at correcting the underlying causes of neurotransmitter imbalance.

One of the most significant reasons why we have so little research success in discovering the underlying causes for imbalances of 5-HT and norepinephrine is that the pharmaceuticals that block these neurotransmitter reuptakes are so profitable. A time will come when the world directs more research into the mechanisms that precede these neurotransmitter imbalances, and at that time, the profits of pharmaceutical companies will drop dramatically. The relatively little research now being conducted to discover these imbalances has uncovered the more complex role of receptors in the disease mechanism, leading to a current drive to promote drugs that affect a large array of neurotransmitter receptors, called antipsychotics. This strategy still fails to understand and correct the underlying homeostatic failures and their causes. This type of research has uncovered the complexity of receptors in the brain, though, and revealed that many, if not most, receptors are triggered by more than just one type of neurotransmitter chemical. These receptors are usually stimulated by more than one neurotransmitter, and by hormones, and potentially by lesser signaling chemicals as well. Research is also discovering that there is a complex quantum effect in the receptor functions as well, and that when there is a change in neurotransmitter concentration, a change in quantity of variants of a neurotransmitter, hormonal changes, and metabolic changes, that these receptors exhibit altered function and reactitivy. In effect, there is a complex balance of chemistry that is needed to insure the healthy function of neurotransmitter receptors, and since the receptors are doing the work, not the neurotransmitters and hormones directly, this is where more advanced research is directed.

Recent theories have led to the belief that reduced nerve cell volume and size in the hippocampus is a key to mood disorders (reduced neurogenesis or neurodegeneration). Neurodegeneration is now a very important focus in discovering the underlying health problems in depressive disorders. Reduced neurogenesis, or neurodegeneration, in patients suffering from chronic depression is now found in the hippocampus, lateral ventricles, and neocortex, which is small in cell number and size but very important to cortical function. The dual role of neurotransmitter chemicals as both hormones and neurotransmitters is also a focus of modern study once again, and subclinical hormone imbalances may be integral to depressive syndromes in a large percentage of patients. The body's intrinsic regulation of mood is also of prime importance, and such mechanisms as GABA modulation may be significantly improved with herbal and nutrient therapies. All of this research points to the need to develop a more complex and multifaceted approach to therapy in depressive disorders, and a more complex and individualized way to diagnose that reveals the differences between one patient and another.

Adherence to the standardized treatment of all of these depressive disorders has been much studied, and non-adherence to this simplified treatment protocol of single drug therapy has been a common problem across the world. Non-adherence to this drug regimen presents problems beyond poor effect of treatment, as intermittent use and dose variance is shown to create many physiological problems and side effects itself. Withdrawal from SSRI and SSNRI medication is also problematic, as neurochemical changes from sudden withdrawal have been show to have negative effects that are quite dramatic. Many books have now been written on the subject of this withdrawal syndrome and the subsequent addiction to these medications. With the promotion of these drugs as a standardized therapy, integration of a multifaceted treatment protocol declined, and depressive disorders that were less severe, such as Minor Depressive Disorder, Disrhythmic Disorder, minor Mood Disorders, and even situational depression and depression related to chronic health problems such as hormonal imbalance, subclinical hypothyroidism, obesity, etc. were all treated the same, with exactly the same drug protocol. The creation of dozens of different names for slight variations of the same drug has given the public the impression that there are significanct choices in treatment, but this aspect is finally being realized as false. The public is now looking to an evolved treatment standard that utilizes a variety of treatment tools and integrates them with an individualized approach.

A crisis of noncompliance with standard drug therapy for depressive disorders, and a drive to find improved treatment protocol

Why is there such a problems with noncompliance in standard drug therapy with Depressive Disorders? Long term studies of SSRIs and SSNRIs (selective serotonin and norepinephrine reuptake inhibitors) have produced some alarming statistics of side effects, and the lack of effectiveness has also played a part in many patients being discouraged and failing to consistently take the drugs. The problems with withdrawal, though, usually create a need to resume medication. Physicians themselves are starting to become alarmed due to the number of health problems linked to SSRI and SSNRI medication. Large class action lawsuits have been generated due to the number of studies linking SSRIs, such as Paxil, to a wide range of birth defects, including heart, abdominal wall, skull shape, lung and blood pressure abnormalities. A 2004 study linked SSRI use to suicidal thoughts and actions, prompting strict FDA warnings, and bans or limits on prescription in a number of countries. Many studies have identified neurotoxicities resulting from chronic use. In 2009, the Japanese Ministry of Health revised the warning labels on SSRI antidepressant medication to read “There are cases where we cannot rule out a causal relationship (of hostility, anxiety, and sudden acts of violence) with the medication.“ Other studies have linked depressed bone health to the hormonal and metabolic changes associated with chronic SSRI use. Researchers at the University of Minnesota reported that “women taking SSRIs lost twice as much bone density at the hip compared to other antidepressants or none at all.” (Diam el al, 2007). SSRI-induced sexual dysfunction has also been a subject of much concern. All of these studies point to an underlying mechanism that inhibits normal homeostatic regulation in the body and has large implications for general health as well. Patient concern has become high, and many patients are exploring a broader protocol for dealing the the underlying mechanisms that cause depression, melancholia and bipolar depressive disorders. For these patients, simply suppressing symptoms is no longer enough, and a restoration of health is sought. Complementary and Integrative Medicine serves as a proven effective adjunct to standard treatment, and also serves to decrease risks and side effects, support homeostatic health, and make standard protocols work better, in a safe, effective and healthy way.

In recent years, prominent experts in the field of psychology and psychiatry voiced doubts about the efficacy of antidepressant drug therapy itself. Irving Kirsch, a professor of psychology at the University of Hull, United Kingdom, and professor emeritus at the University of Connecticut, United States, wrote a book entitled The Emperor’s New Drugs: Exploding the Antidepressant Myth, suggesting that the whole array of data on antidepressant drug trials shows that these drugs barely outperformed placebos for mild to moderate depression. Dr. Kirsch has been a reknowned researcher of both antidepressants and the placebo effect, and is the originator of response expectancy theory, influencing analysis of clinical trials and official treatment guidelines. Marcia Angell M.D. is the first woman to serve as editor-in-chief of the New England Journal of Medicine, and is currently a senior lecturer at Harvard Medical School. Dr. Angell also has now written extensively on the failures of drug therapy for depression, and also on the fact that psychiatrists lead the pack of medical specialties in taking money from drug companies. Her article in The New York Review of Books, entitled The Illusions of Psychiatry, suggests that pharmaceutical companies invested heavily to transform psychiatry to a drug-intensive specialty and rewrite diagnostic guidelines to increase drug prescription despite the lack of objective tests or signs in mental illness. Dr. Angell’s views on the controversies of antidepressant drug use, including her view that the defining of depression and other psychiatric disorders by the often relatively small beneficial effects seen in clinical trials, can be read by clicking this link to her article entitled, The Epidemic of Mental Illness: Why?: http://www.nybooks.com/articles/archives/2011/jun/23/epidemic-mental-illness-why/. More and more experts in the field are suggesting that the patient should consider an integrative approach to treatment for mild to moderate depression, utilizing an array of therapies besides standard drug protocols to quiet symptoms and reestablish a healthy neurocognitive function.

The failure of anti-depressant medications is also spurring a large push in the area of new technology to treat depression and anxiety disorders. The physiological problems in these pathologies involve more than simplified neurochemical imbalances. David Anderson, a professor of biology at the California Institute of Technology, does research with optogenetics, a promising field of therapy that seeks to use fiber optic implants to exert direct effects on neural firing, or even exogenous light beams that affect chemically sensitized neurons in specific areas of the brain. While still in early stages of development, these technologies involve brain studies that reveal much about the physiological problems in depression and anxiety disorders. Dr. Anderson states that: “Psychiatric disorders are probably not due only to chemical imbalances in the brain. It’s more than just a giant bag of serotonin or dopamine whose concentrations sometimes are too low or too high. Rather, they likely involve disorders of specific circuits within specific brain regions.” Dr. Anderson compares the current drug strategies to a sloppy oil change, stating that if you dump oil over your engine, some of it will get to the right place, but a lot of it will end up doing more harm than good. The notion of more harm than good is now gaining a broader acceptance in standard medicine, and even in the patient population. Restoration of brain function is more sensible approach to these problems, and current research is finding quite the role for therapies in Complementary Medicine to help achieve this goal of restoring neuroplasticity and function (see the article entitled Brain Health and Function on this website).

The most prevalent focus to address widespread non-compliance with standard drug therapy in depressive disorders is to expand the treatment protocol and include therapies that proactively engage the patient in their care, as well as afford the possibility of decreasing drug dosages enough to diminish side effects and risks to an acceptable level. The two areas that are being promoted heavily in this new strategy are cognitive-behavioral therapies and Complementary and Integrative Medicine. Large studies to prove efficacy with these strategies have been, and are being, conducted across the world. Of course, there are problems applying the type of clinical study used to judge pharmaceuticals, where the effects are simpler and a placebo is easily substituted by creating a dummy pill. There are no real placebos possible in the study of cognitive-behavioral therapies and acupuncture, and these treatments work best when individualized and nuanced to each patient by the treating physician. The array of effects of Complementary and Integrative Medicine are also broad, and thus difficult to apply to standard studies. Nevertheless, these randomized, double-blinded and supposedly placebo-controlled studies have been widely conducted, and have shown efficacy. This fact alone shows the public how serious medicine is in incorporating these strategies into a more effective multifactorial set of protocols. Designing treatment guidelines and integrated protocols that meet standardized guidelines will be a challenge, but many patients have become educated to these approaches and now seek out physicians that integrate therapeutic disciplines and show knowledge and clinical experience. This array of scientific study is helping such phsyicians as Licensed Acupuncturists and herbalist to also utilize more objective information in their practice, which has greatly improved results.

One practical solution to the problems of antidepressant medication noncompliance, as well as the health concerns about long-term prescription, is the integration of Complementary Medicine and psychotherapies, especially cognitive and behavioral therapy, into a protocol of gradual drug withdrawal once a stabilization of the depressive or bipolar disorder is seen. The problems with withdrawal of these drugs, especially sudden withdrawal, involves both the chemical dependence as well as the negative effects of the drugs themselves. Gradual tapering of dosage over a period of several months is now the normal guideline for withdrawing these drugs, and an increasing number of MDs that prescribe them are finding that an adjunct therapeutic protocol during this withdrawal period, such as the use of acupuncture, herbal and nutrient medicine, as well as cognitive and behavorial counseling, effectively reduces the negative effects of withdrawal, and provides the patient with an alternative maintenance support therapy to prevent relapse. Studies have also shown that about 10% of patients with depressive disorder treated or withdrawn from antidepressant therapy acquire a bipolar depressive disorder, or intiation of a manic phase to the disorder. Use of Complementary and Integrative Medicine may provide for a modulatory, or balancing, physiological effect that could prevent many of these unipolar depressive disorders from advancing to a bipolar disorder. Traditional Chinese Medicine offers a rich history of effective treatment protocol for these depressive and bipolar disorders and is relatively inexpensive, as well as being very safe and free of negative effects. Utilization of this practice when withdrawing from antidepressant and antianxiety medication, along with tapering of the drug dosage, is proving to be a remarkably beneficial and effective protocol.

Underlying physical causes of depressive disorders, and the need to address and treat these underlying health problems

Physical causes of depression include hyperparathyroidism, hypothyroidism, obesity, metabolic syndrome, Vitamin D3 hormonal deficiency, kidney and adrenal insufficiency, and other hormonal imbalances, as well as syndromes or episodes of increased physiological stress. Proper assessment of depressive disorders should include an analysis of these potential problems, and then an analysis of the potential health imbalances that may be contributing to these underlying physical causes of depression. This type of medical analysis is not accomplished in a ten minute office visit.

Postmenopausal depression is very common and directly related to hormonal imbalance. Correction of hormonal imbalance and restoration of natural hormonal homeostasis relieves depression in a large percentage of these patients. Similarly, depression during pregnancy, and post-partum depression are relieved when hormonal homeostasis is recovered. Numerous recent studies show that acupuncture alone is effective to treat depression during pregnancy. The combined use of acupuncture with hormonal restoration utilizing bioidentical hormone therapy and herbal/nutrient medicine has also been shown to be effective for post-menopausal depression. These studies demonstrate how underlying health problems may be responsible for depressive disorders, and treatment of these related, or underlying health problems, with Complementary and Integrative Medicine, may cure or relieve the depression.

Much research has been conducted in recent years as well to explain the link between obesity, metabolic syndrome, and depression. Adipokines, or chemical messengers related to fat cells, have been shown to be dysregulated in depressive disorders, obesity and metabolic syndrome, and the physiological links between these disorders and adipokines have now been well established. The most well studied of these adiopkines are leptin, adiponectin, and resistin. Leptin is a chemical messenger that acts at hormonal receptors and is balanced in the body with insulin. Resistin is a chemical messenger more associated with immune function. There is also a link between adipokine dysregulation and cardiovascular disease. Such studies point to the need to address the problem of depression holistically to achieve the best outcomes. Simple suppression of depressive disorder with drugs will not address these related health problems and insure a great degree of prevention of future health problems and restoration of quality of life.

Pharmaceuticals that treat Major Depressive Disorder

Many of the new pharmaceuticals that are advertised heavily in the treatment of depression first specify that large studies in recent years have found that nearly 2 our of 3 patients treated pharmaceutically for depression had significant symptoms of depression not resolved with their antidepressant treatment. While this has been used as a marketing ploy for these patients to try the newer pharmaceuticals, either as an alternative to standard antidepressants, or as an additional drug, many patients are now wondering whether Complementary and Integrative Medicine may offer more effective and less risky treatment, either as an adjunct to complement their present medication protocol, potentially reducing the dosage need, or as an alternative to the chronic side effects that come with long term use of antidepressants. This is the case especially in milder depressive disorders and when the Major Depressive Disorder or Bipolar Syndrome becomes more controlled with use of a multifaceted approach, incorporating some cognitive and behavior therapy, improved nutrient medicine, and various other mood therapies that more enlightened M.D.s are now utilizing. While Major Depressive Disorder presents great potential risks to the patient, and it has not been suggested by any medical group that medication should be abandoned, patients have not been educated to the array of treatment protocols that has been proven successful as adjunct to medication in a multifaceted approach. While this more complex approach demands more patient time and participation, the outcomes and quality of life are worth the added work. For many patients, the desire to manage these disorders without medication in the future is realized.

For many patients, specialist care is now discourged by insurance companies and hospital corporations and HMOs. Clinical psychiatrists and psychologists are more often kept out of the loop in the treatment of depressive disorders, even as studies in the United States by the government and the NIH have stated that a very high percentage of the population now suffers from some type of depressive disorder. This is because there is a realization that specialists now are more interested in a multifaceted integrated treatment approach. Insurance approval and HMO guidelines often now restrict the medical care to a medical doctor that is not a specialist in these disorders. The explanation for this type of managed care is that there is only one type of drug therapy now utilized, and unless the patient fails with this standardized therapy, it is not cost effective to send them to specialists. The public is becoming alarmed at such strategies as this. Standard medical doctors, general practitioners and other specialists, as well as clinical psychiatrists, have also failed to adequately address patient non-compliance to standard drug protocols, and have largely abandoned, rather than improved, the multifaceted treatment approach, largely because of failure of the insurance industry to pay for treatment. Currently, this is the subject of much debate in government, as health care reforms seek to mandate more of this care for depressive disorders. The cost to society, as well as the individual, is now recognized as a very high cost to us all, as productivity, social spending, lost work days, dissolution of families, and a growing set of related health problems that drive up health care costs for us all, are now recognized in the equation of the cost of inadequate care for depressive disorders.

Many experts in the last ten years see a growing overdiagnosis of clinical Depression by unqualified doctors who are not specialists, and too easily prescribe drugs that once started are not easy to withdraw from the therapy. The long-term side effects and risks, and the addictive nature of these drugs, such as SSRI and SSNRI medication, as well as anti-psychotics, are too easily overlooked. The general medical rule of first prescribing benign therapies that are conservative, which is the ethical rule of Hippocrates (himself a proponent of herbal and nutrient medicine), is generally overlooked in this arena now. A high level of concern and alarm has arisen in the field of medical specialists concerning the problems with withdrawing the patients from these drugs when they are no longer needed, or when the patient is not tolerating chronic side effects. Books such as The Antidepressant Solution: A Step-by-Step Guide to Safely Overcome Antidepressant Withdrawal, Dependence, and Addiction by Joseph Glenmullen, have heralded a new era in medical outlook for many clinical specialists in Depressive Disorders. For many patients, they have found that they must be their own advocate, seeking early treatment for these depressive disorders before they enter the arena of antidepressant addiction. The failure to address Depression as a disease has also been of some concern among specialists. Although a variety of disease mechanisms are identified in depressive disorders, there is a reluctance to acknowledge this aspect of the health problem. Both Insurance Companies and Pharmaceutical companies do not see the economic benefit of treating these disease mechanisms. Both industries also see the future emphasis on treating a complex array of disease mechanisms underlying depressive disorders with a complex array of integrated therapies. Such economic issues should not dominate public health.

Pharmaceutical antidepressant therapy comes with a long history of problems.

Some of the new antidepressant therapies have received a number of drug warnings from the FDA. Antipsychotics are a class of medication that have received the most scrutiny, and many of these drugs are now being heavily marketed for disorders that are not approved by the FDA as those treatable by these drugs. The FDA was created to insure that the public was protected from new drugs introduced into the market, and the FDA approval measures risk versus benefit in drugs, establishing public guidelines for acceptable use, often weighing the seriousness of the disorder against the seriousness of the side effects. For instance, a popularly prescribed antipsychotic is quetiapine fumarate (called Seroquel by AstraZeneca). This second class of antipsychotics, termed atypical, have broad effects in the central nervous system, antagonizing, or inhibiting function, at a variety of neurotransmitter receptors, including 4 types of dopamine cell receptors, 4 types of 5HT (hydroxytryptophan) receptors (associated with serotonin), 2 types of adrenal receptors, a histamine cell receptor, and acetylcholine receptors. These cell receptors, of course, are not confined to the area of the brain that is responsible for depression, and not even confined to the brain, resulting in an antagonism, or inhibition, of functions throughout the body, or unwanted side effects. Histamine is used as a neurohormone throughout the body, especially in membranes of the stomach, intestines and respiratory tract. Acetylcholine is a major neurotransmitter of the parasympathetic autonomic nervous system, which controls our constant organ functions. The lowest dosages of quentiapine act as antihistamines and alpha-adrenergic blockers, but the highest dosages are needed to block significant numbers of cell receptors of dopamine and serotonin. This means that a very significant effect is exerted blocking normal histamine health as well as adrenal function.

In 2005, the U.S. National Institutes of Mental Health (part of the NIH) performed a large study of second generation antipsychotics called CATIE (clinical antipsychotic trials of interventional effectiveness) published in the New England Journal of Medicine. Of the nearly 1500 patient participants in this study, 74% of patients discontinued use of the drugs before the trial ended due to significant side effects and/or lack of effectiveness. A concurrent study in Great Britain, published in the British Medical Journal, found that the popularly prescribed quetiapine fumarate (Seroquel) was prescribed heavily for the elderly, with 29% of the drug prescriptions going to Alzheimer's patients, and the British study revealed that this drug was not only ineffective in reducing Alzheimer agitation, but was found to actually worsen cognitive functioning in elderly patients with dementia. Subsequent studies examined by the FDA produced an FDA warning that quetiapine increased mortality (incidence of death) in elderly patients with dementia, due to a variety of causes. A larger percentage of prescriptions were also given to children, as a means to control agitation and behavior in hyperactivity disorders. The FDA reviewed clinical studies and found that a stern warning (black box) was needed to warn patients and doctors that the drug produced increased risk of suicidal thoughts and injurious behavior in children, adolescents and young adults. The clinical trials that prove efficacy for the disorders of schizophrenia and bipolar depressive disorder type I, as well as Major Depressive Disorder, were all 6 week trials, and long term studies exploring efficacy and chronic health problems associated with use are pending.

The health problems associated with these second class antipsychotics that most concern medical doctors are associated with long-term use. Metabolic syndrome (commonly called diabetes), weight gain, high blood pressure, immune deficiency (leukopenia, neutropenia and agranulocytosis, or the depressed production of these white blood cells and immune mediators), and cataracts (due to the denaturing of regulatory proteins and adverse effects on melanin, producing harmful photoreactivity). An FDA warning indicates that gradual increase in total cholesterol, LDL and triglycerides has been reported in significant number of patients in short clinical trials, as well as decreases in HDL. The side effects that the patient notices the most are the more immediate health effects, though, which include sedation, tiredness, fatique, racing heart (7% reported tachycardia in the short clinical trials), increased appetite, memory problems, and poor cognitive function. While the short term clinical trials reported that with 6 weeks of use these effects individually were significant in only about 1% of the study group, the NIH study found that with longer use, 74% of patients dropped out due to these side effects. This class of drugs also poses significant problems, like many antidepressants and antianxiety drugs, of very adverse effects when reducing dosage and going off of the drugs, with a significant rebound effect when all of these neurohormonal receptors are no longer blocked or inhibited.

Another new popular antidepressant drug is Aripiprazole (marketed as Abilify), which is also an atypical antipsychotic. This drug is marketed as an additional antidepressant for the high percentage of depression sufferers that complain of poor effects in the long term with standard antidepressants (SSRIs). The FDA has approved this drug for the treatment of Major Depressive Disorder and acute manic episodes in Bipolar disorder, but the prescription for depression is only approved if used concurrently with standard antidepressant medications and if these medications are ineffective. The FDA does not approve of the drug being used alone for the treatment of depression. This second class antipsychotic works much differently from Seroquel and the other antipsychotics. Abilify actually enhances some of the neurohormonal receptors that the others block, working as a partial agonist at the D2 (dopamine receptor 2) and at the 5HT-1A receptors (serotonin effects).

Of the many neurological side effects noted from antipsychotic antidepressants, one is of particular note. Akathisia is a symptom that manifests as difficulty sitting still, restless feelings, a disquieting anxiety, malaise (uneasiness, out of sort feeling, general discomfort, or feeling of being unwell), and in some cases episodes of overwhelming anxiety and a sense of impending doom. Akasthisia is seen in most cases as a side effect of antipsychotic medications, but in fewer instances is attributed to SSRI antidepressants, tricyclic antidepressants, benzodiazepine anxiety medications, and amphetamines. Akisthisia is also a term used to describe withdrawal symptoms from alcohol, opiates, barbituates, cocaine and amphetamines. The most well known manifestation in the last decade is associated with benzodiazepine withdrawal syndrome, which in many cases has been so severe as to keep the patient on these anti-anxiety drugs for fear of the withdrawal symptoms, which often time also involve sudden racing heart and high blood pressure. Akathisia is related in many studies to suicide, and many experts see this as accounting for the FDA warnings of increased suicidal thoughts and actions in young adults as a side effect of antipsychotic medications. Recent studies have indicated that akasthisia may be highly associated in a chronic sense with SSRIs as well. Studies are still exploring the pathophysiology of akasthisia, but most experts agreee that there is a strong association with an altered balance in the dopaminergic system. Dopamine disorder and dopamine receptor disorder are key aspects of Parkinson's disease and Attention Deficit and Hyperactivity Disorder. These findings are discouraging a large number of patients from taking these drugs, or starting them.

Complementary Medicine in now widely integrated to treat the side effects of antidepressants and antipsychotic medications that are used to treat depression. As scientific studies increase, medical doctors are now utilizing this evidence-based medicine to treat various problematic symptoms as well as to facilitate healthier withdrawal from these drugs, as well as benzodiazepines prescribed for anxiety, when necessary. Withdrawal from drugs that inhibit neurohormonal receptors often cause alarming symptoms if withdrawn suddenly. Studies have confirmed that Vitamin B6 (the active metabolite is P5P) and N-Acetyl-cysteine help alleviate the symptoms called akasthisia. A variety of herbs and nutrient medicines help balance and restore the central nervous system to facilitate a healthy withdrawal of these receptor inhibitors and drugs that replace natural nervous system modulation. A knowledgeable Complementary Medicine physician may be able to utilize a variety of protocols to both treat the side effects and risks of pharmaceutical medications, and to help with the underlying disease mechanisms and imbalances that have created the individual depressive disorder.

Scientific study confirming the efficacy of Acupuncture and Herbal/Nutrient medicines in the treatment of Depression

Application of standard double-blinded placebo-controlled studies are difficult when studying efficacy of acupuncture in Major Depressive Syndromes, but centuries of clinical experience provide much empirical proof of acupuncture efficacy. In Traditional Chinese Medicine, each individual is assessed to gain an understanding of the root causes of depression, health imbalances, and contributing health problems. Treatment addresses all of these factors while also addressing acute symptoms, creating a holistic protocol that both relieves and restores the patient. Throughout history, individualized acupuncture therapy has been combined with both herbal and nutrient therapy to create a synergistic holistic therapy with better outcomes. Of course, in depression syndromes this may take some time to achieve lasting results. To date, the lack of funding for studies of the efficacy of acupuncture in depressive disorders has also been a problem. Studies that chart short courses of acupuncture are problematic. In all scientific study of depressive syndromes, the measure of outcome is also problematic. Most studies rely on subjective rating scales, and these rating scales often are designed for pharmaceutical drug therapies. Nevertheless, a number of short course, or preliminary studies, of acupuncture in the treatment of Major Depressive Disorder have all produced evidence of significant benefit.

A study at the University of Arizona Department of Psychology in 1998 randomly assigned patients to groups on a waiting list receiving no treatment, nonspecific acupuncture therapy, and acupuncture specific to the individual. The Group of patients receiving acupuncture specific to each individual for 8 weeks scored much better on the Hamilton Rating Scale for Depression (HRSD), with a mean change of depression parameters, or symptoms, of minus 10 with individualized treatment. The patients on the waiting list opted to receive 8 weeks of individualized treatment and improved from a minus 5 score after waiting 8 weeks to a minus 18 score after receiving 8 weeks of individualized acupuncture. The research was peer-reviewed and published in the journal of Psychological Science, but, of course, critized in standard medicine for failure in study design, as only 68 diagnosed patients participated.

A 2004 study of acupuncture in the treatment of major depression during pregnancy was conducted at Stanford University by the Department of Psychiatry and Behavioral Sciences, in conjunction with the University of Arizona, and the University of Texas. The conclusion of these many researchers in a larger randomized and controlled study was: “Despite limitations, this randomized controlled pilot study indicates that acupuncture holds promise as a safe, effective, and acceptable treatment of depression during pregnancy, and that a larger clinical trial is scheduled.” This study was conducted for pregnant patients, as standard pharmaceutical medicine has little or no safe treatments for depression during pregnancy, the the positive results can be extrapolated to the patients who are not pregnant. There is no scientific data that would suggest that acupuncture efficacy is confined to pregnant patients, or that effects of acupuncture are due to physiological aspects unique to pregnancy.

The approaches and treatment protocols utilized in Traditional Chinese Medicine and Complementary and Integrative Medicine for the treatment of Depressive Disorders

In Traditional Chinese Medicine there has always been a holistic perspective in relation to disease and disorder. A physical disease or disorder may have its roots in a mental or emotional disorder, and a mental or emotional disease or disorder may result due to physical disease or imbalance. The foundation text of TCM, the Huang Di Nei Jing, quotes the physicians explaining that in their opinion, most internal disease originates with emotional constraint, or the constraint of natural emotional expression. This is because one of the functions of emotional reaction is to promote healthy physiological balance. This mind-body holistic approach has long established the assessment of each patient in relation to the overall balance of homeostatic mechanisms, both with physical function and systems, and with emotional systems of balance, in TCM. Depressive disorders are thus seen as more than just a neurochemical imbalance, and it has long been noted that treatment of visceral imbalances have a dramatic effect on curing the depressive disorder.

The theory that emotional disorder and depression is rooted in physiological dysfunction is not novel to modern medicine. TCM, though, sees the physiological aspect as a broad set of potential dysfunctions, not merely a problem with neurotransmitter deficiency. In fact, the emphasis is on the underlying physiological systems thoughout the body, not just the brain. This doesn't imply that the neurochemical function, or brain function, and balance of brain functions, is ignored in TCM. Modern research has proven that the acupuncture stimulation has dramatic effects on specific areas of the brain. Research in the last 15 years has demonstrated with functional MRI studies the direct effects needle stimulation has on appropriate areas of the brain, and concurrent laboratory analysis confirms a cascade of chemical events that occur after this stimulation. Scientific study of herbal medicine has also revealed how specific herbal chemicals modulate neurochemicals and brain function, and even nutrient medicine, which has long been used in Chinese history to cure mental and emotional disorders, has been proven to be useful in modulation of neurochemical balance. The treatment protocol in TCM, though, has always addressed both specific therapies to affect the brain, and related imbalances in visceral function.

The fact that the specialty of Traditional Chinese Medicine (TCM) focuses on a holistic mind-body approach to homeostatic balance and underlying health problems does not imply that TCM ignores specific neurochemical and neurohormonal imbalances in the treatment of depression disorders, though. By incorporating modern medical research into the field of TCM, today’s TCM physicians are able to utilize specific treatments to normalize and modulate serotonin and norepinephrine metabolism and receptor function, and add this to the overall holistic treatment strategy. Chemicals found in Chinese herbs are well studied, and many provide a significant effect on these same neurological mechanisms that are addressed by modern allopathic pharmacology. The precursor to serotonin and melatonin, for instance, 5HTP, is found in the griffonia seed, a Chinese herb. Chemicals in a variety of herbs are proven to have significant effects on the serotonin and dopamine receptor functions, on the GABA system, exhibit benzodiazepine-like effects, etc. What is unique to these chemicals that evolved in our complex ecosystem is the evolved modulatory effects, and the synergistic effects of the array of chemicals evolved in these medicinal plants. Nature solves problems through the evolutionary process. Chemicals evolve in nature that can correct our health problems. Modern chemistry and synthetic chemistry does not have a patent on problem-solving chemicals. The modern professional herbalist has not only the empirical knowledge and experience of centuries to guide practice, but modern research as well. In addition, the science of nutritional medicine has uncovered a vast array of safe and effective chemicals that also have specific neurochemical effects. For instance, the common amino acid tryptophan is the precursor to serotonin in the brain, and the common mineral lithium has a proven effect on modulation of neurotransmitters and receptor functions. By combining this vast nutrient science with herbal research, and the research elucidating specific effects on brain function of specialized acupuncture points and stimulating techniques, the options in treatment, and the specialized guidance from research, has expanded the realm of proven treatment protocols for the TCM phsyician dramatically in recent years. Unlike modern allopathic medicine, though, the TCM physician never throws away effective treatment theories, techniques and protocols from the past. The attention to historical concepts and theories always serves as a platform for modern treatment in TCM.

Besides treatment of both the visceral systems and the central nervous system, TCM also has a rich history of counseling, and ideas of natural order in the control of emotions and mental processes. This mind-body approach is now recognized by modern allopathic medicine as well, and efficacy is proven with scienfic study and human clinical trials. TCM is at its root a naturalistic science of Daoism, or the way of Nature, and its patterns. Ancient TCM physicians noted that the emotions and mental processes naturally seek balance, with one emotion flaring to counter another. When we get angry, our mind naturally feels great remorse, or regret. When we are sad, we seek some form of joy, or exuberant expression, to counter the sadness. The emotions form a pattern of five elements that engender, constrain, rebel against, and control each other in a natural pattern. These five elements also relate to the visceral systems, and to the patterns in natural seasonal changes outside the body to which we respond, to types of food, etc. Within this pattern of elements, ther is always a balance and transformation of yin and yang energies as well. All of this is considered as the TCM physician assesses each patient and decides how to restore a natural order and balance that will resolve the depressive syndrome. The patient, when made aware of emotional habits that are not in balance, can exert a conscious effort to restore these emotional checks and balances in an ordered manner. Often, restoring a more natural order of physical habits can also help resolve the disorder, with a set pattern of eating habits, sleep schedule, activity and exercise, etc. Modern medicine has also found great success with such cognitive and behavioral approaches, but has too often resorted to a purely simplified one-size-fits-all approach of medicating due to the complexity of an array of integrated treatment strategies.

Like modern medicine, TCM has also long grouped the individual syndromes of depressive disorders into categories. Historically, the categories have been primarily been termed melancholia, depression, and manic-depression, although various subsets, such as post-partum depression, grief or loss, neurosis and psychosis also are considered. To the TCM physician, these groupings, or types of depressive disorder, imply the type of imbalance that has occurred and is occurring, and this implies that various organ systems are not well regulated. In bipolar, or manic depressive, disorder, the manic state will cause an exuberance, or yang, that gives rise to heat and stagnation, eventually causing an episode of depressed physical function. The depressed physical function will cause a stagnating flow and inner heat that will give rise to the yang energy, or exuberance and mania once again. This pattern needs to be controlled both physically and mentally, and when the exuberant yang is restrained, the pattern of the depressed state will not occur. The treatment varies according to the pattern of the patient, and various signs and symptoms guide the treatment during its course. Failure to look at the daily circumstances of the patient, their habits and changes, changing conditions of the disease, and problems of the patient coping with changes in circumstance, all are cited in TCM literature as failures in diagnosing and treating the individual patient effectively. All of this data is incorporated into the patterns of treatment, both with acupouncture, and with the herbal/nutrient therapies, providing a changing pattern of treatment over time, and nurturing the mind and body back to a healthy balanced state that is not dependent on therapeutic measures forever.

In TCM theory, melancholia is a form of depressive disorder that has its physiological roots in poor flow of that part of the metabolism referred to a the Yang Qi. The poor metabolic flow is attributed to either a blocked or unsmooth state of metabolism. The reasons for this stagnation of Yang Qi metabolic function include emotional stress, resignation to failure, pent-up vexation, discontent, grief, and a number of factors that lead to dysfunction of liver metabolism, or that affect the spleen function, resulting in an array of physiological factors that may contribute to the disorder, including poor blood quality, immune dysfunction, and metabolic syndrome. Poor physiological function may create a sense of depressed emotional function and flow. This manifests as a confusing sense of ill health, and eventually, the patient is stuck in a pattern of sluggishness and fatique that is terribly depressing. The cycle of causative factors, with emotional stress potentially depressing physiological function, which then leads to a reinforcement of emotional ill health, is thought to be the primary mechanism of chronic melancholic depression. The holistic approach to therapy is necessary to efficiently break out of this vicious cycle.

Manic depressive psychosis is theorized in ancient TCM to be associated with the categories of Fire and Phlegm, which refer to a variety of physiological dysfunctions, including inflammation, blood heat, toxicity, coagulation, and accumulation of plaques and reactive oxidants. Episodic heat or inflammation may be generated in the liver or liver system in response to alternating episodic metabolic congestion or coagulative mechanisms. In essence, the slowed metabolism creates a period of a sense of depressed function, and the body reacts by creating a period of heat, or hypermetabolism, leading to the manifestations of mania or hypomania. The underlying causes include over-deliberation, obsession, unsatisfied desires, intermingling of emotions of joy and sorrow that cause emotional confusion, or anger and fright mixed during a traumatic time in life. These types of circumstances may affect more than the liver system, potentially impairing the functions of the systems related to the heart, spleen, gallbladder and kidney. TCM physicians believed that the patients and physicians needed to objectively analyze these origins of emotional imbalance to stop these harmful mechanisms, and fully restore well being. Without analysis of external stressors, and a proactive approach by the patient to change these underlying mechanisms of cause, treatment could only suppress symptoms, and not cure the patient.

While these classic terms in TCM are difficult for the modern physician and patient to understand, modern Western medicine is also rooted in similar theories of Greek physicians. The difference is that modern medicine has rejected such terminology in favor of allopathic medicine and standardized focused treatment protocols. TCM, and holistic medicine, has instead embraced the specifics of modern scientific understanding, and incorporated the findings of research into its classic framework. The fight between these two schools of thought has not benefited the public. There is a place for highly focused and simplified allopathic treatment, and standardization of care. The complexity of human disease calls for this approach to facilitate a broad economy of medical care. Still, we have reached a point where this approach has overtaken its purpose, and itself generated a scale of medical treatment that is no longer economical or efficient, but too self-serving. There needs to be a balance in medical care, where the classic holistic approach to health, and preventative medicine, is again incorporated fully to complement the allopathic approach. The treatment of depressive syndromes, which obviously depresses both physical parameters as well as the emotional and mental states, is the ideal arena to blend both the allopathic and the holistic treatment.

Some nutrient and herbal medicines researched for the treatment of various depressive and bipolar disorders (the complete list of herbs and nutrients is too long for this webpage):

• Choline and Inositol: inositol has been shown in clinical studies to be as effective or more effective than SSRIs for the treatment of obsessive compulsive disorder, and numerous studies now show that high dosage supplementation (e.g. 12 grams daily) of inositol has significant beneficial effects in the adjunct treatment of Major Depressive Disorder, Bipolar Disorder, Panic Disorder, and agoraphobia as well. Patients diagnosed with clinical depression generally have been found to have decreased levels of inositol in their cerebrospinal fluid. Choline is an essential nutrient that is useful in the brain for structural cell integrity, signaling roles in cell membranes, acetylcholine neurotransmission, and as a major source of methyl groups. Deficiency of choline has been linked to anxiety symptoms, but not to depressive symptoms. A percentage of the population has been found to exhibit choline deficiency despite adequate dietary intake. Lecithin is a type of choline, and the active lecithin metabolite, phosphatidylcholine is perhaps a better supplement for cell membrane integrity. Choline may also contribute to neural detoxification and reduction of homocysteine levels. There are 9 known stereoisomers of inositol, and a number of these are now touted as supplements in medical treatment. Inositol functions in the brain as an aid to cellular signaling and cellular processes (secondary messengers). A number of brain functions depend on inositol metabolites, including serotonin activity modulation, nerve guidance with epsin proteins, cell membrane potential maintenance, calcium concentration regulation, and insulin signal transduction (insulin has been shown to be produced by brain cells as well as pancreatic cells, and plays essential roles in brain function). Inositol is an essential component of Coenzyme A, one of the most important metabolic aids in our bodies. Both inositol and choline are synthesized by symbiotic bacteria in the gut, and problems with gut microbial health is potentially one of the contributing causes of deficiency. Some signs of inositol general deficiency include mood swings, irritability, constipation, hair loss, and high cholesterol. Food sources of inositol include buckwheat, lentils, sesame seeds, coconut, peas, brewer's yeast, unrefined molasses, raisins, and many fruits and vegetables. Food sources of choline include eggs, whole grains, legumes, soy, and whole milk. A typical supplement dosage is 650mg, and a 12 gram dosage would require about 16 capsules a day. Studies of high dosage inositol showed no adverse effects. Inositol hexanicotinate is a form of Niacin, or Vitamin B3, which is now widely used in nutrient medicine as well. CDP Choline is a supplement (Cytidine Diphosphate Choline) that is an active choline metabolite found to restore the levels of phophatidylserine, phsophatydilcholine, and sphingomyelin in the brain, as well as improve acetycholine, dopamine and norepinephrine production in the brain. RECOMMENDED: high dosage of Inositol and normal dosage of CDP Choline (Vitamin Research Products: Inositol 650 mg 4-16 capsules per day with meals (increase the dosage slowly and then taper the reduction of dose), and CDP Choline 250 mg, until symptoms improve, then maintenance with Phosphatidylserine 100 Plus).
• Maca root: Maca, or Lepidium meyenii Walp. is a Peruvian native wild taproot and germinating seedling of a high altitude turnip that has been cultivated for centuries, both as a foodstuff and medicinal plant. The dark colored, or red maca, contain significant amounts of natural iodine. The beneficial chemicals in all types are numerous and benefit brain and endocrine function, and have been shown to have antidepressant activity. A study by the Depression Clinical Research Program at Massachusetts General Hospital in Boston found that maca root may alleviate SSRI-induced sexual dysfunction with a dose-related effect, and was well tolerated at higher dosage (see study in 2008 cited below). Maca can be taken as a simple powder dissolved in hot water, or in food, but is usually taken as a pill with concentrated extract. No matter whether you suffer from sexual dysfunction from SSRIs or not, Maca is proven to be beneficial to patients with depression, especially if there is easy fatique, hormonal deficiency, subclinical hypothyroidism, or metabolic syndrome. Studies cited below show proof of efficacy with Maca in treatment of depression in post-menopausal syndromes, and patients with subclinical hypothyroid syndromes may benefit from incorporating Maca into the treatment protocol as well.
• 5-HTP from Griffonia seed extract, and the amino acid L-Tryptophan: 5-HTP is an herbal or nutrient chemical that is found both in plants and animals. 5-hydroxytryptophan precursor (5-HTP) is a natural precursor to tryptophan, an essential amino acid. Tryptophan is an important amino acid in the chain of amino acids that build serotonin, melatonin, and other neurotransmitters. The term essential means that humans must have this amino acid in the diet, or that we can't produce enough of it ourselves. Tryptophan was the most widely used nutrient supplement in the world at the time that SSRI medications were being heavily marketed, and most of the tryptophan was produced by a single Japanese company. In about 1999, 2 children in New Mexico died after taking a contaminated tryptophan supplement, and it was soon discovered in an investigation that a fairly rare bacteria had gotten into a batch of the pills. The media uproar and pressure on the U.S. government by big pharmaceuticals prompted an 11 year ban on sales in the U.S., but the CDC had released a report that tryptophan itself had no possibility of toxicity. Even people with no scientific background should have been able to understand that any essential amino acid, commonly found in our food, could not be toxic. Nevertheless, the collusion of Big Pharm, the U.S. FDA, and the media, created a general fear of tryptophan and severely curbed its use. In response, chemists found the precursor, hydroxytryptophan, or actually the precursor to the precursor, shikimic acid, which was first derived from the Japanes flower shikimi. The Chinese then found that an African native seed, Griffonia, which is a large coffee bean like seed that had been used as a food and medicinal herb for centuries, contained a high concentration of the natural chemical. Shikimic acid creates a wealth of precursor bioavailability for humans, and crosses the brain blood barrier. Shikimic acid is also a precursor for the aromatic amino acids tyrosine and phylanlanine, as well as indole, a number of flavonoids, lignin, and other useful aromatic metabolites. Shikimic acid was also one of the active chemicals found in the Chinese herb star anise, and the result of research also produced the base material for the first successful chemical antiviral pharmaceutical, Tamiflu. 5-HTP was proven to raise serotonin levels in the brain in a modulatory fashion (as needed), and has no side effects. Research also found that most serotonin receptors responded to 5-HT, throughout the body, and the 5-HT was an important modulatory neurotransmitter for regulation of the gastrointestinal functions. Since 5-HTP is the precursor for melatonin as well as serotonin, and the human brain tries to maintain appropriate levels of these neurotransmitters in homeostasis, with serotonin transforming to melatonin and vice versa as neeeded, a combination of herbal and nutrient chemicals has been found to create a better bioavailability for the brain than 5-HTP alone. The combination of 5-HTP, melatonin, Vitamin B6 form as P5P, and St. John's Wort, is a combination that creates very good bioavailability of these neurotransmitters at a low dose (recommended form is Positrol by Vitamin Research). If the effect is not as good as desired in the individual, SamE, a methionine nutrient, can be added for a month to increase the ability of the brain to convert neurotransmitters. SamE is beneficial for a number of reasons, but in this case, improves neural cell membrane functions so that the brain can more readily create or transform neurotransmitters as needed.
• Hypericum perforatum, or St. John's Wort: hypericum is an herb native to the United States, Europe and China, a flowering bush in the magnolia family (other magnolia species are now found to have significant neuroprotective, anti-depressant, and anxiolytic effects). About 370 species of hypericum are known throughout the world, many of which have been used similarly for medicinal purposes for centuries. While St. John's Wort became very famous and popular for the treatment of mild depression in the 90s, it was never used much by Chinese herbalists, and even with European and American herbalists, was historically a topical herb that was very effective to relieve neuropathy and neuralgia. Perhaps because of this, research was conducted to see if the herbal chemicals could effect the neurotransmitters and relieve depression or anxiety. It proved to be very effective for a subset of patients with depression. Subsequently, as it was becoming a big competitor for the emerging SSRI market, many studies were conducted to try to find some toxicity. None was found, yet researchers continued to look for some negative in this remarkable herb. Finally, it was found that the main herbal constituents used the same pathway of breakdown, or catabolism, in the liver, as many pharmaceuticals, the P450 pathway, which regulates the CYP3A4 enzyme rate of catabolism. St. John's Wort chemicals (e.g. hyperforin) are extremely nontoxic (recommended for children by the German health authorities for the treatment of mild depression), yet much publicity has implied that St. John's Wort is dangerous because it could alter the circulating levels of other drugs. The fact that many pharmaceuticals that are commonly prescribed concurrently also use the same P450 catabolic pathway, and yet there is no warning of alarm at this common prescription practice, is quite remarkable. The research into this potential problem of altered circulating drug levels revealed some alarming information, though. The pharmaceuticals are prescribed at a standard dosage, yet the rate of chemical breakdown, or catabolism, sometimes varies widely between humans, making the actual circulating dosage in the body potentially quite variable, and creating many potential toxicities. It turns out from this type of study that St. Johns' Wort is the least of our worries. Further research found that the various chemicals in the herb act in a modulatory fashion, and the flavonoids and other liver protectant chemicals readily modulate the P450 and other pathways in the liver, acting to keep them in homeostasis over time, so that continued use of St. John's Wort may actually reduce the chance that the liver, when stressed by taking too many pharmaceuticals with the same catabolic pathway used, would not protect the organism properly. A second area of abnormally publicized research emerged then claiming that St. John's Wort could be responsible for something called Serotonin Syndrome. The fact is that Serotonin Syndrome has never been found to be produced by taking St. John's Wort, yet is now a part of standard curriculum in medical schools due to some famous cases where it became severe enough to cause death (not due to St. John's Wort, but to improper prescription of serotonin altering pharmaceuticals). These cases occurred when more than one type of antidepressant were prescribed in combination, which occurred, and is still occurring, often. A large number of pharmaceuticals alone or in combination may produced this Serotonin Syndrome, including MOA inhibitors, SSRIs, SNRIs, tricyclic antidepressants (TCAs), antipsychotics, serotonin antagonists and reuptake inhibitors (SARI), 5-HT receptor antagonists, most commonly prescribed opioid pain medications (e.g. Vicodan, Percodan, Codeine, fentanyl), amphetamine, methamphetamine, cocaine, phentermine (e.g. Phen-Fen, and now the new weight loss drug Qnexa), Lithium, Valium, LSD, psilocybin mushrooms, MDA, ecstacy (MDMA), etc. The potential for drug-drug interactions in this way are extensive. Why St. John's Wort, which cannot induce serotonin syndrome even potentially unless combined with these other drugs, and then only as a weak contributor, is singled out in the press, is a question that the public should ask. Now, St. John's Wort became the poster boy for the dangers of Chinese herbs, when it was seldom used by TCM herbalists for the treatment of depression, or any other treatment. A number of Chinese herbs and formulas are commonly used in TCM, but not St. John's Wort, yet the standard medical industry keeps using St. John's Wort as an example of why you should be afraid of TCM herbology. The remarkarble fact is that this worked. Finally, in 2008, the Colleges of Medicine and Pharmacology at the Universities of Arkansas and Mississippi studied the St. John's Wort effect on the P450 catabolism, along with the other purported herbs that could affect this catabolic pathway, Kava-Kava, milk thistle, black cohosh, and goldenseal, and found that none of these herbs produced evidence that they could significantly inhibit the P450 pathway in competition with pharmaceuticals, except goldenseal, which has a slight possibility of negative herb-drug interaction. To see the study, click here: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2562884
• St. John's Wort, part two: So, St. John's Wort, hypericum, is not a common Chinese herb, but it is effective as part of a protocol for depressive syndromes. No, it is not a cure for Major Depressive Disorder by itself, although the studies showing failure to curb symptoms in Major Depressive Disorder were found have used degraded herbal products with too low of a therapeutic dose. Since the herb is nontoxic, dosage is not much of a concern. Today, many standard medical databases, hospitals and clinics, universities, and medical organizations, state that St. John's Wort is safe and mildly effective as an adjunct in a package of treatment for depression. Since herbal medicine uses formulas, a single herb does not need to be dramatically effective. A combination of treatment is always used in Complementary Medicine to achieve effective care. The tincture of St. John's Wort captures various chemicals in alcohol that are not captured with water extraction, and the tincture is found to be more useful in many cases clinically. This tincture may be combined with a number of other herbal tinctures that research has proven effective in clinical human trials, such as passiflora, rhodiola, verbena, etc. A number of research links is available below. Once again, utilizing a quality professional product, combined with other therapies, such as acupuncture and other herbal and nutrient therapy, will be potentially much more effective than a poor quality product bought off the shelf, especially given the history of the pharmaceutical industry as it tried to discourage use of St. John's Wort. The product you buy off the shelf is probably manufactured by a subsidiary of the same pharmaceuticals that spent a fortune trying to blackball this simple herb.
• Lithium orotate: the mineral lithium has a long and proven track record in the treatment of depression, and is still prescribed for both bipolar depressive disorders and major depressive disorder. The problem with lithium therapy is that such large dosages of a type of lithium ion have been prescribed that the risk of toxicity from this therapy is considerable, required careful monitoring, and has thus fallen out of favor. Coupled with this is the fact that lithium is not a synthetic pharmaceutical, and thus the patenting laws do not allow the type of profit seen with other pharmaceuticals. In 2011, guidelines reflecting the need for lower dosages and circulating levels of lithium ion were finally introduced by the University of New South Wales, Australia, and published in the Australian and New Zealand Journal of Psychiatry. A meta-review of scientific literature found that the current target of serum concentration of 0.5 to 1.2 mmol/L in standard guidelines fails to address the issue of toxicity, and that a target level of less than 0.8 mmol/L, and additional precautions in subsets of patients with aging, diabetes insipidus, kidney impairment, thyroid dysfunction, or with concurrent prescription of diuretics, ACE inhibitors, or NSAIDS/Cox-2 inhibitors, with circulating levels not exceeding 0.5 mmmol/L, are now recommended as standard prescribing guidelines (PMID: 21961481). These experts also recommended that the larger dosages of lithium ion (maintaining circulating levels of 0.5 to 0.8) only be prescribed in the management of acute mania and the prophylaxis of mania in more severe bipolar disorders. The recommendations were to use lower dosages of lithium in coordination with other treatments. The same research that these guidelines were based on has also now shown Complementary Medicine that low dosages of lithium within a holistic treatment protocol are effective and appropriate. While not being a treatment for depression by itself, low dosage of lithium, in the safest and most appropriate form, can be a valuable addition to the holistic protocol. Today, research has revealed that lithium orotate is safe and effective, and increasingly popular. It is not a prescription drug. Since widespread marketing of lithium orotate in 2005, almost no cases of toxicity have been reported. A single case of toxicity in 2007, at the University of Pittsburgh Medical Center, reported a young woman that took 18 tablets of lithium oratate in the form of a product called Serenity Now, and came to the emergency room with nausea and vomiting. The only adverse physical finding from this overdose was mild tremor, and the vital signs and ECG were normal. The patient was discharged to psychiatric care after 3 hours of observation (PMID: 18072162). We see from this example that even an extreme attempt to overdose did not produce significant harm with lithium orotate. Lithium orotate is a mineral salt of lithium combined with orotic acid, or Vitamin B13, which is similar to B12, but obtained from the intestinal biota, not the diet. Orotic acid is used as a carrier to increase bioavailability of lithium to the brain, reducing the need for lithium dosage. Standard prescription of lithium as a nutrional medicine is in the form of lithium carbonate, and the efficacy of lithium carbonate is well documented. Lithium carbonate was first used medicinally in 1843 to dissolve urinary stones, and with use, the efficacy for treatment of depression and mania was recognized. Studies have also demonstrated the efficacy in the treatment of ALS, and no other treatment for ALS has been proven as effective to delay progression of symptoms of this neurological degenerative disease. Lithium therapy at lower dosages has been shown to have zero toxicity. Lithium has been proven to reduce protein kinase C (PKC) activity in the brain to effectively reduce manic excitotoxicity. Lithium salts have been shown to be non-addictive, and have anti-inflammatory, antiviral, anti-fungal, and anti-tumor effects. Despite the widespread perception of lithium as a toxic treatment for bipolar depression exclusively, lithium, a naturally occurring mineral in nature, is now becoming widely accepted as a common nutrient supplement to prevent neurodegeneration, renew aging neurological function, treat gout, dermatological disorders, prevent injury following a stroke, reduce excitotoxicity, inhibit NMDA receptor hyperactivity, and relieve cluster headaches. The proven benefits of lithium are well documented, and the long history of success in treating depression and mania are also well documented. The only area of concern with lithium is the excess dosage that was eventually prescribed by medical doctors, which resulted in many cases of lithium toxicity. By incorporating a low dose of lithium orotate for a limited period of time in a holistic treatment regimen, this nutrient supplement could become a valuable part of the treatment protocol for Complementary Medicine and TCM. In addition, scientific study has revealed that some of the toxicity of a higher dosage of lithium ion concerns depletion of inositol in the brain, and that concurrent supplementation with inositol alleviates lithium side effects (PMID: 8712796). Lithium carbonate was first approved for treatment of bipolar depressive disorder in 1970, and is approved for treatment of major depressive disorder as well. This mineral supplement acts to modulate serotonin and tryptophan levels in the brain, and studies in the laboratory with tryptophan depletion induced showed clearly that the effects were blunted by this effect, demonstrating that lithium works mainly via the improved serotonin metabolism. These modulating effects are gradual, and usually 1-3 weeks are needed for even large dosages to have the effect. Studies of the effects on healthy human subjects also noted changes in vigilance and personality, with EEG studies demonstrating an increased left-hemisphere dominance (PMID: 7171912). The left side of the brain processes information in a more linear fashion, helping to analyze data from part to whole, and achieving neuroprocessing in a more sequential fashion. By shifting to a more left-hemisphere dominance, the patient is able to achieve a more objective outlook with an overthinking mind. A right-hemisphere dominance is characterized by starting from preconceived conclusions to form ideas. The patient suffering from depression with anxiety is clearly able to see the benefits of promoting the left-hemisphere dominance in cognition. While a low dose of lithium orotate is not expected to have an immediate and dramatic effect, the use within a holistic protocol with inositol and choline, L-tryptophan, or 5HTP, as well as herbal medicine, acupuncture and cognitive and behavioral therapies, presents many promising potential benefits, even with a relatively short course and low dosage.

Information Resources

1. A 2010 study of acupuncture in the treatment of major depressive disorder concluded that this treatment once or twice a week was effective: http://www.ncbi.nlm.nih.gov/pubmed/20692042
2. A 2010 review of selected treatments in Complementary and Integrative Medicine by The American Psychiatric Association Task Force at the Center for Women's Mental Health, Massachusett's General Hospital, looked at the present randomized controlled trials of common treatment protocols, such as acupuncture, herbal medicine, nutrient medicine, and psychotherapies, and found promising results in these studies: http://www.ncbi.nlm.nih.gov/pubmed/20573326
3. A 2009 randomized, placebo-controlled study at Beijing Meitan General Hospital found that utilizing acupuncture with a lowered dose of antidepresant (1/2 to 1/3 or the dosage of Prozac) produced the same results in a Rating Scale for Depression, and improvement in symptoms of anxiety and fewer anti-depressant side effects: http://www.ncbi.nlm.nih.gov/pubmed/19678773
4. As far back as 1995 we see large long-term studies seeking answers to the high rate of non-adherence to medication strategies, even in a 3 month treatment period, and dissatisfaction of relief of symptoms. This large study by the University of Washington Medical School found that a multifaceted intervention helped to significantly improve effectiveness of treatment with patients suffering from Major Depressive Disorder: http://www.ncbi.nlm.nih.gov/pubmed/7897786
5. By 2002, numerous studies were being reviewed to address non-adherence to standard antidepressant treatment protocols, which for almost all patients consisted of variations of SSRI and SSNRI medication, or Lithium, with the increased knowledge of risks and side effects of other antidepressants, such as MAOI inhibitors, hypnotics,and tricyclic antidepressants. Integrated treatment protocol was not widely used. This Swiss meta-analysis admits that the large array of studies did not address which interventions could solve these problems: http://www.ncbi.nlm.nih.gov/pubmed/11823317
6. As far back as 1999, clinical studies demonstrated that sexual dysfunction secondary to the use of antidepressant drugs, especially SSRIs were affecting up to 60% of these patients with chronic use, and the industry sought to find a chemical solution: http://www.ncbi.nlm.nih.gov/pubmed/10380144
7. By 2002, a meta-analysis of studies of antidepressant-induced sexual dysfunction by the Lewin Group of Virginia, found that between 30-60% of SSRI users experienced some form of SSRI-induced sexual dysfunction over time, but that only 5 randomized controlled trials were found to evaluate this medical problem: http:/www.ncbi.nlm.nih.gov/pubmed/12243609
8. A study in 2008 at the Depression Clinical and Research Program at Massachusetts General Hospital in Boston found that Maca root alleviated SSRI-induce sexual dysfunction in a dose-related effect, and was well tolerated at high dosage: http://www.ncbi.nlm.nih.gov/pubmed/18801111
9. By 2006, a large meta-analysis of non-compliance of standard drug therapies for depression still failed to find adequate critical appraisal and quality evidence on the variety of interventions that could be utilized to address the subject of large non-compliance with standardized pharmaceutical care of depressive disorders:http://www.ncbi.nlm.nih.gov/pubmed/16789991
10. In 2007, an international conference sponsored by the European College of NeuroPsychology arrived at a consensus statement that found that more than 10% of unipolar depressive syndromes progessed to a bipolar syndrome due to medication, that sudden withdrawal of medication exposed patients to serious active drug withdrawal effects, and that drug protocol compliance may be difficult to achieve in clinical practice. An addition of other medical interventions was discussed as an appropriate adjunct to withdrawal of standard pharmaceutical medication during or after the resolution of depressive or manic episodes:http://www.ncbi.nlm.nih.gov/pubmed/18501566
11. Cognitive and behavioral psychotherapy is another significant tool in the integrated protocols recommended to treat depressive disorders, yet, like acupuncture and herbal therapies, this type of treatment must be individualized and designing clear scientific studies with randomized double-blinded placebo-controlled trials is very problematic. Even with these study design obstacles, cognitive and behavioral therapy has proven in meta-analysis by 2010 to be a moderately effective adjunct treatment:http://www.ncbi.nlm.nih.gov/pubmed/19852904
12. A 2002 study of cognitive-behavioral and relationship-focused therapies to treat depressive disorders in adolescent patients by the esteemed University of Pittsburgh School of Medicine found that up to 87% of youths undergoing this type of therapy recovered from their depressive episodes with cognitive-behavioral therapy. Early treatment for depressive symptoms, with various adjunct treatments to cure rather than medicate, is important to individual quality of life:http://www.ncbi.nlm.nih.gov/pubmed/12222084
13. A 2008 study of Maca root at Victoria University in Australia found that there was efficacy for treatment of postmenopausal depression. The study found positive effects in reducing symptoms of both depression and anxiety:http://www.ncbi.nlm.nih.gov/pubmed/12222084
14. A 2010 study at the Mood Disorders Program at McMaster University in Ontario, Canada, found that dysregulation of adipokines, such as leptin, adiponectin, and resistin, was a link between depression, obesity, and metabolic syndrome:http://www.ncbi.nlm.nih.gov/pubmed/20798882
15. A 2010 study at the Medical University of Wien, Department of General Psychiatry, in Austria, found that St. John's Wort extracts differ in chemical constituents between various manufacturers and types of extraction, yet quality extracts were shown to be as effective as standard antidepressant drug therapy, and much better tolerated (nontoxic). It would be wise to get this herbal product from a professional that uses the highest quality professional herbal products:http://www.ncbi.nlm.nih.gov/pubmed/20708905
16. A 2008 meta-analysis of St. John's Wort, hypericum perforatum, by the Cochrane medical database system, which is the most widely used and respected, found that St. John's Wort was proven to be similarly effective as standard antidepressants, have fewer side effects, and proven to be superior in effect to placebo: http://www.ncbi.nlm.nih.gov/pubmed/18843608
17. A 2010 clinical study of St. John's Wort extract in Shanghai found that this herbal treatment produced significant decrease in response to stress in patients with irritable bowel syndrome after 8 weeks of use, and GI symptoms related to IBS were significantly reduced as well: http://www.ncbi.nlm.nih.gov/pubmed/20565044
18. A 2003 study by the University of Munster, Institute of Pharmacology, in Germany, found that St. John's Wort extract worked in a number of physiological ways to benefit patients with Major Depressive Disorder, including mild inhibition of reuptake of serotonin, norepinephrine, dopamine and inbibition of monoamine oxidase, all of which help keep sufficient levels of these neurotransmitters in the brain. The herb also was found to aid GABA and gluatmate receptor functions, upregulate 5-HT(2) receptors, downregulate beta-adrenergic receptors, reduced symptoms of akisthisia (immobility), and helped regulate genes that control the hypothalamic-pituitary-adrenal axis, or endocrine function. All of these mechanism are potentially very helpful in many syndromes with depression: http://www.ncbi.nlm.nih.gov/pubmed/12775192
19. A 2007 meta-analysis of studies concerning herbal treatment of depression and anxiety, conducted by the University of Queensland in Australia, found that evidence at that time supported St. John's Wort and Kava Kava, with robust high-quality clinical evidence, but that other promising herbal therapeutics still needed to be studied, with only proof or potential benefit so far in small studies of Passiflora incarnata, Rhodiola rosacea, and Scutellaria lateriflora (skullcap): http://www.ncbi.nlm.nih.gov/pubmed/17562566
20. A 2009 study at the University of Hong Kong School of Chinese Medicine found that a tincture of Bai shao (Paeonia lactiflora), with extraction of glycosides, exerted significant antidepressant activities via inhbition of monoamine oxidases and attenuation of oxidative stress in animal studies of chronic behavioral stress: http://www.ncbi.nlm.nih.gov/pubmed/19375493
21. Further studies at the University of Hong Kong found that glycosides of Paeonia lactiflora (Bai shao) increased the expression of brain-derived neurotrophic factor and nerve growth factor in both normal and chronic behaviorally stressed laboratory animals, potentially benefitting the pathology of behavioral depression: http://www.ncbi.nlm.nih.gov/pubmed/20176057

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