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BRAVE NEW WORLD OF PSYCHO-PHARMACY
Alternatives

by William R. Ware, PhD

INTRODUCTION

Bill Ware The principal issues addressed in this review concern the risk-benefit of psychiatric drugs and if the decision is made to go against mainstream practice and reject suggestions or recommendations of this therapy, what are the alternatives. The dilemma is far from hypothetical. The prevalence and rate of increase of psychological disorders is large and sooner or later many readers of this review will be forced to confront this issue, either as regards their own problems or those of their children or parents.

Government statistics, ignoring illegal drug or substance abuse, confirm this. Sources include the Centers for Disease Control (CDC), the National Institute of Mental Health (NIMH) and the American Academy of Child and Adolescent Psychiatry.

  • Approximately 1 in 20 of Americans aged 12 or older are diagnosed as depressed. Of these about 80% report symptoms that interfere with their ability to work and 35% report functioning is very or extremely difficult.
  • It is estimated that 3% to 5% of school age children are diagnosed with attention deficient hyperactivity disorder (ADHD).
  • About 2.6% of the U.S. population have bipolar disorder.
  • About 1% to 4% of children are viewed as having conduct disorder and 1% to 6% are viewed as having so-called oppositional defiant disorder.
  • Schizophrenia affects about 1% of Americans.
  • Post-Traumatic Stress Disorder appears to affect about 5.2 million Americans.
  • When major depressive disorders, mild depression and bipolar disorder are combined, the NIMH estimates prevalence at about 10% of the U.S. population over 18.
  • The NIMH also estimates that almost 20% of Americans 18 and older meet the diagnostic criteria for anxiety disorders according to diagnostic criteria in current use.

This list does not include phobias, eating disorders, personality disorders, antisocial personality disorders or avoidant personality disorders. When the new diagnostic manual (DSM-V) comes out in 2013, both the number and prevalence of psychological disorders will considerably increase according to preliminary reports and commentary.2,3

There is no doubt that many of these diagnoses result in medication. The numbers for antidepressants, for example, put them at the top of the prescription frequency list in the U.S. in the period 2003-2004 for female patients of all ages and for both men and women between ages 18 and 44. They are in general the most prescribed drugs in the U.S. Almost all carry FDA black box warnings regarding suicide risk, and if one believes Breggin's view, discussed in Part I, they all disable the brain to a greater or lesser degree. Thus the belief that there is or should be considerable interest in avoiding drug therapy for psychological disorders and for any of a large number of behavior patterns that the conventional wisdom considers outside normal.

Some idea of the growth rate in prescriptions for antidepressants is available from the CDC. When the period 1995-1996 is compared with 2003-2004, based on visits to physicians offices or outpatient clinics and using as a measure the number receiving one or more drug prescriptions per 100 visits over each two-year period, antidepressant growth was 92% in the age group 18-44 and 118% for all ages.

This looks rather like an epidemic. But there are some in the psychiatric community that point to significant overdiagnosis. In fact Dr. Allen Frances, a psychiatrist now emeritus professor and former chairman of the Department of Psychiatry at Duke University, who was the leader in the preparation of the fourth edition of the diagnostic manual (DSM-IV, 1994) currently used as a bible by the profession, made an amazing confession recently. In an editorial in the Los Angeles Times he stated that this manual was, in his opinion, unintentionally responsible for generating epidemics in AHDH, autism and childhood bipolar disorder. This resulted in unnecessary and potentially dangerous medication. In such journals as Psychiatry Times and Psychology Today, he has also repeatedly stated concerns regarding the new edition (DSM-V) currently available in draft form for comment. His message: "Beware of its unintended consequences". Francis believes that the proposals in the DSM-V draft could set off at least eight new false positive epidemics. He comments in the British Journal of Medicine: "The consequences are grave. For individuals, these include unnecessary treatment with drugs that have unproven benefit and known harm; stigma; difficulties in getting life insurance and disability insurance; and a reduced sense of personal responsibility and control".2 It seems that we are well on the way where everyone sometime in life will have symptoms meeting the definition of mental illness and require treatment which at present is mostly in the form of pills.

GUIDANCE FROM POTENTIAL CAUSES FOR THE MENTAL HEALTH EPIDEMIC

One might wonder what has happened over the past few decades that caused over a quarter of Americans to be diagnosed with one or more of a several mental disorders, each classroom to have pupils with mild to serious problems attributed to diseased brains requiring drug therapy and toddlers now coming under close scrutiny by their doctors for treatable mental disorders. After all, the brain is noteworthy for its plasticity, its ability to compensate, its defence mechanisms such as the blood-brain barrier and its protective mechanisms against, for example, starvation or low blood sugar. The roundup of the usual suspects plus a few additions yields this short list.

  • Neurotoxins from environmental sources including tap water, clothing, textiles, products for home use and personal care, pesticides and finally from food.
  • Psychiatric drugs as well as a large number of other medications.
  • Endocrine related disorders such as thyroid problems (hypo- or hyperthyroidism), diabetes and adrenal gland or pancreatic tumors.
  • Polycystic ovary syndrome (risk elevation for depression about 4 times)4
  • Autoimmune diseases such as lupus and Hashimoto's disease.
  • Allergens mainly present in food, such as gluten.
  • Frequent consumption of large amounts of refined sugars.
  • Diets that are micronutrient poor. Candidates include diets made up of junk food, commercially prepared food, food from farmlands depleted over the years of many minerals and diets based on the avoidance of fruits, vegetables and fish.
  • Dysfunction or deregulation of the circadian clock and some of the rhythms it controls.
  • Chemicals used as preservatives or adjuvants in vaccines (substances that increase the immune response). According to the package inserts, in the U.S., childhood vaccines involve the injection of 56 distinct chemicals over the course of recommended vaccination schedules. No studies of adequate design or power and free of industry bias have ever investigated the long term impacts of this load of potential toxins, and this will in fact probably never happen.

Avoiding toxic substances is far from simple when they are produced yearly in mega-ton quantities and permeate our daily existence. Organophosphates which are, for example, implicated in ADHD are found in pesticides5,6 and polyfluoroalkyl chemicals used in non-stick coatings, paper and textile coatings, and personal care products.7 Psychiatric drugs appear to critics be eligible for classification as toxic. However, most of the items on this list suggest relatively simple interventions or diagnostic issues. Thus how does one proceed in an organized and potentially successful fashion, initially considering the individual not on psychiatric drugs and wishing to avoid them?

In terms common to psychiatry, part of the diagnostic challenge is differentiating primary (psychiatric) from secondary (organic) psychosis, the latter being of interest in the context of this review.8 First, there is the matter of thyroid disorders and diabetes. Depression frequently accompanies diabetes but as discussed below, how they interact is unclear. Thus, the diabetic suffering from depression is a rather special case since modern medicine does not generally cure diabetes but only attempts to control the progression of the adverse effects of this disease. The option of curing the diabetes and then seeing if depression persists is not practical. However, as discussed below, bringing blood sugar levels and fluctuations back to normal with diet has been used successfully in this context.

Thyroid disorders are somewhat different. The protocol for eliminating thyroid dysfunction is well established but the diagnosis of this dysfunction, especially if it is subclinical, presents problems that may require consultation with an endocrinologist. However, testing the hypothesis that the problem is hypothyroidism simply by providing hormone treatment can frequently clarify this issue over period of weeks.

In the differential diagnosis of possible causes of psychological symptoms, a number of other diseases, conditions and medications need to be considered as well as the possibility of substance abuse. This is actually a complex subject somewhat beyond the scope of this review, but the importance of ruling out secondary psychosis which can be treated and probably cured is obviously both important and challenging.8 One wonders how often it is done properly and how often instead a psychiatric drug unrelated to the root cause is prescribed.

There remains the possibility that the root cause of the problem is multifactorial. On this basis it can be argued that a simple but multifaceted approach may offer the best hope of a rapid resolution of the problems once thyroid dysfunction and other medical problems have been definitively ruled out. This would mean addressing dietary factors through diet modification and supplementation with a combination of all the potential micronutrients that might be at low levels. Combining this with psychotherapy would represent a fairly comprehensive approach. Adding light and/or melatonin therapy would be a possibility if there were indications of problems with circadian rhythm. To try one intervention at a time, for example adding a micronutrient, eliminating a potential allergen, modifying a macronutrients in the diet (e.g. minimizing refined carbohydrates, especially sugar), trying to adjust circadian rhythms, or introduce psychotherapy may not be nearly as effective as simultaneously trying as many approaches as possible. The reason is simple. An unavoidable ignorance of root causes.

THE THYROID-BRAIN INTERACTION

The book The Thyroid Solution by Ridha Arem, M.D., an endocrinologist and clinical professor of medicine at Baylor College of Medicine, includes a lengthy discussion of the role of a dysfunctional thyroid in the mental problems being discussed in this review. Is a thyroid function assessment routine prior to prescribing antidepressants or antipsychotics, stimulants or tranquilizers? Doubtful indeed. Furthermore, subclinical but still important hypothyroidism would probably be ignored. Yet in some patients, the problems psychopharmacotherapy is trying to solve, apparently not very successfully, can be addressed with thyroid therapy. Such treatments generally involve a natural approach free of side effects and with other health benefits. However, the assessment of thyroid function is complex and the current guidelines or laboratory reference ranges prone to false negatives. In fact, the ideal response to a patient presenting with evidence of the need of psychopharmacy should probably be referral to an endocrinologist with experience in thyroid disorders. Given the widespread prevalence of psychological problems, if this became a standard of care it would overwhelm the endocrinology community!

The peer-reviewed literature on this subject is unclear due to issues with the definition and diagnosis of subclinical hypothyroidism and the approaches used to correct it if found or suspected. The reader is referred to Arem's book for a comprehensive discussion of the importance, diagnosis and treatment of thyroid imbalance and its relation to mental problems. At the end of Chapter 5, which discusses the mind-thyroid connection, he makes the following points:

  • The consequences of thyroid imbalance may include not only mental and emotional problems but even such serious conditions such as manic-depression. However, mild depression is the most common.
  • For individuals prone to mood disorders and emotional problems, thyroid imbalance can magnify the symptoms.
  • Hypothyroidism may be associated with borderline depression that presents as fatigue.
  • It is now recognized that the thyroid hormones have a major biochemical function in the brain and significant impact on mood, emotions and behaviour.
  • For anyone who is suffering from depression or has had depression in the recent past, the question of thyroid imbalance should be addressed, in particular if symptoms of thyroid imbalance are present.

DEPRESSION AND DIABETES

The association between depression and diabetes is well known but poorly understood. There is some evidence of a bidirectional nature, i.e. each is a causal factor for the other. However, two large studies only support the hypothesis that depression in diabetics results from the ongoing psychological stressors associated with a chronic medical condition.9 A number of studies have been reported regarding treatments for depression in diabetes. These involve either antidepressants, psychotherapy or both. Mood improvement wawas reported in both, but in terms of diabetes, neither resulted in better medical outcomes. There is no evidence leading one to believe that the downside of psychopharmacy in this context is any different than described above. However, there is evidence of a strong and significant association between antidepressant use and diabetes risk that is not accounted for by confounders or mediators.10

In his book Dr. Bernstein's Diabetes Solution,11(P.373) the author describes a study done in the late 1970s at Rockefeller University in New York where the methods he promotes for blood glucose control were used on a group of depressed type 1 diabetics. The basis was simply severe carbohydrate restriction, the careful control of the nature of the carbohydrates, insulin when necessary and the use of home glucose monitoring to establish a protocol that works for each individual. The patients were initially tested to quantify the level of their depression, which was in the severely depressed range. The fascinating result was that once the patient's blood sugars came under control, the depression disappeared. By control, Bernstein means fasting, post meal and long-term (HbA1c) glucose levels that approximate that of non-diabetic individuals, something that mainstream diabetes control almost never achieves and in fact the conventional wisdom appears to regard as impractical. Bernstein is internationally recognized as able to achieve this result with many type 1 and type 2 diabetics. Patients simply have to learn to live with rather severe and selective carbohydrate restriction. There are of course several ways of interpreting the impact of this dietary intervention on depression in diabetics, but it is the result that matters, not only in terms of mental health but as regards the long-term neurological and vascular damage caused by chronic hyperglycemia.

LIPID-LOWERING DRUGS AND PSYCHIATRIC ADVERSE REACTIONS

A recent review summarizes the reported adverse reactions associated with lipid-lowering drugs.12 It is well known that the reporting system is highly imperfect and misses almost all cases. Nevertheless, there are reports of the whole spectrum of mood disorders, cognitive disorders, sleep disorders, perception disorders as well as a variety of fatigue related symptoms. A small fraction of the incidents reported were severe, and all showed improvement on discontinuation of the lipid-lowering treatment. Some reports included positive rechallenge experiences. The adverse reactions were seen with both statins and fibrates, which suggest that in some cases it is the lipid lowering rather than the HMG-CoA reductase inhibition that is involved. Thus part of a careful differential diagnosis in this field must include questions about lipid-lowering drug use. Many of the psychiatric disorders ascribed to taking these drugs come under the guidelines as indications for psychopharmaceutical therapy, which obviously fails to get at the root cause. Given the minute percentage of adverse effects that are reported and recorded, this may be a significant and not fully appreciated problem.

There is emerging mechanistic evidence involving statin induced impairment of the function and dynamics of a serotonin receptor.13 It is noteworthy that statins use appears to be associated with transient global amnesia.14 The above indications of potential harm do not agree with those presented in a recent review based on gathering data from statin studies where the impact on mood was part of the side effect assessment rather than from an adverse effect reporting center. However, the studies included were industry supported and the review published in a journal not requiring declaration of conflict of interest.15 Industry studies tend to downplay adverse effects. Accumulated evidence also suggests that there is a connection between low and especially very low cholesterol levels, mood symptoms and the risk of suicide but such results are difficult to correct for confounding.16-18

DIET, SUPPLEMENTS AND MENTAL DISORDERS. THE MICRONUTRIENT DEFICIENCY MODEL

First, the evidence from dietary patterns. Patterns are important because obviously humans generally eat a mixture of foods at each meal. A number of recent studies have looked for dietary patterns that reduce the risk of depression,19,20 the outcome of schizophrenia21 and mental health of adolescents such as avoiding depression/withdrawal and delinquent or aggressive behavior.22 Typically, these studies find the optimum diet in this context to emphasize fruits, vegetables and fish, a diet many individuals do not fancy. One recently published study of Australian women compared a traditional diet rich in vegetables, fruit, meat, fish and whole grains with the Western diet of meat pies, fried foods, pizza, chips, hamburgers, white bread, sugar, flavoured milk drinks and beer.23 They found the traditional diet provided the lowest risk (adjusted for confounders) of developing depression or anxiety disorders. Consistent with these results, studies find an association between adherence to the Mediterranean diet pattern and the a low incidence of depression and a high degree of mental health.24-27 This pattern is characterized by high consumption of vegetables, fruit, nuts, cereal, legumes and fish, a high mono to saturated fatty acid ratio, and moderate alcohol consumption. A large, 12 year follow-up study in Spain found high intake of trans-fatty acids increased the risk of depression whereas monounsaturated and polyunsaturated fatty acids and olive oil were protective. These results are important since the consumption of trans-fatty acids is six times greater in North America as compared to Spain.28 The beneficial nature of certain diet patterns relates to some of the suspected factors listed above since they tend to be micronutrient rich but not calorie dense and are low in sugars and food additives. However, the mechanisms for various pattern associations are not clear. Inflammatory processes, antioxidant content, and the ability to influence protective factors in the brain have been evoked.23

The question of which micronutrients, i.e. vitamins, minerals, classes of fatty acid, or individual amino acids, might be most important in connection with mental health has interested nutritionists for a long time. The classic example is vitamin B1 deficiency causing pellagra which in terms of neurological symptoms is indistinguishable from schizophrenia. It is cured by vitamin B1 supplementation. In a recent review of micronutrients implicated in mental health, Kaplan et al29 list folate--folic acid, vitamins B1, B6, B12, lecithin, calcium, chromium, magnesium and selenium. They cite 15 studies with endpoints related to mood and depression, 8 of which are randomized controlled trials. All found benefit with regard to single micronutrient interventions. Other micronutrients with known brain functions are vitamin E, choline, iron and zinc. While single micronutrient studies satisfy the purist who insists that only one variable can be changed at a time, the fact remains that the human diet contains a grand mixture with highly variable amounts of these substances. It can be argued that it is therefore more realistic to study interventions using mixtures of micronutrients. This in fact has produced some very interesting and significant results, which is not surprising since the synthesis, uptake and breakdown of neurotransmitters require enzymes, and every enzyme reaction or action involves one or more cofactors, many of which are vitamins and minerals. Therefore, multiple deficiencies become very important.

Kaplan et al29 list 13 studies involving supplement mixtures of which 6 were randomized controlled trials (RCTs). The mixtures varied considerably with some using only folate and B12 or mixtures of a few vitamins. However, they also discuss five case-series studies that used a proprietary 36-ingredient formula of vitamins, minerals and amino acids (EMP+), and two RCTs that used either 26- or 23-ingredient formulas of vitamins, minerals, and essential fatty acids. These studies revealed very significant benefits for individuals with mood, temper, rage and anxiety disorders and children and adults with bipolar disorder. One of the RCTs involved young adult prisoners with a history of antisocial and violent behaviour. There was a significant decrease in these behavioral problems between the 26-ingredient intervention group and the placebo group. Another RTC involved schoolchildren disciplined for violating school rules. A 23-ingredient supplement resulted in a significant decrease in rule infractions as compared to the placebo group. Since the publication of the review by Kaplan et al, seven additional studies using the 36-component mixture have been published.30-36 Beneficial results were found for bipolar disorders in children and adolescents, the management of autism, ADHD and obsessive compulsive disorder (OCD). The mixtures containing a large number of components should have considerable appeal since it is difficult to identify and characterize deficiency, especially on the scale of 36 items, and also there are few useful guidelines for what constitutes a deficiency, given that there is great human variability in the amounts of some micronutrients required for optimum health, mental or otherwise.

A landmark study by Bruce Ames and colleagues, then at the University of California at Berkeley, examined a number of minerals and vitamins for their role as cofactors (coenzymes) in enzyme mediated processes or in genetic expression.37 Genetic variations alone accounted for a large variation in levels of cofactors necessary for normal biological function, and both minerals and vitamins were implicated as cofactors in a wide assortment of processes. One single micronutrient may be involved in dozens of processes. Cofactors are non-protein chemical compounds that bind to proteins and are required for their biological activity. These proteins are frequently enzymes critically involved in innumerable biochemical processes.38 Some enzymes require several cofactors and zinc for example, is an essential cofactor for more than 100 enzymes. We obviously evolved to acquire from diet the required cofactors in the required amounts in order for our biochemistry to function properly. However, there are large variations in the levels of cofactors required for any given biochemical step, and some are caused by mutations. The levels required relate to the strength of binding of the cofactor to the target protein. When it is low, greatly enhanced concentrations of a given cofactor may be required to achieve normal function. This can translate into a large dose of a vitamin or mineral. A number of these enzymes are critical in the brain biochemistry.37,38

While the above is an oversimplification, it indicates why it is nonot particularly informative to study just single micronutrients in the context of a dysfunctional state and why studies using a large number of micronutrients make more sense. In the field of the nutritional aspects of mental disorders, the principle of one variable at a time offers a huge if not insurmountable barrier to progress. Furthermore, failures of studies that change only one micronutrient provide live ammunition for the anti-supplement community which further retards progress. Fortunately, there are a number of medical scientists who recognize this and have contributed greatly to progress in this field.

The micronutrient deficiency model is also particularly relevant to children, especially considering the prevalence of nutrient-poor diets. The study of Ames and colleagues underscores the serious nature of the decline in the nutrient value of foods over time. Furthermore, for various reasons, parents may make poorer and poorer choices for their own food and that of their children. There are generational aspects to food choice. Children reject parents' old-fashioned ideas about fruits, vegetables and variety. There emerges a new generation of parents and with it the potential for changed attitudes that impact this new generation's children. Also, as children are allowed wider scope in eating, junk food approaches the norm at noon in many school environments or when a fast meal is required. Nutrient poor but high-energy foods have become common, are very successfully marketed to children and are major sources of calories. It is not only obesity that results, but also a deficiency in micronutrients. Children can become successful in influencing what they eat at home. The net result may be a slow, progressive development of deficiencies in micronutrients that are critical cofactors for numerous biochemical reactions and critical for brain function. These deficiencies start to impact brain function resulting in behavior problems which increase child's ability to oppose nutritional suggestions of parents. A feedback loop develops. The worst cases are the institutionalized. Micronutrient deficiency obviously occurs in adults as well.

My favourite Supplements

THE MOST STUDIED SUPPLEMENT MIXTURE

The supplement mixture that has received the most clinical attention is EMPowerplus (EMP+). As mentioned above, twelve studies have all found beneficial effects. These were all case or database analysis studies. The mixture contains most of the vitamins and minerals that are found in popular multivitamin preparations and in addition, undisclosed amounts of phenylalanine, citrus bioflavonoids, the amino acids L-glutamine and L-methionine, grape seed extract, ginkgo biloba, germanium sesquioxide, and nickel. If one compares the vitamin-mineral content of the typical daily dose from 15 capsules of EMP+ with, for example, the Life Extension One-A-Day supplement, the only significant differences (ignoring calcium and magnesium) are as follows. According to data on the manufacturer's website (Truehope), EMP+ contains about three times as much folic acid, vitamin B12, biotin and chromium, five times the manganese, and 10 times the potassium. Life Extension multivitamin contains 4 times as much thiamine, five times the pantothenic acid and three times the riboflavin, but no amino acids, grape seed extract, ginkgo, germanium or nickel. Thus EMP+ cannot be regarded as providing mega doses. If one ignores some of the more esoteric non-vitamin and mineral components the two could be made roughly equivalent simply by adding a low-dose B complex supplement and a bit of chromium and manganese.

How important the other differences are is of course unknown, but several of the items are readily available and taken by millions of people every day (grape seed extract, ginkgo, and citrus bioflavonoid). The packaging of EMP+ allows the administration to be spread out over the day. How important this is appears unknown. EMP+ also contains considerably more calcium and 600 vs 100 mg of magnesium. The one-a-day multivitamins in general tend to have very little of these two micronutrients since the amounts generally regarded as optimum would make the pills or capsules too large. Anyone wishing to attempt to duplicate the results of studies that used EMP+ can easily make up a roughly equivalent supplement. The three amino acids are also readily available but the company does not disclose the dose levels.

If one takes a large sample of individuals with, for example, major depression or bipolar disorder, and finds that EMP+ significantly relieves their symptoms or puts them in remission, this result could be due to just one or two of the components of the mixture or to a synergism between a numbers of the ingredients. In addition, which ingredient or ingredients are most active will probably vary from person to person. Thus, mixtures obviously address the problem of unavoidable ignorance as to specific deficiencies. But this has for ages been the basic philosophy of taking a multivitamin, something that is now recommended even by mainstream medicine.39

If one compares the EMP+ protocol with that used in the prison inmate study described above, what is striking is that good results were obtained in the prison study with much lower doses of vitamins and minerals (similar to government daily requirements). To the vitamin mineral mix was added essential fatty acids and all but the omega-6 linoleic acid were also at low doses, and the jail study did not use the other non-vitamin-mineral supplements found in EMP+. Similar observations apply to the unruly student study. This suggests that micronutrient deficiencies correctable by small levels of supplementation may be of much greater significance in mental health than generally appreciated.

OMEGA-3 DEFICIENCY AND THERAPY

The role in mental health of the omega-3 polyunsaturated fatty acids, and in particular the two long-chain acids EPA and DHA, is controversial due to inconsistent results. However, many studies were of low quality or used intervention doses that appear inadequate. In the case of patients with depression, a recent meta-analysis indicated that lower levels of EPA, DHA and total omega-3 fatty acids were associated with depression. However, intervention studies suggest that only high omega-3 doses and only DHA are relevant in this context.40 Consistent with this, long-term fish intake is also associated with less severe depressive symptoms among both elderly men and women.41 In the case of schizophrenia, as Malcolm Peet discusses in a recent review, most observational studies have shown reduced levels of DHA, and there is evidence from randomized placebo controlled trials that omega-3 fatty acids might prevent the conversion to a first-episode psychosis and reduce the drug requirement for treating first-episode patients.42 However, Peet points to the dangers of single nutrient therapy and comments that in his own practice attention is given to the reduction of harmful nutrients and increasing nutrients that are important for mental health. From the description of his intervention, it appears that it is similar to the use of the multivitamin-mineral mixture described above plus DHA and EPA.

In the context of ADHD, a recent study examined the association between omega-3 levels and various mental problems in schoolchildren. Some associations were found with omega-3 levels and high levels were associated with decreased inattention, hyperactivity and behavior, emotional and conduct difficulties as well as increased prosocial activity. These observation were based on teacher and parental reports.43

ROLE OF VITAMIN D IN MENTAL HEALTH

The multiple roles of vitamin D in health become more and more apparent each month as new studies appear. In fact, it was hard to believe that the Institute of Medicine in the U.S. very recently took a highly publicized and ultraconservative position advising Americans that most of them had adequate levels and that the evidence was weak for higher levels being generally beneficial. The IOM panel was focused on bone health, had no vitamin D experts, and yet the consensus was put to the media as a general condemnation of anything but near trivial supplementation. In the context of mental health, vitamin D has increasingly been implicated in the pathology of mental illness including depression, bipolar disorder and schizophrenia.

With regard to depression, there appears to be only one randomized clinical trial vs. a placebo. The intervention involved 20,000 to 40,000 IU per week for a year. Vitamin D supplementation was found to ameliorate depressive symptoms on the basis of changes in assessment scores.44 Another recent intervention study confirmed these results.45 A recent study found that vitamin D deficiency (25-hydroxyvitamin D =10 ng/mL) was associated with late-life depression and deficiency was also associated with living in northern latitudes.46 However, taken as a whole, cross-sectional studies (snapshot studies) have provided a mixed picture. One recent review recommends greater supplementation in older adults,47 whereas another takes a more conservative position which gave greater weight to the inconsistent cross sectional studies.48

There do not appear to be any randomized clinical trials concerning the use of vitamin D supplementation to treat schizophrenia. However, there is considerable evidence that vitamin D status is important in the etiology of this disorder, both early in life and in general.49-53 For example, a Finnish birth-cohort study found that supplementation during the first year of life reduced the risk of diagnosis of schizophrenia over the next 31 years. The risk reductions were very large (75% to over 90%). But the risk reduction was restricted to males.52 The accumulation of positive data has led to a call for a clinical trials of vitamin D supplementation for both prevention and therapy.54

GLUTEN SENSITIVITY AND FOOD ALLERGY

Gluten sensitivity involves heightened immune response to ingested gluten. Glutens are the main storage proteins of wheat, but there are a large number of members of this class of protein. The most common medical problem associated with gluten sensitivity is celiac disease. Early studies found that untreated patients presented evidence of psychological disturbances, especially depression. In one study, 35% of patients with celiac disease reported a history of psychiatric disorders including depression, personality changes and psychosis.55 In these early studies, gluten-free diets seemed to provide benefit. However, depression in celiac disease may simply be associated with difficulties in adjusting to this chronic disorder rather than to the disease itself.56 It is noteworthy that in patients where the hallmark intestinal problems associated with celiac disease resolved, this did not prevent the development of neurological problems.

There is a more convincing association between gluten sensitivity and schizophrenia. A recent review documented a drastic reduction if not full remission of schizophrenic symptoms after an intervention involving gluten elimination.57 However, this only occurs in a subset of patients. For them, gluten elimination is obviously highly beneficial if not essential. An antibody study of recent-onset and multi-episode schizophrenia found that while patients may share some immunological features with celiac disease, their immune response to one of the principal glutens was different from those with this disease. In addition, individuals with recent onset of psychosis or multi-episode schizophrenia do not in general have clinical manifestations of celiac disease nor laboratory parameters diagnostic of this disorder. However, they may share some of the pathobiologic features of celiac disease.58

It is interesting in this context that one of the cornerstones of the alternative treatment of schizophrenia championed for decades by the Canadian psychiatrist Abram Hoffer was that patients avoid any foods to which they were allergic. This of course included glutens. He suggested that while elimination diets were recommended, a simple food allergy history may reveal the presence and identity of allergens.59 The remainder of Hoffer's approach involved supplements of B vitamins including B3 (niacin), B6, and as well vitamin C, zinc, and manganese. In addition, no sugar at all was allowed. Patients also underwent psychotherapy.

MELATONIN, LIGHT THERAPY AND SLEEP DEPRIVATION

The amazing complexity of humans and other living species is illustrated by the presence of an internal master clock influenced by the time of day through an interaction with light and the day-night fluctuation. A number of biological processes have so-called circadian rhythms which repeat over each 24 hour interval and are driven by this clock. Blind individuals, for example are unable to synchronize to the day/night cycle or do so at abnormal times. For individuals with normal sight, it is possible to adjust circadian rhythms either with the hormone melatonin, bright light or sleep deprivation. Melatonin is secreted by the pineal gland in response to the onset of darkness and its level builds and then declines during sleep. Its secretion can be inhibited by exposure to bright light during the night.

Disturbance of sleep or secondary insomnia is frequently associated with psychiatric disorders and circadian rhythm abnormalities have been observed as a comorbidity of depression and other psychiatric problems. The night time peak in melatonin secretion is blunted in drug-free schizophrenic subjects and this pattern is not improved after antipsychotic drug therapy. The stimulants used to treat ADHD frequently are associated with insomnia, which interacts unfavourably with the disorder. The traditional response to sleeping problems involves the class of drug termed hypnotics. These have two very undesirable aspects. One involves dysfunctional carry-over to the next day. The other is addiction, now also called dependence, which is common in long-term use and is also associated with withdrawal symptoms. Because hypnotics, while commonly used, are not indicated nor regarded desirable for long-term treatment of insomnia, some physicians have turned to antidepressants. Part of the rationale is that some believe (erroneously) that all or most insomnia is a symptom of depression, and thus antidepressant therapy is the treatment of choice.60 The reasons why this is not a good idea have been outlined in Part I of this review. In addition, one side effect of antidepressants is insomnia (!), which occurs in a few percent to over a quarter of those taking this class of drug.61 In addition, there is a carry-over to the next day involving drowsiness.

Insomnia also accompanies jet lag and reflects a mal-adjusted internal circadian clock in need of resetting. Thus supplementation with melatonin, a commonly used treatment for jet lag insomnia and resetting the circadian clock, is of interest in mental health since it involves merely enhancing an endogenous hormone level timed to generate peak melatonin at the optimum period during the night, and accomplishing this without side effects such as next-day mental and functional problems. The connection between sleep patterns and melatonin has prompted the industry to develop patentable drugs guided by the physiology of melatonin and to tinker with melatonin receptors through targeted drugs. This is motivated mostly by the desire for patent protection. Thus the important issues include the efficacy of melatonin in the context of bringing about normal sleep patterns and the impact of this on mood and functionality in individuals with psychiatric problems.

Another way to reset the circadian clock is with bright light used at a certain time. This is a well known treatment for seasonal affective disorder (SAD), also known as winter depression. Individuals suffering from SAD sit in front of a bright light in the early morning and may experience considerable if not total relief from seasonal depression.

Light therapy turns out to be a complicated subject since the color of the light (wavelength) is important as well as the intensity and timing relative to the rise and fall of melatonin during darkness. In addition, the use of melatonin must be timed properly and care must be taken with exposure to light during the melatonin secretion period. Proper use of these two tools also requires establishing the strength, length and timing of secretion relative to the day/night cycle. This can be accomplished by urine tests for a metabolite. A detailed discussion of the use of melatonin is beyond the scope of this review, which will only include a discussion of some clinical trials that relate to the treatment of disorders under consideration in this review. The following clinical trials with melatonin supplementation appear of interest.

  • Melatonin was used to treat individuals with what is called delayed sleep phase syndrome (DSPS), which is characterized by the inability to fall asleep and to awake at conventional times (e.g. awake well past midnight and wake-up past noon).62 The study was randomized, double blind, cross-over and placebo controlled. For analysis, the subjects were divided into two groups, depressed and not depressed. It was found that melatonin significantly reduced depression scores in the depressed group. Sleep continuity improved in both groups compared to the placebo. In the depressed group, melatonin supplementation altered favourably the internal melatonin cycle. In fact, one of the principal differences between DSPS patients with or without depressive symptoms was their temporal melatonin excretion patterns. The authors comment that it is likely that the melatonin treatment phase advances the delayed circadian rhythms in DSPS patients and this may mediate the amelioration of depressive symptoms. A steady internal and external phase relationship appears to be crucial for stable and normal mood state (i.e. the timing between core body temperature and cortisol as well as the timing of sleep with respect to the day/night cycle. Incidentally, the patients in this study were not taking psychiatric drugs.

  • The impact of melatonin therapy was examined in a randomized double blind placebo controlled study of schizophrenic patients with insomnia.63 It was observed that relative to the placebo, melatonin significantly improved the quality and depth of night time sleep and increased its duration with no morning hangover. The intervention also significantly reduced sleep onset latency, heightened freshness on awaking, improved mood and improved daytime functioning. All the patients were taking an antipsychotic drug.

  • A recent review of randomized and observational studies from 2003 to 2007 involving ADHD patients with insomnia found that melatonin appears safe and well tolerated in most children with this problem. Clinically relevant advances in sleep onset and total sleep time were found. The only RTC with a long-term follow-up found melatonin therapy also improved behaviour and mood as reported by parents. In this study the patients were 100% stimulant free.64,65

These studies reinforce the notion of a connection between mood and sleep patterns and the value of melatonin therapy.

Light therapy and sleep deprivation have passed the experimental development phase and are now considered powerful clinical interventions for everyday treatment of depression with response and relapse rates similar to those obtained with antidepressant drugs. Good results are even obtained in difficult-to-treat conditions such as bipolar depression. This subject has recently been reviewed by Benedetti et al. 66

While light therapy, sleep deprivation and supplemental melatonin therapy can easily be accomplished at home without professional assistance, the therapies are of sufficient inherent complexity that this is not recommended. Rather, consultation with a sleep clinic or an expert in this area is strongly advised. However, this therapeutic modality should not be ignored since it appears almost totally free of adverse side effects or withdrawal problems and furthermore can presumably be combined with other alternative approaches described in this review. A major advantage is the rapid onset of benefit.

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ST. JOHN'S WORT

This plant extract became popular in the late 1980s, mostly in Europe and especially in Germany. A recent meta-analysis by the Cochrane Collaboration of studies that compared St. John's wort and either a placebo or various antidepressants found the extracts superior to a placebo in patients with major depression and of similar effectiveness as standard antidepressants but with fewer side effects.67 There may be issues with product variability, with the interaction with other medications and with the absence of long-term studies focused on adverse effects. The mechanism of action is not clear, but it is suspected that it acts like psychiatric medications. Its use would depart from the general philosophy of the alternatives discussed in this review in that its use does not represent an adjustment in macro- or micronutrients that form part of the normal human diet, hormone levels or aspects of lifestyle. "Nature's medicines" are not a priori harmless.

PHYSICAL EXERCISE

There is considerable evidence that physical exercise is beneficial for depression, including major depression and anxiety. However, most of the studies addressing this issue have methodological problems and thus the evidence base is somewhat weak.68 The use of exercise as a treatment for depression has been tried for individuals of all ages, for postpartum depressive symptoms, and as an addition to drug treatment. In general, beneficial results have been obtained either for all groups, judged alone or in comparison with no exercise. It is significant that when compared with psychotherapy or drugs, exercise was found to be about as effective, and exercise enhances to some extent the effects of drug therapy. Various forms of exercise have been studied including walking, walking briskly, jogging and gym workouts.69,70 There is some evidence that duration of exercise sessions is more important than frequency.70 Evidence generated by controlled studies for benefit in ADHD appears very limited since there seems to be very little interest in the question. However, a recent book by John J. Ratey, M.D. titled Spark. The Revolutionary New Science of Exercise and the Brain, deals with this subject at length with many case histories drawn from the author's clinical experience. Included is his experience with exercise and ADHD and its beneficial effect.

Exercise is obviously an important therapeutic intervention, which should be free of side effects, unless there are medical contraindications, and obviously has many non-psychological benefits as well. If one can treat depression as successfully or even better with an exercise program than with drug therapy, given what has been discussed above about the latter, the choice seem obvious. Adding exercise to other alternative approaches appears straightforward.

WITHDRAWAL OF MEDICATION

A significant problem in this field is the individual on medication who is not doing well or getting worse. While drug withdrawal is not really an alternative therapy, withdrawal, either alone or accompanied by alternative therapy is an option. Withdrawal from medication is associated with considerable risk and must be done under the supervision of someone trained in the field. Typically, the substitute therapy would be some form of psychotherapy, but the other alternatives described above might be appropriate as well. When confronted with patients under psychiatric polytherapy and doing poorly, mainstream medicine does not appear to have medication withdrawal on their radar screen.

In Chapter 16 of his book Anatomy of an Epidemic Robert Whitaker describes his visit to Seneca Center in California, which may be the last residential facility where severely troubled children under county or state control are treated without psychiatric drugs.1 The Center's therapeutic philosophy is nicely summarized by the approach which asks not what is wrong with this child but what has happened to the child. When the children come to the center, they are lethargic, they are just a "blank" and there is only minimal engagement possible. The staff can simply not "get through to them". Withdrawal can take a month or two and can be difficult for all concerned. Behavior modification therapy is used. The staff describes what happens once the kids are off medication with the descriptive phrase - "they come alive". One can engage them and get a sense of who they are, their personality, their sense of humor, and what kinds of things they like to do. They begin to think of themselves in a new way and the find that they can control their own behavior. The behavior modification program is accompanied by house rules but the focus is on reinforcing positive behavior and the children are given increasing responsibilities. Whitaker does not mention any other alternative therapy. It is quite possible that the diet provided by the center corrected some of the micronutrient deficiencies likely present at this stage in the evolution of the mental problems of these young people. One is left to wonder if there was anything fundamentally wrong with these kids before a drug treatment program which in the end involved failed polypharmacy and ultimately what amounted to commitment to an institution.

Withdrawal of medication is the antithesis of the "absolute devotion to the paradigm" approach of ever-increasing doses and changing medications while the patient simply appears to get worse and worse. Thus, it appears to be an integral part of the alternative approach once someone has been unsuccessfully medicated, and it lends itself nicely to many other alternative therapies.

PSYCHOTHERAPY

Classical psychotherapy has evolved to include changes in the traditional focus common a half-century ago and as well as a number of distinct variations including behaviour modification and cognitive remediation therapy. Individuals saying no to psychopharmaceutical interventions clearly should consider this alternative, either alone or in combination with other alternative approaches. Both clinical psychologists (mostly Ph.D.s), psychiatrists and other highly trained and licensed practitioners are involved in this area and it is not uncommon in studies that include a psychotherapy arm that the results are comparable to drug interventions. It is also easy to argue that psychotherapy has a stronger evidence base than the psychopharmaceutical approach, given the profound weakness in the evidence base for the latter. A detailed discussion of this subject is beyond the scope of this review.

CONCLUSIONS

If we accept Peter Breggin's assertion, supported by hundreds of peer-reviewed studies and his clinical experience as well as that of other critics in the psychiatry community, many drugs directed at real and not-so-real psychological problems actually work by disabling the brain. We must also accept the net result which is a deficit in many of the mental attributes we normally view as part of our humanness. It is no wonder that the drop-out rate in clinical studies is so high. It has frequently been observed that depression is an essential aspect, perhaps necessary, of the human experience. Huxley in the Brave New World predicted that everybody can be cured from depression once the right pharmaceutical-biological intervention is found. But this aspect of utopia is equivalent to changing the very nature of the human condition.71 This is not to deny the partial benefits, although sometimes temporary, in some acute disorders, but there appears to be little doubt that this is a speciality in trouble with no mainstream way out. Breggin is far from alone crying in the wilderness - he just has a high and well deserved profile.

The original belief in chemical imbalances in the brain as the causal factor in mental disorders appears to have led researchers and clinicians down the wrong road and to a dead end. We appear to be witnessing unacknowledged desperation implied by individuals treated with higher and higher doses and more and more drugs. It is not uncommon to see lists in the baseline data tables of a study where many subjects were on three to four psychiatric drugs. What is not listed is how many are zombies or near zombies. Promotion of the conventional wisdom has been so successful that turning back now would represent a huge admission of error. The natural history of well-established therapies that work poorly if at all is that they endure long after the cat is out of the bag.

The approaches described in Part II of this review can be divided into two categories. The first involves looking for medical conditions or medication that could account for the symptoms and dealing with this possibility first. This includes ruling out street drug use. It is hard to think of any other term than malpractice when someone with a medical disorder such as subclinical hypothyroidism presents with depression and is given a psychiatric drug as the first line of treatment. The second category includes the interventions discussed above. Many can be tried simultaneously. Professionals' assistance in some cases is important; good examples being therapy directed at circadian rhythm problems and of course psychotherapy. High on the list should be addressing the possibility of micronutrient deficiencies with a multi-component supplement and as well, embracing a Mediterranean-type diet or a diet rich in fruits, vegetables and fish. Obtaining a 25-hydroxyvitamin D assay and acting on the results appears to be important. The importance of exercise is hard to overemphasize. Finally, a very strong argument can be made for starting psychotherapy, either with a psychiatrist, a psychologist, or someone with specialized training and certification in this field. The strong placebo effects seen in studies of psychiatric drugs are interesting because they point to the self-correcting ability of the human mind-brain system. Non-drug interventions such as psychotherapy and its variations presumably augment this natural tendency to self-correct, whereas drug interventions appear to have the potential to hinder it.

It is not possible to predict a priori which approach will successful, or if several will work together to produce favourable results. But the most important point is that by electing the alternative approach one is avoiding the side effects, the spellbinding, the potential for a downward spiral and polypharmacy, and the withdrawal problems associated with psychiatric drugs. There appears to be no way ahead of time of ascertaining whether or not one is going to be lucky with psychiatric drugs and not have serious problems, but the large numbers who do experience problems, single drug failure, multiple drug failure and even disability appears far from insignificant and should provide a powerful incentive for seeking alternatives unless the condition in question is severe or represents a true crisis.

Of necessity, alternative approaches will for at least the foreseeable future, suffer from inadequate studies or the absence of evidence that satisfies mainstream purists, simply because adequate studies are so expensive that the industry becomes the principal potential source of financing, and the industry views alternatives to drugs with fear and quite correctly as incapable of producing profits regarded as significant. Reflect on 36 large, randomized, placebo controlled trials to satisfy purists regarding the efficacy of each individual component in the EMP+ supplement. These would be preceded by phase I and phase II studies to establish safety and dose guidelines. Government bodies can and have provided support for studies of alternative approaches, but it traditionally and historically has been only token support. Thus, anyone wishing to solve a personal mental problem without pharmaceutical intervention must be satisfied with a level of evidence that is, with the exception of psychotherapy, generally unacceptable to mainstream medicine, and they should expect opposition from mainstream caregivers. But critics maintain that the evidence for the benefits of the pharmaceutical approach is fatally flawed and corrupted by the suppression of negative clinical study results, biased selection of study subjects, the downplaying, at least in public, of serious if not devastating side effects, the inflation of benefits and the avoidance of long-term studies and marketing practices that end up triggering legal proceedings.72-74 This industry behaviour pattern does not inspire confidence or respect, but it is accepted as generating what the profession widely promotes as evidence-based medicine.

Preparing this review was accompanied by a unique revelation. It appears that literally huge, perhaps unprecedented numbers of individuals are being treated with drugs that not only do not work very well, if at all, but do harm, in some cases permanent, to their most precious possession, the brain. This is even tacitly acknowledged, at least to some extent, by mainstream psychiatry which is now seeking a new direction, a new paradigm and is witnessing major drug companies abandoning the field. Ignoring medical disorders which are root causes of psychological problems and which are readily amenable to curative therapy outside the realm of psychiatry dooms the patient at best to long-term therapeutic failure. Nevertheless, the remarkably extensive use of psychiatric drugs, not only by psychiatrists but by internists and family doctors, makes it clear that this so-called standard of care is the norm, supported by professional organizations, guidelines, government regulators, standard approved textbooks and prestigious institutes. An eye opener, indeed.

Finally, the reader is advised that it is not the intention of this review to downplay the serious nature of some mental disorders, their connection with disability, nor the value or necessity of pharmaceutical intervention in some situations.


DISCLAIMER

The information presented in this review is not intended to be medical advice nor should it be regarded as such. The reader is also advised that stopping taking psychiatric drugs is associated with significant risk and that withdrawal can be very dangerous and should be carried out only under the close supervision of a medical professional. Please consult your healthcare provider if you are interested in following up on the information presented in this review.

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This article was first published in the March 2011 issue of International Health News

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