OMEGA-3 DEFICIENCY AND THERAPYThe 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.41In 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.

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.