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-'''Orthomolecular psychiatry''' is a branch of [[orthomolecular medicine]], an [[alternative medicine]] known for its claims that [[dietary supplement]]s and other unorthodox nutritional treatments can be effective in treating [[mental illness]].  The approach uses unorthodox forms of individualized testing and diagnosis to attempt to establish an [[etiology]] for each patient's specific [[symptom]]s, and claims to tailor the treatment accordingly, using a combination of nutrients, dietary changes and [[medication]]s that are claimed to enhance quality of life and functionality as well as to reduce or eliminate symptoms and the use of [[xenobiotic]] drugs.
-The origins of orthomolecular psychiatry date to the 1920s, and the work of [[Abram Hoffer]] in the 1950s established the orthodoxy of the field. Hoffer's therapies focused on using [[niacin]], among other nutrients, to treat acute schizophrenia, which was identified using the Hoffer-Osmond test. In 1973, a task force of the [[American Psychiatric Association]] examined and rejected the practice and it has been considered an [[Alternative medicine|alternative therapy]] since that time.  However, the conclusions of this APA report were strongly criticized by proponents of orthomolecular psychiatry for being politically motivated and scientifically unfounded.<ref>Menolascino FJ, et al. "Orthomolecular Therapy: Its History and Applicability to Psychiatric Disorders", ''Child Psychiatry and Human Development'', Vol.18(3), Spring 1988, pp 140-1 </ref> Currently there is a clinical trial being conducted on the basis that previous trials were done without taking into account Hoffer's distinction between acute and chronic schizophrenia.<ref name=NIMHtrial />
-Since Hoffer's early work, other possible nutritional treatments for mental illnesses from both inside and outside the orthomolecular community, and some mainly preliminary current scientific research is consistent with some the hypotheses advanced by orthomolecular psychiatrists,<ref>Syd Baumel (Aug 2000) "Chapter 5, [http://books.google.com/books?id=7QvKqNZrxocC&pg=PA84&lpg=PA84&dq=%22bill+w%22&source=web&ots=ITyDirbJHE&sig=b27plgzOn0P1ZRbR5tLwVqmjdIo&hl=en#PPA75,M1  The Orthomolecular Medical Approach to Depression]", "Chapter 6, [http://books.google.com/books?id=7QvKqNZrxocC&pg=PA84&lpg=PA84&dq=%22bill+w%22&source=web&ots=ITyDirbJHE&sig=b27plgzOn0P1ZRbR5tLwVqmjdIo&hl=en#PPA81,M1  Vitamin Power]",  ''Dealing with Depression Naturally: Complementary and Alternative Therapies'', 2nd ed, McGraw-Hill; ISBN 0658002910</ref> but most orthomolecular practices have not been extensively tested by conventional [[clinical trial]]s, instead practitioners rely on their interpretations of biochemical research, [[case report]]s and [[case series| clinical series]].{{Fact|date=July 2008}}
-== History ==
-The origins of orthomolecular psychiatry can be traced to as early as 1927,<ref>Reiter PJ: Behandlung von Dementia Praecox mit metallsalzen. Mangan. Z. Neur., 108:464-480, 1927  As quoted in Carl C. Pfeiffer, Ph.D., M.D. and Scott LaMola, B.S. Zinc and Manganese in the Schizophrenias, Journal of Orthomolecular Psychiatry, Vol. 12, No. 3, 1983</ref> and the broad roots of modern orthomolecular medicine involving Linus Pauling trace back to the 1930s.<ref>{{cite book |author=Kay, Lily E. |title=The molecular vision of life: Caltech, the Rockefeller Foundation, and the rise of the new biology |publisher=Oxford University Press |location=Oxford [Oxfordshire] |year=1993 |pages= |isbn= 0195111435 |oclc= |doi=}}</ref> Orthomolecular psychiatry ''per se'' is generally accepted to have begun in the 1950s with the work of [[Abram Hoffer]] and [[Humphry Osmond]], continued by the work of [[Carl Pfeiffer (pharmacologist)|Carl Pfeiffer]].<!-- [[David Horrobin]].<ref>{{cite web | url = http://www.lapinskas.com/publications/dfh_bibliography/ | title = David Horrobin Bibliography }}</ref> THIS WEB PAGE DOESN'T DEMONSTRATE A CONNECTION BETWEEN HORROBIN AND ORTHOMOLECULAR PSYCHIATRY--> For a time in the late 1950s and early 1960s, research into orthmolecular treatments was given much more prominence but the availability of faster acting orthodox tranquilizers and antidepressants, with clinically proven effects, began to dominate conventional psychiatric practice.<ref>{{cite web | last = Olson | first = G | url = http://commonground.ca/iss/0604177/cg177_ortho.shtml | title = Orthomolecular medicine: Vitamins are key to mental health | publisher = Common Ground | date = 2006-04-01 | accessdate = 2008-01-15}}</ref> In 1968, [[Linus Pauling]] gave the name and principle to the discipline of 'orthomolecular psychiatry'.<ref>{{cite journal |author=Pauling L |title=Orthomolecular psychiatry. Varying the concentrations of substances normally present in the human body may control mental disease |journal=[[Science (journal)|]]|volume=160 |issue=825 |pages=265–71 |year=1968 |pmid=5641253 |doi=| url = http://profiles.nlm.nih.gov/MM/B/B/J/Q/_/mmbbjq.pdf }}</ref><ref name="Pauling2">{{cite book |coauthors=Hawkins, D | last = Pauling | first = L | authorlink = Linus Pauling |title=Orthomolecular Psychiatry: Treatment of Schizophrenia |publisher=Freeman |location= San Francisco |year= 1973 |pages= 697|isbn=0716708981}}</ref>
-The earliest assertions by proponents of orthomolecular psychiatry were rejected in 1973 by a panel of the [[American Psychiatric Association]].<ref name="Pauling">{{cite journal |author=Pauling L, Wyatt RJ, Klein DF, Lipton MA |title=On the orthomolecular environment of the mind: orthomolecular theory |journal=The [[American Journal of Psychiatry]] |volume=131 |issue=11 |pages=1251–67 |year=1974 |pmid=4608217 |doi=}}</ref> <!-- , which instead INSTEAD OF WHAT?  NEEDS CLARIFICATIONS - THE TEXT MENTIONS ASSERTIONS, NOT TRIALS; COULD BE WORDED AS 'TESTED THE OMP PROTOCOL USING...'-->  The protocols used by the APA to test the theories of orthomolecular psychiatry involved populations with chronic schizophrenia <!-- IS THERE SUCH THING AS ACUTE SCHIZOPHRENIA, OR DOES THIS REFER TO ACUTE PSYCHOSIS? --> as well as populations not expected to benefit from the approach (notably populations with [[schizoaffective disorder|schizoaffective]] and [[bipolar disorder]]).<ref name=NIMHtrial>{{cite web | title = Treatment of Acute Schizophrenia With Vitamin Therapy | url = http://clinicaltrials.gov/ct2/show/NCT00140166?show_desc=Y#desc | publisher = Clinicaltrials.gov| date = 2005-08-31 | last = Lerner | first = V | accessdate = 2008-01-15 }}</ref> Orthomolecular psychiatry has subsequently found scant support in mainstream psychiatry<ref name=QW>{{cite web | url = http://www.quackwatch.org/01QuackeryRelatedTopics/ortho.html | title = Orthomolecular Therapy | last = Barrett M.D.| first = Stephen | authorlink = Stephen Barrett | publisher = [[Quackwatch|Quackwatch.org]] | date = 2000-07-12 | accessdate = 2008-01-02 }}</ref> and is currently considered to be an unproven system of treatments. After 1975, research directly associated with orthomolecular psychiatry was primarily reported in ''Orthomolecular Psychiatry'', now the ''[[Journal of Orthomolecular Medicine]]''.  A [[National Institute of Mental Health]] listed, [[randomized controlled trial]] of treatment, with two additional orthomolecular related nutrients originated later in the 1950s, is being tested, and is expected to be complete in 2009.<ref name=NIMHtrial/>
-== Diagnosis ==
-Proponents of orthomolecular psychiatry claim to have identified the causes of some psychiatric syndromes, in particular those that cause [[psychosis]]; according to orthomolecular proponents, testing for these causes guides diagnosis and treatment. Diagnostic measures and therapies commonly employed include "individual biochemical workup", [[fasting]], identifying suggested [[allergy|allergies]], dietary changes, [["megavitamin" therapy]], [[aminoacids]], and other so-called pharmacologic  nutrients.<ref name = Edelman>{{cite book |author=Eva Edelman |title=Natural Healing for Schizophrenia: And Other Common Mental Disorders |publisher=Borage Books |location= |date=2001 |pages= |isbn=0-9650976-7-6 |oclc= |doi=}}</ref>
-==Treatment==
-Treatment generally involves the administration of the 'right' substances (''ortho'' meaning ''right'' in [[Greek language|Greek]]); generally this involves administration of high doses of [[vitamin]]s, [[essential fatty acid]]s and other substances already produced or required by the body.  Orthomolecular psychiatrists do not categorically refuse to prescribe psychotropic medications; antipsychotics are often used to stabilize a patient, and anti-epileptics (dilantin in particular) are occasionally used to treat the conditon called by orthomolecular doctors, '[[histadelia]].'<ref name = Edelman/>  Not infrequently, the improvements orthomolecular psychiatrists can adduce are claimed to be sufficient to allow patients to reduce, but not eliminate, their reliance on conventional psychotropic drugs.{{Fact|date=January 2008}}
-Orthomolecular methods have been claimed as effective in treating  [[bipolar disorder]],{{Fact|date=January 2008}} [[schizophrenia]],<ref name = Edelman/> [[Attention deficit hyperactivity disorder|ADHD]] and some of its sub-types.<ref name = ABCHoffer>{{cite book |author=Hoffer, Abram |title=Dr. Hoffer's ABC of Natural Nutrition for Children: With Learning Disabilities, Behavioral Disorders, and Mental State Dysfunctions |publisher=Quarry press |location= |year=1999 |pages= |isbn=1550821857 |oclc= |doi=}}</ref>, and [[tardive dyskinesia]].<ref>{{cite journal| url = http://orthomolecular.org/library/jom/1999/abstracts/1999-v14n01-p028.shtml | title = The adverse effects of manganese deficiency on reproduction and health: A literature review | first = Tuula  | last = Tuormaa | journal = J Orthomolecular Med | volume = 11 | issue = 2 | year = 1996 | accessdate = 2007-12-18 | format = abstract}}</ref> The [[Journal of Orthomolecular Medicine]] has also referred to a reported case of a recovery from a diagnosis of Alzheimer's attributed partly to orthomolecular treatment to [[Chelation|chelate]] and reduced exposure to [[aluminium]].<ref>{{cite journal | url =http://orthomolecular.org/library/jom/2000/pdf/2000-v15n01-p021.pdf | format = pdf | title = How aluminum causes Alzheimer's disease:  The implications for prevention and treatment of Foster's Multiple Antagonist hypothesis | last = Foster | first = HD | journal = The [[Journal of Orthomolecular Medicine]] | volume = 15 | issue = 1 | year = 2000 | pages = 21–51 }}</ref>
-==Specific conditions==
-===Schizophrenia===
-According to orthomolecular psychiatry, the causes of psychotic disorders include [[pyroluria]],  [[histadelia]] (elevated histamine and basophiles), histapenia with high serum copper (low histamine with high copper), [[food allergy]], [[hypoglycemia]], [[hypothyroidism]] in the presence of normal thyroid values, [[heavy metal]] intoxications, as well as other rarer conditions.<ref name = Edelman/>  <!-- This clearly belongs in the psychotic disorders -->
-Hoffer and Osmond developed and used the "Hoffer-Osmond Diagnostic test" of  perception, their biochemical research as available in the 1950s and 1960s, and length of illness, acute vs. chronic, to identify, differentiate and monitor schizophrenic patients' progress, with more specific classifications in schizophrenia for orthomolecular treatment than the then accepted, broader classifications of the schizophrenizas.<!-- USED CURRENTLY?  SHOULD THIS BE DISCUSSED IN HISTORY, THEN MENTIONED HERE AS JUST THE HOD? --><!-- The use of the [[Niacin#Toxicity|'niacin flush']] to evaluate patients is also being explored.<ref>{{cite web | url = http://www.ness-foundation.org.uk/Niacin-Abnormalities.htm | title = Niacin Abnormalities | publisher = The Ness Foundation}};  {{dlw| url = http://www.ness-foundation.org.uk/Niacin-Abnormalities.html |date=March 2005}}</ref> GIVEN THAT THIS IS A 2005 CACHE PAGE, IT'S DUBIOUS TO USE 'IS' - RESULTS SHOULD BE AVAILABLE NOW-->  Many orthomolecular physicians still prescribe an initial course of [[antipsychotic]]s for [[Schizophrenia|schizophrenic]] patients with the long-term goal returning patients to health, and avoiding antipsychotics due to their [[Antipsychotic#Side_effects|side-effects]].  Orthomolecular psychiatry's goal of weaning patients from conventional neuroleptic drugs<ref name = Edelman/> follows '[[Carl Pfeiffer (pharmacologist)|Pfeiffer's]] Law', "For every drug that benefits a patient, there is a natural substance that can achieve the same effect".<ref>{{cite book |author=Paul Barney |title=Doctor's Guide to Natural Medicine: The Complete and Easy-To-Use Natural Health Reference from a Medical Doctor's Perspective |publisher=Woodland Publishing |location=Pleasant Grove, UT |year= |pages= |isbn=1-885670-84-2 |oclc= |doi=}}</ref>
-A single study of megavitamin and dietary therapy to treat schizophrenia was tested in 1999 and found to be effective at increasing serum levels of vitamins, but did not show any impact on symptoms of schizophrenia.<ref>{{cite journal |author=Vaughan K, McConaghy N |title=Megavitamin and dietary treatment in schizophrenia: a randomised, controlled trial |journal=Aust N Z J Psychiatry |volume=33 |issue=1 |pages=84–8 |year=1999 |pmid=10197889 |doi=10.1046/j.1440-1614.1999.00527.x}}</ref>
-===Bipolar disorder===
-[[Omega 3 fatty acid]]s have been demonstrated to assist in treating [[bipolar disorder]],<ref>{{cite journal |author=Stoll AL, Locke CA, Marangell LB, Severus WE |title=Omega-3 fatty acids and bipolar disorder: a review |journal=Prostaglandins Leukot. Essent. Fatty Acids |volume=60 |issue=5-6 |pages=329–37 |year=1999 |pmid=10471117 |doi=10.1016/S0952-3278(99)80008-8}}</ref> in keeping with orthomolecular psychiatry's assertion that foods can be used to treat mental illness.  Omega fatty acids also show promise or use in treating many other conditions.<ref name = Kidd>{{cite journal |author=Kidd PM |title=Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids |journal=Altern Med Rev |volume=12 |issue=3 |pages=207–27 |year=2007 |pmid=18072818 |doi=}}</ref>
-===Depression===
-The orthomolecular treatment of depression generally consists of treating histadelia, which can cause depression with and without psychosis, with methionine, or augmenting other amino acid imbalances.  The coenzyme [[S-adenosyl methionine]] is effective in treating some forms of depression.<ref>{{cite journal |author=Kagan BL, Sultzer DL, Rosenlicht N, Gerner RH |title=Oral S-adenosylmethionine in depression: a randomized, double-blind, placebo-controlled trial |journal=Am J Psychiatry |volume=147 |issue=5 |pages=591–5 |year=1990 |pmid=2183633 |doi=| url = http://www.ajp.psychiatryonline.org/cgi/content/abstract/147/5/591| accessdate = 2007-02-16 |format=abstract }}
-</ref><ref>{{ cite journal |author=Rosenbaum JF, Fava M, Falk WE, ''et al'' |title=The antidepressant potential of oral S-adenosyl-l-methionine |journal=[[Acta Psychiatrica Scandinavica]] |volume=81 |issue=5 |pages=432–6 |year=1990 |pmid=2113347 |doi=10.1111/j.1600-0447.1990.tb05476.x}}</ref> One paper in the [[Lancet]] reported that S-adenosylmethionine was as effective as conventional antidepressants, and linked depression to a disorder of [[methylation]].<ref name="Reynolds">{{cite journal |author=Reynolds EH, Carney MW, Toone BK |title=Methylation and mood |journal=Lancet |volume=2 |issue=8396 |pages=196–8 |year=1984 |pmid=6146753 |doi=10.1016/S0140-6736(84)90482-3}}</ref> Pfeiffer and others advocate the use of methionine, which is a precursor to S-adenosyl methionine, to treat some forms of depression, but have not published any clinical trials that would test the effectiveness of this therapy.<ref name = Pfeiffer>{{cite book |author=Pfeiffer, Carl C. |title=Nutrition and Mental Illness: An Orthomolecular Approach to Balancing Body Chemistry |publisher=Healing Art Press |location= |year= |pages= |isbn=0-89281-226-5}}</ref>  Mainstream [[psychiatry]] is, however, coming to report that some depressive disorders linked to suicide are linked to very elevated rates of methylation.<ref name = Poulter>{{cite journal |author=Poulter MO |title=GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes. |journal=Biol Psychiatry  |volume=64 |issue=8 |pages=645-52 |year=2008 |pmid=18639864 |doi=}}</ref>
-The amino acid [[tryptophan]], a precursor of [[serotonin]], is also used to treat some forms of depression; significant differences were found between plasma tryptophan levels in patients suffering from depression and healthy controls.<ref name="Breverman">{{cite book |coauthors=Breverman MD ER | last = Pfeiffer MD PhD | first = Carl | authorlink = Carl Pfeiffer |title=The Healing Nutrients Within |publisher=Basic Health Publications |location= San Francisco |year= 2003|pages= 448|isbn=1591200377}} </ref>  Mainstream psychiatry often treats depression with [[selective serotonin reuptake inhibitor]]s.  There are reports that tryptophan is effective in the treatment of mania.<ref>{{cite journal |author=Chouinard G et al |title=A controlled clinical trial of L-tryptophan in acute mania |journal=Biol Psychiatry |volume=20|issue=5 |pages=546–57 |year=1985|pmid=10471117 |doi=10.1016/0006-3223(85)90026-5}}</ref>
-==Treatment centers==
-Currently, orthomoleculary psychiatry continues to be investigated by a small number of researchers. The [[Pfeiffer Treatment Center]] is dedicated to the research and use of orthomolecular psychiatry in the treatment of [[schizophrenia]], [[bipolar disorder]], [[autism]], and violent criminal behavior.
-== Relationship to mainstream psychiatry ==
-Orthomolecular psychiatry has been rejected by the mainstream medical community, as has been the use of dietary interventions to treat psychological health,<ref>{{cite journal |author=Miller M |title=Diet and psychological health |journal=Altern Ther Health Med |volume=2 |issue=5 |pages=40–8 |year=1996 |pmid=8795935 |doi=}}</ref> although in recent years the psychiatric research community has cautiously began to reevaluate their skepticism of the use of dietary interventions to optimize mental well-being.<ref name="Economist">[http://www.economist.com/science/displaystory.cfm?story_id=10601460 Eat it up and be a good boy.] ''The Economist'',  February 2, 2008</ref> <ref name="Gesch">Gesch CB et al, [http://bjp.rcpsych.org/cgi/reprint/181/1/22?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=nutrition&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners. Randomised, placebo-controlled trial.], Br J Psych, 2002, Vol. 181, pp. 22-28 2002</ref>  <ref>{{cite journal |author=Stoll AL, Locke CA, Marangell LB, Severus WE |title=Omega-3 fatty acids and bipolar disorder: a review |journal=Prostaglandins Leukot. Essent. Fatty Acids |volume=60 |issue=5-6 |pages=329–37 |year=1999 |pmid=10471117 |doi=10.1016/S0952-3278(99)80008-8}}</ref>  Critics have noted that the claims advanced by its proponents are considered unsubstantiated, and even false, by conventional psychiatry. Authoritative bodies such as the National Institute of Mental Health<ref name = QW>{{cite web | url = http://www.quackwatch.org/01QuackeryRelatedTopics/ortho.html | title = Orthomolecular Therapy | last = Barrett M.D.| first = Stephen | authorlink = Stephen Barrett | publisher = [[Quackwatch]] |date=2000-07-12 | accessdate = 2008-01-02 }}</ref> and American Academy of Pediatrics<ref>{{cite web | url = http://pediatrics.aappublications.org/cgi/content/abstract/72/5/707 | title = Vitamin and Mineral Supplementation in Down's Syndrome | first = Forrest C. | last = Bennett | accessdate = 2007-02-13}}</ref> have criticized orthomolecular treatments as ineffective and potentially toxic.
-A 1973 task force of the American Psychiatric Association charged with investigating orthomolecular claims, but instead focused on niacin monotherapeutically<ref name="Pauling"/> (the earliest version of treatment, ca. 1952) for a different kind of patient population, unanimously concluded:
-<blockquote>This review and critique has carefully examined the literature produced by megavitamin proponents and by those who have attempted to replicate their basic and clinical work. It concludes in this regard that the credibility of the megavitamin proponents is low. Their credibility is further diminished by a consistent refusal over the past decade to perform controlled experiments and to report their new results in a scientifically acceptable fashion.
-Under these circumstances this Task Force considers the massive publicity which they promulgate via radio, the lay press and popular books, using catch phrases which are really misnomers like "megavitamin therapy" and "orthomolecular treatment," to be deplorable.<ref>{{citation | author = Lipton M et al. | title = Task Force Report on Megavitamin and Orthomolecular Therapy in Psychiatry | location = [[Washington D.C.]] | year = 1973 | publisher = [[American Psychiatric Association]]}}; as cited in {{cite web | url = http://www.quackwatch.org/01QuackeryRelatedTopics/ortho.html | title = Orthomolecular Therapy | last = Barrett M.D.| first = Stephen | authorlink = Stephen Barrett | publisher = [[Quackwatch|Quackwatch.org]] | date = 2000-07-12 | accessdate = 2008-01-02 }}</ref></blockquote>
-A study of the effectiveness of an orthomolecular treatment for acute schizophrenia began in 2005, attempting to adequately address the failings of previous APA studies to use an appropriate treatment group and intervention. <blockquote>Controlled studies using the orthomolecular approach have been few. Those that were done were performed in chronic schizophrenia or in populations that included bipolar and schizoaffective patients. Both of these diagnostic groups are not today considered to benefit from the orthomolecular approach. Moreover, some negative studies of high-dose niacin were done in patients who were not otherwise given general counseling for good diet.";<ref name=NIMHtrial/> compared with a basic, modern orthomolecular regimen.</blockquote>
-Proponents consider the 1973 APA task force report error laden with sweeping, scientifically unfounded conclusions,<ref name="Pauling"/> highly politicized, and that its studies failed to use similar methods, materials and subjects as the original work.<ref name = MVT>{{cite web | url = http://www.iahf.com/orthomolecular/reply_to_apa_tfr_7.pdf | title = Megavitamin Therapy In Reply To Task Force Report on Megavitamin and Orthomolecular Therapy in Psychiatry | source = Canadian Schizophrenia Foundation | year = 1976}}</ref>  The APA report's criticism alleges inadequate controlled trials because [[Abram Hoffer|Hoffer]] quit running additional blinded tests that he had come to view as unethical for his patients, especially since the results of his previous double blinded tests went unheeded.<ref>{{cite book | first = Abram | last = Hoffer | title = Adventures in Psychiatry: The Scientific Memoirs of Dr. Abram Hoffer | publisher = KOS Publishing | location = Toronto | year = 2005}} [http://www.searpubl.ca/Adventures_review.pdf Review] </ref>  The APA's assertion is made despite Hoffer's claim to have run the first double blind controlled test in psychiatry, on megavitamin therapies, with a total four double blinded tests, up to 19 years before the APA task force report, as well as being supported by two independent double blinded tests
-<ref name = witten>{{cite journal |author=Wittenborn JR, Weber ES, Brown M |title=Niacin in the long-term treatment of schizophrenia |journal=Arch. Gen. Psychiatry |volume=28 |issue=3 |pages=308–15 |year=1973 |pmid=4569673 |doi=}}</ref> and an extensive biochemical research program.<ref>{{cite journal | url = http://www.orthomolecular.org/library/jom/1999/pdf/1999-v14n01-p049.pdf | first = A | last =  Hoffers | coauthors = Osmond, H. | title = The adrenochrome hypothesis | journal = Journal of Orthomolecular Medicine | volume = 14 | issue = 1 | year = 1999}}</ref>   One of the APA report's five authors, psychologist JR Wittenborn, reacting to Hoffer's specific criticisms, later re-analyzed his original double blind study<ref name = witten/> favorably with respect to orthomolecular psychiatry, obtaining the same result as Hoffer,<ref>{{cite journal |author=Wittenborn JR |title=A search for responders to niacin supplementation |journal=Arch. Gen. Psychiatry |volume=31 |issue=4 |pages=547–52 |year=1974 |pmid=4607587 |doi=}}</ref> and never received NIMH or APA support again.<ref>{{cite web | url = http://www.doctoryourself.com/hoffer_paradigm.html | first = Abram | last = Hoffer | title = The Vitamin Paradigm Wars, Townsend Letter for Doctors and Patients | year = 1996}}</ref> According to Hoffer, APA task force co-author Thomas Ban was well known for his tranquilizer studies and that Ban previously stated that much of his income derived from grants from companies and other sources interested in selling tranquilizers.<ref name = MVT/>  APA task force co-author, then NIMH member [[Loren Mosher]], prior to the serving on the panel, had stated forcefully that if every psychiatrist in the USA believed that megavitamin therapy helped schizophrenic patients, he would not believe it.<ref name = MVT/>   Mosher later resigned from the American Psychiatric Association in total disgust for reasons unrelated to orthomolecular psychiatry,<ref>[http://www.moshersoteria.com/resig.htm] Loren R. Mosher, M.D. to Rodrigo Munoz, M.D., President of the American Psychiatric Association (APA), Letter of Resignation from the American Psychiatric Association, 4 December 1998</ref> and referred to the organization as a "drug company patsy."<ref>{{cite news | url = http://www.washingtonpost.com/wp-dyn/articles/A63107-2004Jul19.html | last = Bernstein | first = Adam | title = Contrarian Psychiatrist Loren Mosher, 70 (obituary}| publisher = [[The Washington Post]] |date=2004-07-20 | accessdate = 2007-12-18}}</ref>  In any event, allegations of misconduct surround panels that influence mainstream psychiatry to this day.<ref>{{cite news | url = http://www.tampabay.com/news/health/article454391.ece | last = Farley| first = Robert | title =Drug research to test or to tout?| publisher = St. Petersburg Times |date=2008-04-12 | accessdate = 2008-04-16}}</ref> <ref>{{cite news | url = http://www.dallasnews.com/sharedcontent/dws/news/texassouthwest/stories/DN-cmap_26tex.ART.State.Edition1.4a88179.html| last = Remshaw| first = Emily| title =State medication protocol researchers sought money from drug firms | publisher = Dallas Morning News |date=2008-10-28 | accessdate = 2008-10-28}}</ref>
-== Current research ==
-===Food allergies===
-A 2006 literature review noted that studies had found that the frequency of schizophrenia in patients with celiac disease to be significantly above average; one study found schizophrenia to occur in patients with celiac disease 3.2 times as often as in the general population.<ref>{{cite journal |author=Eaton W et al |title=Coeliac disease and schizophrenia: population based case control study with linkage of Danish national registers |journal=BMJ |volume=328  |pages=438–9 |year=2004 |pmid=14976100 |doi=10.1136/bmj.328.7437.438}}</ref>  The review reported that some studies suggest that removal of gluten from the diet of a subset of schizophrenic patients may reduce symptoms in a subset of patients, but that others have seen no effect from dietary changes.  It noted that the sample sizes in the studies that found no improvement were very small, so that if only a relatively small subset of schizophrenics do improve, the odds of these studies, one of which was otherwise flawed, not including any of these less common cases was between 48% and 75%. The review attributed the hesitancy with which these positive results have been been received to the fact that many of them had been reported by a group lead by the same researcher, FC Dohan.  Dohan reported in one study of 102 patients that 62% of the patients in a locked ward could be discharged to an unlocked ward within 7 days compared to only 36% on a high cereal diet.<ref>{{cite journal |author=Dohan FC, et al.|title=Relapsed schizophrenics: more rapid improvement on a milk- and cereal-free diet |journal=Br J Psychiatry|volume=115|issue=5|pages=595–6 |year=1969 |pmid=5820122 |doi=}}</ref>  Another study found that after 90 days, 37.2% of the patients on a gluten and milk-free diet had been discharged from the locked ward compared to 16.1% on a diet rich in cereals.  Neither study was double blind, however secretly adding gluten unbeknownst to patients or staff was found to negate the observed different rate of recovery.<ref>{{cite journal |author=Dohan FC, et al.|title=Relapsed schizophrenics: earlier discharge from the hospital after cereal-free, milk-free diet |journal=Am J Psychiatry|volume=130|issue=(6)|pages=685–8|year=1973 |pmid=4739849 |doi=}}</ref>  Other studies not conducted by Dohan have reported similar findings,<ref>{{cite journal |author=Singh MM, et al.|title=Study of gluten effect in schizophrenia |journal=Arch Gen Psychiatry|volume=40|issue=(3)|pages=345–6|year=1983 |pmid=6830414 |doi=}}</ref> <ref>{{cite journal |author=Rice JR, et al.|title=Another look at gluten in schizophrenia |journal=Am J Psychiatry.|volume=135|issue=(11)|pages=1417–8|year=1978|pmid=707651|doi=}}</ref> or symptom improvement on a gluten-free diet which dramatically worsened when gluten was reintroduced.<ref>{{cite journal |author=Vlissides DN, et al.|title=A double-blind gluten-free/gluten-load controlled trial in a secure ward population|journal=Br J Psychiatry|volume=148|issue=(4)|pages=447–52|year=1986 |pmid=3524724 |doi=}}</ref>
-Also mentioned was a 1997 article about a woman with schizophrenia and [[celiac disease]] who experienced a remission of both illnesses when gluten was removed from her diet.  [[SPECT]] scans before and after the adoption of a gluten-free diet change showed a remarkable resolution of the decreased blood flow to the brain's cortex, which is associated with schizophrenia.<ref>{{cite journal |author=De Santis A et al |title=Schizophrenic symptoms and SPECT abnormalities in a coeliac patient: regression after a gluten-free diet |journal=J Intern Med |volume=242  |pages=421–423 |year=1997 |pmid=9408073 |doi=10.1046/j.1365-2796.1997.00200.x}}</ref>  The review concluded that large randomized clinical trials (RCTs) will be required to verify if there is a genuine causal relationship between diet and schizophrenia.<ref name = Eaton>{{cite journal |pmid = 16423158 |first =  A.E.  |last = Kalaydjian |coauthors = Eaton W., Cascella N. & Fasano A. | year = 2006 |title = The gluten connection: the association between schizophrenia and celiac disease |journal = [[Acta Psychiatrica Scandinavica]] |volume = 113| issue = 2 | pages = 82–90 |doi = 10.1111/j.1600-0447.2005.00687.x}}</ref> The problem is that RCTs are very costly, and since it is impossible to patent a diet, there is no motivation for the pharmaceutical or other industry to  fund such a trial. Removing gluten and other allergens had long been recommended by orthomolecular psychiatrists when indicated.<ref name = Edelman/><ref name = Pfeiffer/>
-===Copper===
-The only neurological disease that has been unambiguously proved to be caused by an accumulation of copper to toxic levels is a [[genetic disorder]] called [[Wilson's disease]].<ref>{{cite journal |author=de Bie P, Muller P, Wijmenga C, Klomp LW |title=Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes |journal=J. Med. Genet. |volume=44 |issue=11 |pages=673–88 |year=2007 |pmid=17717039 |doi=10.1136/jmg.2007.052746}}</ref>  Carl Pfeiffer proposed that a form of schizophrenia or [[dementia]] he named histapenia could sometimes be accompanied by the accumulation of [[Copper#Toxicity|toxic levels of copper]] without the liver damage copper toxicity causes in Wilson's disease;<ref name = Pfeiffer/> his beliefs were dismissed by the mainstream medical community.  More recently there has been considerable mainstream scientific interest in the hypothesis that [[Alzheimer's disease]] may instead involve reductions in the levels of copper in the brain.<ref name=Donnelly>{{cite journal |author=Donnelly PS, Xiao Z, Wedd AG |title=Copper and Alzheimer's disease |journal=Curr Opin Chem Biol |volume=11 |issue=2 |pages=128–33 |year=2007 |pmid=17300982 |doi=10.1016/j.cbpa.2007.01.678}}</ref><ref>{{cite journal |author=Rossi L, Squitti R, Calabrese L, Rotilio G, Rossini PM |title=Alteration of peripheral markers of copper homeostasis in Alzheimer's disease patients: implications in aetiology and therapy |journal=J Nutr Health Aging |volume=11 |issue=5 |pages=408–17 |year=2007 |pmid=17657362}}</ref> These results have led to initial clinical trials of copper supplements as a possible treatment for Alzheimer's disease.<ref>{{cite journal |author=Pajonk FG, Kessler H, Supprian T, ''et al'' |title=Cognitive decline correlates with low plasma concentrations of copper in patients with mild to moderate Alzheimer's disease |journal=J. Alzheimers Dis. |volume=8 |issue=1 |pages=23–7 |year=2005 |pmid=16155346}}</ref> The use of the copper [[chelation|chelator]] [[clioquinol]] to treat changes in copper levels has also been proposed. This compound showed promise in initial studies,<ref>{{cite journal |author=Ritchie CW, Bush AI, Mackinnon A, ''et al'' |title=Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial |journal=Arch. Neurol. |volume=60 |issue=12 |pages=1685–91 |year=2003 |pmid=14676042 |doi=10.1001/archneur.60.12.1685}}</ref> but a recent [[meta-analysis]] stated that firm conclusions cannot be made from these small-scale trials.<ref>{{cite journal |author=Jenagaratnam L, McShane R |title=Clioquinol for the treatment of Alzheimer's Disease |journal=Cochrane Database Syst Rev |volume= |issue=1 |pages=CD005380 |year=2006 |pmid=16437529 |doi=10.1002/14651858.CD005380.pub2}}</ref> However, if this effect is genuine, the mechanism of action of this drug is unclear.  One scientist investigating clioquinol theorizes that the cause of Alzheimer's is a build-up of copper and [[zinc]] in the brain, and believes clioquinol will be useful in absorbing the metals and dissolving the [[amyloid]] plaques associated with the disease,<ref name = USAT>{{cite news | url = http://www.usatoday.com/tech/news/techinnovations/2003-12-26-alz-advance_x.htm | title = Scientist is winning converts on Alzheimer's | publisher = [[USA Today]] | last = Wysocki | first = Bernard |date = 2003-12-26 | accessdate = 2008-01-16}}</ref> but others suggest that clioquinol may be an [[ionophore]] that transports copper into the brain.<ref name=Donnelly/><ref>{{cite journal |author=Cherny RA, Atwood CS, Xilinas ME, ''et al'' |title=Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice |journal=Neuron |volume=30 |issue=3 |pages=665–76 |year=2001 |pmid=11430801 |doi=10.1016/S0896-6273(01)00317-8}}</ref>
-A scientist specifically pursuing research in orthomolecular psychiatry has found that women who suffer from postpartum depression on average have a strongly significant higher level of plasma copper than women who haven't suffered from postpartum depression,<ref>{{cite journal |author=Crayton JW et al. |title=Elevated serum copper levels in women with a history of post-partum depression |journal=J Trace Elem Med Biol. |volume=21|issue=1 |pages=17–21 |year=2007|pmid=17317521 |doi=10.1016/j.jtemb.2006.10.001}}</ref> and that males with a history of violence and assault have a significantly higher median blood copper / zinc ratio.<ref>{{cite journal |author=Walsh JW et al. |title=Elevated blood copper/zinc ratios in assaultive young males |journal=Physiol Behav. |volume=62|issue=2 |pages=327–329 |year=2007|pmid=9251975 |doi=10.1016/S0031-9384(97)88988-3}}</ref>
-===Histadelia===
-Carl Pfeiffer posited the existence of a syndrome called "[[histadelia]]"; this is claimed to be marked by unnaturally high blood levels of the naturally occurring chemical messenger [[histamine]] as well as so-called "undermethylation", which Pfeiffer suggested might cause depression and psychosis. Pfeiffer gave the amino acid [[methionine]] to people that he considered had this syndrome. Although there is no published scientific evidence that methionine is effective in the treatment of these mental illnesses, one trial has been published that suggested the [[coenzyme]] [[S-Adenosyl methionine|''S''-adenosyl methionine]] is effective in the treatment of depression.<ref>{{cite journal |author=Mischoulon D, et al. |title=Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence |journal=Am J Clin Nutr. |volume=76|issue=(5) |pages=1158S–61S |year=2002 |pmid=12420702}}</ref>
-===Amalgam intoxication===
-Between 1997 and 1999 the Journal of Orthomolecular Medicine published articles that suggested there was a [[correlation]] between [[Amalgam (dentistry)|amalgam]] fillings and schizophrenia,<ref >{{cite journal | format = pdf | url = http://orthomolecular.org/library/jom/1999/pdf/1999-v14n04-p201.pdf | author= Sibelrud RL, et al. | year = 1999 |title = Psychometric evidence that dental amalgam mercury may be an etiological factor in schizophrenia |journal = J Orthomolecular Med |volume = 14| issue = 4 | pages = 201–209| accessdate = 2008-01-12}}</ref> bipolar disorder,<ref>{{cite journal | url = http://orthomolecular.org/library/jom/1998/pdf/1998-v13n01-p031.pdf | format = pdf |author= Sibelrud RL, et al. | year = 1998 |title = Psychometric evidence that dental amalgam  mercury may be an etiological factor in manic depression |journal = J Orthomolecular Med |volume = 13| issue = 1 | pages = 31–40| accessdate = 2008-01-12}}</ref> and [[multiple sclerosis]].<ref>{{cite journal | url = http://orthomolecular.org/library/jom/1997/pdf/1997-v12n03-p169.pdf | format = pdf | author= Sibelrud RL, et al. | year = 1997 |title = Evidence that mercury from silver dental fillings may Be an etiological factor in reduced nerve Conduction velocity in multiple sclerosis patients |journal = J Orthomolecular Med |volume = 12| issue = 3 | pages = 169–172| accessdate = 2008-01-12}}</ref>  Anecdotal accounts also suggested similar ideas, with in 1998 a dentist publishing that a patient who had been diagnosed with multiple sclerosis, but whose symptoms resolved after her amalgam fillings were replaced.  The patient's neurologist subsequently concluded that she had never suffered from multiple sclerosis.<ref name="Engel">{{cite journal | url = http://www.amalgam-info.ch/beobac-e.pdf | format = pdf |author= Engel P | year = 1998 |title = Health observations before and after amalgam removal |journal = Schweiz. Monatsschrift f. Zahnmed |volume = 108| issue = 8|pmid=9776669 | accessdate = 2008-01-12}}</ref><!-- ANECDOTAL EVIDENCE AND HOW RELIABLE IS THE JOURNAL? -->  Another patient described in this study had been almost completely unable to work because of psychological and physical ailments deemed to be psychosomatic, almost completely recovered after her amalgam fillings were removed.<ref name="Engel"/>  Another dentist has written a book describing what he claims are recoveries from multiple sclerosis after the removal of amalgam fillings.<ref>{{cite book |author=Huggins HA | title= Solving the MS Mystery: Help, Hope and Recovery |publisher= Matrix Inc. |location= |year=2002 |pages= 405 |isbn= 0972461116|doi=}}</ref><!-- ALSO ANECDOTAL -->  A paper on the effects of amalgam fillings on the immune system reported that they can cause the appearance of [[basophil granulocyte]]s, which are seldom seen in amalgam-free patients.<ref>{{cite book |author=Huggins, Hal A. |title=Mercury and Other Toxic Metals in Humans: Proceedings of the First International Conference on Biocompatiblity of Materials : 1988, Colorado Springs, |publisher=Life Sciences Pr |location= |year= |pages= |isbn=0-943685-08-7 |oclc= |doi=}}</ref> Pfeiffer reported that some schizophrenic patients had extremely high basophil counts.<ref>{{cite journal |author=Pfeiffer CC |title=Extreme basophil counts and blood histamine levels in schizophrenic outpatients as compared to normals |journal=Res Commun Chem Pathol Pharmacol.  |volume=4 |issue=(1) |pages=51–9 |year=1972 |pmid=4671910 |doi=| |doi_brokendate=2008-06-23}}</ref> These ideas are not accepted in mainstream science, and a recent [[meta-analysis]] of four [[epidemiology|epidemiological]] studies found significant differences between the findings of the individual studies, but on average only a slight but insignificant association between amalgam fillings and multiple sclerosis.<ref>{{cite journal |author=Aminzadeh KK, Etminan M |title=Dental amalgam and multiple sclerosis: a systematic review and meta-analysis |journal=J Public Health Dent |volume=67 |issue=1 |pages=64–6 |year=2007 |pmid=17436982 |doi=10.1111/j.1752-7325.2007.00011.x}}</ref>  The [[United States Public Health Service]] and [[American Dental Association]]'s position statements on dental amalgams is that they do not pose a significant risk of adverse health consequences and are a cost-effective, durable and effective option for dental fillings,<ref name = FDA>{{cite web | url = http://www.fda.gov/cdrh/consumer/amalgams.html | title = Questions and Answers on Dental Amalgam | date = 2006-10-30 | accessdate = 2008-01-04 | publisher = [[Food and Drug Administration]] }}</ref><ref>{{cite web | url = http://www.ada.org/prof/resources/positions/statements/amalgam.asp | title = ADA Statement on Dental Amalgam | date = 2007-04-06 | accessdate = 2008-01-04 | publisher = [[American Dental Association]]}}</ref> though an [[Food and Drug Administration|FDA]] panel felt that there was insufficient research for an unequivocal statement on the safety of amalgams for children, pregnant women and individuals sensitive to mercury.<ref name = FDA/>
-==Aging==
-The orthomolecular approach claims that it might be effective in the treatment of age-related brain deterioration.<ref name="pmid18046879">{{cite journal |author=Janson M |title=Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging |journal=Clin Interv Aging |volume=1 |issue=3 |pages=261–5 |year=2006 |pmid=18046879 |doi=10.2147/ciia.2006.1.3.261}}</ref>
-==Notable patients==
-[[Abram Hoffer]] reports that actress [[Margot Kidder]] credits orthomolecular psychiatry with helping her overcome bipolar disorder.<ref>{{cite book | first = Abram | last = Hoffer | title = Masks of Madness: Orthomolecular Treatment of Mental Illness  | publisher = Quarry Press | isbn= 1550822608 | year = 2001}} </ref>  [[Mark Vonnegut]] attributed his recovery from schizophrenia to orthomolecular psychiatry and advocated its adoption by mainstream medicine, but later disavowed his statements.<ref name = Edelman/>
-== References ==
-{{reflist|3}}
-== Bibliography ==
-* {{cite book |author=Braverman, Eric R. |title=The Healing Nutrients Within: Facts, Findings, and New Research on Amino Acids |publisher=Basic Health Publications |location= |year= 2003|pages= |isbn=1-59120-037-7 |oclc= |doi=}}<!-- 2003 VERSION IS A SINGLE AUTHOR -->
-*{{cite book |coauthors=Hawkins, D MD| last = Pauling PhD | first = Linus | authorlink = Linus Pauling |title=Orthomolecular Psychiatry: Treatment of Schizophrenia |publisher=Freeman |location= San Francisco |year= 1973 |pages= 697}}
-*{{cite book |author=Pfeiffer, Carl J. | authorlink = Carl Pfeiffer (pharmacologist) |title=Nutrition and Mental Illness: An Orthomolecular Approach to Balancing Body Chemistry |publisher=Healing Art Press |location= |year= |pages= |isbn=0-89281-226-5 |oclc= |doi=}}
-* {{cite book |author=Werbach, Melvyn R. |title=Nutritional influences on mental illness: a sourcebook of clinical research |publisher=Third Line Press |location=Tarzana, Calif |year=1999 |pages= |isbn=0-9618550-8-8 |oclc= |doi=}}
-== External links ==
-* [http://www.orthomed.org/ Orthomolecular Medicine Online]
-* [http://www.earthhouse.org/  The Earth House], orthomolecular treatment center whose predecessor was founded by [[Carl Pfeiffer]]
-* [http://www.orthomolecularvitamincentre.com/index.php/ Orthomolecular Vitamin Information Centre.]
-[[Category:Orthomolecular medicine]]
-[[Category:Psychiatry]]
-[[Category:Psychiatric treatments]]
-[[de:Orthomolekulare Psychiatrie]]