Treatment of schizophrenia

The concept of a cure as such in the treatment of schizophrenia remains controversial, as there is no consensus on the definition of "treatment" in the case of schizophrenia, although some criteria for the remission of symptoms have recently been suggested.van Os J, Burns T, Cavallaro R, "et al" (2006). Standardized remission criteria in schizophrenia. "Acta Psychiatrica Scandinavica", 113(2), 91–5. PMID 16423159]

Management of symptoms and improving function is thought to be more achievable than a cure. A recovery model is increasingly adopted, emphasizing hope, empowerment and social inclusion.Bellack AS. (2006) Scientific and consumer models of recovery in schizophrenia: concordance, contrasts, and implications. "Schizophrenia Bulletin." Jul;32(3):432-42. PMID 16461575]

Antipsychotics have been a mainstay of therapy since the introduction of chlorpromazine in the mid 1950s, which revolutionized treatment of the illness. However all antipsychotics have a considerable array of side effects, many unpleasant and some harmful or even fatal. Thus their use has attracted much controversy in the five decades they have been prescribed. Older concerns over sedation, tardive dyskinesia and neuroleptic malignant syndrome have been largely replaced with those of drug-related obesity and diabetes.

In many non-Western societies, schizophrenia may only be treated with more informal, community-led methods. The outcome for people diagnosed with schizophrenia in non-Western countries may actually be better than for people in the West.Kulhara P (1994). Outcome of schizophrenia: some transcultural observations with particular reference to developing countries. "European Archives of Psychiatry and Clinical Neuroscience", 244(5), 227–35. PMID 7893767] The reasons for this effect are not clear, although cross-cultural studies are being conducted.

Prognosis

Numerous international studies have demonstrated favorable long-term outcomes for around half of those diagnosed with schizophrenia, with substantial variation between individuals and regions.Harrison G, Hopper K, Craig T, Laska E, Siegel C, Wanderling J, Dube KC, Ganev K, Giel R, an der Heiden W, Holmberg SK, Janca A, Lee PW, León CA, Malhotra S, Marsella AJ, Nakane Y, Sartorius N, Shen Y, Skoda C, Thara R, Tsirkin SJ, Varma VK, Walsh D, Wiersma D. (2001) Recovery from psychotic illness: a 15- and 25-year international follow-up study. "Br J Psychiatry." Jun;178:506-17. PMID 11388966] One retrospective study found that about a third of people made a full recovery, about a third showed improvement but not a full recovery, and a third remained ill.Harding CM, Brooks GW, Ashikaga T, Strauss JS, Breier A (1987). The Vermont longitudinal study of persons with severe mental illness, II: Long-term outcome of subjects who retrospectively met DSM-III criteria for schizophrenia. "American Journal of Psychiatry", 144(6), 727–35. PMID 3591992] A clinical study using strict recovery criteria (concurrent remission of positive and negative symptoms and adequate social and vocational functioning continuously for two years) found a recovery rate of 14% within the first five years.Robinson DG, Woerner MG, McMeniman M, Mendelowitz A, Bilder RM (2004). Symptomatic and functional recovery from a first episode of schizophrenia or schizoaffective disorder. "American Journal of Psychiatry", 161, 473–479. PMID 14992973] A 5-year community study found that 62% showed overall improvement on a composite measure of symptomatic, clinical and functional outcomes. [Harvey, C.A., Jeffreys, S.E., McNaught, A.S., Blizard, R.A., King, M.B.(2007) [http://isp.sagepub.com/cgi/content/abstract/53/4/340 The Camden Schizophrenia Surveys III: Five-Year Outcome of a Sample of Individuals From a Prevalence Survey and the Importance of Social Relationships.] "International Journal of Social Psychiatry," Vol. 53, No. 4, 340-356] Rates are not always comparable across studies because an exact definition of what constitutes recovery has not been widely accepted, although standardized criteria have been suggested.

The World Health Organization conducted two long-term follow-up studies involving more than 2,000 people suffering from schizophrenia in different countries. These studies found patients have much better long-term outcomes in developing countries (India, Colombia and Nigeria) than in developed countries (USA, UK, Ireland, Denmark, Czech Republic, Slovakia, Japan, and Russia),Hopper K, Wanderling J (2000). Revisiting the developed versus developing country distinction in course and outcome in schizophrenia: results from ISoS, the WHO collaborative follow up project. International Study of Schizophrenia. "Schizophrenia Bulletin", 26 (4), 835–46. PMID 11087016] despite the fact antipsychotic drugs are typically not widely available in poorer countries, raising questions about the effectiveness of such drug-based treatments.

Several factors are associated with a better prognosis: Being female, acute (vs. insidious) onset of symptoms, older age of first episode, predominantly positive (rather than negative) symptoms, presence of mood symptoms and good premorbid functioning.Davidson L, McGlashan TH. (1997) The varied outcomes of schizophrenia. "Canadian Journal of Psychiatry", 42 (1), 34–43. PMID 9040921] Lieberman JA, Koreen AR, Chakos M, Sheitman B, Woerner M, Alvir JM, Bilder R. (1996) Factors influencing treatment response and outcome of first-episode schizophrenia: implications for understanding the pathophysiology of schizophrenia. "Journal of Clinical Psychiatry", 57 Suppl 9, 5–9. PMID 8823344] Most studies done on this subject, however, are correlational in nature, and a clear cause-and-effect relationship is difficult to establish. Evidence is also consistent that negative attitudes towards individuals with schizophrenia can have a significant adverse impact. In particular, critical comments, hostility, authoritarian and intrusive or controlling attitudes (termed high 'Expressed Emotion' or 'EE' by researchers) from family members have been found to correlate with a higher risk of relapse in schizophrenia across cultures.Bebbsington PE, Kuipers E (1994). The predictive utility of expressed emotion in schizophrenia: an aggregate analysis. "Psychological Medicine", 24, 707–718. PMID 7991753]

Assessment of effectiveness

The effectiveness of schizophrenia treatment is often assessed using standardized methods, one of the most common being the positive and negative syndrome scale (PANSS).Kay SR, Fiszbein A, Opler LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. "Schizophrenia Bulletin", 13(2), 261–76. PMID 3616518]

Admission to hospital

Hospitalization may occur with severe episodes of schizophrenia. This can be voluntary or (if mental health legislation allows it) involuntary (called civil or involuntary commitment). Long-term inpatient stays are now less common due to deinstitutionalization, although can still occur.Becker T, Kilian R. (2006) Psychiatric services for people with severe mental illness across western Europe: what can be generalized from current knowledge about differences in provision, costs and outcomes of mental health care? "Acta Psychiatrica Scandinavica Supplement", 429, 9–16. PMID 16445476] Following (or in lieu of) a hospital admission, support services available can include drop-in centers, visits from members of a community mental health team or Assertive Community Treatment team, supported employment [McGurk, SR, Mueser KT, Feldman K, Wolfe R, Pascaris A (2007). Cognitive training for supported employment: 2–3 year outcomes of a randomized controlled trial. "Am J Psychiatry." Mar;164(3):437–41. PMID 17329468] and patient-led support groups.

pecific treatments

Medication

The mainstay of psychiatric treatment for schizophrenia is an antipsychotic medication.The Royal College of Psychiatrists & The British Psychological Society (2003). [http://www.nice.org.uk/download.aspx?o=289559 "Schizophrenia. Full national clinical guideline on core interventions in primary and secondary care"] (PDF). London: Gaskell and the British Psychological Society. Retrieved on 2007-05-17.] These can reduce the "positive" symptoms of psychosis. Most antipsychotics take around 7–14 days to have their main effect.

Treatment was revolutionized in the mid 1950s with the development and introduction of the first antipsychotic chlorpromazine.cite journal | author=Turner T. | title=Unlocking psychosis | journal=Brit J Med | year=2007 | volume=334 | issue=suppl | pages=s7 | doi=10.1136/bmj.39034.609074.94 ] Others such as haloperidol and trifluoperazine soon followed.

Though expensive, the newer atypical antipsychotic drugs are usually preferred for initial treatment over the older typical antipsychotics; they are often better tolerated and associated with lower rates of tardive dyskinesia, although they are more likely to induce weight gain and obesity-related diseases.Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. (2005). Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. "The New England Journal of Medicine", 353 (12), 1209–23. PMID 16172203] Of the atypical antipsychotics, olanzapine and clozapine are the most likely to induce weight gain. [Wirshing DA, Wirshing WC, Kysar L, Berisford MA. (1999) Novel antipsychotics: comparison of weight gain liabilities. "Journal of Clinical Psychology" 60 358-63] The effect is more pronounced if high doses of olanzapine are used. [Green B (1999) Focus on olanzapine "Current Med Res Opin" 15 79-85] Smaller amounts of weight gain are induced by risperidone and quetiapine. Ziprasidone and aripiprazole are considered to be weight neutral antipsychotics.

It remains unclear whether the newer antipsychotics reduce the chances of developing neuroleptic malignant syndrome, a rare but serious and potentially fatal neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs.Ananth J, Parameswaran S, Gunatilake S, Burgoyne K, Sidhom T. (2004) Neuroleptic malignant syndrome and atypical antipsychotic drugs. "Journal of Clinical Psychiatry", 65 (4), 464-70. PMID 15119907]

The two classes of antipsychotics are generally thought equally effective for the treatment of the positive symptoms. Some researchers have suggested that the atypicals offer additional benefit for the negative symptoms and cognitive deficits associated with schizophrenia, although the clinical significance of these effects has yet to be established. Recent reviews have refuted the claim that atypical antipsychotics have fewer extrapyramidal side effects than typical antipsychotics, especially when the latter are used in low doses or when low potency antipsychotics are chosen.Leucht S, Wahlbeck K, Hamann J, Kissling W (2003). New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. "The Lancet", 361(9369), 1581–9. PMID 12747876]

Response of symptoms to mediation is variable; "Treatment-resistant schizophrenia" is a term used for the failure of symptoms to respond satisfactorily to at least two different antipsychotics. [cite journal | author = Meltzer HY | title = Treatment-resistant schizophrenia--the role of clozapine | journal = Current Medical Research and Opinion | volume = 14 | issue = 1 | pages = 1–20 | date = 1997 | pmid=9524789 ] Patients in this category may be prescribed clozapine, [cite journal | author = Wahlbeck K, Cheine MV, Essali A | title = Clozapine versus typical neuroleptic medication for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = | issue = 2 | pages = | publisher = John Wiley and Sons, Ltd. | date = 2007 | pmid=10796289 | doi = 10.1002/14651858.CD000059 | id = ISSN 1464-780X] a medication of superior effectiveness but several potentially lethal side effects including agranulocytosis and myocarditis. [cite journal | author = Haas SJ, Hill R, Krum H | title = Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis associated with the use of clozapine in Australia during 1993–2003 | journal = Drug Safety | volume = 30 | pages = 47–57 | date = 2007 | pmid=17194170 ] For other patients who are unwilling or unable to take medication regularly, long-acting depot preparations of antipsychotics may be given every two weeks to achieve control. America and Australia are two countries with laws allowing the forced administration of this type of medication on those who refuse but are otherwise stable and living in the community.

Nevertheless, some findings indicate that, in the long term, many schizophrenic individuals function better without antipsychotic medicine. [Fenton W., and McGlashan T. (1987). "Sustained remission in drug-free schizophrenic patients," "Am J Psychiatry". 144:1306–1309.] In a 2007 study, only 28% of patients who were not being treated medicinally showed signs of psychotic activity, while 64% of those on antipsychotics had psychotic activity. The authors of the study cautioned that some of this gap may be accounted for by the increased likelihood of symptomatic patients to be placed on antipsychotic medicine, but also noted that some of the difference held even when on-antipsychotic and off-medicine patients of similar prognosis were compared. [Harrow M., and Jobe T.H. (2007). " [http://psychrights.org/Research/Digest/NLPs/OutcomeFactors.pdf Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications: a 15-year multifollow-up study.] " "J Nerv Ment Dis." May;195(5):406-14. PMID 17502806]

"LY2109823"

A new schizophrenia drug "LY219873" yielded promising results, as it targets in the brain – glutamate receptors rather than dopamine and had few side effects. The Nature Medicine study, by drug firm Eli Lilly found it promising and Dr.Sandeep Patil's team proved that LY2140023 appear to work as antipsychotics when tested upon rodents. [ [http://news.bbc.co.uk/2/hi/health/6971037.stm BBC NEWS, Schizophrenia trials 'promising'] ]

Nicotine patch

Following an observation that tobacco smoking eases effects of schizophrenia, Dr. Tony George from the Yale School of Medicine proposed nicotine patch as a treatment for schizophrenia. [http://www.abc.net.au/rn/healthreport/stories/2002/614060.htm Smoking and schizophrenia] ]

Psychological and social interventions

Psychotherapy is also widely recommended and used in the treatment of schizophrenia, although services may often be confined to pharmacotherapy because of reimbursement problems or lack of training. [Moran, M (2005). [http://pn.psychiatryonline.org/cgi/content/full/40/22/24-b Psychosocial Treatment Often Missing From Schizophrenia Regimens.] "Psychiatr News" November 18 2005, Volume 40, Number 22, page 24. Retrieved on 2007-05-17.]

Cognitive behavioral therapy (CBT) is used to reduce symptoms and improve related issues such as self-esteem, social functioning, and insight. Although the results of early trials were inconclusive,Cormac I, Jones C, Campbell C (2002). Cognitive behaviour therapy for schizophrenia. "Cochrane Database of systematic reviews", (1), CD000524. PMID 11869579] more recent reviews suggest that CBT can be an effective treatment for the psychotic symptoms of schizophrenia.Zimmermann G, Favrod J, Trieu VH, Pomini V (2005). The effect of cognitive behavioral treatment on the positive symptoms of schizophrenia spectrum disorders: a meta-analysis. "Schizophrenia Research", 77, 1–9. PMID 16005380] Another approach is cognitive remediation therapy, a technique aimed at remediating the neurocognitive deficits sometimes present in schizophrenia. Based on techniques of neuropsychological rehabilitation, early evidence has shown it to be cognitively effective, with some improvements related to measurable changes in brain activation as measured by fMRI.Wykes T, Brammer M, Mellers J, "et al" (2002). Effects on the brain of a psychological treatment: cognitive remediation therapy: functional magnetic resonance imaging in schizophrenia. "British Journal of Psychiatry", 181, 144–52. PMID 12151286] A similar approach known as cognitive enhancement therapy, which focuses on social cognition as well as neurocognition, has shown efficacy. [Hogarty GE, Flesher S, Ulrich R, Carter M, "et al" (2004). Cognitive enhancement therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior. "Arch Gen Psychiatry." Sep;61(9):866–76.PMID 15351765]

Family Therapy or Education, which addresses the whole family system of an individual with a diagnosis of schizophrenia, has been consistently found to be beneficial, at least if the duration of intervention is longer-term. [McFarlane WR, Dixon L, Lukens E, Lucksted A (2003). Family psychoeducation and schizophrenia: a review of the literature. "J Marital Fam Ther." Apr;29(2):223–45. PMID 12728780 ] [Glynn SM, Cohen AN, Niv N (2007). New challenges in family interventions for schizophrenia. " Expert Rev Neurother." Jan;7(1):33–43. PMID 17187495] [Pharoah F, Mari J, Rathbone J, Wong W. (2006) [http://www.cochrane.org/reviews/en/ab000088.html Family intervention for schizophrenia] Cochrane Database of Systematic Reviews, Issue 4] Aside from therapy, the impact of schizophrenia on families and the burden on careers has been recognized, with the increasing availability of self-help books on the subject. [cite book | author = Jones, S., Hayward, P. | title = Coping with Schizophrenia: A Guide for Patients, Families and Caregivers | publisher = Oneworld Pub. | date = 2004 | location = Oxford, England | id = ISBN 1-85168-344-5] [cite book | last = Torrey | first = EF | authorlink = E. Fuller Torrey | title = Surviving Schizophrenia: A Manual for Families, Consumers, and Providers (5th Edition) | publisher = HarperCollins | date = 2006 | id = ISBN 0-06-084259-8] There is also some evidence for benefits from social skills training, although there have also been significant negative findings. [Kopelowicz A, Liberman RP, Zarate R (2006). Recent advances in social skills training for schizophrenia. "Schizophrenia Bulletin." 2006 Oct;32 Suppl 1:S12–23. PMID 16885207 ] [American Psychiatric Association (2004) Practice Guideline for the Treatment of Patients With Schizophrenia. Second Edition.] Some studies have explored the possible benefits of music therapy and other creative therapies. [Talwar N, Crawford MJ, Maratos A, Nur U, McDermott O, Procter S (2006). Music therapy for in-patients with schizophrenia: Exploratory randomised controlled trial. "The British Journal of Psychiatry." Nov;189:405–9. PMID 17077429 [http://bjp.rcpsych.org/cgi/content/abstract/189/5/405 Full text available.] ] [Ruddy R, Milnes D. (2005) [http://www.cochrane.org/reviews/en/ab000088.html Art therapy for schizophrenia or schizophrenia-like illnesses.] Cochrane Database of Systematic Reviews, Issue 4] [Ruddy RA, Dent-Brown K. (2007) [http://www.cochrane.org/reviews/en/ab005378.html Drama therapy for schizophrenia or schizophrenia-like illnesses.] Cochrane Database of Systematic Reviews, Issue 1.]

Other

Electroconvulsive therapy is not considered a first line treatment but may be prescribed in cases where other treatments have failed. It is more effective where symptoms of catatonia are present, [cite journal |author=Greenhalgh J, Knight C, Hind D, Beverley C, Walters S |year=2005 |month=March |title= Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modeling studies.|journal= Health Technol Assess.|volume= 9|issue=9 |pages=1–156 |url=http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15774232 (abstract) |accessdate= 2007-06-17] and is recommended for use under NICE guidelines in the UK for catatonia if previously effective, though there is no recommendation for use for schizophrenia otherwise. [cite web |url=http://www.nice.org.uk/page.aspx?o=TA059 |title= The clinical effectiveness and cost effectiveness of electroconvulsive Therapy (ECT) for depressive illness, schizophrenia, catatonia and mania.|accessdate=2007-06-17 |author= National Institute for Health and Clinical Excellence|year= 2003|month=April |publisher= National Institute for Health and Clinical Excellence|language= English] Psychosurgery has now become a rare procedure and is not a recommended treatment for schizophrenia.Mashour GA, Walker EE, Martuza RL. (2005) Psychosurgery: past, present, and future. "Brain Research: Brain Research Reviews", 48 (3), 409-19. PMID 15914249]

Alternative approaches

Service-user led movements have become integral to the recovery process in Europe and America; groups such as the Hearing Voices Network and the Paranoia Network have developed a self-help approach that aims to provide support and assistance outside the traditional medical model adopted by mainstream psychiatry. By avoiding framing personal experience in terms of criteria for mental illness or mental health, they aim to destigmatize the experience and encourage individual responsibility and a positive self-image. Partnerships between hospitals and consumer-run groups are becoming more common, with services working toward remediating social withdrawal, building social skills and reducing rehospitalization.Goering P, Durbin J, Sheldon CT, Ochocka J, Nelson G, Krupa T. Who uses consumer-run self-help organizations?"American Journal of Orthopsychiatry", 76 (3), 367-73. PMID 16981815]

The Soteria model is an alternative treatment to institutionalization and early use of antipsychotics. [cite journal | author = Bola JR, Mosher LR | title = Treatment of Acute Psychosis Without Neuroleptics: Two-Year Outcomes From the Soteria Project | journal = The Journal of Nervous and Mental Disease | publisher = Lippincott Williams & Wilkins, Inc | volume = 191 | pages = 219–229 | date = April 2003 | url = http://www.moshersoteria.com/bola.pdf | format=PDF | pmid=12695732|accessdate=2007-06-13] It is described as a milieu-therapeutic recovery method, characterized by its founder as "the 24 hour a day application of interpersonal phenomenologic interventions by a nonprofessional staff, usually without neuroleptic drug treatment, in the context of a small, homelike, quiet, supportive, protective, and tolerant social environment."Mosher LR (1999). "Soteria and Other Alternatives to Acute Psychiatric Hospitalization: A Personal and Professional Review." Journal of Nervous and Mental Disease, 187, 142–149.] Soteria or Soteria-based houses are currently run in Sweden, [Perris, C.M. Cognitive Therapy with Schizophrenic Patients. Guilford, New York, NY, 1989.] Germany, [ [http://www.zfp-web.de/K3/html/artikel.php3?path=0:3:32:138&a_id=83 Allgemeine Psychiatrie I / Soteria] ] [ [http://www.toll-haus.de/index.html Toll - Haus] ] [ [http://www.lunaticpride.de/SOTERIA.HTM Soteria] ] Switzerland, [ [http://www.soteria.ch Soteria Bern] ] and Hungary. [ [http://www.soteria.hu/ Soteria Alapítvány] ] The Soteria house in Berne, Switzerland is associated with a psychiatrist who teaches at the University of Berne, and has been featured in the "Schweizerische Aertzezeitung", the Bulletin of Swiss Physicians. [http://www.soteria.ch/pdf/Soteria%20Bern%20SAEZ.pdf Soteria]

The biologically based branch of alternative medicine that deals with schizophrenia is known as orthomolecular psychiatry. Some scientists claim that schizophrenia can be treated effectively with nutrients like niacin, vitamin C and B₆, omega-3 EFAs (fish oil) along with various minerals and amino acids. [Hoffer and Walker, "Orthomolecular Nutrition". Keats Publishing, 1978] [Abram Hoffer (1999) [http://books.google.com/books?id=wT4HUH3Vgg8C&pg=PA29&lpg=PA29&dq=%22orthomolecular+treatment+for+schizophrenia%22+(fish%7Comega)+hoffer&source=web&ots=0sX_JFtan7&sig=2407TmHj7yudMqA4vJKYcI3hGeo#PPA32,M1 Orthomolecular treatment for Schizophrenia] , McGraw-Hill, ISBN 0879839104] The body's adverse reactions to gluten and other allergens are implicated in some alternative theories as the cause of some cases. This theory—discussed by one author in three British journals in the 1970s [ Dohan FC (1970). Coeliac disease and schizophrenia. "Lancet", 1970 April 25;1(7652):897–8. PMID 4191543
*Dohan FC (1973). Coeliac disease and schizophrenia. "British Medical Journal", 3(5870): 51–52. PMID 4740433
* Dohan FC (1979). Celiac-type diets in schizophrenia. " Am J Psychiatry", 1979 May;136(5):732–3. PMID 434265] —is unproven. A 2006 literature review suggests that gluten may be a factor for a subset of patients with schizophrenia, but further study is needed to confirm the association between gluten and schizophrenia. Kalaydjian AE, Eaton W, Cascella N, Fasano A (2006). The gluten connection: the association between schizophrenia and celiac disease. "Acta Psychiatrica Scandinavica" 2006 Feb;113(2):82–90. PMID 16423158]

An unconventional approach is the use of omega-3 fatty acids, with one study finding some benefits from their use as a dietary supplement. [Peet M, Stokes C (2005). Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs, 65(8), 1051–9. PMID 15907142]

odium - a once trialed approach

In the petri dish, sodium converts d2high (the psychotic state of the receptor) to d2low [Philip Seeman's article SYNAPSE 49:209 –215 (2003) "Dopamine Displaces [3H] Domperidone From High-Affinity Sites of the Dopamine D2 Receptor, But Not [3H] Raclopride or [3H] Spiperone in Isotonic Medium: Implications for Human Positron Emission Tomography" PHILIP SEEMAN, TERESA TALLERICO, AND FRANCOISE KO1, they point out that in the petri dish brain samples with d2high, are converted to d2low by NaCl. Even with the benefits of this new method, Dr Seeman recommended future experiments to be done in hypotonic medium to halt the conversion to d2low.] . While stable schizophrenics show no difference in the sodium content of their CSF [SODIUM OF CEREBROSPINAL POTASSIUM AND CONTENT FLUID COLLECTED FROM PATIENTS WITH CHRONIC SCHIZOPHRENIC REACTIONS’by TURGUT ZILELI, M.D., LORING FO CHAPMAN, PH.D.,HAROLD C. WOLFF, M.D. Am J Psychiatry 118:449-450, November 1961] , subjects who are in need of hospitalisation benefit significantly from the addition of sodium valpoarate until they become stable (after a month) [Sodium Valproate as an Adjunctive Drug in Treatment of Schizophrenia Victoria Omranifard MD, Afsaneh Karbasi Amel MD , Siamak Amanat MD Iranian Journal of Psychiatry and Behavioral Sciences(IJPBS) , Volume 1, Number 1, Spring and Summer 2007: 12-15] and chronic schizophrenics often have hyponatremia [ Lack of association between antipsychotics and hyponatremia in chronic schizophrenia. Schizophrenia Research, Volume 83, Issue 2 - 3, Pages 307 - 309 M . Jessani, J . Montgomery, J . Fedde, R . Josiassen] .

Several of the body's natural salts increase sodium naturally [SAN-E ISHIKAWA, KOJI OKADA, AND TOSHIKAZU SAITO 1992 Increases in Cellular Sodium Concentration by Arginine Vasopressin and Endothelin in Cultured Rat Glomerular Mesangial Cells Endocrinology 131 3 1429] . As one, AVP (Arginine Vasopressin) is inhibited by caffeine [Martin Muschol CAFFEINE INHIBITS RELEASE OF ARGININE VASOPRESSIN FROMNERVE TERMINALS OF THE MAMMALIAN NEUROHYPOPHYSIS http://meeting.biophysj.org/cgi/reprint/82/1/617/a.pdf 20-07-08] . Schizophrenics on caffeine can show worse symptoms [Peter B. Lucas, David Pickar, John Kelsoe, Mark Rapaport, Carlos Pato, and Daniel Hommer 1990 Effects of the Acute Administration of Caffeine in Patients with Schizophrenia BIOL PSYCHIATRY 1990;28:35-4o] , including positive symptoms [John R. Hughes, M.D., Pauline McHugh, M.D. and Stephen Holtzman, Ph.D 1998 Alcohol & Drug Abuse: Caffeine and Schizophrenia Psychiatr Serv 49:1415-1417, November 1998] (although there are conflicting results).

In the clinical setting, while still being treated with antipsychotics, negative and residual symptoms were greatly improved by l-arginine (in the case of negative symptoms) and modestly improved in the case of residual symptoms - perhaps only a modest improvement was necessary for antipsychotic treated residual symptoms ... This study references four other studies on l-arginine and schizophrenia [(Andrei-C.lager, M.D., Darrell G. Kirch, M.D., Llewellyn B. Bigelow,M.D., and Craig N. Karson,M.D. Treatment of Schizophrenia With a Vasopressin Analogue American Journal of Psychiatry 143:375-377, 1986)] - the article points out that some patients experienced unusual electrolyte or fluid measures. Responders to a blog say they had bad experiences with l-arginine [http://www.schizophrenia.com/sznews/archives/005764.html as at 25-07-08]

A more recent article says: "It is concluded from our study that nitric oxide produces conflicting results on various models of psychosis. L-arginine might be useful as an antipsychotic without causing extrapyramidal symptoms" [(http://cat.inist.fr/?aModele=afficheN&cpsidt=13460412 as at 01-05-08) "Role of nitric oxide in experimental models of psychosis in rats" GUPTA M; BALAKRISHNAN S.; PANDHI P; Methods and findings in experimental and clinical pharmacology 2001, vol. 23, no9, pp. 497-500.] (Amphetamine was used to simulate psychosis.)

However, plasma AVP levels may vary in hyponatremia, yet serum sodium levels are the same [Nobutoshi Kawai,U , Atsuomi Babab, Toshihito Suzuki, Hiroyasu Shiraishi Roles of arginine vasopressin and atrial natriuretic peptide in polydipsia-hyponatremia of schizophrenic patients Psychiatry Research 101 Ž2001. p43 ] and seem predetermined.

Although sodium may have helped the exacerbated schizophrenics mentioned before - and perhaps only because of a calming influence in exacerbation, it is not a cure for chronic schizophrenia as, if it was, the saline solutions used in experiments would have been noted to improve it. Sodium excretion is caused by prenatal factors [http://en.wikipedia.org/wiki/Causes_of_schizophrenia#Hypoxia] .

(An early edition of American Journal of Insanity tested infusion of salt solution in schizophrenics and found positive results: "Comparing these percentages with those recorded in Table I, I am led to infer that common salt in the blood of catatonic patients as well as those with other clinical forms of dementia precox might be deficient and that the infusion ...of the physiological salt solution would meet this deficiency, though the results might be transitory," said the author [NOBORU ISHIDA, RESULTS PRODUCED iN DEMENTIA PR)ECOX OR SO-CALLED ENDOGENOUS DEMENTIA BY THE INFUSION OF SODIUM CHLORIDE SOLUTION.American Journal of Insanity 73:541-547, January 1917] )

References