Schizophrenia treatment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

## Contents

* 1 Overview
* 2 Prognosis
* 3 Assessment of effectiveness
* 4 Admission to hospital
* 5 Specific treatments
* 5.1 Medication
* 5.1.1 "LY2109823"
* 5.1.2 Nicotine patch
* 5.2 Psychological and social interventions
* 5.3 Other
* 5.4 Alternative approaches
* 6 References

## Overview[edit | edit source]

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.[1]

Management of symptoms and improving function is thought to be more achievable than a current cure, as the cause of the illness is currently unknown. A recovery model is increasingly adopted, emphasizing hope, empowerment and social inclusion.[2]

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, some unpleasant and some harmful or even fatal. Thus, their use has attracted much controversy in the last 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, developing 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.[3] The reasons for this effect are not clear, although cross-cultural studies are being conducted.

## Prognosis[edit | edit source]

Numerous international studies have demonstrated favorable long-term outcomes for around half of those diagnosed with schizophrenia, with substantial variation between individuals and regions.[4] 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.[5] 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.[6] A 5-year community study found that 62% showed overall improvement on a composite measure of symptomatic, clinical and functional outcomes.[7] 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.[1]

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),[8] 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.[9][10] 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.[11]

## Assessment of effectiveness[edit | edit source]

The effectiveness of schizophrenia treatment is often assessed using standardized methods, one of the most common being the positive and negative syndrome scale (PANSS).[12]

## Admission to hospital[edit | edit source]

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.[13] 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[14] and patient-led support groups.

## Specific treatments[edit | edit source]

### Medication[edit | edit source]

The mainstay of psychiatric treatment for schizophrenia is an antipsychotic medication.[15] These can reduce the "positive" symptoms of psychosis. Most antipsychotics take around 7–14 days to have their main effect.

Risperidone (trade name Risperdal) is a common atypical antipsychotic medication.

Treatment was revolutionized in the mid 1950s with the development and introduction of the first antipsychotic chlorpromazine.[16] 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.[17] Of the atypical antipsychotics, olanzapine and clozapine are the most likely to induce weight gain.[18] The effect is more pronounced if high doses of olanzapine are used.[19] 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.[20]

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.[21]

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.[22] Patients in this category may be prescribed clozapine,[23] a medication of superior effectiveness but several potentially lethal side effects including agranulocytosis and myocarditis.[24] 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.[25] 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. [26]

#### "LY2109823"[edit | edit source]

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.[27]

#### Nicotine patch[edit | edit source]

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.[28]

### Psychological and social interventions[edit | edit source]

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.[29]

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,[30] more recent reviews suggest that CBT can be an effective treatment for the psychotic symptoms of schizophrenia.[31] 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.[32] A similar approach known as cognitive enhancement therapy, which focuses on social cognition as well as neurocognition, has shown efficacy.[33]

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.[34][35][36] Aside from therapy, the impact of schizophrenia on families and the burden on carers has been recognized, with the increasing availability of self-help books on the subject.[37][38] There is also some evidence for benefits from social skills training, although there have also been significant negative findings.[39][40] Some studies have explored the possible benefits of music therapy and other creative therapies.[41][42][43]

### Other[edit | edit source]

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,[44] 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.[45] Psychosurgery has now become a rare procedure and is not a recommended treatment for schizophrenia.[46]

### Alternative approaches[edit | edit source]

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.[47]

The Soteria model is an alternative treatment to institutionalization and early use of antipsychotics.[48] 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."[49] Soteria or Soteria-based houses are currently run in Sweden,[50] Germany,[51][52][53] Switzerland,[54] and Hungary.[55] 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.[56]

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.[57][58] 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[59]—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.[60]

An unconventional approach is the use of omega-3 fatty acids, with one study finding some benefits from their use as a dietary supplement.[61]

## References[edit | edit source]

1. ↑ 1.0 1.1 van Os J, Burns T, Cavallaro R, et al (2006). Standardized remission criteria in schizophrenia. Acta Psychiatrica Scandinavica, 113(2), 91–5. PMID 16423159
2. ↑ Bellack AS. (2006) Scientific and consumer models of recovery in schizophrenia: concordance, contrasts, and implications. Schizophrenia Bulletin. Jul;32(3):432-42. PMID 16461575
3. ↑ 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
4. ↑ 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
5. ↑ 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
6. ↑ 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
7. ↑ Harvey, C.A., Jeffreys, S.E., McNaught, A.S., Blizard, R.A., King, M.B.(2007) 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
8. ↑ 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
9. ↑ Davidson L, McGlashan TH. (1997) The varied outcomes of schizophrenia. Canadian Journal of Psychiatry, 42 (1), 34–43. PMID 9040921
10. ↑ 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
11. ↑ Bebbsington PE, Kuipers E (1994). The predictive utility of expressed emotion in schizophrenia: an aggregate analysis. Psychological Medicine, 24, 707–718. PMID 7991753
12. ↑ Kay SR, Fiszbein A, Opler LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13(2), 261–76. PMID 3616518
13. ↑ 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
14. ↑ 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
15. ↑ The Royal College of Psychiatrists & The British Psychological Society (2003). 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.
16. ↑ Turner T. (2007). "Unlocking psychosis". Brit J Med. 334 (suppl): s7.
17. ↑ 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
18. ↑ Wirshing DA, Wirshing WC, Kysar L, Berisford MA. (1999) Novel antipsychotics: comparison of weight gain liabilities. Journal of Clinical Psychology 60 358-63
19. ↑ Green B (1999) Focus on olanzapine Current Med Res Opin 15 79-85
20. ↑ 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
21. ↑ 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
22. ↑ Meltzer HY (1997). "Treatment-resistant schizophrenia--the role of clozapine". Current Medical Research and Opinion. 14 (1): 1–20. PMID 9524789.
23. ↑ Wahlbeck K, Cheine MV, Essali A (2007). "Clozapine versus typical neuroleptic medication for schizophrenia". The Cochrane Database of Systematic Reviews. John Wiley and Sons, Ltd. (2). doi:10.1002/14651858.CD000059. PMID 10796289. ISSN 1464-780X.CS1 maint: Multiple names: authors list (link)
24. ↑ Haas SJ, Hill R, Krum H (2007). "Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis associated with the use of clozapine in Australia during 1993–2003". Drug Safety. 30: 47–57. PMID 17194170.CS1 maint: Multiple names: authors list (link)
25. ↑ Fenton W., and McGlashan T. (1987). "Sustained remission in drug-free schizophrenic patients," Am J Psychiatry. 144:1306–1309.
26. ↑ Harrow M., and Jobe T.H. (2007). "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
27. ↑ BBC NEWS, Schizophrenia trials 'promising'
28. ↑ Smoking and schizophrenia
29. ↑ Moran, M (2005). Psychosocial Treatment Often Missing From Schizophrenia Regimens. Psychiatr News November 18 2005, Volume 40, Number 22, page 24. Retrieved on 2007-05-17.
30. ↑ Cormac I, Jones C, Campbell C (2002). Cognitive behaviour therapy for schizophrenia. Cochrane Database of systematic reviews, (1), CD000524. PMID 11869579
31. ↑ 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
32. ↑ 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
33. ↑ 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
34. ↑ 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
35. ↑ Glynn SM, Cohen AN, Niv N (2007). New challenges in family interventions for schizophrenia.  Expert Rev Neurother. Jan;7(1):33–43. PMID 17187495
36. ↑ Pharoah F, Mari J, Rathbone J, Wong W. (2006) Family intervention for schizophrenia Cochrane Database of Systematic Reviews, Issue 4
37. ↑ Jones, S., Hayward, P. (2004). Coping with Schizophrenia: A Guide for Patients, Families and Caregivers. Oxford, England: Oneworld Pub. ISBN 1-85168-344-5.CS1 maint: Multiple names: authors list (link)
38. ↑ Torrey, EF (2006). Surviving Schizophrenia: A Manual for Families, Consumers, and Providers (5th Edition). HarperCollins. ISBN 0-06-084259-8.
39. ↑ 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
40. ↑ American Psychiatric Association (2004) Practice Guideline for the Treatment of Patients With Schizophrenia. Second Edition.
41. ↑ 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 Full text available.
42. ↑ Ruddy R, Milnes D. (2005) Art therapy for schizophrenia or schizophrenia-like illnesses. Cochrane Database of Systematic Reviews, Issue 4
43. ↑ Ruddy RA, Dent-Brown K. (2007) Drama therapy for schizophrenia or schizophrenia-like illnesses. Cochrane Database of Systematic Reviews, Issue 1.
44. ↑ Greenhalgh J, Knight C, Hind D, Beverley C, Walters S (2005). (abstract) "Clinical and cost-effectiveness of electroconvulsive therapy for depressive illness, schizophrenia, catatonia and mania: systematic reviews and economic modeling studies" Check `|url=` value (help). Health Technol Assess. 9 (9): 1–156. Retrieved 2007-06-17. Unknown parameter `|month=` ignored (help)CS1 maint: Multiple names: authors list (link)
45. ↑ National Institute for Health and Clinical Excellence (2003). "The clinical effectiveness and cost effectiveness of electroconvulsive Therapy (ECT) for depressive illness, schizophrenia, catatonia and mania". National Institute for Health and Clinical Excellence. Retrieved 2007-06-17. Unknown parameter `|month=` ignored (help)
46. ↑ Mashour GA, Walker EE, Martuza RL. (2005) Psychosurgery: past, present, and future. Brain Research: Brain Research Reviews, 48 (3), 409-19. PMID 15914249
47. ↑ 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
48. ↑ Bola JR, Mosher LR (April 2003). "Treatment of Acute Psychosis Without Neuroleptics: Two-Year Outcomes From the Soteria Project" (PDF). The Journal of Nervous and Mental Disease. Lippincott Williams & Wilkins, Inc. 191: 219–229. PMID 12695732. Retrieved 2007-06-13.
49. ↑ 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.
50. ↑ Perris, C.M. Cognitive Therapy with Schizophrenic Patients. Guilford, New York, NY, 1989.
51. ↑ Allgemeine Psychiatrie I / Soteria
52. ↑ Toll - Haus
53. ↑ Soteria
54. ↑ Soteria Bern
55. ↑ Soteria Alapítvány
56. ↑ http://www.soteria.ch/pdf/Soteria Bern SAEZ.pdf Soteria
57. ↑ Hoffer and Walker, Orthomolecular Nutrition. Keats Publishing, 1978
58. ↑ Abram Hoffer (1999) Orthomolecular treatment for Schizophrenia, McGraw-Hill, ISBN 0879839104
59. ↑ 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
60. ↑ 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
61. ↑ Peet M, Stokes C (2005). Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs, 65(8), 1051–9. PMID 15907142

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