MENTAL HEALTH

Health Evidence Bulletins - Wales
Team Leader: Dr Lyn Harris

Date of completion: 3.3.98

SCHIZOPHRENIA

This document is a supplement to, not a substitute for, professional skills and experience. Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation

The Statements The Evidence
7.1 Prevention and promotion
7.1a. Public Education is an effective way to reduce
stigma i.
i. Wolff G, Pathare S, Craig T, Leff J. Public education for community care: a new approach. British Journal of Psychiatry 1996; 168: 441-447
(Type III evidence - before and after survey in intervention and control areas)
7.1b. The following interventions appear promising but require further evaluation i:
  • Treatment of hearing impairment in the elderly
  • Genetic counselling
i. Original Protocol. Welsh Health Planning Forum. Protocol for investment in health gain. Mental health. Cardiff: Welsh Office, April 1993
(Type V evidence - expert opinion)
7.2 Assessment
7.2a. Medical assessment to exclude physical illness should be carried out i. i. Original Protocol. Welsh Health Planning Forum. Protocol for investment in health gain. Mental health. Cardiff: Welsh Office, April 1993
(Type V evidence - expert opinion)
7.2b A full multidisciplinary assessment including an assessment of social and occupational functioning may be beneficiali. i. Original Protocol. Welsh Health Planning Forum. Protocol for investment in health gain. Mental health. Cardiff: Welsh Office, April 1993
(Type V evidence - expert opinion)
7.3 Treatment and Care
7.3a. There is no evidence that large loading doses of neuroleptics speed or enhance treatment responsei. i. Dixon LB, Lehman AF, Levine J. Conventional antipsychotic medications for schizophrenia. Schizophrenia Bulletin 1995; 21(4): 567-577
(Type I evidence -with some flaws)
7.3b. There are no significant advantages to using high dosages of haloperidol (greater than 10-20mg per day) for acute treatment, and even dosages of 20mg per day could be associated with a substantial number of adverse neurological effects i. i. Dixon LB, Lehman AF, Levine J. Conventional antipsychotic medications for schizophrenia. Schizophrenia Bulletin 1995; 21(4): 567-577
(Type I evidence -with some flaws)
7.3c. There is no evidence, that on average, high maintenance doses (>600mg chlorpromazine equivalents) are more efficacious in preventing relapse than are lower, standard doses i.
The results of a meta-analysis suggest that moderate doses of neuroleptic drugs (roughly between 165 and 375mg equivalent of chlorpromazine) should be preferred in the maintenance treatment of chronic psychosis. Higher doses fail to produce incremental improvement but significantly increase the occurrence of adverse reactions ii.
i. Dixon LB, Lehman AF, Levine J. Conventional antipsychotic medications for schizophrenia. Schizophrenia Bulletin 1995; 21(4): 567-577
(Type I evidence -with some flaws)
ii. Bollini, P. Pampallona, S. Orza, M.J. Adams, M.E. and Chalmers, T.C. Antipsychotic drugs: is more worse? A meta-analysis of the published randomised controlled trials. Psychological Medicine 1994; 24(2): 307-316 (Type 1 evidence - systematic review, using MEDLINE only).

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7.3d. Clozapine is convincingly more effective than 'typical' neuroleptic drugs in reducing symptoms of schizophrenia, producing clinically meaningful improvements and postponing relapse. This clinical effect, however is not reflected in measures of global functioning, at least in the short term and the clinical improvements have to be weighted against the risk of potentially fatal side effects i.
The clinical efficacy of clozapine was more pronounced in patients resistant to typical neuroleptics in terms of clinical improvement (random effects odds ratio, OR= 0.2 CI 0.1-0.5 Number needed to treat, NNT=5) and symptom reduction i.
i. Wahlbeck K, Cheine M, Essali MA, Rezk E. Clozapine vs 'typical' neuroleptic medication for schizophrenia. Cochrane Database of Systematic Reviews. Cochrane Library. 1998 Issue 2
(Type I evidence - systematic review)
7.3e. A review is currently underway to evaluate the effectiveness of clozapine versus the newer atypical neuroleptic drugsi i. Tuunainen A, Gilbody S. Clozapine vs newer 'atypical' neuroleptic medication for schizophrenia [Protocol]. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2. Review in preparation.
7.3f. Little can be concluded about the long term effects of risperidone and generalising results beyond a comparison with haloperidol would be imprudent. Risperidone may be more acceptable to those with schizophrenia and have marginal benefits in terms of limited clinical improvement and side effect profile compared to haloperidol. The superiority of risperidone in these respects may have been overestimated due to a possible publication bias in favour of risperidone. Any marginal benefit has to be balanced against the greater cost of the drug and its tendency to cause other side effects such as weight gain. Seventeen people have to be treated with risperidone in order to allow a single additional person to "clinically improve" as compared to control medication (Number Needed to Treat - NNT = 17, 95% CI 9 - 43)i i. Kennedy E, Song F, Hunter R, Gilbody S. Risperidone versus 'conventional' antipsychotic medication for schizophrenia. Cochrane Database of Systematic Reviews. Cochrane Library. 1998 Issue 2
(Type I evidence - systematic review)
7.3g. Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most trials present important methodological flaws and findings are poorly reported. One review did not find any suggestion that zuclopenthixol acetate is more effective in controlling aggressive/disorganised behaviour, acute psychotic symptoms, or preventing side effects. There were no data directly related to tranquillisation, but it may produce earlier and more intense sedation than oral haloperidol i. i. Fenton M, Coutinho E, Campbell C Zuclopenthixol acetate in the treatment of acute schizophrenia and similar serious mental illnesses. Cochrane Database of Systematic Reviews. Cochrane Library. 1998 Issue 2
(Type I evidence - systematic review)

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7.3h. A review is currently underway to determine the clinical effectiveness and safety of olanzapine as compared with placebo and conventional antipsychotic agents for schizophrenia and related psychoses i. i. De Oliveira IR, Dardennes RM, El-Dosoky A, Indran S. Olanzapine for schizophrenia [Protocol] Cochrane Database of Systematic Reviews. Cochrane Library. 1998 Issue 2. Review in preparation.
7.3i. Social skills training is effective in treatment-based assessment, but the benefit for the patient in a wider social context remains to be demonstrated i. i. Roth AD, Fonagy P. What works for whom? A critical review of psychotherapy research. New York: Guilford Press, 1996 p. 195
(Type I evidence - systematic review)
7.3j. There is some evidence to suggest that courses of electroconvulsive therapy (ECT), comprising of up to 12 treatments, when added to antipsychotic medication, can result in a significant increase in the extent of symptom resolution in some people with schizophrenia in the short term. With the available data, it appears that one out every five or six people with schizophrenia treated with ECT would experience this benefit. There is no suggestion that ECT should be the sole treatment or treatment of first choice in schizophrenia. There is a lack of clear evidence to support or refute the use of ECT for any particular subtype or subgroup of those with schizophrenia. Limited evidence suggests that people with predominantly positive symptoms of schizophrenia are likely to respond to ECT while those with chronic schizophrenia in institutions are less likely to benefit i i. Tharyan P. Electroconvulsive therapy for schizophrenia. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2
(Type I evidence - systematic review)
7.3k. Cognitive behavioural techniques for the management of delusions and hallucinations are of demonstrable benefit to patients i. Reviews are underway on the effectiveness of cognitive behavioural techniques for those with schizophreniaii and the use of cognitive rehabilitation techniques for people with schizophrenia and related conditions iii. i. National Health Service Executive, Review of psychotherapy services. Wetherby: Department of Health, 1996. p. 53
(Type I evidence - systematic review)
ii. Jones C, Cormac I, Mota Neto JIS, Campbell C. Cognitive behaviour therapy for schizophrenia. [Protocol] Cochrane Database of Systematic Reviews. Cochrane Library. 1998 Issue 2. Review in preparation
iii. Hayes RL, McGrath JJ. Cognitive rehabilitation for schizophrenia and related conditions. [Protocol] Cochrane Database of Systematic Reviews. Cochrane Library. 1998 Issue 2. Review in preparation

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7.3l. Following a systematic review, no clear statement about the efficacy of benzodiazepine drugs i to treat neuroleptic-induced tardive dyskinesia (TD) could be provided. The same also holds for calcium channel blockers ii, GABA agonist drugs iii and anticholinergic medication iv. The available data on the efficacy of cholinergic medications for the treatment of neuroleptic-induced TD are insufficient to recommend their use to clinicians given their documented side-effects v. i. McGrath JJ, Soares KVS. Benzodiazepines for neuroleptic-induced tardive dyskinesia. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2.
(Type I evidence - systematic review)
ii. Soares KVS, McGrath JJ. Diltiazem, nifedipine, nimodipine or verapamil for neuroleptic-induced dyskinesia. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2.
(Type I evidence - systematic review)
iii. Soares KVS, McGrath JJ, Deekes JJ. GABA agonist medication for those with neuroleptic-induced tardive dyskinesia. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2.
(Type I evidence - systematic review)
iv. Soares KVS, McGrath JJ. Anticholinergic medication for neuroleptic-induced tardive dyskinesia. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2.
(Type I evidence - systematic review)
v. McGrath JJ, Soares KVS. Cholinergic medication for neuroleptic-induced tardive dyskinesia. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2.
(Type I evidence - systematic review)
7.3m. A systematic review (based on trials with uncertain quality of randomisation) concluded that people who used vitamin E showed some improvement and less deterioration of the TD symptoms (Number needed to treat, NNT= 5 for clinical improvement and 4 for any improvement). No difference could be found regarding the presence of adverse effects or drop-outs before the end of the study i. i. Soares KVS, McGrath JJ. Neuroleptic-induced tardive dyskinesia: efficacy of vitamin E. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2.
(Type I evidence - systematic review)
7.3n. There is no strong evidence to support the use of cerultide, essential fatty acids, estrogen, lithium or insulin to treat neuroleptic-induced tardive dyskinesia (TD). There was a significant improvement in TD with the use of insulin compared to placebo (Odds Ratio=0.04, 95% CI, 0.01-0.24). However, this association requires replication i. i. McGrath JJ, Soares KVS. Neuroleptic-induced tardive dyskinesia: miscellaneous treatments. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2
(Type I evidence - systematic review)
7.3o. The effectiveness of tetrabenzene for tardive dyskinesia remains uncertain and requires further evaluationi. i. Original Protocol. Welsh Health Planning Forum. Protocol for investment in health gain. Mental health. Cardiff: Welsh Office, April 1993
(Type V evidence - expert opinion)
7.3p. Neuroleptic cessation or reduction to reduce tardive dyskinesia is not supported by the evidence and the risk of relapse makes this a hazardous treatmenti. i. McGrath JJ, Soares KVS. Tardive dyskenesia: neuroleptic reduction and/or cessation and neuroleptics as specific treatments for tardive dyskinesia. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2
7.3q. Long -term and routine administration of anti-parkinsonism drugs should be abandoned in the light of the available evidencei. i. Original Protocol. Welsh Health Planning Forum. Protocol for investment in health gain. Mental health. Cardiff: Welsh Office, April 1993
(Type V evidence - expert opinion)

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7.3r. Dynamic psychotherapy has been tried but has not been demonstrated to be effective with patients with schizophrenia i i. Roth AD, Fonagy P. What works for whom?: a critical review of psychotherapy research. New York: Guilford Press, 1996. p. 194
(Type I evidence - systematic review)
7.3s. A short-stay policy for hospital care does not encourage a 'revolving door' pattern of admission and disjointed care of people with serious mental illness. On planned short stays (<28 days) there were no more abrupt discharges (Odds Ratio, OR=0.4, 95% CI, 0.12-1.38), re-admissions (OR= 0.77, 95% CI 0.57-1.04) or losses to follow up (OR= 1.01, 95% CI 0.55-1.85). When allocated to short-stay, people with serious mental illness were more likely to be discharged on time (OR=0.44, 95% CI 0.24-0.83) and had a greater chance of being employed i. i. Johnstone P, Zolese G. Length of hospitalization for those with severe mental illness. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2
(Type I evidence - systematic review)
7.3t. At present beta-blockers cannot be recommended as adjuncts to neuroleptic medication in the treatment of schizophreniai. i. Ahonen J, Cheine M, Wahlbeck K. Supplementing standard drug treatment of those with schizophrenia with beta-blocking medication. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 1
(Type I evidence - systematic review)
7.4 Rehabilitation and continuing care
7.4a. Family intervention decreases the frequency of relapse (Odds Ratio at one year = 0.42, 95% CI 0.26-0.67) and hospitalization (OR at one year = 0.45, 95% CI 0.2-0.99). It encourages compliance with medication and may help people stay in employment. Family intervention therapy does not obviously affect the tendency of individuals/families to drop out of care nor the levels of expressed emotion and family burden. Family therapy reduces relapse during the year following treatment: it is necessary to treat at least six families to prevent one relapse at one year (95% CI, 4.3 - 14.0). There is a similar reduction in re-admission to hospital, and an improvement with compliance with medication i. i. Mari JJ, Streiner D. Family intervention for schizophrenia. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2
(Type I evidence - systematic review)
7.4b. There is evidence that depot medication reduces the risk of relapse in the maintenance phase. However, the design limitations of existing controlled clinical trials limit this conclusion i. A review (of limited data) comparing depot fluphenazine with oral fluphenazine found no difference for many outcomes and concluded that the use of depot fluphenazine continues to be based on clinical judgement rather than evidence from methodical evaluation within
trials i.
i. Adams CE, Eisenbruch M. Depot versus oral fluphenazine for those with schizophrenia. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2
(Type I evidence - systematic review)

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7.4c. The following appear to be promising but require further evaluation i:
  • Maximising potential in social and work functioning
  • Appropriate accommodation
  • Skills for daily living programmes
    A review of the use of life skills programmes for chronic mental illness is currently underway ii.
i. Original Protocol. Welsh Health Planning Forum. Protocol for investment in health gain. Mental health. Cardiff: Welsh Office, April 1993
(Type V evidence - expert opinion)
ii. Robertson L, Connaughton JA, Nicol MM. Life skills programmes for chronic mental illnesses [Protocol]. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2. Review in preparation.
7.4d. No definite conclusions can be offered as to whether vocational rehabilitation interventions enhance the vocational outcomes of persons with schizophrenia. Nor is there enough information about the capacity of vocational rehabilitation interventions to enhance outcomes other than vocational functioning i. i. Lehmen AF. Vocational rehabilitation in schizophrenia. Schizophrenia Bulletin 1995; 21(4): 645-656
(Type I evidence - systematic review with some limitations)
7.4e. Case management ensures that more people remain in contact with psychiatric services (Number needed to treat, NNT=15) but it also increases hospital admission rates and may increase duration of hospital stay. Compliance is increased but there is no significant improvement in mental state, social functioning or quality of life and this may increase health care costs i. Thus it is difficult to justify case management as the 'cornerstone' of community mental health care. The authors propose to compare case management to the main alternative approach (Assertive Community Treatment) in a forthcoming review. i. Marshall M, Gray A, Lockwood A, Green R. Case management for people with severe mental disorders.
Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 2
(Type I evidence - systematic review)
7.4f. Community mental health team (CMHT) management is not inferior to non-team standard care in any important respect and is superior in promoting greater acceptance of treatment. It may also be superior in reducing hospital admission and death by suicide i. i. Tyrer P, Coid J, Simmonds S, Joseph P, Marriott S. Community mental health team management for those with severe mental illnesses and disordered personality. Cochrane Database of Systematic Reviews. Cochrane Library 1998 Issue 1
(Type I evidence - systematic review)
7.4g. It would seem helpful to attempt to reduce the social isolation of people with schizophrenia but this approach requires further evaluation i. i. Original Protocol. Welsh Health Planning Forum. Protocol for investment in health gain. Mental health. Cardiff: Welsh Office, April 1993
(Type V evidence - expert opinion)

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7.4h. There is overwhelming evidence that conventional antipsychotic agents reduce the risk of relapse of the positive symptoms of schizophrenia.
Patients should stay on standard dose neuroleptics to minimise the risk of relapse - low dose and "drug holiday or targeted" strategies significantly increase the risk of relapse i.
i. Dixon LB, Lehman AF, Levine J. Conventional Antipsychotic Medication for Schizophrenia. Schizophrenia Bulletin 1995; 21(4): 567-577
(Type I evidence - systematic review with some flaws)
7.4i. Low-dose neuroleptic therapy (equivalent to 50-100mg chlorpromazine) was not as effective as standard-dose (equivalent to 200-500mg Chlorpromazine) in preventing relapse, pooled odds ratio was 2.08 (95% CI: 1.3-3.3, p< 0.005) at 12 months and 1.09 (95% CI: 0.55-2.1) at 24 months. The relative risk reduction was -47% (95% CI: -15,-88%) at 12 months and -5% (95%CI: 28%,-52%) at 24 months (on an intention to treat analysis) i. i. Barbui C, Saraceno B, Liberati A, Garattini S. Low dose neuroleptic therapy and relapse in schizophrenia: a meta-analysis of randomised controlled trials. European Psychiatry 1996; 11(6): 306-313
(Type 1 evidence - A thorough systematic review of six double blind randomised controlled trials. The limited search strategy raises the possibility of publication bias).
7.4j. Chlorpromazine reduces relapse over 6 months to 2 years (Odds Ratio, OR=0.3, 95% CI 0.16-0.56; Number needed to treat, NNT=3, 95% CI 2.5-4) and there is convincing evidence from trials that it promotes a global improvement in a person's symptoms and functioning (OR=0.33, 95%CI 0.3-0.4; NNT=7, 95% CI 6-11) although placebo response is also considerable (nearly 40%). Less people allocated to chlorpromazine leave trials early (OR=0.52, 95% CI 0.4-0.7; NNT= 14, 95% CI 9-31) i. i. Thornley B, Adams CE, Awad G. Chlorpromazine versus placebo for those with schizophrenia. Cochrane Database of Systematic Reviews. Cochrane Library. 1998 Issue 2
(Type I evidence - systematic review)

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Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: weightmanal@cardiff.ac.uk