A substantive amendment to this systematic review was last made on 24 August 1998. Cochrane reviews are regularly checked and updated if necessary.Several investigators have shown high lifetime prevalence rates for general behavioural and psychiatric disorders in people with learning disabilities. These rates vary widely, from 20%-64%, and are dependent upon the setting and diagnostic criteria used (Rutter 1970, Corbett 1979, Eaton 1982, Lund 1985, Gillberg 1986). Gillberg (1986) found that rates seem to increase with the severity of learning disability. This matter is complicated by the fact that the diagnosis of a specific psychiatric disorder becomes more difficult as the severity of learning disability increases. For these people symptoms and signs of illness become ever more difficult to elucidate and interpret. For example, behavioural disturbances that might be symptomatic of mental illness in someone of normal intelligence could have other explanations in a person with learning disability. Despite these difficulties the lifetime prevalence of the psychotic illnesses (disorders that feature loss of contact with reality) in the learning disabled population has been estimated to range from 3.4% - 12.4% (Heaton-Ward 1977, Parson 1984). This compares with a lifetime prevalence of schizophrenia in the whole population of 0.25% - 0.53% (Jablensky 1986).Background and objectives: To determine the efficacy of any antipsychotic medication for treating people with a dual diagnosis of learning disability and schizophrenia.
Search strategy: Electronic searching of Biological Abstracts (1982-1997), the Cochrane Schizophrenia Group s Register of trials (1997), the Cochrane Library (1997, Issue 3), EMBASE (1980-1997), MEDLINE (1966-1997) and PsycLIT (1974-1997). Unpublished data were sought from pharmaceutical companies. Both authors independently selected the relevant studies from the reports identified in this way.
Selection criteria: 1. All randomised controlled trials of antipsychotic medication, regardless of dosage, versus a placebo control, of longer than 1 month duration.
2. Anyone over 18 years of age with both learning disability and schizophrenia. Learning disability was defined as a measured IQ of 70 or less. Any mode of diagnosis of schizophrenia was acceptable.Data collection and analysis: The two reviewers independently attempted to select and then extract data but it was not possible to do this with the single study that met the inclusion criteria.
Main results: Only one relevant randomised trial was found by the searches (Foote 1958). This study included four people with a dual diagnosis of schizophrenia and learning disability, but results were available for only two. The groups to which the other two people were allocated were unclear. In order to display the data, too many assumptions would have to have been made about these other two people and any results would be uninformative and potentially misleading.
Reviewers conclusions: Using the methods described the reviewers found no trial evidence to guide the use of antipsychotic medication for those with both learning disability and schizophrenia.
Until the urgent need for randomised controlled trials is met clinical practice will continue to be guided by evidence from trials involving people with schizophrenia but without learning disability.
Antipsychotic medication is very widely used for people with the dual diagnoses of both mental illnesses and learning disability. There is conflicting opinion and research whether or not people with learning disability, when exposed to antipsychotic medication, may be at different risk of developing unpleasant, potentially disabling, short and long-term side effects, than those without low IQ. It is feasible that, as a consequence of their underlying neurological damage, people with learning disability may be at greater risk of developing movement disorders (Youseff 1988, Rogers 1991, Sachdev 1992, Gingell 1994). (Movement disorders are involuntary and abnormal movements of face, mouth, shoulders, neck and trunk that may be difficult to reverse when medication is stopped; potentially distressing restlessness; tremor and disturbances of expression and gait.) Aman (1984) has also raised concerns regarding the detrimental effect of antipsychotic medication on learning and cognitive abilities in people with learning disability.
In addition, many people with learning disability and behavioural disorders but no psychiatric diagnosis are treated with antipsychotic medication (Clarke 1990). For these people the antipsychotic medication is being used for its tranquillising rather than its antipsychotic properties (Wressell 1990).
Before looking at the literature it was decided not to use data from studies where those who simply had a diagnosis of psychosis had been randomised. The reasoning behind this was that:
1. When used to describe people with a learning disability, the term psychosis includes an even more varied collection of conditions than when it is used among the general, non-learning-disabled population. The authors felt it reasonable to suggest that people with conditions such as autism (commonly subsumed under the umbrella term, �psychotic ) would have a differential response to antipsychotic medication than those with schizophrenia; and
2. In clinical practice large numbers of people with learning disability are given the specific diagnosis of schizophrenia and therefore a review focusing on this particular population was justified.
A review focusing on those with �psychosis and learning disability will be the focus of another review.
The definition of antipsychotic medication used was that given in the British National Formulary section 4.2.1:
Phenothiazine group - chlorpromazine, fluphenazine, methotrimeprazine, pericyazine, perphenazine, pipothiazine, prochlorperazine, promazine, thioridazine, trifluoperazine.
Butyrophenone group - benperidol, droperidol and haloperidol.
Diphenylbutylpiperidine group - pimozide.
Thioxanthene group - flupenthixol and zuclopenthixol.
Substituted benzamide group - sulpiride.
Tricyclic dibenzoxazepine group - loxapine and oxypertine.
Newer antipsychotic drugs (atypical antipsychotics) - amisulpiride, clozapine, olanzapine, risperidone and sertindole.
1. Relapse - either readmission or serious deterioration (mental state; behaviour; social functioning);
2. Mental state - either dichotomous measures of state or change or continuous, scale-derived data;
3. Behaviour - either dichotomous measures of state or change or continuous, scale-derived data;
4. Social functioning - either dichotomous measures of state or change or continuous, scale-derived data;
5. Side effects - either dichotomous measures of state or change or continuous, scale-derived data; and
6. Leaving the study early.
It was hoped to group outcome data into those measured at 1-5 months, 6-11 months, 12-23 months, and over 24 months.
See: Collaborative Review Group search strategy
1. Electronic Searchingb. The Cochrane Library (Issue 3, 1997) was searched using the phrase
(MENTAL* near2 (HANDI* or RETARD*) or LEARNING near2 (DISAB* or DIFFICULT*) or PHENYLKETONURIA or FRAGILE* near2 SYNDROME or SUBNORMAL near INTELL* or (DOWN or DOWN S) or
explode ""MENTAL-RETARDATION""/ all subheadings)
c. The Cochrane Schizophrenia Group s Register of Trials (August 1997) was searched using the following terms:
((MENTAL* and HANDI*) or (LEARNING and DISAB*) or (COGNITIVE* and IMPAIR*))
d. EMBASE (August 1997) was searched using the both phrases used to identify trials and articles relating to schizophrenia as published in the Cochrane Schizophrenia Group s search strategy combined with the phrase:
(MENTAL* near2 (HANDI* or RETARD*) or LEARNING near2 (DISAB* or DIFFICULT*) or PHENYLKETONURIA or FRAGILE* near2 SYNDROME or SUBNORMAL near INTELL* or (DOWN or DOWN S) near1 SYNDROME or explode ""MENTAL-DEFICIENCY""/ all subheadings or explode ""LEARNING-DISORDER""/ all subheadings)
e. MEDLINE (August 1997) was searched using phrases used to identify controlled trials and articles relating to schizophrenia as published in the Cochrane Schizophrenia Group s search strategy combined with the phrase:
(MENTAL* near2 (HANDI* or RETARD*) or LEARNING near2 (DISAB* or DIFFICULT*) or PHENYLKETONURIA or FRAGILE* near2 SYNDROME or SUBNORMAL near INTELL* or (DOWN or DOWN S) or
explode ""MENTAL-RETARDATION""/ all subheadings)
f. PsycLIT (August 1997) was searched using phrases used to identify controlled trials and articles relating to schizophrenia as published in the Cochrane Schizophrenia Group s search strategy combined with the phrase:
(MENTAL* near2 (HANDI* or RETARD*) or LEARNING near2 (DISAB* or DIFFICULT*) or PHENYLKETONURIA or FRAGILE* near2 SYNDROME or SUBNORMAL near INTELL* or (DOWN or DOWN S) or
explode ""MENTAL-RETARDATION""/ all subheadings)
2. Industry
Companies producing antipsychotic medication were contacted and requests for additional studies were made.
3. Reference searching
Citations of all selected trials were searched for additional studies.
Assessment of Methodological Quality
Two reviewers independently allocated trials to quality categories as per the Cochrane Collaboration Handbook (Mulrow 1997). Disagreement was resolved by discussion and where this was not possible the study was assigned to those awaiting assessment and the first author contacted for clarification. Only studies rated A or B were included.
Data Collection
Data were independently extracted by each reviewer and disagreements again resolved by discussion. Where no data were possible to extract, or further information was needed, the trial was added to the list of those awaiting assessment and the first author contacted for clarification. Where some data were possible to extract, comments on the methods, participants, interventions and outcomes are presented in the Included Studies table.
Data management
(For clarification of terms please see Cochrane Library Glossary)
There are two main types of data, continuous and dichotomous, and data management was slightly different for each. Data were excluded from studies where more than 50% of subjects were lost to follow up.
Data synthesis
Data types: Outcomes are assessed using continuous (for example changes on a behaviour scale), categorical (for example, one of three categories on a behaviour scale, such a little change , moderate change or much change ) or dichotomous measures (for example, either no important changes or important changes in a persons behaviour). Currently RevMan does not support categorical data so they were presented only in the text of the review.
Dichotomous data: Where possible efforts were made to convert outcome measures to dichotomous data. Identifying cut off points on rating scales may do this and dividing subjects accordingly into clinically improved or not clinically improved . If the authors of a study had used a designated cut off point for determining clinical effectiveness this was used by the reviewers where appropriate. For dichotomous outcomes, a Mantel-Haenszel odds ratio (OR) with the 95% confidence interval (CI) around this was estimated. As a summary measure of effectiveness, the number needed to treat statistic (NNT) was also calculated.
Continuous data: A wide range of rating scales is available to measure outcomes in mental health trials. These scales vary in quality and many are questionably validated, or even ad hoc. It is generally accepted that measuring instruments should have the properties of reliability (the extent to which a test effectively measures anything at all) and validity (the extent to which a test measures that which it is supposed to measure). Before publication of an instrument, most scientific journals insist that reliability and validity be demonstrated to the satisfaction of referees. It was therefore decided, as a minimum standard, not to include any data from a rating scale in this review unless its properties had been published in a peer-reviewed journal. In addition, the following minimum standards for rating scales were set: the rating scale should either be (a) a self-report, or (b) completed by an independent rater or relative. More stringent standards for instruments may be set in future editions of this review.
Whenever possible we took the opportunity to make direct comparisons between trials that used the same measurement instrument to quantify specific outcomes. Where continuous data was presented from different scales rating the same effect, both sets of data were presented and the general direction of effect inspected.
Data on outcomes in neuroleptic trials is often not normally distributed. To avoid the pitfall of applying parametric tests to non-parametric data the following standards were applied to data derived from continuous endpoint measures of state . The criteria were used before inclusion:
(i) standard deviations and means were reported in the paper or were obtainable from the authors;
(ii) the standard deviation (SD), when multiplied by 2 was less than the mean (as otherwise the mean was unlikely to be an appropriate measure of the centre of the distribution) (Altman 1996). Data that did not meet the first or second standard were not entered into RevMan software for analysis, but were reported in the text of the results section.
For continuous mean change data (endpoint minus baseline) the situation is even more problematic. In the absence of individual patient data it is impossible to know if change data is skewed. The RevMan meta-analyses of continuous data are based on the assumption that the data are, at least to a reasonable degree, normally distributed. It is quite feasible that change data is skewed but it was entered into RevMan in order to summarise the data. In doing this it is assumed that either data were not skewed or that the analyses within RevMan could cope with the unknown degree of skewness. Without individual trial data it is not possible to formally check this assumption. However, after consulting the ALLSTAT electronic statistics mailing list, the decision was taken that such data should be presented in graphical form.
General
In all cases the data was entered into RevMan in such a way that the area to the left of the line of no effect indicates a favourable outcome for the antipsychotic drug. As well as inspecting the graphical presentations, differences between the results of each included trial were checked using a test of heterogeneity.
Sensitivity analysis
The sensitivity of the results from the main outcomes was tested for change when adding the assumption that those who did not complete the study had a poor outcome.
Only one study fulfilled the inclusion criteria (Foote 1958). This included four people with schizophrenia and learning disability. The study was primarily focused on the effect of antipsychotic drugs on a generally disturbed group of people and not specifically on those with learning disability.
Blinding: good efforts were made to blind both participants and raters.
Outcomes: The fact that data could not be extracted for those with both schizophrenia and learning disability was not a reflection on the overall quality of the study as it was attempting to address a quite different question than that of this review.
Only one study fulfilled the inclusion criteria (Foote 1958). Four people with both learning disability and schizophrenia were randomised within this study but results were available for only two. One person, allocated to the control group, was classified in group A (good recovery) and discharged. The other person with learning disability and schizophrenia, allocated to the active drug group, was withdrawn due to status epilepticus (difficult to control seizures). The groups to which the other two people were allocated were unclear. In order to display the data, too many assumptions would have to have been made about these other two people and any results would be uninformative.
There is no trial-based evidence for the effectiveness, or ineffectiveness, of any antipsychotic medication for those with learning disability and schizophrenia.There are debates about the processes that cause a person to have both learning disability and schizophrenia, and how the two processes may be similar or dissimilar (Matson 1994, Weinberger 1995). These debates have raised questions about the practice of extrapolating information gained from people with schizophrenia of normal intelligence to populations with the dual diagnoses of learning disabilities and schizophrenia. This debate will continue until researchers and clinicians working with those with learning disability produce good, relevant, evidence of the effectiveness of these powerful drugs.
Recipients of care or their carers
Currently recipients of care or their carers should know that the use of these powerful drugs is based on data relating to a quite different client group - those with schizophrenia but free of learning disability. Until trials are forthcoming those involved in giving or taking these drugs should be aware of the likely differences in outcomes, including side effects, between those with and without learning disability.
Trials often exclude the learning disabled population. Where people with learning disability were included it was difficult or impossible to tell to which treatment groups they had been allocated and their results were not analysed with reference to their learning disability.
There is an urgent need for randomised controlled trials of efficacy of antipsychotics in people with learning disability and schizophrenia.
Additional acknowledgements
The authors wish to thank Professor Zwanniken and Dr MacKay for replying to our enquiries.
References to studies included in this review
Foote 1958 (published data only) Foote ES. Combined chlorpromazine and reserpine in the treatment of chronic psychotics. Journal of Mental Science 1958; 104: 201-5. * indicates the major publication for the study References to studies excluded from this review Brenner 1984 Brenner HD, Alberti L, Keller F, Schaffner l. Pharmacotherapy of agitational states in psychiatric gerontology: double-blind study: Febarbamat-pipamperon. Neuropsychobiology 1984; 11: 187-90. Cohen 1994 Cohen SA, Underwood MT. The use of clozapine in a mentally retarded and aggressive population. Jounal of Clinical Psychiatry 1994; 55: 440-4. De Cuyper 1985 De Cuyper H, van Praag HM, Verstraeten D. The effect of milenperone on the agressive behavior of oligophrenic patients: a double-blind placebo-controlled study. Neuropsychobiology 1985; 13: 101-5. De Guzman 1971 De Guzman R, Diaz D. Experiencia clinica con conductasa. Archivos de Neurobiologia 1971; 34: 71-84. Feldman 1966 Feldman HS, Mulinos MG. Lack of addiction from high doses of tybamate. Journal of New Drugs 1966; 6: 354-60. Fracassi 1976 Fracassi MJ, Delvecchio FR. Evaluacion clinica de un neuroleptico semanal de mantenimiento: penfluridol (R16341). Acta Psiquiatrica y Psicologica de America Latina 1976; 22: 302-5. Godleski 1989 Godleski LS, Kerler R, Barber JW, Glick JL, Kellogg E, Vieweg WV, Yank GR. Multiple versus single antipsychotic drug treatment in chronic psychosis. Journal of Nervous Mental Disease 1989; 177: 686-9. Gravem 1981 Gravem A, Elgen K. Cis(Z)-clopenthixol--the neuroleptically active isomer of clopenthixol: A presentation of five double-blind clinical investigations and other studies with cis(Z)-clopenthixol (Cisordinol, Clopixol). Acta Psychiatrica Scandinavica Supp; 294: 5-12. Heikkila 1981 Heikkila L, Karsten D, Valli K. A double-blind clinical investigation of cis(Z)-clopenthixol and clopenthixol in chronic schizophrenic patients. Acta Psychiatrica Scandinavica Supplementum 1981; 294: 25-9. Karsten 1981 Karsten D, Kivimaki T, Linna SL, Pollari L, Turunen S. Neuroleptic treatment of oligophrenic patients. A double-blind multicentre trial of cis(z)-clopenthixol and haloperidol. Acta Psychiatrica Scandinavica Supplementum 1981; 294: 39-45. Kumpel 1971 Kumpel O. Srovnani prochlorperazinu, perfenazinu a octoclotepinu u eretickych oligofrenii. Activitas Nervosa Superior 1971; 13: 177-8. McKenzie 1966 McKenzie ME, Rosswell-Harris D. A controlled trial of prothipendyl (tolnate) in mentally subnormal patients. British Journal of Psychiatry 1966; 112: 95-100. McKenzie ME, Rosswell-Harris D. A controlled trial of prothipendyl (tolnate) in mentally subnormal patients. British Journal of Psychiatry 1966; 112(482): 95-100. Menolascino 1985 Menolascino FJ, Ruedrich SL, Wilson TE. Diagnosis and pharmacotherapy of schizophrenia in the retarded. Psychopharmacology Bulletin 1985; 21: 316-22. Nielson 1967 Nielsen B. Oligofrene patienter behandlet med flupentixol. Nordisk Psykiatrisk Tidsskrift 1967; 21: 244-53. Pislova 1974 Pislova J, Pisl I, Petrova M. Clinical experience with carpipramine (Defekton). Activitas Nervosa Superior 1974; 16: 168-9. Sajatovic 1994 Sajatovic M, Ramirez LF, Kenny JT, Meltzer HY. The use of clozapine in borderline-intellectual-functioning and mentally retarded schizophrenic patients. Comprehensive Psychiatry 1994; 35: 29-33. Smith 1992 Smith DA, Perry PJ. Nonneuroleptic treatment of disruptive behavior in organic mental syndromes. Annals of Pharmacotherapy 1992; 26: 1400-8. St-Jean 1966 St-Jean A, Ban TA, Scott J. The effect of a protriptyline-perphenazine combination in chronic psychiatric patients. Current Therapeutic Research Clinical and Experimental 1966; 8: 483-6. Tiihonen 1993 Tiihonen J, Hakola P, Paanila J, Turtiainen M. Eltoprazine for aggression in schizophrenia and mental retardation. Lancet 1993; 341: 307-. Varga 1971 Varga E, Simpson GM. Loxapine succinate in the treatment of uncontrollable destructive behavior. Current Therapeutic Research Clinical Experimental 1971; 13: 737-42. Versiani 1980 Versiani M, da Silva JA, Mundim FD. Loxapine versus thioridazine in the treatment of organic psychosis. Journal of International Medical Research 1980; 8: 22-30. Zwanikken 1971 Zwanikken GJ, Remans B, Dewulf P, Amery W. Clinical evaluation of the long-acting injectable neuroleptic, fluspirilene, in the treatment of schizophrenic and mentally retarded patients. Acta Psychiatrica Scandinavica 1971; 47: 334-48. Zwanikken 1973 Zwanikken GJ. Penfluridol ( R16341). A long-acting oral neuroleptic, as maintainance therapy for schizophrenic and mentally retarded patients. A placebo-controlled double-blind trial. Psychiatria, Neurologia, Neurochirugia 1973; 76: 83-92. References to studies awaiting assessment Angst 1970 Angst J, Cornu F, Heimann H, Steiner H. 2-chloro-11(4 -mehtylpiperazino)-dibenzo-(b,f)(1,4)-oxazepin (sum 3170), ein neues neurolepticum. Ergebnisse einer interklinischen prufung. Arzneimittelforschung 1970; 20: 967-70. Bayle 1979 Kuhn 1966 Kuhn R, Taescher M, Schoch J. Pharmakologische und klinische eigenschaften eines neuen butyrophenon-derivates(FR33). Psychopharmacologia 1966; 9: 351-62. Additional references Altman 1996 Altman DG, Bland JM. Detecting skewness from summary information. BMJ 1996; 313: 1200-. Aman 1984 Aman MG. Drugs and learning in mentally retarded persons. In: Burrows GD, Werry JS, editors. Advances in human psychopharmacology. Greenwich CT; : JAI Press,-. BNF 1998 British National Formulary. British Medical Association and Royal Pharmaceutical Society of Great Britain,. 35.1; : -. Clarke 1990 Clarke DJ, Kelley S, Thinn K, Corbett JA. Psychotropic drugs and mental retardation: I. Disabilities and the prescription of drugs for behaviour and for epilepsy in three residential settings. Journal of Mental Deficiency Research 1990; 34: 385-95. Corbett 1979 Eaton 1982 Eaton LF, Menolascino FJ. Psychiatric disorders in the mentally retarded: types, problems and challenges. American Journal of Psychiatry 1982; 139: 1297-303. Gillberg 1986 Gillberg C, Persson E, Grufman M, Themner U. Psychiatric disorders in mildly and severely mentally retarded urban children and adolescents: epidemiological aspects. British Journal of Psychiatry 1986; 49: 68-74. Gingell 1994 Gingell K, Nadarajah J. A controlled community study of movement disorder in people with learning difficulties on antipsychotic medication. Journal of Intellectual Disability Research 1994; 37: 53-9. Heaton-Ward 1977 Heaton-Ward A. Psychosis in mental handicap. British Journal of Psychiatry 1977; 130: 525-33. Jablensky 1986 Jablensky A. Epidemiology of schizophrenia: a European perspective. Schizophrenia Bulletin 1986; 12: 52-73. Lund 1985 Lund J. The prevalence of psychiatric morbidity in mentally retarded adults. Acta Psychiatrica Scandinavica 1985; 72: 563-70. Matson 1994 Matson JL, Sevin JA. Theories of dual diagnosis in mental retardation. Journal of Consulting and Clinical Psychology 1994; 62: 6-16. Mulrow 1997 Parson 1984 Parson J, May J, Menoslascino FJ. The nature and incidence of mental illness in mentally retarded individuals. In: Menolascino FJ, Stark JA, editors. New York; : Plenum Pre-. Rogers 1991 Rogers D, Karki C, Bartlett C, Pocock P. The motor disorders of mental handicap. An overlap with the motor disorders of severe psychiatric illness. British Journal of Psychiatry 1991; 158: 97-102. Rutter 1970 Sachdev 1992 Sachdev P. Drug induced movement disorders in institutionalised adults with mental retardation. Clinical characteristics and risk factors. Australian and New Zealand Journal of Psychiatry 1992; 26: 242-8. Weinberger 1995 Weinberger DR, Lipska BK. Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground. Schizophrenia Research 1995; 16: 87-110. Wressell 1990 Wressell SE, Tyrer SP, Berney TP. Reduction in antipsychotic drug dosage in mentally handicapped patients; a hospital study. British Journal of Psychiatry 1990; 157: 101-6. Youseff 1988 Youseff HA, Waddington JL. Involuntary orofacial movements in hospitalised patients with mental handicap or epilepsy; relationship to developmental/ intellectual deficit and presence or absence of long term exposure to neuroleptics. Journal of Neurology, Neurosurgery and Psychiatry 1988; 51: 863-5. Extramural sources of support to the review Intramural sources of support to the reviewBayle BJ, Bezaury JP. Clinical trial with a new psychotropic agent : carpipramine. Psychologie Medicale 1979;2695-703.
Corbett J. Psychiatric morbidity and mental retardation. In: James FE, Snaith RP, editors. Psychiatric illness and mental handicap. London: Gaskell, 1979:11-25.
Mulrow CD, Oxman AD (editors). Cochrane Collaboration Handbook (updated 1 March 1997). In: The Cochrane Library (database on disk and CDROM). The Cochrane Collaboration. Oxford: Update Software; 1996-. Updated quarterly.
Rutter M, Graham P, Yule W. A neuropsychiatric study in childhood. In: Clinics in developmental medicine, London: Heineman/Spastics, 1970:35-6.
Reviewer(s) Duggan L, Brylewski J Date of most recent amendment 22 February 1999 Date of most recent substantive amendment 24 August 1998 Contact address Dr Lorna Duggan
West Berkshire Priority Care NHS Trust
Fair Mile Hospital
Cholsey
Oxfordshire
UK
OX10 9HH
Telephone: +44 1491 651281 extension: 4020
Facsimile: +44 1491 652336
E-mail: [email protected]Cochrane Library number CD000030 Editorial group Cochrane Schizophrenia Group Editorial group code HM-SCHIZ This review should be cited as :
Duggan L, Brylewski J. Antipsychotic medication for people with both schizophrenia and learning disability (Cochrane Review). In: The Cochrane Library, Issue 2, 1999. Oxford: Update Software.Sources of support
Keywords
ANTIPSYCHOTIC-AGENTS / therapeutic-use; SCHIZOPHRENIA / drug-therapy; LEARNING-DISORDERS / drug-therapy; RANDOMIZED-CONTROLLED-TRIALS; SCHIZOPHRENIA / complications; LEARNING-DISORDERS / complications; MENTAL-RETARDATION / complications; HUMANList of comparisons
Fig 01 ANY ANTIPSYCHOTIC DRUG VS PLACEBO
Tables of other data
Any antipsychotic drug vs placebo: Any outcome
| Study | Description |
|---|---|
| Foote 1958 | No data usable for any outcome |
| Study | Method | Participants | Interventions | Outcomes | Notes |
|---|---|---|---|---|---|
| Foote 1958 | Allocation: randomisation stated - method not described. Blindness: double - drugs identically presented, chocolate-flavoured tablets. Duration: 5 months. | Diagnosis: 53 schizophrenia only, 4 both learning disability & schizophrenia*, 9 manic depressive illness, 2 eplipsy, 2 psychopathic PD. N=70. Sex: 70 F. History: ""long-stay"". Setting: single centre, UK. | 1. Chlorpromazine 50 mg & reserpine 0.5 mg (combined tablet): 3/day changed to chlorpromazine 25 mg & reserpine 0.25 mg daily.** N=45. 2. Placebo. N=25. | Leaving the study early. Clinical ratings (non-standardized scale). Side-effects. Attendance at occupational therapy. Physiological measures. | *Impossible to clarify to which group the 4 with dual diagnoses were allocated. Data on 2 people with learning disability available but not usable (see text). **Dose revised due to high incidence of movement disorder side-effects. |
| Study | Reason for exclusion |
|---|---|
| Brenner 1984 | Allocation: randomised. Participants: aggressive patients with diffuse psycho-organic syndrome - not schizophrenia. Intervention: febarbamate versus pipamperon, not placebo-controlled. |
| Cohen 1994 | Allocation: not randomised, case reports. |
| De Cuyper 1985 | Allocation: randomised. Participants: oligophrenic adults. Interventions: milenperone versus placebo. Outcomes: unable to extract data for those with mental retardation alone, as mixed in with mental retardation and psychosis. |
| De Guzman 1971 | Allocation: not randomised. |
| Feldman 1966 | Allocation: not randomised. Participants: psychotic inpatients. Intervention: tybamate (not an antipsychotic) versus placebo. |
| Fracassi 1976 | Allocation: not randomised. |
| Godleski 1989 | Allocation: not randomised. |
| Gravem 1981 | Allocation: not randomised, a review. |
| Heikkila 1981 | Allocation: not randomised. Participants: mix of those with schizophrenia, and those with both schizophrenia and mental retardation. Intervention: cis(Z)-clopenthixol versus clopenthixol, not placebo-controlled. Outcomes: impossible to ascertain results for those with both mental retardation and schizophrenia. |
| Karsten 1981 | Allocation: randomised. Participants: children and adults, oligophrenic in-patients with and without mental illness. Interventions: cis(Z)-zuclopenthixol vs placebo and haloperidol vs placebo. Outcomes: data could not be extracted for those with schizophrenia and learning disability. |
| Kumpel 1971 | Allocation: not randomised. Participants: not schizophrenia. |
| McKenzie 1966 | Allocation: randomised. Participants: severely subnormal in-patients with behaviour disorders. 4 had schizophrenia, some were under 18 years. Interventions: prothipendyl vs placebo. Outcomes: aggression, leaving the study early, side effects, psychological data. Data impossible to extract as unable to separate out the children and those with both learning disabilities schizophrenia. The authors suggested these individuals responded better than the remainder. |
| Menolascino 1985 | Allocation: randomised. Participants: retarded and non-retarded adults with schizophrenia. Intervention: thiothixene versus thioridazine, not placebo-controlled. |
| Nielson 1967 | Allocation: not randomised, case series. |
| Pislova 1974 | Allocation: not randomised, open study . |
| Sajatovic 1994 | Allocation: not randomised, case series. |
| Smith 1992 | Allocation: not randomised, a systematic review of non-antipsychotic treatment for disruptive behaviour in organic mental syndromes, not schizophrenia. |
| St-Jean 1966 | Allocation: not randomised, open study. |
| Tiihonen 1993 | Allocation: not randomised, open study. |
| Varga 1971 | Allocation: not randomised, open study. |
| Versiani 1980 | Allocation: randomised. Participants: chronic psychosis associated with organic brain syndrome or mental retardation, not schizophrenia. Intervention: loxapine versus thioridazine. |
| Zwanikken 1971 | Allocation: not randomised, open study. |
| Zwanikken 1973 | Allocation: randomised. Participants: mentally retarded in-patients with and without schizophrenia and non retarded in-patients with schizophrenia. Interventions: penfluridol vs placebo. Outcomes: Impossible to extract data for those with learning disability and schizophrenia. Author contacted and relevant data not avaiable. |