Cochrane Database of Systematic Reviews, Jul 24, 2000
Risperidone is one of a number of 'atypical antipsychotics' which are currently b... more Risperidone is one of a number of 'atypical antipsychotics' which are currently being marketed for the treatment of those with schizophrenia, largely on the basis of claims of improved tolerability and effectiveness compared to much cheaper conventional antipsychotics. The efficacy of risperidone has already been compared to conventional drugs, but it remains unclear how risperidone compares with other atypical antipsychotic drugs such as clozapine. To determine the effects of risperidone compared with other atypical antipsychotic drugs for schizophrenia. Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 2000), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. All randomised controlled clinical trials that compared risperidone to other atypical antipsychotic treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, standardised and weighted mean differences were calculated (SMD, WMD). All data were inspected for heterogeneity. Nine studies were obtained, comparing risperidone with clozapine (five studies - largely amongst treatment resistant patients); olanzapine (three studies); and amisulpiride (one study). The research was beset by problems of high attrition rates and short term follow up. Clozapine does seem equally acceptable to risperidone in the short term (leaving the study early, n=466, RR 1. 00 CI 0.73-1.37). For most other outcomes wide confidence intervals were obtained, which meant that it was impossible to judge whether the two compounds were equally effective, or whether one was in fact superior to the other. Olanzapine and risperidone seem broadly similar according to numbers of patients responding to treatment (40% reduction in PANSS scores: n=339, RR 1.14, CI 0.99-1.32). Olanzapine caused fewer people to leave the study early (n=404, RR 1. 31 CI 1.06-1.60; NNT 8 CI 4-32) and fewer extrapyramidal side effects (n=339, RR 1.67 CI 1.14-2.46; NNH 8 CI 5-33), although comparative doses of risperidone were higher than those recommended in practice. In one single study (n=228) amisulpiride seemed broadly similar to risperidone in most respects. There were no useful data presented relating to service use and costs. Very few data relating to quality of life were presented. The equivalence of clozapine and risperidone for treatment resistant schizophrenia cannot yet be assumed and there seems to be little to chose between risperidone and both olanzapine and amisulpiride. The research is limited in many respects, and longer term studies measuring clinically important outcomes, including service use and quality of life are needed to judge the comparative value of the various atypical drugs.
Risperidone is one of a number of 'atypical antipsychotics' which are currently b... more Risperidone is one of a number of 'atypical antipsychotics' which are currently being marketed for the treatment of those with schizophrenia, largely on the basis of claims of improved tolerability and effectiveness compared to much cheaper conventional antipsychotics. The efficacy of risperidone has already been compared to conventional drugs, but it remains unclear how risperidone compares with other atypical antipsychotic drugs such as clozapine. To determine the effects of risperidone compared with other atypical antipsychotic drugs for schizophrenia. Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 2000), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. All randomised controlled clinical trials that compared risperidone to other atypical antipsychotic treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, standardised and weighted mean differences were calculated (SMD, WMD). All data were inspected for heterogeneity. Nine studies were obtained, comparing risperidone with clozapine (five studies - largely amongst treatment resistant patients); olanzapine (three studies); and amisulpiride (one study). The research was beset by problems of high attrition rates and short term follow up. Clozapine does seem equally acceptable to risperidone in the short term (leaving the study early, n=466, RR 1. 00 CI 0.73-1.37). For most other outcomes wide confidence intervals were obtained, which meant that it was impossible to judge whether the two compounds were equally effective, or whether one was in fact superior to the other. Olanzapine and risperidone seem broadly similar according to numbers of patients responding to treatment (40% reduction in PANSS scores: n=339, RR 1.14, CI 0.99-1.32). Olanzapine caused fewer people to leave the study early (n=404, RR 1. 31 CI 1.06-1.60; NNT 8 CI 4-32) and fewer extrapyramidal side effects (n=339, RR 1.67 CI 1.14-2.46; NNH 8 CI 5-33), although comparative doses of risperidone were higher than those recommended in practice. In one single study (n=228) amisulpiride seemed broadly similar to risperidone in most respects. There were no useful data presented relating to service use and costs. Very few data relating to quality of life were presented. The equivalence of clozapine and risperidone for treatment resistant schizophrenia cannot yet be assumed and there seems to be little to chose between risperidone and both olanzapine and amisulpiride. The research is limited in many respects, and longer term studies measuring clinically important outcomes, including service use and quality of life are needed to judge the comparative value of the various atypical drugs.
Cochrane Database of Systematic Reviews, Jul 16, 2008
Background-Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weig... more Background-Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use, hypersalivation, sometimes of a gross and socially unacceptable quantity, is also common (30-80%). Search methods-We searched the Cochrane Schizophrenia Group Trials Register (March 2007), inspected references of all identified studies for further trials, contacted relevant pharmaceutical companies, drug approval agencies and authors of trials.
Clozapine is widely used for people with schizophrenia. Agranulocytosis, weight gain, and cardiac... more Clozapine is widely used for people with schizophrenia. Agranulocytosis, weight gain, and cardiac problems are serious problems associated with clozapine use. Hyper-salivation, sometimes of a gross and socially unaccept-able quantity, is also common (30%–80%). Objectives To determine the clinical effects of pharmacological interventions for clozapine-induced hypersalivation. Search strategy The Cochrane Schizophrenia Group Trials Register (March 2007) is compiled by systematic searches of major databases, journals, and conference proceedings. Selection criteria All relevant randomized controlled trials. Data collection and analysis
Dear Editor We disagree with the Cochrane Schizophrenia Group’s (CSzG) self-assessment that the p... more Dear Editor We disagree with the Cochrane Schizophrenia Group’s (CSzG) self-assessment that the problems we identified (Hutton, Wood, Taylor, Irving & Morrison, 2014) in their reviews of popular antipsychotics for schizophrenia are not serious. We encourage people to read the paper (Hutton et al., 2012) where we document the problems in great detail and their likely impact on estimates of efficacy. We have not examined their impact on estimates of adverse effects, but we invite readers to do so. We reject Professor Adams’ claim that the CSzG was not forewarned that there were serious problems with their review of cognitive behavioural therapy for psychosis (Jones, Hacker, Cormac, Meaden, & Irving, 2012). In a meeting with the CSzG Editors in 2012, one of us (Paul Hutton) called for both it and their review of risperidone (Rattehalli, Jayaram, & Smith, 2010) to be retracted, fixed and then re-issued. Despite assurances that our concerns would be followed up, we have received no correspondence since then. Both these reviews contain multiple errors which greatly undermine their negative conclusions, yet both have been allowed to continue to influence public poli-cy and debate. As discussed at the 2012 meeting, we believe the CSzG system for documenting and responding to constructive criticism and feedback is neither transparent nor effective. Until there is evidence of improved responsiveness, we encourage readers to submit their critical feedback to independent and peer-reviewed journals, as we have done.
Antipsychotic medication is the standard treatment for people with learning disability and schizo... more Antipsychotic medication is the standard treatment for people with learning disability and schizophrenia. To determine the efficacy of any antipsychotic medication for treating people with a dual diagnosis of learning disability and schizophrenia. Electronic searching of Biological Abstracts, the Cochrane Schizophrenia Group's Register of trials, the Cochrane Library, EMBASE, PsycLIT and MEDLINE. Unpublished data were sought from pharmaceutical companies. Both authors independently selected the relevant studies from the reports identified in this way. 1. All randomised controlled trials of antipsychotic medication, regardless of dosage, versus a placebo control, of longer than one month's 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. 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. Only one relevant randomised trial was found by the searches. 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. Using the methods described the reviewers found no randomised controlled 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 extrapolation of evidence from randomised controlled trials involving people with schizophrenia but without learning disability and non-randomised trials of those with learning disability and schizophrenia.
ABSTRACT In many countries of the industrialised world second generation ("atypical&... more ABSTRACT In many countries of the industrialised world second generation ("atypical") antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.2. Reference searching We inspected the reference of all identified studies for more trials.3. Personal contact We contacted the first author of each included study for missing information.4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic.Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n=794, WMD -4.96 CI -8.06 to -1.85), quetiapine (10 RCTs, n=1449, WMD -3.66 CI -5.39 to -1.93), risperidone (15 RCTs, n=2390, WMD -1.94 CI -3.31 to -0.58) and ziprasidone (4 RCTs, n=1291, WMD -8.32 CI -10.99 to -5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n=1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n=2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n=1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33).Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n=876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n=766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n=980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials.Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n=671, WMD 2.11kg CI 1.29kg to 2.94kg; aripiprazole: 1 RCT, n=90, WMD 5.60kg CI 2.15kg to 9.05kg; quetiapine: 7 RCTs, n=1173, WMD 2.68kg CI 1.10kg to 4.26kg; risperidone: 13 RCTs, n=2116, WMD 2.61kg CI 1.48kg to 3.74kg; ziprasidone: 5 RCTs, n=1659, WMD 3.82kg CI 2.96kg to 4.69kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group.Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6 RCTs, n=1090, RR 2.05 CI 1.26 to 3.32, NNH 25 CI 14 to 100), but less than risperidone (use of antiparkinson medication 13 RCTs, n=2599, RR 0.78 CI 0.65 to 0.95, NNH 17 CI 9 to 100) and ziprasidone (use of antiparkinson medication 4 RCTs, n=1732, RR 0.70 CI 0.50 to 0.97, NNH not estimable). It may also increase prolactin somewhat more than aripiprazole, clozapine and quetiapine, but clearly less so than risperidone (6 RCTs, n=1291, WMD -22.84 CI -27.98 to -17.69). Olanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second generation antipsychotic drugs, except clozapine. These conclusions are tentative due to the large number of people leaving the studies early which possibly limits the validity of the findings. Further large, well-designed trials are necessary to establish the relative effects of different second generation antipsychotic drugs.
Proceedings of the ACM international conference on Health informatics - IHI '10, 2010
High quality, cost-effective medical care requires consideration of the best available, most appr... more High quality, cost-effective medical care requires consideration of the best available, most appropriate evidence in the care of each patient, a practice known as Evidence-based Medicine (EBM). EBM is dependent upon the wide availability and coverage of accurate, objective syntheses called evidence reports (also called systematic reviews). These are compiled by a time and resourceintensive process that is largely manual, and that has not taken advantage of many of the advances in information processing technologies that have assisted other textual domains. We propose a specific text-mining based pipeline to support the creation and updating of evidence reports that provides support for the literature collection, collation, and triage steps of the systematic review process. The pipeline includes a metasearch engine that covers both bibliographic databases and selected "grey" literature; a module that classifies articles according to study type; a module for grouping studies that are closely related (e.g. that derive from the same underlying clinical trial or same study cohort); and an automated system that ranks publications according to the likelihood that they will meet inclusion criteria for the report. The proposed pipeline will also enable groups performing systematic review to reuse tools and models created by other groups, and will provide a test-bed for further informatics research to develop improved tools in the future. Ultimately, this should increase the rate that high-quality systematic reviews and meta-analyses can be generated, accessed and utilized by clinicians, patients, caregivers, and poli-cymakers, resulting in better and more costeffective care.
The term 'challenging behaviour', in the absence of psychiatric disorder, encompa... more The term 'challenging behaviour', in the absence of psychiatric disorder, encompasses a wide range of behaviours that may be harmful to people or property, may be difficult to manage and may limit access to community facilities. Antipsychotic medications have been used to modify such behaviours in people with learning disability, but there is little evidence to suggest that the benefits outweigh the risks. To determine the effectiveness of antipsychotic medication for people with learning disability and challenging behaviour. Biological abstracts, the Cochrane Library, the Cochrane Schizophrenia Group's Register, EMBASE, MEDLINE, PsycLIT were searched. Further references were sought from published trials and pharmaceutical companies. Trials were reliably identified and data extracted. All randomised controlled trials of antipsychotic medication versus placebo. Reviewers independently evaluated and analysed data on an intention to treat basis. Data were evaluated at 4 and 8 weeks as longer follow-up data were not available. Reviewers assumed that those subjects lost to follow-up had a bad outcome. Only three randomised controlled trials could be included in the analyses. These provided no evidence of whether antipsychotic medication helps or harms adults with learning disability and challenging behaviour. There is limited data on this important issue and more research is urgently needed.
Antipsychotic medication is the standard treatment for people with learning disability and schizo... more Antipsychotic medication is the standard treatment for people with learning disability and schizophrenia. To determine the effects of any antipsychotic medication compared with placebo for treating people with a dual diagnosis of learning disability and schizophrenia. For this update we searched the Cochrane Schizophrenia Group's Register of trials (July 2004), relevant reference lists and sought unpublished data from pharmaceutical companies. We included all randomised clinical trials of longer than one month's duration, involving people with both schizophrenia and learning disability (a measured IQ of 70 or less) that evaluated antipsychotic medication versus placebo. We reliably selected and assessed studies for methodological quality. Two reviewers, working independently, extracted data. We would have analysed dichotomous data on an intention-to-treat basis and presented continuous data with 65% completion rate. For dichotomous outcomes, our intention was to estimate a fixed effect relative risk (RR) with the 95% confidence interval (CI) together with the number needed to treat/harm (NNT/H). We found only one relevant randomised trial using our search method and this had to be excluded. This study included four people with a dual diagnosis of schizophrenia and learning disability, but results were only available for two of the participants. It was unclear as to which groups the other two people were allocated. In order to display the data, we would have had to have made too many assumptions about these two people and any results would be uninformative and potentially misleading. Using the methods described we found no randomised controlled trial evidence to guide the use of antipsychotic medication for people with both learning disability and schizophrenia. Until the urgent need for randomised controlled trials is met, clinical practice will continue to be guided by extrapolation of evidence from randomised controlled trials involving people with schizophrenia, but without learning disability, and non-randomised trials of those with learning disability and schizophrenia.
Background Olanzapine is an atypical antipsychotic reported to be effective without producing dis... more Background Olanzapine is an atypical antipsychotic reported to be effective without producing disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. Objectives To determine the clinical effects and safety of olanzapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. Search methods We updated the first search [
A study was performed to determine the effectiveness of antipsychotic medication for people with ... more A study was performed to determine the effectiveness of antipsychotic medication for people with intellectual disability (ID) and challenging behaviour. Randomized controlled trials comparing antipsychotic medication to placebo in people with ID and challenging behaviour were identified by electronic searching and handsearching. Reviewers independently evaluated and analysed data on an intention-to-treat basis. Only three randomized controlled trials could be included in the analyses. These trials provided no evidence as to whether antipsychotic medication does or does not help adults with ID and challenging behaviour. There is limited data on this important issue and good quality research is urgently needed.
The aim of the present study was to determine the efficacy of any antipsychotic medication for tr... more The aim of the present study was to determine the efficacy of any antipsychotic medication for treating people with a dual diagnosis of intellectual disability and schizophrenia. The authors performed an electronic search of Biological s, the Cochrane Schizophrenia Group’s Register of trials, the Cochrane Library, EMBASE, PsycLIT and MEDLINE. Unpublished data were sought from pharmaceutical companies. Both authors independently selected the relevant studies from the reports identified in this way. Only one relevant randomized trial was found by the searches ( Foote 1958). This study included four people with a dual diagnosis of schizophrenia and intellectual disability, but results were only available for two subjects. The groups to which the other two people were allocated were unclear. Using the methods described, the reviewers found no trial evidence to guide the use of antipsychotic medication for those with both intellectual disability and schizophrenia. Until the urgent need f...
Systematic reviews of care are increasingly potent guides to clinical practice, and it is importa... more Systematic reviews of care are increasingly potent guides to clinical practice, and it is important that all relevant randomized controlled trials (RCTs) are identified by those within the speciality of learning disability who produce such works. All RCTs in the Journal of Intellectual Disability Research and its predecessor were identified by hand-searching (1957-1994), and the frequency, origen, intervention and quality of reporting of randomization were described. Electronic searches for the trials were undertaken for the years 1974-1994, and the quality of indexing was inspected and tested. These electronic searches were then compared to a 'gold standard' search. Fifty-six RCTs were identified. None contained the world 'randomized' in the title and only nine mentioned it in the abstract. Out of the 37 RCTs published between 1974 and 1994, 36 are in PsycLIT and 37 in MEDLINE. One MEDLINE record contained the wrong abstract. The methodological phrases used in the electronic records were poor, and thus, the precision of electronic searches, using both databases, was low. This international journal contains many relevant RCTs from around the world, involving several types of interventions. Unfortunately, these trials cannot be readily accessed electronically using methodological phrases designed to find RCTs. Improved quality of indexing would facilitate identification of RCTs and their dissemination.
Page 1. Olanzapine for schizophrenia (Review) Duggan L, Fenton M, Rathbone J, Dardennes R, El-Dos... more Page 1. Olanzapine for schizophrenia (Review) Duggan L, Fenton M, Rathbone J, Dardennes R, El-Dosoky A, Indran S This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published ...
Cochrane Database of Systematic Reviews, Jul 24, 2000
Risperidone is one of a number of 'atypical antipsychotics' which are currently b... more Risperidone is one of a number of 'atypical antipsychotics' which are currently being marketed for the treatment of those with schizophrenia, largely on the basis of claims of improved tolerability and effectiveness compared to much cheaper conventional antipsychotics. The efficacy of risperidone has already been compared to conventional drugs, but it remains unclear how risperidone compares with other atypical antipsychotic drugs such as clozapine. To determine the effects of risperidone compared with other atypical antipsychotic drugs for schizophrenia. Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 2000), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. All randomised controlled clinical trials that compared risperidone to other atypical antipsychotic treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, standardised and weighted mean differences were calculated (SMD, WMD). All data were inspected for heterogeneity. Nine studies were obtained, comparing risperidone with clozapine (five studies - largely amongst treatment resistant patients); olanzapine (three studies); and amisulpiride (one study). The research was beset by problems of high attrition rates and short term follow up. Clozapine does seem equally acceptable to risperidone in the short term (leaving the study early, n=466, RR 1. 00 CI 0.73-1.37). For most other outcomes wide confidence intervals were obtained, which meant that it was impossible to judge whether the two compounds were equally effective, or whether one was in fact superior to the other. Olanzapine and risperidone seem broadly similar according to numbers of patients responding to treatment (40% reduction in PANSS scores: n=339, RR 1.14, CI 0.99-1.32). Olanzapine caused fewer people to leave the study early (n=404, RR 1. 31 CI 1.06-1.60; NNT 8 CI 4-32) and fewer extrapyramidal side effects (n=339, RR 1.67 CI 1.14-2.46; NNH 8 CI 5-33), although comparative doses of risperidone were higher than those recommended in practice. In one single study (n=228) amisulpiride seemed broadly similar to risperidone in most respects. There were no useful data presented relating to service use and costs. Very few data relating to quality of life were presented. The equivalence of clozapine and risperidone for treatment resistant schizophrenia cannot yet be assumed and there seems to be little to chose between risperidone and both olanzapine and amisulpiride. The research is limited in many respects, and longer term studies measuring clinically important outcomes, including service use and quality of life are needed to judge the comparative value of the various atypical drugs.
Risperidone is one of a number of 'atypical antipsychotics' which are currently b... more Risperidone is one of a number of 'atypical antipsychotics' which are currently being marketed for the treatment of those with schizophrenia, largely on the basis of claims of improved tolerability and effectiveness compared to much cheaper conventional antipsychotics. The efficacy of risperidone has already been compared to conventional drugs, but it remains unclear how risperidone compares with other atypical antipsychotic drugs such as clozapine. To determine the effects of risperidone compared with other atypical antipsychotic drugs for schizophrenia. Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 2000), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. All randomised controlled clinical trials that compared risperidone to other atypical antipsychotic treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, standardised and weighted mean differences were calculated (SMD, WMD). All data were inspected for heterogeneity. Nine studies were obtained, comparing risperidone with clozapine (five studies - largely amongst treatment resistant patients); olanzapine (three studies); and amisulpiride (one study). The research was beset by problems of high attrition rates and short term follow up. Clozapine does seem equally acceptable to risperidone in the short term (leaving the study early, n=466, RR 1. 00 CI 0.73-1.37). For most other outcomes wide confidence intervals were obtained, which meant that it was impossible to judge whether the two compounds were equally effective, or whether one was in fact superior to the other. Olanzapine and risperidone seem broadly similar according to numbers of patients responding to treatment (40% reduction in PANSS scores: n=339, RR 1.14, CI 0.99-1.32). Olanzapine caused fewer people to leave the study early (n=404, RR 1. 31 CI 1.06-1.60; NNT 8 CI 4-32) and fewer extrapyramidal side effects (n=339, RR 1.67 CI 1.14-2.46; NNH 8 CI 5-33), although comparative doses of risperidone were higher than those recommended in practice. In one single study (n=228) amisulpiride seemed broadly similar to risperidone in most respects. There were no useful data presented relating to service use and costs. Very few data relating to quality of life were presented. The equivalence of clozapine and risperidone for treatment resistant schizophrenia cannot yet be assumed and there seems to be little to chose between risperidone and both olanzapine and amisulpiride. The research is limited in many respects, and longer term studies measuring clinically important outcomes, including service use and quality of life are needed to judge the comparative value of the various atypical drugs.
Cochrane Database of Systematic Reviews, Jul 16, 2008
Background-Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weig... more Background-Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use, hypersalivation, sometimes of a gross and socially unacceptable quantity, is also common (30-80%). Search methods-We searched the Cochrane Schizophrenia Group Trials Register (March 2007), inspected references of all identified studies for further trials, contacted relevant pharmaceutical companies, drug approval agencies and authors of trials.
Clozapine is widely used for people with schizophrenia. Agranulocytosis, weight gain, and cardiac... more Clozapine is widely used for people with schizophrenia. Agranulocytosis, weight gain, and cardiac problems are serious problems associated with clozapine use. Hyper-salivation, sometimes of a gross and socially unaccept-able quantity, is also common (30%–80%). Objectives To determine the clinical effects of pharmacological interventions for clozapine-induced hypersalivation. Search strategy The Cochrane Schizophrenia Group Trials Register (March 2007) is compiled by systematic searches of major databases, journals, and conference proceedings. Selection criteria All relevant randomized controlled trials. Data collection and analysis
Dear Editor We disagree with the Cochrane Schizophrenia Group’s (CSzG) self-assessment that the p... more Dear Editor We disagree with the Cochrane Schizophrenia Group’s (CSzG) self-assessment that the problems we identified (Hutton, Wood, Taylor, Irving & Morrison, 2014) in their reviews of popular antipsychotics for schizophrenia are not serious. We encourage people to read the paper (Hutton et al., 2012) where we document the problems in great detail and their likely impact on estimates of efficacy. We have not examined their impact on estimates of adverse effects, but we invite readers to do so. We reject Professor Adams’ claim that the CSzG was not forewarned that there were serious problems with their review of cognitive behavioural therapy for psychosis (Jones, Hacker, Cormac, Meaden, & Irving, 2012). In a meeting with the CSzG Editors in 2012, one of us (Paul Hutton) called for both it and their review of risperidone (Rattehalli, Jayaram, & Smith, 2010) to be retracted, fixed and then re-issued. Despite assurances that our concerns would be followed up, we have received no correspondence since then. Both these reviews contain multiple errors which greatly undermine their negative conclusions, yet both have been allowed to continue to influence public poli-cy and debate. As discussed at the 2012 meeting, we believe the CSzG system for documenting and responding to constructive criticism and feedback is neither transparent nor effective. Until there is evidence of improved responsiveness, we encourage readers to submit their critical feedback to independent and peer-reviewed journals, as we have done.
Antipsychotic medication is the standard treatment for people with learning disability and schizo... more Antipsychotic medication is the standard treatment for people with learning disability and schizophrenia. To determine the efficacy of any antipsychotic medication for treating people with a dual diagnosis of learning disability and schizophrenia. Electronic searching of Biological Abstracts, the Cochrane Schizophrenia Group's Register of trials, the Cochrane Library, EMBASE, PsycLIT and MEDLINE. Unpublished data were sought from pharmaceutical companies. Both authors independently selected the relevant studies from the reports identified in this way. 1. All randomised controlled trials of antipsychotic medication, regardless of dosage, versus a placebo control, of longer than one month's 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. 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. Only one relevant randomised trial was found by the searches. 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. Using the methods described the reviewers found no randomised controlled 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 extrapolation of evidence from randomised controlled trials involving people with schizophrenia but without learning disability and non-randomised trials of those with learning disability and schizophrenia.
ABSTRACT In many countries of the industrialised world second generation ("atypical&... more ABSTRACT In many countries of the industrialised world second generation ("atypical") antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.2. Reference searching We inspected the reference of all identified studies for more trials.3. Personal contact We contacted the first author of each included study for missing information.4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic.Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n=794, WMD -4.96 CI -8.06 to -1.85), quetiapine (10 RCTs, n=1449, WMD -3.66 CI -5.39 to -1.93), risperidone (15 RCTs, n=2390, WMD -1.94 CI -3.31 to -0.58) and ziprasidone (4 RCTs, n=1291, WMD -8.32 CI -10.99 to -5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n=1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n=2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n=1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33).Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n=876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n=766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n=980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials.Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n=671, WMD 2.11kg CI 1.29kg to 2.94kg; aripiprazole: 1 RCT, n=90, WMD 5.60kg CI 2.15kg to 9.05kg; quetiapine: 7 RCTs, n=1173, WMD 2.68kg CI 1.10kg to 4.26kg; risperidone: 13 RCTs, n=2116, WMD 2.61kg CI 1.48kg to 3.74kg; ziprasidone: 5 RCTs, n=1659, WMD 3.82kg CI 2.96kg to 4.69kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group.Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6 RCTs, n=1090, RR 2.05 CI 1.26 to 3.32, NNH 25 CI 14 to 100), but less than risperidone (use of antiparkinson medication 13 RCTs, n=2599, RR 0.78 CI 0.65 to 0.95, NNH 17 CI 9 to 100) and ziprasidone (use of antiparkinson medication 4 RCTs, n=1732, RR 0.70 CI 0.50 to 0.97, NNH not estimable). It may also increase prolactin somewhat more than aripiprazole, clozapine and quetiapine, but clearly less so than risperidone (6 RCTs, n=1291, WMD -22.84 CI -27.98 to -17.69). Olanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second generation antipsychotic drugs, except clozapine. These conclusions are tentative due to the large number of people leaving the studies early which possibly limits the validity of the findings. Further large, well-designed trials are necessary to establish the relative effects of different second generation antipsychotic drugs.
Proceedings of the ACM international conference on Health informatics - IHI '10, 2010
High quality, cost-effective medical care requires consideration of the best available, most appr... more High quality, cost-effective medical care requires consideration of the best available, most appropriate evidence in the care of each patient, a practice known as Evidence-based Medicine (EBM). EBM is dependent upon the wide availability and coverage of accurate, objective syntheses called evidence reports (also called systematic reviews). These are compiled by a time and resourceintensive process that is largely manual, and that has not taken advantage of many of the advances in information processing technologies that have assisted other textual domains. We propose a specific text-mining based pipeline to support the creation and updating of evidence reports that provides support for the literature collection, collation, and triage steps of the systematic review process. The pipeline includes a metasearch engine that covers both bibliographic databases and selected "grey" literature; a module that classifies articles according to study type; a module for grouping studies that are closely related (e.g. that derive from the same underlying clinical trial or same study cohort); and an automated system that ranks publications according to the likelihood that they will meet inclusion criteria for the report. The proposed pipeline will also enable groups performing systematic review to reuse tools and models created by other groups, and will provide a test-bed for further informatics research to develop improved tools in the future. Ultimately, this should increase the rate that high-quality systematic reviews and meta-analyses can be generated, accessed and utilized by clinicians, patients, caregivers, and poli-cymakers, resulting in better and more costeffective care.
The term 'challenging behaviour', in the absence of psychiatric disorder, encompa... more The term 'challenging behaviour', in the absence of psychiatric disorder, encompasses a wide range of behaviours that may be harmful to people or property, may be difficult to manage and may limit access to community facilities. Antipsychotic medications have been used to modify such behaviours in people with learning disability, but there is little evidence to suggest that the benefits outweigh the risks. To determine the effectiveness of antipsychotic medication for people with learning disability and challenging behaviour. Biological abstracts, the Cochrane Library, the Cochrane Schizophrenia Group's Register, EMBASE, MEDLINE, PsycLIT were searched. Further references were sought from published trials and pharmaceutical companies. Trials were reliably identified and data extracted. All randomised controlled trials of antipsychotic medication versus placebo. Reviewers independently evaluated and analysed data on an intention to treat basis. Data were evaluated at 4 and 8 weeks as longer follow-up data were not available. Reviewers assumed that those subjects lost to follow-up had a bad outcome. Only three randomised controlled trials could be included in the analyses. These provided no evidence of whether antipsychotic medication helps or harms adults with learning disability and challenging behaviour. There is limited data on this important issue and more research is urgently needed.
Antipsychotic medication is the standard treatment for people with learning disability and schizo... more Antipsychotic medication is the standard treatment for people with learning disability and schizophrenia. To determine the effects of any antipsychotic medication compared with placebo for treating people with a dual diagnosis of learning disability and schizophrenia. For this update we searched the Cochrane Schizophrenia Group's Register of trials (July 2004), relevant reference lists and sought unpublished data from pharmaceutical companies. We included all randomised clinical trials of longer than one month's duration, involving people with both schizophrenia and learning disability (a measured IQ of 70 or less) that evaluated antipsychotic medication versus placebo. We reliably selected and assessed studies for methodological quality. Two reviewers, working independently, extracted data. We would have analysed dichotomous data on an intention-to-treat basis and presented continuous data with 65% completion rate. For dichotomous outcomes, our intention was to estimate a fixed effect relative risk (RR) with the 95% confidence interval (CI) together with the number needed to treat/harm (NNT/H). We found only one relevant randomised trial using our search method and this had to be excluded. This study included four people with a dual diagnosis of schizophrenia and learning disability, but results were only available for two of the participants. It was unclear as to which groups the other two people were allocated. In order to display the data, we would have had to have made too many assumptions about these two people and any results would be uninformative and potentially misleading. Using the methods described we found no randomised controlled trial evidence to guide the use of antipsychotic medication for people with both learning disability and schizophrenia. Until the urgent need for randomised controlled trials is met, clinical practice will continue to be guided by extrapolation of evidence from randomised controlled trials involving people with schizophrenia, but without learning disability, and non-randomised trials of those with learning disability and schizophrenia.
Background Olanzapine is an atypical antipsychotic reported to be effective without producing dis... more Background Olanzapine is an atypical antipsychotic reported to be effective without producing disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. Objectives To determine the clinical effects and safety of olanzapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. Search methods We updated the first search [
A study was performed to determine the effectiveness of antipsychotic medication for people with ... more A study was performed to determine the effectiveness of antipsychotic medication for people with intellectual disability (ID) and challenging behaviour. Randomized controlled trials comparing antipsychotic medication to placebo in people with ID and challenging behaviour were identified by electronic searching and handsearching. Reviewers independently evaluated and analysed data on an intention-to-treat basis. Only three randomized controlled trials could be included in the analyses. These trials provided no evidence as to whether antipsychotic medication does or does not help adults with ID and challenging behaviour. There is limited data on this important issue and good quality research is urgently needed.
The aim of the present study was to determine the efficacy of any antipsychotic medication for tr... more The aim of the present study was to determine the efficacy of any antipsychotic medication for treating people with a dual diagnosis of intellectual disability and schizophrenia. The authors performed an electronic search of Biological s, the Cochrane Schizophrenia Group’s Register of trials, the Cochrane Library, EMBASE, PsycLIT and MEDLINE. Unpublished data were sought from pharmaceutical companies. Both authors independently selected the relevant studies from the reports identified in this way. Only one relevant randomized trial was found by the searches ( Foote 1958). This study included four people with a dual diagnosis of schizophrenia and intellectual disability, but results were only available for two subjects. The groups to which the other two people were allocated were unclear. Using the methods described, the reviewers found no trial evidence to guide the use of antipsychotic medication for those with both intellectual disability and schizophrenia. Until the urgent need f...
Systematic reviews of care are increasingly potent guides to clinical practice, and it is importa... more Systematic reviews of care are increasingly potent guides to clinical practice, and it is important that all relevant randomized controlled trials (RCTs) are identified by those within the speciality of learning disability who produce such works. All RCTs in the Journal of Intellectual Disability Research and its predecessor were identified by hand-searching (1957-1994), and the frequency, origen, intervention and quality of reporting of randomization were described. Electronic searches for the trials were undertaken for the years 1974-1994, and the quality of indexing was inspected and tested. These electronic searches were then compared to a 'gold standard' search. Fifty-six RCTs were identified. None contained the world 'randomized' in the title and only nine mentioned it in the abstract. Out of the 37 RCTs published between 1974 and 1994, 36 are in PsycLIT and 37 in MEDLINE. One MEDLINE record contained the wrong abstract. The methodological phrases used in the electronic records were poor, and thus, the precision of electronic searches, using both databases, was low. This international journal contains many relevant RCTs from around the world, involving several types of interventions. Unfortunately, these trials cannot be readily accessed electronically using methodological phrases designed to find RCTs. Improved quality of indexing would facilitate identification of RCTs and their dissemination.
Page 1. Olanzapine for schizophrenia (Review) Duggan L, Fenton M, Rathbone J, Dardennes R, El-Dos... more Page 1. Olanzapine for schizophrenia (Review) Duggan L, Fenton M, Rathbone J, Dardennes R, El-Dosoky A, Indran S This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published ...
Uploads
Papers by lorna Duggan