• Benzodiazepines for psychosis-induced aggression or agitation

      Rathbone, John (2005)
      Background: Acute psychotic illness, especiallywhen associatedwith agitated or violent behaviour, can require urgent pharmacological tranquillisation or sedation. In several countries, clinicians often use benzodiazepines (either alone or in combination with antipsychotics) for this outcome. Objectives: To estimate the effects of benzodiazepines, alone or in combination with antipsychotics, when compared to placebo or antipsychotics, to control disturbed behaviour and reduce psychotic symptoms. Search strategy: We searched the Cochrane Schizophrenia Group's register (October 2002 and April 2005), inspected reference lists of included and excluded studies and contacted authors of relevant studies. Selection criteria: We included all randomised clinical trials comparing benzodiazepines, alone or in combination with antipsychotics, with placebo or sole use of antipsychotics, for people with acute psychotic illnesses. Data collection and analysis We reliably selected studies, quality assessed themand extracted data. For binary outcomeswe calculated standard estimates of relative risk (RR) and their 95% confidence intervals (CI), and weighted number needed to treat or harm (NNT/NNH) statistics. For continuous outcomes we estimated a weighted mean difference between groups. If heterogeneity was found, we used a random effects model. Main results: We included eleven studies with a total of 648 participants. When comparing benzodiazepines with placebo, sedation was equally prevalent (n=102, 1 RCT, RR 1.67 CI 0.4 to 6.6), however, fewer people allocated lorazepam remained excited at 24 hours (n=102, RR 0.62 CI 0.4 to 1.0, NNT 5 CI 3 to 59). The lorazepam and placebo group experienced similar non-significant, low levels of adverse effects. In the comparison of benzodiazepines versus use of antipsychotics without use of anticholinergics/antihistamines, people allocated benzodiazepines did not clearly need additional medication compared with those given antipsychotics (n=216, 2 RCTs, RR 1.28 CI 0.5 to 3.2). Numbers sedated were also equivocal between groups (n=324, 6 RCTs, RR 0.76 CI 0.5 to 1.2) as were mental state ratings. Extrapyramidal symptoms were significantly higher in the antipsychotic treatment group (n=391, 7 RCTs, RR 0.17 CI 0.1 to 0.4, NNT 6 CI 2 to 17). Two trials (total n=83) comparing lorazepam plus haloperidol with lorazepam alone found no clear difference for the need of additional medication (n=83, 2 RCTs, RR 1.02 CI 0.8 to 1.3) or 'not improved' at one hour (n=20, 1 RCT, RR 1.47 CI 0.66 to 3.25). There was no difference in the incidence of extrapyramidal symptoms (n=83, 2 RCTs, RR 1.94 CI 0.2 to 20.3). Finally when the benzodiazepine plus antipsychotic combination was compared with antipsychotics alone (2 RCTs, n=95) there was no difference between groups in the need for additional medications (n=67, 1 RCT, RR 0.95 CI 0.8 to 1.2) or for mental state measures. Extrapyramidal symptoms were significantly lower for people receiving both benzodiazepines and antipsychotics compared with those receiving antipsychotics alone (n=95, 2 RCTs, RR 0.45 CI 0.2 to 0.9, NNH2 CI 1 to 5). There was no significant difference in the number of participants unfit for early discharge (n=28, 1 RCT, RR 0.90 CI 0.54 to 1.5). Authors' conclusions: There is insufficient data from these studies to support or refute the use of benzodiazepines with or without antipsychotics where emergency drugs are needed. The sole use of older antipsychotics unaccompanied by anticholinergic drugs may be problematic, but studies in this review are not large enough to identify any serious adverse effects of benzodiazepines such as respiratory depression. Larger, more informative studies are needed before definite conclusions can be drawn as to the efficacy of benzodiazapines. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
    • Bifeprunox versus placebo for schizophrenia

      Frey, Stephen; Green, Ghiselle (2016)
      Background: Bifeprunox is a novel antipsychotic drug designed to treat schizophrenia. However, research into the drug was ceased in 2009 due to rejection of licence to go to market by the US Food and Drug Administration (FDA), who could not approve the drug for acute or long-term symptoms of schizophrenia because more research was required to demonstrate convincing effects "beyond those already achieved" with currently licenced drugs. There were also concerns expressed over one death of a person whilst on the drug. Objectives: To investigate the clinical and adverse effects of bifeprunox for people with schizophrenia. Search methods: We searched the Cochrane Schizophrenia Group's Trials Register on 23 October 2015, which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and clinical trials registries. There are no language, date, document type, or publication status limitations for inclusion of records in the register. Selection criteria: All randomised clinical trials focusing on bifeprunox versus placebo for schizophrenia. Data collection and analysis: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effects model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. Main results: We included four randomised controlled trials (RCTs). We found evidence of missing data and poor reporting. When bifeprunox 20 mg was compared with placebo for schizophrenia, the drug resulted in a reduction of the Positive and Negative Syndrome Scale (PANSS) positive subscale score regarding positive symptoms (n = 549, 2 RCTs, MD -1.89, 95% CI -2.85 to -0.92, low-quality evidence) and the PANSS negative subscale regarding negative symptoms (n = 549, 2 RCTs, MD -1.53, 95% CI -2.37 to -0.69, low-quality evidence). There was a clear improvement regarding deterioration in the bifeprunox 20 mg group (n = 231, 1 RCT, RR 0.71 95% CI, 0.54 to 0.93, very low-quality evidence). The total number of participants with equal to or greater than 7% weight increase was similar between bifeprunox and placebo (n = 483, 1 RCT, RR 1.02 95% CI 0.31 to 3.33 moderate-quality evidence). There were no useable data for quality of life, economic outcomes, and service use. Authors' conclusions: Our results showed some positive effects and a favourable adverse effect profile for bifeprunox, although there were few data overall and none were of high quality. It would seem that these data alone would not have been enough for the FDA to decide to halt progress of the drug to market. We can only assume that we are missing important data. Both the FDA and the relevant pharmaceutical companies have not made all relevant data accessible. As some of these trials also involved an additional haloperidol, olanzapine, quetiapine, or risperidone arm, these data are not only relevant to evaluation of bifeprunox. In not making all data accessible, it is hard to see how the FDA and the drug companies have fulfilled their full obligations to people with schizophrenia or their clinicians. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
    • Bifeprunox vs placebo for schizophrenia

      Frey, Stephen; Green, Ghiselle; Harkness, Alexandra; McDermott, Alice; Yates, Anna (2016)
      This article reviews the effects of bifeprunox compared with placebo for schizophrenia. The results from this review alone show some positive effects and favorable adverse effect profile for bifeprunox— although there are few data overall and none are of high quality. These data alone would not seem to have been enough for the FDA to make their decision to halt progress of the drug to market. One can only assume that we are missing important data. Both the FDA and the relevant pharmaceutical companies have not made all relevant data accessible. Because some of these trials also involved an additional haloperidol, olanzapine, quetiapine, or risperidone arm, these data are relevant to not only to evaluation of bifeprunox. In not making all data accessible it is hard to see how the FDA and the drug companies have fulfilled their full obligations to people with schizophrenia or their clinicians. (PsycINFO Database Record (c) 2017 APA, all rights reserved)
    • "Brain Connectivity Deviates by Sex and Hemisphere in the First Episode of Schizophrenia"—A Route to the Genetic Basis of Language and Psychosis?

      Palaniyappan, Lena (2019)
      Schizophrenia is genetic in origin and associated with a fecundity disadvantage. The deficits in schizophrenia have been attributed to variation related to the human capacity for language or brain laterality. How sex influences the relative connectivity of the 2 hemispheres is a route to understanding these 2 functions. Using resting-state functional magnetic resonance imaging (fMRI) we searched for sex- and hemisphere-specific changes in whole-brain functional-connectivity in multi-site datasets (altogether 672 subjects including 286 patients, all right-handed) in the first-episode schizophrenia (illness duration ≤ 1 year, mostly drug naive) and in chronic stages of schizophrenia (illness duration > 1 year), respectively. We used meta-analyses to integrate data from different sources concerning individuals at the same illness stage. We found first-episode male patients are predominantly left-lateralized in aberrant connectivity with a focus on Broca's area. Female patients show a lesser degree of lateralization than males, but to the right particularly in orbital frontal cortex. In the chronic stage, the focus of aberrant connectivity shifted from anterior to posterior structures with prominent involvement of the thalamus and pre- and post-central gyri bilaterally and in both sexes. While the "deviant connectivity" is right-sided in both the first-episode and the chronic stages in females, in males there is a shift between stages from the left to the right hemisphere. We hypothesized that the pathophysiology of schizophrenia may lie in the interaction between sex and lateralization, ie, in genetic mechanisms located on the X and Y chromosomes, intrinsic to the evolution of language.
    • Brain-wide analysis of functional connectivity in first-episode and chronic stages of schizophrenia

      Palaniyappan, Lena (2016)
      Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naive), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.
    • Brief family intervention for schizophrenia

      Adams, Clive E. (2012)
      This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of brief family interventions for people with schizophrenia or schizophrenia-like conditions
    • Bromperidol decanoate (depot) for schizophrenia

      Adams, Clive E. (2011)
      Background: Antipsychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of long-term maintenance treatment. Objectives: To assess the effects of depot bromperidol versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. Search methods: For this 2011 update we searched the Cochrane Schizophrenia Group's Register (February 2011). Selection criteria: We sought all randomised trials focusing on people with schizophrenia where depot bromperidol, oral antipsychotics or other depot preparations. Primary outcomes were clinically significant change in global function, service utilisation outcomes (hospital admission, days in hospital), relapse. Data collection and analysis: For this 2011 update MP independently extracted data, CEA carried out the reliability check. We calculated fixed-effect risk ratios (RR) and 95% confidence intervals (CI) for dichotomous data, and calculated weighted or standardised means for continuous data. Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat. Main results: We have included no new trials in this 2011 update (4 RCTs, total n = 117). A single, small study of six months' duration compared bromperidol decanoate with placebo injection. Similar numbers left the study before completion (n = 20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there were no clear differences between bromperidol decanoate and placebo for a list of adverse effects (n = 20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69). When bromperidol decanoate was compared with fluphenazine depot, we found no important change on global outcome (n = 30, RR no clinical important improvement 1.50 CI 0.29 to 7.73). People allocated to fluphenazine decanoate and haloperidol decanoate had fewer relapses than those given bromperidol decanoate (n = 77, RR 3.92 Cl 1.05 to 14.60, NNH 6 CI 2 to 341). People allocated bromperidol decanoate required additional antipsychotic medication somewhat more frequently than those taking fluphenazine decanoate and haloperidol decanoate, but the results did not reach conventional levels of statistical significance (n = 77, 2 RCTs, RR 1.72 CI 0.7 to 4.2). The use of benzodiazepine drugs was very similar in both groups (n = 77, 2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol decanoate group more frequent than those taking other depot preparation due to any cause (n = 97, 3 RCTs, RR 2.17 CI 1.00 to 4.73). Anticholinergic adverse effects were equally common between bromperidol and other depots (n = 47, RR 3.13 CI 0.7 to 14.0) and additional anticholinergic medication was needed with equal frequency in both depot groups, although results did tend to favour the bromperidol decanoate group (n = 97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders was similar in both depot groups (n = 77, 2 RCTs, RR 0.74 CI 0.47 to 1.17). Authors' conclusions: Minimal poorly reported trial data suggests that bromperidol decanoate may be better than placebo injection but less valuable than fluphenazine or haloperidol decanoate. If bromperidol decanoate is available it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol decanoate. Well-conducted and reported randomised trials are needed to inform practice.
    • Bromperidol decanoate (depot) for schizophrenia

      Adams, Clive E. (2012)
      Antipsychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of long-term maintenance treatment. To assess the effects of depot bromperidol versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. For this 2012 update we searched the Cochrane Schizophrenia Group's Register (February 2012). We sought all randomised trials focusing on people with schizophrenia where depot bromperidol, oral antipsychotics or other depot preparations. Primary outcomes were clinically significant change in global function, service utilisation outcomes (hospital admission, days in hospital), relapse. For the 2011 update MP independently extracted data, CEA carried out the reliability check. We calculated fixed-effect risk ratios (RR) and 95% confidence intervals (CI) for dichotomous data, and calculated weighted or standardised means for continuous data. Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat.For the 2012 update, data collection and analysis was not carried out as no new studies were found. The 2012 search found no new studies, we have therefore included no new trials in this 2012 update. The number of included trials remain 4 RCTs, total n = 117. A single, small study of six months' duration compared bromperidol decanoate with placebo injection. Similar numbers left the study before completion (n = 20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there were no clear differences between bromperidol decanoate and placebo for a list of adverse effects (n = 20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69). When bromperidol decanoate was compared with fluphenazine depot, we found no important change on global outcome (n = 30, RR no clinical important improvement 1.50 CI 0.29 to 7.73). People allocated to fluphenazine decanoate and haloperidol decanoate had fewer relapses than those given bromperidol decanoate (n = 77, RR 3.92 Cl 1.05 to 14.60, NNH 6 CI 2 to 341). People allocated bromperidol decanoate required additional antipsychotic medication somewhat more frequently than those taking fluphenazine decanoate and haloperidol decanoate, but the results did not reach conventional levels of statistical significance (n = 77, 2 RCTs, RR 1.72 CI 0.7 to 4.2). The use of benzodiazepine drugs was very similar in both groups (n = 77, 2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol decanoate group more frequent than those taking other depot preparation due to any cause (n = 97, 3 RCTs, RR 2.17 CI 1.00 to 4.73). Anticholinergic adverse effects were equally common between bromperidol and other depots (n = 47, RR 3.13 CI 0.7 to 14.0) and additional anticholinergic medication was needed with equal frequency in both depot groups, although results did tend to favour the bromperidol decanoate group (n = 97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders was similar in both depot groups (n = 77, 2 RCTs, RR 0.74 CI 0.47 to 1.17). Minimal poorly reported trial data suggests that bromperidol decanoate may be better than placebo injection but less valuable than fluphenazine or haloperidol decanoate. If bromperidol decanoate is available it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol decanoate. Well-conducted and reported randomised trials are needed to inform practice.
    • Calcium channel blockers for neuroleptic-induced tardive dyskinesia

      Adams, Clive E. (2011)
      Background: Schizophrenia and related disorders affect a sizable proportion of any population. Neuroleptic (antipsychotic) medications are the primary treatment for these disorders. Neuroleptic medications are associated with a variety of side effects including tardive dyskinesia. Dyskinesia is a disfiguring movement disorder of the orofacial region that can be tardive (having a slow or belated onset). Tardive dyskinesia is difficult to treat, despite experimentation with several treatments. Calcium channel blockers (diltiazem, nifedipine, nimodipine, verapamil) have been among these experimental treatments. Objectives: To determine the effects of calcium-channel blocker drugs (diltiazem, nifedipine, nimodipine, verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses. Search methods: We updated previous searches in May 2010 by searching the Cochrane Schizophrenia Group Register using the Cochrane Schizophrenia Group search strategy. Selection criteria: Randomised clinical trials comparing calcium-channel blockers with placebo, no intervention or any other intervention for people with both tardive dyskinesia and schizophrenia or serious mental illness. Data collection and analysis: We planned to extract and analyse data on an intention-to-treat (ITT) basis. We intended to calculate the relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data using a random-effects model, and, where possible, calculate the number needed to treat. We planned to calculate mean differences (MD) for continuous data. Main results: We did not include any trials in this review. We excluded 15 studies; eight were not randomised, one did not use calcium channel blockers, five small, randomised, studies reported no usable data and one did not include people with both tardive dyskinesia and schizophrenia. Authors' conclusions: The effects of calcium-channel blockers for antipsychotic induced tardive dyskinesia are unknown. Their use is experimental and should only be given in the context of well designed randomised clinical trials.
    • Cannabis use linked to altered functional connectivity of the visual attentional connectivity in patients with psychosis and controls

      Sami, Musa (2020)
      Background: Both chronic cannabis use and psychotic disorders are associated with abnormalities in visual attentional processing. Using functional magnetic resonance imaging (fMRI), we sought to determine whether there would be a difference in functional connectivity in patients and controls with and without a history of cannabis use in the visual and dorsal attention networks. Methods: Resting-state fMRI data were acquired in patients with early psychosis with (EPC = 29) and without (EPNC = 25); and controls with (HCC = 16) and without (HCNC = 22) cannabis use. Results: There was a patient effect in both Visual-Dorsal Attention Internetwork (F(1,87) = 5.326, P = .023) and the Visual Network (F(1,87) = 4.044, P = .047) and a cannabis effect in the Dorsal Attention Network (F(1,87) = 4.773, P = .032). These effects were specific to the networks examined with no evidence for significant patient or cannabis effects in other canonical networks. Patients with a history of cannabis use showed increased connectivity in the Dorsal Attention Network (134%, P = .019) and Visual Dorsal Attention Internetwork (285%, P = .036) compared to non-using controls. In the EPC group connectivity of the Visual Network (ρ = 0.379, P = .042) and Visual-Dorsal Attention Internetwork (ρ = 0.421, P = .023) correlated with visual hallucinations which were significantly different from EPNC (P = .011). Dorsal attention network strength correlated with severity of dependence for cannabis (ρ = 0.215, P = .04). Conclusion: We demonstrate specific cannabis and patient effects in networks associated with visual attentional processing. There is a differential association with hallucinatory symptoms in patients with and without a history of cannabis use. This may indicate that dysconnectivity in these networks serves different roles in the context of cannabis use.
    • Cedars community: Using a therapeutic community approach in a high security hospital

      Davies, Steffan; Bennion, Lorna; McPhee, Dave; Osgerby, Catherine; Wylie, Bill (2005)
      This paper describes the establishment and first year of a therapeutic community (TC) for patients with treatment resistant psychosis at a high security psychiatric hospital. We outline the contributions of different members of the multi-disciplinary team, the ward programme and look at the outcomes after the first year. © The Authors.
    • Characterization of hemodynamic alterations in schizophrenia and bipolar disorder and their effect on resting-state fMRI functional connectivity

      Liddle, Peter F. (2021)
      Common and distinct neural bases of Schizophrenia (SZ) and bipolar disorder (BP) have been explored using resting-state fMRI (rs-fMRI) functional connectivity (FC). However, fMRI is an indirect measure of neural activity, which is a convolution of the hemodynamic response function (HRF) and latent neural activity. The HRF, which models neurovascular coupling, varies across the brain within and across individuals, and is altered in many psychiatric disorders. Given this background, this study had three aims: quantifying HRF aberrations in SZ and BP, measuring the impact of such HRF aberrations on FC group differences, and exploring the genetic basis of HRF aberrations. We estimated voxel-level HRFs by deconvolving rs-fMRI data obtained from SZ (N = 38), BP (N = 19), and matched healthy controls (N = 35). We identified HRF group differences (P < .05, FDR corrected) in many regions previously implicated in SZ/BP, with mediodorsal, habenular, and central lateral nuclei of the thalamus exhibiting HRF differences in all pairwise group comparisons. Thalamus seed-based FC analysis revealed that ignoring HRF variability results in false-positive and false-negative FC group differences, especially in insula, superior frontal, and lingual gyri. HRF was associated with DRD2 gene expression (P < .05, 1.62 < |Z| < 2.0), as well as with medication dose (P < .05, 1.75 < |Z| < 3.25). In this first study to report HRF aberrations in SZ and BP, we report the possible modulatory effect of dopaminergic signalling on HRF, and the impact that HRF variability can have on FC studies in clinical samples. To mitigate the impact of HRF variability on FC group differences, we suggest deconvolution during data preprocessing.
    • Childhood abuse and psychosis; a critical review of the literature

      Manning, Claire (2009)
      Childhood trauma has long been recognised as a potential cause for a range of affective mental health problems arising in adulthood. Only in recent years has the association between childhood abuse and psychosis begun to be investigated. This paper provides a critical review of the literature addressing the relationship between childhood abuse and psychosis. Implications for practitioners are discussed, including practice, policy, treatment and child protection issues. A significant proportion of people develop psychosis in adulthood following all types of childhood abuse, including people diagnosed with schizophrenia, major depressive disorders, dissociative identity disorder and post-traumatic stress disorder. Evidence suggests the possibility of a causal relationship between childhood abuse and psychosis in adulthood. Mental health nurses are ideally placed to offer help, care and support to those individuals who experience psychosis by acknowledging and listening to their life events, including experiences of childhood abuse.
    • Childhood risk factors for offending before first psychiatric admission for people with schizophrenia: A case-control study of high security hospital admissions

      Ferriter, Michael (2010)
      Background: People with schizophrenia who offend do not constitute a homogenous population. Pre-illness characteristics may distinguish groups. Aims: To test for differences in prevalence of childhood risk factors for offending between serious offenders with schizophrenia who had started offending before their first ever psychiatric admission (pre-admission offenders) and those who had started after it (post-admission offenders). Our hypothesis was that such adverse childhood factors would be more prevalent in the pre-admission offenders. Method: Retrospective interview and records case-control study of all first high security hospital admissions diagnosed with schizophrenia in England 1972-2000. Risk factors were identified by multivariate logistic regression. Results: 853 patients were pre- and 741 post-admission offenders. Our hypothesis was confirmed in that factors associated with pre-admission offending were paternal criminal convictions, larger family size, and younger age at first use of illicit drugs, on first smoking cigarettes, and at maternal separation. There were differences too in pre-high security hospital treatment: pre-admission offenders had been younger at first court appearance and had more criminal justice system disposals, post-admission offenders were younger at first ever psychiatric hospital admission and more often hospitalized. Conclusions: While early offending among people with schizophrenia may delay treatment, making the distinction between pre-admission and post-admission offending may be useful in understanding the aetiology of the offending, and establishment of such a history may help in targeting interventions supplementary to treatment specific for die psychosis. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
    • Chlorpromazine dose for people with schizophrenia

      Dudley, Katharine (2017)
      BACKGROUND: The World Health Organization (WHO) Model Lists of Essential Medicines lists chlorpromazine as one of its five medicines used in psychotic disorders. OBJECTIVES: To determine chlorpromazine dose response and dose side-effect relationships for schizophrenia and schizophrenia-like psychoses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (December 2008; 2 October 2014; 19 December 2016). SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) comparing low doses of chlorpromazine (</= 400 mg/day), medium dose (401 mg/day to 800 mg/day) or higher doses (> 800 mg/day) for people with schizophrenia, and which reported clinical outcomes. DATA COLLECTION AND ANALYSIS: We included studies meeting review criteria and providing useable data. Review authors extracted data independently. For dichotomous data, we calculated fixed-effect risk ratios (RR) and their 95% confidence intervals (CIs). For continuous data, we calculated mean differences (MD) and their 95% CIs based on a fixed-effect model. We assessed risk of bias for included studies and graded trial quality using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: As a result of searches undertaken in 2014, we found one new study and in 2016 more data for already included studies. Five relevant studies with 1132 participants (585 are relevant to this review) are now included. All are hospital-based trials and, despite over 60 years of chlorpromazine use, have durations of less than six months and all are at least at moderate risk of bias. We found only data on low-dose (</= 400 mg/day) versus medium-dose chlorpromazine (401 mg/day to 800 mg/day) and low-dose versus high-dose chlorpromazine (> 800 mg/day).When low-dose chlorpromazine (</= 400 mg/day) was compared to medium-dose chlorpromazine (401 mg/day to 800 mg/day), there was no clear benefit of one dose over the other for both global and mental state outcomes (low-quality and very low-quality evidence). There was also no clear evidence for people in one dosage group being more likely to leave the study early, over the other dosage group (moderate-quality evidence). Similar numbers of participants from each group experienced agitation and restlessness (very low-quality evidence). However, significantly more people in the medium-dose group (401 mg/day to 800 mg/day) experienced extrapyramidal symptoms in the short term (2 RCTS, n = 108, RR 0.47, 95% CI 0.30 to 0.74, moderate-quality evidence). No data for death were available.When low-dose chlorpromazine (</= 400 mg/day) was compared to high-dose chlorpromazine (> 800 mg/day), data from one study with 416 patients were available. Clear evidence of a benefit of the high dose was found with regards to global state. The low-dose group had significantly fewer people improving (RR 1.13, 95% CI 1.01 to 1.25, moderate-quality evidence). There was also a marked difference between the number of people leaving the study from each group for any reason, with significantly more people leaving from the high-dose group (RR 0.60, 95% CI 0.40 to 0.89, moderate-quality evidence). More people in the low-dose group had to leave the study due to deterioration in behaviour (RR 2.70, 95% CI 1.34 to 5.44, low-quality evidence). There was clear evidence of a greater risk of people experiencing extrapyramidal symptoms in general in the high-dose group (RR 0.43, 95% CI 0.32 to 0.59, moderate-quality evidence). One death was reported in the high-dose group yet no effect was shown between the two dosage groups (RR 0.33, 95% CI 0.01 to 8.14, moderate-quality evidence). No data for mental state were available. AUTHORS' CONCLUSIONS: The dosage of chlorpromazine has changed drastically over the past 50 years with lower doses now being the preferred of choice. However, this change was gradual and arose not due to trial-based evidence, but due to clinical experience and consensus. Chlorpromazine is one of the most widely used antipsychotic drugs yet appropriate use of lower levels has come about after many years of trial and error with much higher doses. In the absence of high-grade evaluative studies, clinicians have had no alternative but to learn from experience. However, such an approach can lack scientific rigor and does not allow for proper dissemination of information that would assist clinicians find the optimum treatment dosage for their patients. In the future, data for recently released medication should be available from high-quality trials and studies to provide optimum treatment to patients in the shortest amount of time.
    • Chlorpromazine for psychosis induced aggression or agitation

      Gul, Muhammad; Ahmed, Uzair; Adams, Clive E. (2008)
      Background: Agitated or violent behaviour constitutes 10% of all emergency psychiatric treatment. Some guidelines do not recommend the use of chlorpromazine for rapid tranquillisation but it is still often used for this purpose. Objectives: To examine the effects of oral or intramuscular chlorpromazine for psychosis induced agitation or aggression. Search methods: We searched the Cochrane Schizophrenia Group Trials Register (up to July 2009) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. Selection criteria: Randomised control trials or double blind trials (implying randomisation) comparing chlorpromazine with another drug or placebo for people who are thought to be acutely aggressive or agitated due to psychotic illness. Data collection and analysis: 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 fixed-effects model. Main results: One study (total n=30) met the inclusion criteria. When compared with haloperidol (Man 1973) (1 RCT, n=30) people allocated chlorpromazine were no more likely to have one additional injection than those allocated haloperidol (RR 3.00 CI 0.13 to 68.26). This remained true for 2-4 injections (RR 0.90 CI 0.52 to 1.55) and for 5 or more injections (RR 0.75 CI 0.20 to 2.79). Two people allocated chlorpromazine had sudden, serious hypotension while no one allocated haloperidol had such an effect (RR 5.00 CI 0.26 to 96.13). No extrapyramidal symptoms were observed. One person allocated chlorpromazine developed status epilepticus (RR 3.00 CI 0.13 to 68.26). Authors' conclusions: Overall the quality of evidence is limited, poor and dated. Where drugs that have been better evaluated are available, it may be best to avoid use of chlorpromazine. Where chlorpromazine is used for acute aggression or where choices are limited, relevant trials are possible and urgently needed.
    • Chlorpromazine for psychosis induced aggression or agitation

      Jones, Hannah F.; Adams, Clive E. (2010)
      Background Agitated or violent behaviour constitutes 10% of all emergency psychiatric treatment. Some guidelines do not recommend the use of chlorpromazine for rapid tranquillisation but it is still often used for this purpose. Objectives To examine the effects of oral or intramuscular chlorpromazine for psychosis induced agitation or aggression. Search strategy We searched the Cochrane Schizophrenia Group Trials Register (up to July 2009) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. Selection criteria Randomised control trials or double blind trials (implying randomisation) comparing chlorpromazine with another drug or placebo for people who are thought to be acutely aggressive or agitated due to psychotic illness. Data collection and analysis 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 fixed-effects model. Main results One study (total n=30) met the inclusion criteria. When compared with haloperidol (Man 1973) (1 RCT, n=30) people allocated chlorpromazine were no more likely to have one additional injection than those allocated haloperidol (RR 3.00 CI 0.13 to 68.26). This remained true for 2-4 injections (RR 0.90 CI 0.52 to 1.55) and for 5 or more injections (RR 0.75 CI 0.20 to 2.79). Two people allocated chlorpromazine had sudden, serious hypotension while no one allocated haloperidol had such an effect (RR 5.00 CI 0.26 to 96.13). No extrapyramidal symptoms were observed. One person allocated chlorpromazine developed status epilepticus (RR 3.00 CI 0.13 to 68.26). Authors' conclusions Overall the quality of evidence is limited, poor and dated. Where drugs that have been better evaluated are available, it may be best to avoid use of chlorpromazine. Where chlorpromazine is used for acute aggression or where choices are limited, relevant trials are possible and urgently needed.
    • Chlorpromazine for psychosis-induced aggression or agitation

      Jones, Hannah F.; Adams, Clive E. (2011)
      This article aims to examine whether chlorpromazine oral or intramuscular is an effective treatment for psychosis-induced agitation or aggression. We searched the Cochrane Schizophrenia Group Trials Register, which is based on regular searches of several databases. For dichotomous data, we calculated relative risks (RR) and their 95% CI on an intention-to-treat basis based on a fixed-effects model. Overall, the quality of evidence is limited, poor, and dated. Chlorpromazine was just as effective at reducing aggression due to psychosis as similar medicines, but this finding is only based on one small study. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
    • Chlorpromazine versus atypical antipsychotic drugs for schizophrenia

      Xia, Jun; Sampson, Stephanie (2020)
      Background: Chlorpromazine is an aliphatic phenothiazine, which is one of the widely‐used typical antipsychotic drugs. Chlorpromazine is reliable for its efficacy and one of the most tested first generation antipsychotic drugs. It has been used as a ‘gold standard’ to compare the efficacy of older and newer antipsychotic drugs. Expensive new generation drugs are heavily marketed worldwide as a better treatment for schizophrenia, but this may not be the case and an unnecessary drain on very limited resources. Objectives: To compare the effects of chlorpromazine with atypical or second generation antipsychotic drugs, for the treatment of people with schizophrenia. Search methods: We searched the Cochrane Schizophrenia Group's Trials Register up to 23 September 2013. Selection criteria: We included randomised controlled trials (RCTs) that compared chlorpromazine with any other atypical antipsychotic drugs for treating people with schizophrenia. Adults (as defined in each trial) diagnosed with schizophrenia, including schizophreniform, schizoaffective and delusional disorders were included in this review. Data collection and analysis: At least two review authors independently screened the articles identified in the literature search against the inclusion criteria and extracted data from included trials. For homogeneous dichotomous data, we calculated the risk ratio (RR) and the 95% confidence intervals (CIs). For continuous data, we determined the mean difference (MD) values and 95% CIs. We assessed the risk of bias in included studies and rated the quality of the evidence using the GRADE approach. Main results: This review includes 71 studies comparing chlorpromazine to olanzapine, risperidone or quetiapine. None of the included trials reported any data on economic costs. 1. Chlorpromazine versus olanzapine In the short term, there appeared to be a significantly greater clinical response (as defined in each study) in people receiving olanzapine (3 RCTs, N = 204; RR 2.34, 95% CI 1.37 to 3.99, low quality evidence). There was no difference between drugs for relapse (1 RCT, N = 70; RR 1.5, 95% CI 0.46 to 4.86, very low quality evidence), nor in average endpoint score using the Brief Psychiatric Rating Scale (BPRS) for mental state (4 RCTs, N = 245; MD 3.21, 95% CI −0.62 to 7.05,very low quality evidence). There were significantly more extrapyramidal symptoms experienced amongst people receiving chlorpromazine (2 RCTs, N = 298; RR 34.47, 95% CI 4.79 to 248.30,very low quality evidence). Quality of life ratings using the general quality of life interview (GQOLI) ‐ physical health subscale were more favourable with people receiving olanzapine (1 RCT, N = 61; MD −10.10, 95% CI −13.93 to −6.27, very low quality evidence). There was no difference between groups for people leaving the studies early (3 RCTs, N = 139; RR 1.69, 95% CI 0.45 to 6.40, very low quality evidence). 2. Chlorpromazine versus risperidone In the short term, there appeared to be no difference in clinical response (as defined in each study) between chlorpromazine or risperidone (7 RCTs, N = 475; RR 0.84, 95% CI 0.53 to 1.34, low quality of evidence), nor in average endpoint score using the BPRS for mental state 4 RCTs, N = 247; MD 0.90, 95% CI −3.49 to 5.28, very low quality evidence), or any observed extrapyramidal adverse effects (3 RCTs, N = 235; RR 1.7, 95% CI 0.85 to 3.40,very low quality evidence). Quality of life ratings using the QOL scale were significantly more favourable with people receiving risperidone (1 RCT, N = 100; MD −14.2, 95% CI −20.50 to −7.90, very low quality evidence). There was no difference between groups for people leaving the studies early (one RCT, N = 41; RR 0.21, 95% CI 0.01 to 4.11, very low quality evidence). 3. Chlorpromazine versus quetiapine In the short term, there appeared to be no difference in clinical response (as defined in each study) between chlorpromazine or quetiapine (28 RCTs, N = 3241; RR 0.93, 95% CI 0.81 to 1.06, moderate quality evidence) nor in average endpoint score using the BPRS for mental state (6 RCTs, N = 548; MD −0.18, 95% CI −1.23 to 0.88, very low quality evidence). Quality of life ratings using the GQOL1‐74 scale were significantly more favourable with people receiving quetiapine (1 RCT, N = 59; MD −6.49, 95% CI −11.30 to −1.68, very low quality evidence). Significantly more people receiving chlorpromazine experienced extrapyramidal adverse effects (8 RCTs, N = 644; RR 8.03, 95% CI 4.78 to 13.51, low quality of evidence). There was no difference between groups for people leaving the studies early in the short term (12 RCTs, N = 1223; RR 1.04, 95% CI 0.77 to 1.41,moderate quality evidence). Authors' conclusions: Most included trials included inpatients from hospitals in China. Therefore the results of this Cochrane review are more applicable to the Chinese population. Mostincluded trials were short term studies, therefore we cannot comment on the medium and long term use of chlorpromazine compared to atypical antipsychotics. Low qualityy evidence suggests chlorpromazine causes more extrapyramidal adverse effects. However, all studiesused varying dose ranges, and higher doses would be expected to be associated with more adverse events.