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The Cochrane Database of Systematic... 2000Pimozide was first formulated in the late 1960s and continues to be marketed for the care of those with schizophrenia or related psychoses such as delusional disorder.... (Review)
Review
BACKGROUND
Pimozide was first formulated in the late 1960s and continues to be marketed for the care of those with schizophrenia or related psychoses such as delusional disorder. Pimozide is generally well tolerated apart from extrapyramidal side effects. It has, however, been associated with cardiotoxicity and sudden unexplained deaths and electrocardiogram monitoring is now required before and during its use.
OBJECTIVES
To assess the effects of pimozide for people with schizophrenia, non-affective psychotic mental illness and delusional disorder in terms of clinical, social and economic outcomes.
SEARCH STRATEGY
Electronic searches of Biological Abstracts (1982-1995), The Cochrane Schizophrenia Group's Register, EMBASE (1980-1995), Janssen-Cilag UK's register of studies (1999), MEDLINE (1966-1995), PsycLIT (1974-1995), hand-searching the references of all included studies and contacting the manufacturers of the compound.
SELECTION CRITERIA
All randomised trials relating to people with schizophrenia, or similar disorders comparing pimozide to other drug treatments were sought. Studies where randomisation was implied rather than stated were included if they did not change the results. Primary outcomes were clinically significant change in global function, mental state, relapse, hospital admission, death, adverse events and acceptability of treatment.
DATA COLLECTION AND ANALYSIS
Studies were selected, rated and data extracted. For dichotomous data Relative Risks (RR) based on a random effects model with 95% confidence intervals (CI) were estimated. The number needed to treat statistic (NNT) was calculated where indicated. Analysis was by intention-to-treat.
MAIN RESULTS
This review currently includes 34 studies focusing on those with schizophrenia, none on people with delusional disorder. Few people have been randomised to pimozide versus placebo. Data from two longer term studies does suggest that the active drug prevents relapse (n=66, RR 0.45 CI 0.24-0.86, NNT 4, CI 3-22) but the confidence interval is wide. Pimozide has similar efficacy to that of typical antipsychotic drugs for the outcomes of change in global functioning, mental state, relapse and leaving the study early. People allocated to pimozide did not have a higher mortality than those taking other antipsychotics. Pimozide was more likely to cause parkinsonian tremor (RR 1.6 CI 1.1-2.3, NNH 6 CI 3-44) and lead to a requirement for antiparkinsonian medication more frequently (RR 1.8, CI 1.2-2.6, NNH 3 CI 2-5) than other drugs. It was, however, less likely to cause sedation (RR 0.38 CI 0.2-0.7, NNH 6 CI 4-16).
REVIEWER'S CONCLUSIONS
Although there are shortcomings in the data there is enough overall consistency, over different outcomes and time scales, to confirm that pimozide is a drug with similar efficacy to other more commonly used antipsychotics such as chlorpromazine for those with schizophrenia. There are no data to support or refute its use for those with delusional disorder.
Topics: Antipsychotic Agents; Humans; Pimozide; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology
PubMed: 10908518
DOI: 10.1002/14651858.CD001949 -
The Journal of Clinical Psychiatry Apr 2012To perform a meta-analysis of antidepressant-antipsychotic cotreatment versus antidepressant or antipsychotic monotherapy for psychotic depression. (Comparative Study)
Comparative Study Meta-Analysis Review
Are antipsychotics or antidepressants needed for psychotic depression? A systematic review and meta-analysis of trials comparing antidepressant or antipsychotic monotherapy with combination treatment.
OBJECTIVE
To perform a meta-analysis of antidepressant-antipsychotic cotreatment versus antidepressant or antipsychotic monotherapy for psychotic depression.
DATA SOURCES
We performed an electronic search (from inception of databases until February 28, 2011) in PubMed/MEDLINE, Cochrane Library, and PsycINFO, without language or time restrictions. Search terms were (psychosis OR psychotic OR hallucinations OR hallucinating OR delusions OR delusional) AND (depression OR depressed OR major depressive disorder) AND (random OR randomized OR randomly).
STUDY SELECTION
Eight randomized, placebo-controlled acute-phase studies in adults (N = 762) with standardized criteria-defined psychotic depression (including Research Diagnostic Criteria, DSM-III, DSM-IV, or ICD-10) were meta-analyzed, yielding 10 comparisons. Antidepressant-antipsychotic cotreatment was compared in 5 trials with 6 treatment arms (n = 337) with antidepressant monotherapy and in 4 trials with 4 treatment arms (n = 447) with antipsychotic monotherapy.
DATA EXTRACTION
Primary outcome was study-defined inefficacy; secondary outcomes included all-cause discontinuation, specific psychopathology ratings, and side effects. Using random effects models, we calculated relative risk (RR) with 95% confidence intervals (CIs), number-needed-to-treat/harm (NNT/NNH), and effect size (ES).
RESULTS
Antidepressant-antipsychotic cotreatment outperformed antidepressant monotherapy regarding less study-defined inefficacy (no. of comparisons = 6; n = 378; RR = 0.76; 95% CI, 0.59-0.98; P = .03; heterogeneity [I2] = 34%) (NNT = 7; 95% CI, 4-20; P = .009) and Clinical Global Impressions-Severity of Illness scores (no. of comparisons = 4; n = 289; ES = -0.25; 95% CI, -0.49 to -0.02; P = .03; I2 = 0%), with trend-level superiority for depression ratings (no. of comparisons = 5; n = 324; ES = -0.20; 95% CI, -0.44 to 0.03; P = .09; I2 = 10%), but not regarding psychosis ratings (no. of comparisons = 3; n = 161; ES = -0.24; 95% CI, -0.85 to 0.38; P = .45; I2 = 70%). Antidepressant-antipsychotic cotreatment also outperformed antipsychotic monotherapy regarding less study-defined inefficacy (no. of comparisons = 4; n = 447; RR = 0.73; 95% CI, 0.63-0.84; P < .0001; I2 = 0%) (NNT = 5; 95% CI, 4-8; P < .0001) and depression ratings (no. of comparisons = 4; n = 428; ES = -0.49; 95% CI, -0.75 to -0.23; P = .0002; I2 = 27%), while anxiety (P = .11) and psychosis (P = .06) ratings only trended toward favoring cotreatment. All-cause discontinuation and reported side-effect rates were similar, except for more somnolence with antidepressant-antipsychotic cotreatment versus antidepressants (P = .02). Only 1 open-label, 4-month extension study (n = 59) assessed maintenance/relapse-prevention efficacy of antidepressant-antipsychotic cotreatment versus antidepressant monotherapy, without group differences.
CONCLUSIONS
Antidepressant-antipsychotic cotreatment was superior to monotherapy with either drug class in the acute treatment of psychotic depression. These results support recent treatment guidelines, but more studies are needed to assess specific combinations and maintenance/relapse-prevention efficacy.
Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Drug Therapy, Combination; Humans; Psychotic Disorders; Treatment Outcome
PubMed: 22579147
DOI: 10.4088/JCP.11r07324 -
L'Encephale Dec 2009Tragic and high profile killings by people with mental illness have been used to suggest that the community care model for mental health services has failed. It is also... (Review)
Review
INTRODUCTION
Tragic and high profile killings by people with mental illness have been used to suggest that the community care model for mental health services has failed. It is also generally thought that schizophrenia predisposes subjects to homicidal behaviour.
OBJECTIVE
The aim of the present paper was to estimate the rate of mental disorder in people convicted of homicide and to examine the relationship between definitions. We investigated the links between homicide and major mental disorders.
METHODS
This paper reviews studies on the epidemiology of homicide committed by mentally disordered people, taken from recent international academic literature. The studies included were identified as part of a wider systematic review of the epidemiology of offending combined with mental disorder. The main databases searched were Medline. A comprehensive search was made for studies published since 1990.
RESULTS
There is an association of homicide with mental disorder, most particularly with certain manifestations of schizophrenia, antisocial personality disorder and drug or alcohol abuse. However, it is not clear why some patients behave violently and others do not. Studies of people convicted of homicide have used different definitions of mental disorder. According to the definition of Hodgins, only 15% of murderers have a major mental disorder (schizophrenia, paranoia, melancholia). Mental disorder increases the risk of homicidal violence by two-fold in men and six-fold in women. Schizophrenia increases the risk of violence by six to 10-fold in men and eight to 10-fold in women. Schizophrenia without alcoholism increased the odds ratio more than seven-fold; schizophrenia with coexisting alcoholism more than 17-fold in men. We wish to emphasize that all patients with schizophrenia should not be considered to be violent, although there are minor subgroups of schizophrenic patients in whom the risk of violence may be remarkably high. According to studies, we estimated that this increase in risk could be associated with a paranoid form of schizophrenia and coexisting substance abuse. The prevalence of schizophrenia in the homicide offenders is around 6%. Despite this, the prevalence of personality disorder or of alcohol abuse/dependence is higher: 10% to 38% respectively. The disorders with the most substantially higher odds ratios were alcohol abuse/dependence and antisocial personality disorder. Antisocial personality disorder increases the risk over 10-fold in men and over 50-fold in women. Affective disorders, anxiety disorders, dysthymia and mental retardation do not elevate the risk. Hence, according to the DMS-IV, 30 to 70% of murderers have a mental disorder of grade I or a personality disorder of grade II. However, many studies have suffered from methodological weaknesses notably since obtaining comprehensive study groups of homicide offenders has been difficult.
CONCLUSIONS
There is an association of homicide with mental disorder, particularly with certain manifestations of schizophrenia, antisocial personality disorder and drug or alcohol abuse. Most perpetrators with a history of mental disorder were not acutely ill or under mental healthcare at the time of the offence. Homicidal behaviour in a country with a relatively low crime rate appears to be statistically associated with some specific mental disorders, classified according to the DSM-IV-TR classifications.
Topics: Alcoholism; Antisocial Personality Disorder; Comorbidity; Cross-Sectional Studies; Dangerous Behavior; Female; Homicide; Humans; Incidence; Male; Odds Ratio; Risk Factors; Schizophrenia; Schizophrenic Psychology; Substance-Related Disorders; Violence
PubMed: 20004282
DOI: 10.1016/j.encep.2008.10.009 -
Psychopathology 2019Capgras' delusion has captured psychiatrists' imaginations, but the clinical features of the delusion have rarely been studied and presented systematically.
BACKGROUND
Capgras' delusion has captured psychiatrists' imaginations, but the clinical features of the delusion have rarely been studied and presented systematically.
AIMS
The present study systematically reviews all case reports on Capgras' delusion in the English language in order to better understand differences between organic and functional aetiologies.
METHODS
All medical and psychiatric databases were searched, as were the bibliographies of published case reports, narrative reviews, and book chapters.
RESULTS
A total of 258 cases were identified from 175 papers. Functional Capgras' delusion was more associated with a wider variety of imposters; multiple imposters; other misidentification syndromes; auditory hallucinations; other delusions; and formal thought disorder. Organic cases were associated with age; inanimate objects; memory and visual-spatial impairments; right hemispheric dysfunction; and visual hallucinations. Executive dysfunction and aggression were associated with both types.
CONCLUSIONS
Specific features of the -Capgras' delusional content and associated signs point to either organic or functional aetiology. The delusion is more amorphous than many theorists have supposed, which challenges their explanatory models.
Topics: Adult; Capgras Syndrome; Delusions; Female; Humans; Male; Middle Aged
PubMed: 31326968
DOI: 10.1159/000500474 -
The British Journal of Clinical... Sep 2022The relationship between attachment and paranoia is now well established. There is good theoretical reason and evidence to indicate that attachment style affects...
BACKGROUND
The relationship between attachment and paranoia is now well established. There is good theoretical reason and evidence to indicate that attachment style affects cognitive, affective, and behavioural processes which, in turn, contribute to the maintenance of paranoia, but this research has not been integrated. We critically and systematically review research that examines relevant cognitive, affective, and behavioural processes, which may explain how attachment insecurity leads to paranoia and constitute key targets in psychotherapeutic interventions for people with psychosis.
METHOD
We conducted three systematic searches across six databases (PsycINFO, CINAHL, Medline, Web of Science, Embase, and Google Scholar), from inception to September 2021, to investigate key cognitive, affective, and behavioural processes in the attachment-paranoia association.
RESULTS
We identified a total of 1930 papers and critically reviewed 16. The literature suggests that negative self- and other-beliefs, inability to defuse from unhelpful cognitions, and use of maladaptive emotion regulation strategies mediate the association between attachment insecurity and paranoia in people with psychosis/psychotic experience. Attachment-secure people with psychosis are more likely to seek help and engage with services than attachment-insecure people.
CONCLUSIONS
Attachment styles impact help-seeking behaviours in people with psychosis and are likely to influence paranoia via self- and other-beliefs, cognition fusion, and emotion regulation - these candidate mechanisms may be targeted in psychological therapy to improve clinical outcomes for people with psychosis, characterized by paranoia.
PRACTITIONER POINTS
Insecure attachment is likely to lead to paranoia via negative beliefs about self and others, cognitive fusion, and use of maladaptive emotion regulation strategies. These mechanisms can be targeted in psychotherapeutic interventions for psychosis, such as cognitive behaviour therapy, to improve clinical and recovery outcomes. People with psychosis who are attachment-secure are more likely to seek help and engage with services than those who are attachment-insecure (particularly avoidant). Attachment style can be assessed to predict service engagement and help-seeking behaviours in people with psychosis. Attachment styles are important predictors of key cognitive, affective, and behavioural processes in people with psychosis. These processes can be assessed and incorporated into individualised formulations, and then targeted in therapy to effect psychotherapeutic change.
Topics: Cognition; Emotional Regulation; Humans; Object Attachment; Paranoid Disorders; Psychotic Disorders
PubMed: 35178714
DOI: 10.1111/bjc.12361 -
Neuroscience and Biobehavioral Reviews Apr 2020Clozapine (CLZ) is prescribed to (relatively) treatment-resistant patients with schizophrenia spectrum disorders. Currently, it is unknown what factors predict response... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Clozapine (CLZ) is prescribed to (relatively) treatment-resistant patients with schizophrenia spectrum disorders. Currently, it is unknown what factors predict response to CLZ. Therefore, we performed meta-analyses to identify predictors of CLZ response, hence aiming to facilitate timely and efficient prescribing of CLZ.
METHODS
A systematic search was performed in 'Pubmed' and 'Embase' until 1 January 2019. Articles were eligible if they provided data on predictors of CLZ response measured demographic and clinical factors at baseline or biochemical factors at follow-up in schizophrenia spectrum disorder patients.
RESULTS
A total of 34 articles, total number of participants = 9386; N unique = 2094, were eligible. Factors significantly associated with better CLZ response were: lower age, lower PANSS negative score and paranoid schizophrenia subtype.
CONCLUSION
The results of our meta-analyses suggest that three baseline demographic and clinical features are associated with better clozapine response, i.e. relatively young age, few negative symptoms and paranoid schizophrenia subtype. These variables may be taken into account by clinicians who consider treating a specific patient with CLZ.
Topics: Antipsychotic Agents; Clozapine; Humans; Outcome Assessment, Health Care; Schizophrenia
PubMed: 31982601
DOI: 10.1016/j.neubiorev.2020.01.017 -
Psychiatry and Clinical Neurosciences May 2023
Rapidly responding Geschwind syndrome comorbid with Othello syndrome in a case of post-stroke dementia and post-stroke epilepsy: A case report and a brief systematic review of classical and atypical cases.
Topics: Humans; Comorbidity; Dementia; Epilepsy; Schizophrenia, Paranoid; Stroke
PubMed: 36856332
DOI: 10.1111/pcn.13539 -
Journal of Forensic Sciences Sep 2021The illegal construction of explosive devices for recreational purposes has become increasingly widespread in recent years. This phenomenon is spurred on by numerous...
The illegal construction of explosive devices for recreational purposes has become increasingly widespread in recent years. This phenomenon is spurred on by numerous websites that explain how to build a self-made device. The correlation between the use of firearms and suicide is known in the literature, but the use of explosive devices and self-harm is little studied. Unfortunately, the risk associated with the manufacture of homemade explosives is poorly known. For this purpose, we describe a rare suicide carried out by a man suffering from depressive disorder with psychotic and delusional features. The forensic investigations at the scene showed that the man had designed a homemade device, and disseminated numerous suicide notes in his home, transcribed in the previous weeks in which he revealed his suicidal motivation. Crime scene investigation showed on the body and on the road in front of the explosion point: multiple fragments of glass (zone 1), a lighter with blood stains (zone 2), and shreds of clothing scattered along the road (zone 3). Autopsy revealed that the cause of death was extensive blunt injury to head and trunk due to barotrauma due to the explosion of a homemade device. The case is compared with data from a systematic review of the forensic literature on suicides involving explosives. The study proposes the analysis of planimetric areas in these crime scene investigations and active surveillance in these subjects.
Topics: Aged; Blast Injuries; Explosive Agents; Forensic Medicine; Humans; Male; Suicide, Completed
PubMed: 34042187
DOI: 10.1111/1556-4029.14757 -
The Lancet. Psychiatry Nov 2018An influential psychological model of persecutory delusions proposed that they are caused by a bias towards holding others responsible for negative events (an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An influential psychological model of persecutory delusions proposed that they are caused by a bias towards holding others responsible for negative events (an externalising attributional bias), preventing the individual from becoming aware of underlying low self-esteem. An early version of the model predicted self-esteem would, therefore, be preserved in people with these delusions, but a later version suggested it would be unstable, and that there would be a discrepancy between explicit and implicit self-esteem, with the latter being lower. We did a comprehensive meta-analytical test of the key predictions of this model and assessed the quality of evidence.
METHODS
We searched PubMed from Jan 1, 1994, to July 31, 2018, and collated systematic reviews of the defensive model's predictions in relation to persecutory delusions. We also searched PsycINFO, MEDLINE, Embase, and Web of Science for articles published from Jan 1, 2012, to Sept 10, 2016. Cross-sectional data from case-control, longitudinal, or experimental studies that examined self-esteem or the externalising attributional bias in individuals diagnosed as having schizophrenia-spectrum disorder were eligible for meta-analyses of group differences if at least 50% of participants with psychosis also had current persecutory delusions. Uncontrolled and longitudinal studies were included in meta-analyses of correlations and self-esteem instability, respectively. Study and outcome quality were assessed with the Agency for Healthcare Research and Quality assessment tool, and a modified version of Grading of Recommendations Assessment, Development and Evaluation, respectively. The study protocol is registered with PROSPERO, number CRD42016032782.
FINDINGS
We screened 3053 records, examined 104 full-text reports, and included 64 eligible studies. Consistent with the predictions of both versions of the model, paranoia severity in psychosis was positively correlated with the degree of externalising attributional bias (21 studies involving 1128 individuals; r=0·18, 95% CI 0·08 to 0·27, with moderate quality evidence). People with persecutory delusions also had a greater externalising attributional bias than non-clinical individuals (27 studies involving 1442 individuals; g=0·48, 95% CI 0·23 to 0·73) and depressed individuals (ten studies involving 421 individuals; g=1·06, 0·48 to 1·63), and people with psychosis without persecutory delusions (11 studies involving 480 individuals; g=0·40, 0·12 to 0·68), all based on moderate quality evidence. Contrary to the predictions in the early version of the model, paranoia severity in psychosis was negatively correlated with explicit self-esteem (23 studies involving 1866 individuals; r=-0·26, 95% CI -0·34 to -0·17, with high quality evidence). People with persecutory delusions also had lower explicit self-esteem than non-clinical individuals (22 studies involving 1256 individuals; g=-0·88, 95% CI -1·10 to -0·66, with high quality evidence) and explicit self-esteem similarly low to that in people with psychosis without persecutory delusions (11 studies involving 644 individuals; g=-0·26, -0·54 to 0·02, with moderate quality evidence). Consistent with the predictions in the later version of the model, self-esteem instability was positively correlated with paranoia severity in psychosis (four studies involving 508 individuals; r=0·23, 95% CI 0·11-0·34, with high quality evidence), and people with persecutory delusions had a greater discrepancy between their implicit and explicit self-esteem than depressed individuals (seven studies involving 398 individuals; g=0·61, 95% CI 0·37 to 0·85, with moderate quality evidence). They had higher explicit self-esteem than depressed individuals (13 studies involving 647 individuals; g=0·89, 95% CI 0·51 to 1·28, with moderate quality evidence), but similarly low implicit self-esteem (seven studies involving 398 individuals; g=-0·19, -0·45 to 0·07, with low quality evidence). In contrast to the later predictions, people with persecutory delusions did not have a greater self-esteem discrepancy than non-clinical individuals (ten studies involving 592 individuals; g=-0·17, 95% CI -0·45 to 0·12), although the evidence was very low quality. People with psychosis with or without persecutory delusions did not differ for implicit self-esteem (four studies involving 167 individuals; g=-0·24, 95% CI -0·77 to 0·30, with low quality evidence) or self-esteem discrepancies (four studies involving 165 individuals; g=0·17, -0·19 to 0·53, with moderate quality evidence).
INTERPRETATION
The predictions that self-esteem would be preserved in people with persecutory delusions in the early version of the paranoia as defence model and that implicit-explicit self-esteem discrepancy would be greater in people with persecutory delusions than in non-clinical individuals and people with psychosis without persecutory delusions in the later version of the model were not supported. By contrast, the later version correctly predicted that people with persecutory delusions have a greater self-esteem discrepancy than people with depression and a greater externalising attributional bias than all control groups, and that both this bias and self-esteem instability are associated with increased paranoia severity. Nevertheless, the reviewed data had limitations. Experimental studies, which might include interventionist-causal trials, are needed.
FUNDING
None.
Topics: Bias; Delusions; Humans; Models, Psychological; Paranoid Disorders; Psychotic Disorders; Self Concept; Surveys and Questionnaires
PubMed: 30314852
DOI: 10.1016/S2215-0366(18)30339-0