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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 -
Schizophrenia Research Jul 2020Sleep disturbance is a common clinical issue for patients with psychosis. It has been identified as a putative causal factor in the onset and persistence of psychotic... (Review)
Review
BACKGROUND
Sleep disturbance is a common clinical issue for patients with psychosis. It has been identified as a putative causal factor in the onset and persistence of psychotic experiences (paranoia and hallucinations). Hence sleep disruption may be a potential treatment target to prevent the onset of psychosis and reduce persistent psychotic experiences. The aim of this review is to describe developments in understanding the nature, causal role, and treatment of sleep disruption in psychosis.
METHOD
A systematic literature search was conducted to identify studies, published in the last five years, investigating subjective sleep disruption and psychotic experiences.
RESULTS
Fifty-eight papers were identified: 37 clinical and 21 non-clinical studies. The studies were correlational (n = 38; 20 clinical, 18 non-clinical), treatment (n = 7; 1 non-clinical), qualitative accounts (n = 6 clinical), prevalence estimates (n = 5 clinical), and experimental tests (n = 2 non-clinical). Insomnia (50%) and nightmare disorder (48%) are the most prevalent sleep problems found in patients. Sleep disruption predicts the onset and persistence of psychotic experiences such as paranoia and hallucinations, with negative affect identified as a partial mediator of this relationship. Patients recognise the detrimental effects of disrupted sleep and are keen for treatment. All psychological intervention studies reported large effect size improvements in sleep and there may be modest resultant improvements in psychotic experiences.
CONCLUSIONS
Sleep disruption is a treatable clinical problem in patients with psychosis. It is important to treat in its own right but may also lessen psychotic experiences. Research is required on how this knowledge can be implemented in clinical services.
Topics: Delusions; Hallucinations; Humans; Paranoid Disorders; Psychotic Disorders; Schizophrenia; Sleep
PubMed: 31831262
DOI: 10.1016/j.schres.2019.11.014 -
The Cochrane Database of Systematic... Dec 2019Primary delusional infestation (DI) is a primary psychiatric disorder characterised by delusions and abnormal tactile sensations. The pathophysiology is undecided and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary delusional infestation (DI) is a primary psychiatric disorder characterised by delusions and abnormal tactile sensations. The pathophysiology is undecided and treatment includes both pharmacological and non-pharmacological options. There is currently no Cochrane Review of the treatments used. Primary DI is a diagnosis often encountered by both dermatologists and psychiatrists, with a large associated disease burden.
OBJECTIVES
To evaluate the effectiveness of different treatments in primary delusional infestation (DI).
SEARCH METHODS
On 24 December 2014 and 19 March 2019, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including registries of clinical trials.
SELECTION CRITERIA
Randomised controlled trials involving the treatment of adults with primary DI.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened and assessed studies for inclusion using pre-specified inclusion criteria.
MAIN RESULTS
We did not identify any studies for inclusion.
AUTHORS' CONCLUSIONS
Currently there is no evidence from RCTs available to compare treatment of primary DI with placebo. We cannot, therefore, make any conclusions regarding the effects of treatments (pharmacological or non-pharmacological) for primary DI. This lack of evidence for treatment of primary DI has implications for research and practice. Robust randomised trials are indicated.
Topics: Antipsychotic Agents; Humans; Psychotherapy; Randomized Controlled Trials as Topic; Schizophrenia, Paranoid; Self Concept
PubMed: 31821546
DOI: 10.1002/14651858.CD011326.pub2 -
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 -
International Clinical... Sep 2018This review aimed to examine and analyse the definitions used for antipsychotic response in delusional disorder (DD) and to provide a discussion of the methodology used....
This review aimed to examine and analyse the definitions used for antipsychotic response in delusional disorder (DD) and to provide a discussion of the methodology used. A systematic review was performed using the PubMed, Scopus and PsycINFO databases (1990-October 2017) according to the PRISMA statement. In addition, reference searches were performed manually through identified studies to obtain other relevant articles. The search terms included 'antipsychotic response', 'antipsychotics', 'treatment response' and 'delusional disorder'. After the screening and selection processes, 11 studies fulfilled our inclusion criteria using different methods to define antipsychotic response in DD. Studies included chart reviews (n=5) and observer-rated scales (n=6), in which two studies used the Clinical Global Impression-Improvement scale, two studies evaluated antipsychotic response by mean changes from the baseline to endpoint scores [Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale], one study combined the Clinical Global Impression-Improvement scale and mean changes from baseline scores (PANSS) and one study reported responder rates on the basis of a scale-derived cut-off (PANSS). A lack of consensus in the definitions of antipsychotic response in DD and a high degree of heterogeneity of the methods used are reflected. Recent proposals on the use of scale-derived cut-offs to evaluate antipsychotic response in schizophrenia would be highly recommended for DD research.
Topics: Antipsychotic Agents; Humans; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Schizophrenia, Paranoid
PubMed: 29912058
DOI: 10.1097/YIC.0000000000000227 -
Journal of Clinical Psychopharmacology Aug 2018
Topics: Antipsychotic Agents; Humans; Medication Adherence; Schizophrenia, Paranoid
PubMed: 29851708
DOI: 10.1097/JCP.0000000000000893 -
Human Molecular Genetics Aug 2018We present a systematic review of genome-wide research on psychotic experience and negative symptom (PENS) traits in the community. We integrate these new findings, most...
We present a systematic review of genome-wide research on psychotic experience and negative symptom (PENS) traits in the community. We integrate these new findings, most of which have emerged over the last four years, with more established behaviour genetic and epidemiological research. The review includes the first genome-wide association studies of PENS, including a recent meta-analysis, and the first SNP heritability estimates. Sample sizes of <10 000 participants mean that no genome-wide significant variants have yet been replicated. Importantly, however, in the most recent and well-powered studies, polygenic risk score prediction and linkage disequilibrium (LD) score regression analyses show that all types of PENS share genetic influences with diagnosed schizophrenia and that negative symptom traits also share genetic influences with major depression. These genetic findings corroborate other evidence in supporting a link between PENS in the community and psychiatric conditions. Beyond the systematic review, we highlight recent work on gene-environment correlation, which appears to be a relevant process for psychotic experiences. Genes that influence risk factors such as tobacco use and stressful life events are likely to be harbouring 'hits' that also influence PENS. We argue for the acceptance of PENS within the mainstream, as heritable traits in the same vein as other sub-clinical psychopathology and personality styles such as neuroticism. While acknowledging some mixed findings, new evidence shows genetic overlap between PENS and psychiatric conditions. In sum, normal variations in adolescent and adult thinking styles, such as feeling paranoid, are heritable and show genetic associations with schizophrenia and major depression.
Topics: Adult; Affect; Bipolar Disorder; Depressive Disorder, Major; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Genetic Testing; Genome-Wide Association Study; Genotype; Humans; Linkage Disequilibrium; Male; Multifactorial Inheritance; Phenotype; Polymorphism, Single Nucleotide; Psychiatry; Psychometrics; Psychotic Disorders; Risk Factors; Schizophrenia
PubMed: 29741616
DOI: 10.1093/hmg/ddy157 -
Psychological Medicine Feb 2018Over the last two decades, there has been a rapid increase of studies testing the efficacy and acceptability of virtual reality in the assessment and treatment of mental... (Review)
Review
Over the last two decades, there has been a rapid increase of studies testing the efficacy and acceptability of virtual reality in the assessment and treatment of mental health problems. This systematic review was carried out to investigate the use of virtual reality in the assessment and the treatment of psychosis. Web of Science, PsychInfo, EMBASE, Scopus, ProQuest and PubMed databases were searched, resulting in the identification of 638 articles potentially eligible for inclusion; of these, 50 studies were included in the review. The main fields of research in virtual reality and psychosis are: safety and acceptability of the technology; neurocognitive evaluation; functional capacity and performance evaluation; assessment of paranoid ideation and auditory hallucinations; and interventions. The studies reviewed indicate that virtual reality offers a valuable method of assessing the presence of symptoms in ecologically valid environments, with the potential to facilitate learning new emotional and behavioural responses. Virtual reality is a promising method to be used in the assessment of neurocognitive deficits and the study of relevant clinical symptoms. Furthermore, preliminary findings suggest that it can be applied to the delivery of cognitive rehabilitation, social skills training interventions and virtual reality-assisted therapies for psychosis. The potential benefits for enhancing treatment are highlighted. Recommendations for future research include demonstrating generalisability to real-life settings, examining potential negative effects, larger sample sizes and long-term follow-up studies. The present review has been registered in the PROSPERO register: CDR 4201507776.
Topics: Humans; Patient Acceptance of Health Care; Patient Safety; Psychotic Disorders; Randomized Controlled Trials as Topic; User-Computer Interface; Virtual Reality Exposure Therapy
PubMed: 28735593
DOI: 10.1017/S0033291717001945 -
The American Journal of Psychiatry Oct 2017Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences.
METHOD
The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects. Potential moderators of efficacy were analyzed by meta-regression.
RESULTS
The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38. At least a "minimal" response occurred in 51% of the antipsychotic group versus 30% in the placebo group, and 23% versus 14% had a "good" response. Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27). Quality of life (SMD 0.35) and functioning (SMD 0.34) improved even in the short term. Antipsychotics differed substantially in side effects. Of the response predictors analyzed, 16 trial characteristics changed over the decades. However, in a multivariable meta-regression, only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time.
CONCLUSIONS
Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response. Effect sizes were reduced by industry sponsorship and increasing placebo response, not decreasing drug response. Drug development may benefit from smaller samples but better-selected patients.
Topics: Antipsychotic Agents; Bayes Theorem; Depression; Drug-Related Side Effects and Adverse Reactions; Humans; Multivariate Analysis; Patient Dropouts; Psychotic Disorders; Quality of Life; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology; Treatment Outcome
PubMed: 28541090
DOI: 10.1176/appi.ajp.2017.16121358 -
The Cochrane Database of Systematic... Apr 2016In the 1940s reserpine, refined from a plant extract that had been used for centuries, began to be used as a treatment for people with mental disorders and was one of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the 1940s reserpine, refined from a plant extract that had been used for centuries, began to be used as a treatment for people with mental disorders and was one of the very first antipsychotic drugs. Its irreversible pharmacological potency and adverse effects meant that it has been withdrawn in the UK and its role has been superceded by 'newer' compounds. The effects of reserpine are of historical interest although there are some reports of it still being used in highly specialist situations in psychiatry. Chlorpromazine is also an old drug but it is still used for treatment of people with schizophrenia.
OBJECTIVES
To investigate the effects of two old medications (reserpine and chlorpromazine) for people with schizophrenia. Reserpine is now rarely used while chlorpromazine remains on the essential list of drugs of the World Health Organization (WHO).
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (24 March 2016).
SELECTION CRITERIA
We included randomised clinical trials focusing on chlorpromazine versus reserpine for schizophrenia that presented useable data.
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. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The review currently includes nine studies with an average 60 participants per study. All of these studies are now over 60 years old, conducted between 1955 and 1962. When chlorpromazine was compared with reserpine for people with schizophrenia, improvement in global state was better at short term for those receiving chlorpromazine (n = 781, 6 RCTs, RR 'not improved' 0.75 95% CI 0.62 to 0.92, low-quality evidence). Short-term improvement in paranoid distortion was measured using the Multidimensional Scale for Rating Psychiatric Patients (MSRPP). Data showed no clear difference between treatment groups (n = 19, 1 RCT, RR 1.33 95% CI 0.62 to 2.89, very low-quality evidence). There was no difference in functioning: occupational adjustment, medium term (n = 40, 1 RCT, RR 0.83 95% CI 0.47 to 1.47, moderate-quality evidence) and general behaviour (n = 98, 1 RCT, RR 0.79 CI 0.41 to 1.53, moderate-quality evidence). Adverse events were poorly reported. For 'toxic reaction' there was, again, no obvious difference between the two compounds (n = 210, 3 RCTs, RR 1.68 95% CI 0.43 to 6.54, moderate-quality evidence), and this also applied to leaving the study early (n = 229, 4 RCTs, RR 1.16 95% CI 0.94 to 1.42, moderate-quality evidence).
AUTHORS' CONCLUSIONS
Judged by standards of today, the evidence is largely of limited quality. However, some of these 1950s studies are remarkable in their foresight and clarity. Reserpine did have some effect on global state - but chlorpromazine did seem to perform better. Important issues regarding adverse effects were not really addressed by these trials. Chlorpromazine remains on the WHO list of essential drugs. Reserpine is now almost obsolete, although, probably as a result of evidence other than that reported in the pioneering trials used in this review.
Topics: Antipsychotic Agents; Chlorpromazine; Humans; Randomized Controlled Trials as Topic; Reserpine; Schizophrenia
PubMed: 27124109
DOI: 10.1002/14651858.CD012122.pub2