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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 -
Early Intervention in Psychiatry Dec 2022Thinking biases are posited to be involved in the genesis and maintenance of delusions. Persecutory delusions are one of the most commonly occurring delusional subtypes... (Review)
Review
AIM
Thinking biases are posited to be involved in the genesis and maintenance of delusions. Persecutory delusions are one of the most commonly occurring delusional subtypes and cause substantial distress and disability to the individuals experiencing them. Their clinical relevance confers a rationale for investigating them. Particularly, this review aims to elucidate which cognitive biases are involved in their development and persistence.
METHODS
MEDLINE, Embase, PsycINFO and Global Health were searched from the year 2000 to June 2020. A formal narrative synthesis was employed to report the findings and a quality assessment of included studies was conducted.
RESULTS
Twenty five studies were included. Overall, 18 thinking biases were identified. Hostility and trustworthiness judgement biases appeared to be specific to persecutory delusions while jumping to conclusions, self-serving attributional biases and belief inflexibility were proposed to be more closely related to other delusional subtypes. While the majority of the biases identified were suggested to be involved in delusion maintenance, hostility biases, need for closure and personalizing attributional biases were believed to also have aetiological influences.
CONCLUSIONS
These findings show that some cognitive biases are specific to paranoid psychosis and appear to be involved in the formation and/or persistence of persecutory delusions.
Topics: Humans; Delusions; Paranoid Disorders; Bias; Psychotic Disorders
PubMed: 35396904
DOI: 10.1111/eip.13292 -
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 -
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 -
Schizophrenia Research Apr 2016Aggression in the context of schizophrenia has significant detrimental personal, clinical and societal implications. Whilst understanding the precise pathways to... (Review)
Review
Aggression in the context of schizophrenia has significant detrimental personal, clinical and societal implications. Whilst understanding the precise pathways to aggression in people with a diagnosis of schizophrenia is critical for risk management and treatment, these pathways remain unclear. A paranoid belief that others intend harm is one psychotic symptom that might contribute to aggressive behaviours. This is the first review to investigate the relationship between paranoia and aggression in psychosis. A systematic review of published literature pertinent to the relationship between paranoia and aggression was conducted. A search of online databases from inception to November 2014 was performed with keywords related to 'schizophrenia', 'paranoia' and 'aggression'. Fifteen studies, primarily cross-sectional in design (n=9), met eligibility criteria. Studies reviewed showed mixed support for an association between paranoia and aggression in both inpatients and community settings. However, when study quality was taken into account, more methodologically rigorous studies tended to show a positive association between factors. Mixed findings are most likely due to important methodological shortcomings, including heterogeneous samples and studies using a diverse range of aggression/violence measures. In light of methodological limitations of individual studies reviewed, further investigation of the relationship between paranoia and aggression in psychosis using robust methodology is needed before definitive clinical recommendations regarding the hypothesised relationship between paranoia and aggression can be made. This paper sets out key recommendations for future studies, including operationalizing the specific components of aggression and paranoia under investigation and methods to delineate important mediators in the paranoia and aggression relationship.
Topics: Aggression; Humans; Paranoid Disorders; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology
PubMed: 26879588
DOI: 10.1016/j.schres.2016.02.009 -
The Cochrane Database of Systematic... May 2015Delusional disorder is commonly considered to be difficult to treat. Antipsychotic medications are frequently used and there is growing interest in a potential role for... (Review)
Review
BACKGROUND
Delusional disorder is commonly considered to be difficult to treat. Antipsychotic medications are frequently used and there is growing interest in a potential role for psychological therapies such as cognitive behavioural therapy (CBT) in the treatment of delusional disorder.
OBJECTIVES
To evaluate the effectiveness of medication (antipsychotic medication, antidepressants, mood stabilisers) and psychotherapy, in comparison with placebo in delusional disorder.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Trials Register (28 February 2012).
SELECTION CRITERIA
Relevant randomised controlled trials (RCTs) investigating treatments in delusional disorder.
DATA COLLECTION AND ANALYSIS
All review authors extracted data independently for the one eligible trial. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis with a fixed-effect model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again with a fixed-effect model. We assessed the risk of bias of the included study and used the GRADE approach to rate the quality of the evidence.
MAIN RESULTS
Only one randomised trial met our inclusion criteria, despite our initial search yielding 141 citations. This was a small study, with 17 people completing a trial comparing CBT to an attention placebo (supportive psychotherapy) for people with delusional disorder. Most participants were already taking medication and this was continued during the trial. We were not able to include any randomised trials on medications of any type due to poor data reporting, which left us with no usable data for these trials. For the included study, usable data were limited, risk of bias varied and the numbers involved were small, making interpretation of data difficult. In particular there were no data on outcomes such as global state and behaviour, nor any information on possible adverse effects.A positive effect for CBT was found for social self esteem using the Social Self-Esteem Inventory (1 RCT, n = 17, MD 30.5, CI 7.51 to 53.49, very low quality evidence), however this is only a measure of self worth in social situations and may thus not be well correlated to social function. More people left the study early if they were in the supportive psychotherapy group with 6/12 leaving early compared to 1/6 from the CBT group, but the difference was not significant (1 RCT, n = 17, RR 0.17, CI 0.02 to 1.18, moderate quality evidence). For mental state outcomes the results were skewed making interpretation difficult, especially given the small sample.
AUTHORS' CONCLUSIONS
Despite international recognition of this disorder in psychiatric classification systems such as ICD-10 and DSM-5, there is a paucity of high quality randomised trials on delusional disorder. There is currently insufficient evidence to make evidence-based recommendations for treatments of any type for people with delusional disorder. The limited evidence that we found is not generalisable to the population of people with delusional disorder. Until further evidence is found, it seems reasonable to offer treatments which have efficacy in other psychotic disorders. Further research is needed in this area and could be enhanced in two ways: firstly, by conducting randomised trials specifically for people with delusional disorder and, secondly, by high quality reporting of results for people with delusional disorder who are often recruited into larger studies for people with a variety of psychoses.
Topics: Cognitive Behavioral Therapy; Humans; Psychotherapy; Randomized Controlled Trials as Topic; Schizophrenia, Paranoid; Self Concept
PubMed: 25997589
DOI: 10.1002/14651858.CD009785.pub2 -
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 -
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 -
Frontiers in Psychiatry 2022The hierarchy of evidence coming from evidence-based medicine favors meta-analyses and randomized controlled trials over observational studies and clinical cases....
BACKGROUND
The hierarchy of evidence coming from evidence-based medicine favors meta-analyses and randomized controlled trials over observational studies and clinical cases. Nonetheless, in the field of psychiatry, where conditions are much more complex, additional evidence coming from real-world clinical practice is necessary to complement data from these gold standards. Thus, in this systematic review, the aim is to summarize the evidence coming from clinical case reports regarding cariprazine, a third-generation antipsychotic drug that has been approved for the treatment of schizophrenia and bipolar I disorder with manic, depressive or mixed features in adults.
METHODS
A systematic review was performed using Embase and Pubmed databases searching for English-language cases published in peer-reviewed journals between 2000 January and 2021 September with the following search terms: (cariprazin OR "rgh-188" OR rgh188 OR vraylar OR reagila) AND ("case report" OR "case report"/de OR "case stud" OR "case study"/de OR "case seri").
RESULTS
After the removal of duplicates, 49 articles were retrieved via the search, from which 22 were suitable for this review. These 22 articles encompassed 38 cases from which 71% described patients with schizophrenia, 16% patients with psychotic disorders, 5% patients with mood disorder and 8% described patients with other disorders such as Wernicke-Korsakoff syndrome, borderline personality disorder and obsessive-compulsive disorder with paranoid schizophrenia. The median age of patients was 31, and half of them were female. The majority of patients (76%) started cariprazine with 1.5 mg/day, and the most common maintenance dose was 4.5 mg/day (34%) and 3.0 mg/day (29%).
CONCLUSION
Cariprazine was found to be safe and effective in a wide range of psychiatric conditions with different symptom profiles from acute psychotic symptoms through addiction to negative and cognitive symptoms. The results are in-line with the established evidence from clinical trials, however, they also show how cariprazine can be successfully utilized for treating certain symptoms irrespective of the indication.
PubMed: 35370825
DOI: 10.3389/fpsyt.2022.827744 -
Psychiatry Research Jan 2022Paranoia is an important psychiatric symptom with a remarkable effect on daily life. Virtual reality (VR)-based treatments are influential and safe for patients with... (Review)
Review
BACKGROUND AND OBJECTIVE
Paranoia is an important psychiatric symptom with a remarkable effect on daily life. Virtual reality (VR)-based treatments are influential and safe for patients with paranoia. This study aimed to evaluate the effectiveness, and define the clinical and technical characteristics of available VR strategies for the treatment of patients with paranoia.
MATERIALS AND METHODS
Studies published up to 25/11/2021 reporting VR-based interventions for the treatment of patients with paranoia were reviewed in five databases, including PubMed, Embase, Web of Science, PsycINFO, and Scopus.
RESULTS
Out of 302 initial search results, eight were included in the present study based on the inclusion criteria. Six studies were randomized clinical trials with the interventions in the experimental group being based on VR, compared to routine interventions as controls. Two were before-after studies. The most commonly used hardware and software were head-mounted display and Unity3D, respectively. Interventions had a range of 1-16 sessions with follow-up durations of 0-6 months. All investigations showed positive results in the main target, including improved social participation, reduced level of anxiety, as well as diminished suspicious ideas and paranoid symptoms.
CONCLUSIONS
Our findings demonstrated that VR-based interventions are effective treatments. Although the use of VR technology is limited for a variety of reasons, such as cost, it improves symptoms in patients with paranoia.
Topics: Anxiety; Humans; Paranoid Disorders; Virtual Reality; Virtual Reality Exposure Therapy
PubMed: 34922239
DOI: 10.1016/j.psychres.2021.114338