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Journal of Geriatric Psychiatry and... Sep 2023The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood. (Meta-Analysis)
Meta-Analysis
Comparative Efficacy, Safety, and Acceptability of Pimavanserin and Other Atypical Antipsychotics for Parkinson's Disease Psychosis: Systematic Review and Network Meta-Analysis.
BACKGROUND
The current comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) in treating Parkinson's Disease Psychosis (PDP) are not entirely understood.
OBJECTIVE
To evaluate comparative efficacy, safety, and acceptability of AAPs in patients with PDP.
METHODS
We conducted a systematic review and a network meta-analysis to compare the efficacy, safety, and acceptability of pimavanserin, quetiapine, olanzapine, clozapine, ziprasidone, and risperidone. We estimated relative standardized mean differences (SMDs) for continuous outcomes and odds ratios (OR) for binary outcomes, with their respective 95% confidence intervals (CIs).
RESULTS
We included 19 unique studies evaluating AAPs in a total of 1,242 persons with PDP. Based on Clinical Global Impression Scale for Severity, pimavanserin (SMD, -4.81; 95% CI, -5.39, -4.24) and clozapine (SMD, -4.25; 95% CI, -5.24, -3.26) significantly improved symptoms compared with placebo. Also, compared to placebo, pimavanserin (OR, 1.16; 95% CI, 1.07, 1.24) significantly improved psychotic symptoms based on Scale for Assessment of Positive Symptoms for Parkinson's Disease Psychosis/Hallucinations and Delusions scores. In comparison to placebo, clozapine (SMD, -0.69; 95% CI, -1.35, -0.02), pimavanserin (SMD, -0.01; 95% CI, -0.56, 0.53), and quetiapine (SMD, 0.00; 95% CI, -0.68, 0.69) did not impair motor function per Unified Parkinson's Disease Rating scale. Based on Mini-Mental State Examination scale, quetiapine (SMD, 0.60; 95% CI, 0.07, 1.14) significantly impaired cognition compared to placebo.
CONCLUSIONS
In patients with PDP, pimavanserin and clozapine demonstrated significant improvement in psychosis without affecting motor function. With quetiapine being associated with a significant decline in cognition and despite not impairing motor function, our findings suggest that it should be avoided in patients with PDP and reduced cognitive abilities.
Topics: Humans; Antipsychotic Agents; Parkinson Disease; Clozapine; Quetiapine Fumarate; Network Meta-Analysis; Psychotic Disorders
PubMed: 36720473
DOI: 10.1177/08919887231154933 -
Advances in Therapy May 2022Dementia-related psychosis (DRP) is characterized by hallucinations and delusions, which may increase the debilitating effects of underlying dementia. This network... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Dementia-related psychosis (DRP) is characterized by hallucinations and delusions, which may increase the debilitating effects of underlying dementia. This network meta-analysis (NMA) evaluated the comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) commonly used off label to treat DRP.
METHODS
We included 22 eligible studies from a systematic literature review of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) used off label to treat DRP. Study outcomes were: (1) efficacy-neuropsychiatric inventory-nursing home (NPI-NH psychosis subscale), (2) safety-mortality, cerebrovascular events (CVAEs), and others (somnolence, falls, fractures, injuries, etc.), and (3) acceptability-discontinuations due to all causes, lack of efficacy, and adverse events (AEs). We used random-effects modeling to estimate pooled standardized mean differences (SMDs) for NPI-NH psychosis subscale scores and odds ratios (OR) for other dichotomous outcomes, with their respective 95% confidence intervals (CIs).
RESULTS
Compared with placebo, aripiprazole (SMD - 0.12; 95% CI - 0.31, 0.06), and olanzapine (SMD - 0.17; 95% CI - 0.04; 0.02) demonstrated small, non-significant numerical improvements in NPI-NH psychosis scores (5 studies; n = 1891), while quetiapine (SMD 0.04; 95% CI - 0.23, 0.32) did not improve symptoms. The odds of mortality (15 studies, n = 4989) were higher for aripiprazole (OR 1.58; 95% CI 0.62, 4.04), brexpiprazole (OR 2.22; 95% CI 0.30, 16.56), olanzapine (OR 2.21; 95% CI 0.84, 5.85), quetiapine (OR 1.68; 95% CI 0.70, 4.03), and risperidone (OR 1.63; 95% CI 0.93, 2.85) than for placebo. Risperidone (OR 3.68; 95% CI 1.68, 8.95) and olanzapine (OR 4.47; 95% CI 1.36, 14.69) demonstrated significantly greater odds of CVAEs compared to placebo. Compared with placebo, odds of all-cause discontinuation were significantly lower for aripiprazole (OR 0.71; 95% CI 0.51, 0.98; 20 studies; 5744 patients) and higher for other AAPs. Aripiprazole (OR 0.5; 95% CI 0.31, 0.82) and olanzapine (OR 0.48; 95% CI 0.31, 0.74) had significantly lower odds of discontinuation due to lack of efficacy (OR 12 studies; n = 4382) compared to placebo, while results for quetiapine and risperidone were not significant. Compared with placebo, the odds of discontinuation due to AEs (19 studies, n = 5445) were higher for olanzapine (OR 2.62; 95% CI 1.75, 3.92), brexpiprazole (OR 1.80; 95% CI 0.80, 4.07), quetiapine (OR 1.25; 95% CI 0.82, 1.91), aripiprazole (OR 1.38; 95% CI 0.90, 2.13), and risperidone (OR 1.41; 95% CI 1.02, 1.94).
CONCLUSIONS
Overall results demonstrate that, compared with placebo, quetiapine is not associated with improvement in psychosis in patients with dementia, while olanzapine and aripiprazole have non-significant small numerical improvements. These off-label AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) are associated with greater odds of mortality, CVAEs, and discontinuations due to AEs than placebo. These results underscore the ongoing unmet need for newer pharmacological options with a more favorable benefit-risk profile for the treatment of DRP.
Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dementia; Humans; Network Meta-Analysis; Off-Label Use; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome
PubMed: 35247186
DOI: 10.1007/s12325-022-02075-8 -
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 International Journal of Social... Mar 2023Schizoaffective psychosis is a severe and chronic psychiatric disorder defined by the presence of mood symptoms, like mania and/or depression and schizophrenia, such as... (Review)
Review
BACKGROUND
Schizoaffective psychosis is a severe and chronic psychiatric disorder defined by the presence of mood symptoms, like mania and/or depression and schizophrenia, such as hallucinations and/or delusions.
AIMS
We aim to find out whether there is a correlation between schizoaffective psychosis and being homeless.
METHOD
To do so, a literature search was carried out in the PubMed platform in April 2022, using the keywords 'schizoaffective' and 'homeless'.
RESULTS
In this review, 28 articles from this search were included. Intrinsic characteristics, rates of psychiatric readmission, prediction of homelessness, medication noncompliance, and substance use were explored, as they were the main themes of the results.
CONCLUSIONS
The homeless population suffers from great diagnostic variability and the diagnosis schizoaffective psychosis is still evolving contributing to such diagnostic and treatment difficulties. Their frequent visits to the healthcare services, especially emergency room leads to consequent interaction with multiple healthcare professionals, resulting in a myriad of diagnoses, with clinical remission and therapeutic goals not being attained. More studies are necessary for a better evaluation of this super difficult population.
Topics: Humans; Psychotic Disorders; Schizophrenia; Hallucinations; Ill-Housed Persons
PubMed: 36317594
DOI: 10.1177/00207640221131247 -
Journal of Psychiatric Research Dec 2023Transcranial alternating current stimulation (tACS) is an innovative noninvasive technique in brain stimulation that involves applying a low-intensity electrical current... (Review)
Review
BACKGROUND
Transcranial alternating current stimulation (tACS) is an innovative noninvasive technique in brain stimulation that involves applying a low-intensity electrical current to the scalp. And increasing evidence has revealed its potential in schizophrenia treatment.
OBJECTIVE
This systematic review aimed to evaluate the efficacy of tACS as a novel neurostimulation technique for improving cognitive impairment and alleviating psychotic symptoms in schizophrenia. Additionally, this review attempted to explore the impact of stimulation parameters on the effectiveness of tACS treatment.
METHODS
A systematic literature search was conducted across five databases, including Web of Science, Embase, PubMed, CENTRAL, and PsycINFO, to identify studies investigating the use of tACS in schizophrenia. Only studies that involved the experimental use of tACS in patients with schizophrenia were included in this review.
RESULTS
Nineteen studies were included in this review. The most frequently used current intensities were 2 mA and 1 mA, and the most commonly used frequencies were alpha (10 Hz), theta (4.5 Hz and 6 Hz), and gamma (40 Hz). Some studies showed that tACS may have a potential therapeutic effect by improving cognitive functions in various cognitive domains and/or ameliorating negative symptoms, hallucinations, and delusions in patients with schizophrenia, while others showed no significant change. These studies also implicated that tACS treatment is safe and well tolerated.
CONCLUSIONS
Overall, this systematic review suggests that tACS has promise as a novel, effective, and adjunctive treatment approach for treating schizophrenia. Future research is needed to determine the optimal parameters of tACS for treating this complex disorder.
Topics: Humans; Schizophrenia; Transcranial Direct Current Stimulation; Hallucinations; Cognition
PubMed: 37897837
DOI: 10.1016/j.jpsychires.2023.10.021 -
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 -
Frontiers in Psychiatry 2021Culture can affect psychiatric disorders. Clinical Lycanthropy is a rare syndrome, described since Antiquity, within which the patient has the delusional belief of...
Culture can affect psychiatric disorders. Clinical Lycanthropy is a rare syndrome, described since Antiquity, within which the patient has the delusional belief of turning into a wolf. Little is known on its clinical or therapeutic correlates. We conducted a systematic review (PRISMA) on PubMed and Google Scholar, until January 2021. Case reports, data on neurobiological hypotheses, and cultural aspects were included. Language was not restricted to English. Forty-three cases of clinical lycanthropy and kynanthropy (delusion of dog transformation) were identified. Associated diagnoses were: schizophrenia, psychotic depression, bipolar disorder, and other psychotic disorders. Antipsychotic medication may be an efficient treatment for this rare transnosographic syndrome. In case of depression or mania, the treatment included antidepressants or mood regulators. The neuroscientific hypotheses include the conception of clinical lycanthropy as a cenesthopathy, as a delusional misidentification of the self-syndrome, as impairments of sensory integration, as impairments of the belief evaluation system, and right hemisphere anomalies. Interestingly, there is a clinical overlap between clinical lycanthropy and other delusional misidentification syndromes. Clinical lycanthropy may be a culture-bound syndrome that happens in the context of Western cultures, myths, and stories on werewolves, and today's exposure to these narratives on cultural media such as the internet and the series. We suggest the necessity of a cultural approach for these patients' clinical assessment, and a narrative and patient-centered care. Psychiatric transtheoretical reflections are needed for complementaristic neurobiological and cultural approaches of complex delusional syndromes such as clinical lycanthropy. Future research should include integrative frameworks.
PubMed: 34707519
DOI: 10.3389/fpsyt.2021.718101 -
Neuropsychology Review Jun 2024Most people with dementia experience neuropsychiatric symptoms (NPS), including anxiety, depression or disinhibition. There is growing interest in the relationship... (Meta-Analysis)
Meta-Analysis Review
Most people with dementia experience neuropsychiatric symptoms (NPS), including anxiety, depression or disinhibition. There is growing interest in the relationship between NPS and cognitive impairment, but data is still limited. This study aimed to investigate the specific associations between NPS and cognition in people with dementia. MEDLINE, EMBASE and PsycINFO were searched for published, peer-reviewed studies of associations between at least one NPS and one cognitive ability in people with dementia. The quality of the studies was assessed with the NIH National Heart, Lung and Blood Institute's quality assessment tools. A meta-analysis was conducted using Robumeta package for R. Ninety studies were included. We found significant associations between NPS, global cognition and cognitive domains, e.g. apathy was associated with global cognitive and memory impairment; dysphoria was associated with worse attention; delusions with executive dysfunction. Increased NPS in people with dementia are associated with worse cognitive performance. There were few studies looking at associations between some neuropsychiatric clusters and cognitive abilities, and there was little research on causal relationships. Our review was limited by the inclusion of studies that reported associations in specific formats, and most included people with a diagnosis of Alzheimer's disease (AD). However, given the large number of studies, this is unlikely to have biased results. More research is needed that includes diverse people with different dementia syndromes. Registration: PROSPERO 2020 CRD42020165565.
Topics: Humans; Dementia; Cognitive Dysfunction; Cognition; Alzheimer Disease
PubMed: 37477839
DOI: 10.1007/s11065-023-09608-0 -
The Lancet. Psychiatry Jun 2022Delusions are a common transdiagnostic feature of psychotic disorders, and their treatment remains suboptimal. Despite the pressing need to better understand the nature,...
BACKGROUND
Delusions are a common transdiagnostic feature of psychotic disorders, and their treatment remains suboptimal. Despite the pressing need to better understand the nature, meaning, and course of these symptoms, research into the lived experience of delusional phenomena in psychosis is scarce. Thus, we aimed to explore the lived experience and subjective apprehension of delusions in help-seeking individuals with psychosis, regardless of diagnosis and thematic content of the delusion.
METHODS
In our systematic review and qualitative evidence synthesis, we searched MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science for qualitative studies published in English from database inception, with the last search on Sept 9, 2021. Grey literature search and hand-searching of relevant journals were also done. Studies were eligible if they provided an analysis of lived experience of delusions or predelusional phenomena presented from the perspective of individuals (age 14-65 years) who had developed a clinical high-risk stage of psychosis, or a diagnosable affective or non-affective psychotic disorder (as clinically defined, self-reported, or assessed within the primary study). Studies with only a subset of relevant participants were eligible only if data for the population of interest were reported separately. Studies that did not discriminate between the experience of delusion and other positive symptoms (eg, hallucinations) were included only if data for delusions were reported separately or could be extracted. First-person accounts (and author interpretations) discussing changes in the sense of self, lived world, and meaning in relation to delusions were extracted and synthesised using a novel thematic synthesis approach informed by a critical realist stance and a phenomenological theoretical framework. Analytic themes were developed into a new overarching framework for understanding the emergence of delusional phenomena. The study was registered with PROSPERO, CRD42020222104.
FINDINGS
Of the 3265 records screened, 2115 were identified after duplicate removal. Of these, 1982 were excluded after title and abstract screening and 106 after full-text eligibility assessment. Of the 27 studies entering quality assessment, 24 eligible studies were included in the qualitative evidence synthesis, representing the perspectives of 373 help-seeking individuals with lived experience of delusions in the context of psychosis. Gender was reported as male (n=210), female (n=110), transgender (n=1), or not reported (n=52). Only 13 studies reported ethnicity, with White being predominant. The age of most participants ranged from 15 to 65 years. We found no eligible studies investigating subclinical or predelusional experiences in at-risk mental state populations through qualitative methods. Most studies were undertaken in western, educated, industrialised, rich, and democratic (WEIRD) societies, and most included participants had received or self-reported a diagnosis within the schizophrenia spectrum. Studies differed in relation to whether they focused on one kind or theme of delusion or delusional phenomena more generally as a unified category. Three superordinate themes relating to experiential changes and meanings in delusion were identified: (1) a radical rearrangement of the lived world dominated by intense emotions; (2) doubting, losing, and finding oneself again within delusional realities; and (3) searching for meaning, belonging, and coherence beyond mere dysfunction. Based on the review findings and thematic synthesis, we propose the Emergence Model of Delusion to advance understanding of delusional phenomena in psychosis.
INTERPRETATION
Delusions are best understood as strongly individualised and inherently complex phenomena emerging from a dynamic interplay between interdependent subpersonal, personal, interpersonal, and sociocultural processes. Integrative approaches to research on delusion, which consider their potential adaptiveness and favour explanatory pluralism, might be advantageous. Effective clinical care for individuals with psychosis might need adapting to match more closely, and take account of, the subjective experience and meaning of delusions as they are lived through, which might also help redress power imbalances and enduring epistemic injustices in mental health.
FUNDING
Priestley Scholars, Wellcome Trust.
Topics: Adolescent; Adult; Aged; Delusions; Emotions; Female; Humans; Male; Middle Aged; Psychotic Disorders; Qualitative Research; Schizophrenia; Young Adult
PubMed: 35523211
DOI: 10.1016/S2215-0366(22)00104-3 -
Current Alzheimer Research 2023Alzheimer's disease (AD) ranks first among the causes of dementia worldwide. AD can develop a psychotic manifest at a significant rate. AD prognosis worsens by added...
Alzheimer's disease (AD) ranks first among the causes of dementia worldwide. AD can develop a psychotic manifest at a significant rate. AD prognosis worsens by added psychosis clinic. There is no treatment approved by the United States Food and Drug Administration (FDA) among antipsychotics for Alzheimer's disease Psychosis (ADP). However, pimavanserine, an atypical antipsychotic, has been approved by the FDA for Parkinson's psychosis. It is predicted that pimavanserin, a new antipsychotic, will fill an important gap in this area. In clinical trials, it appears to be effective in the treatment of delusions and hallucinations at psychosis in both Parkinson's and AD. In this systematic review, we evaluated the analysis of current literature data on pimavanserin used in ADP. We searched the existing literature on clinical studies on pimavanserin therapy used in ADP. Data were determined by systematically searching PubMed, MEDLINE, EMBASE, and Google Scholar until December 2022. A total of 35 citations were found and uploaded on the Mendeley program. Abstracts and full texts of literature data were examined. Pimavanserin was observed, and satisfactory results were obtained in treating ADP. Pimavanserin has a unique mechanism of action. Pimavanserin, an atypical antipsychotic drug, has a low affinity for 5-HT2C receptors and has selective 5-HT2A reverse agonist/antagonist action. Pimavanserin has no clinically significant affinity for dopaminergic, histaminergic, muscarinic or adrenergic receptors. This agent may also achieve significant positive results in resistant psychosis treatments.
Topics: United States; Humans; Psychotic Disorders; Alzheimer Disease; Parkinson Disease; Antipsychotic Agents; Urea
PubMed: 37641988
DOI: 10.2174/1567205020666230825124922