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Pharmacotherapy Dec 2023Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring... (Review)
Review
Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life-threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: (i) the impact of clozapine on inflammatory markers, (ii) monitoring cardiac and other organ function during clozapine-associated inflammatory processes, and (iii) monitoring non-specific signs and symptoms of inflammation. Elevated levels of C-reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4-8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine-associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence-based guidelines for the monitoring of clozapine-associated inflammation.
Topics: Humans; Clozapine; Antipsychotic Agents; Myocarditis; Inflammation; Pneumonia
PubMed: 37842767
DOI: 10.1002/phar.2887 -
Psychopharmacology Oct 2023Clozapine is a unique medication with a potential role in the treatment of severe borderline personality disorder (BPD). (Review)
Review
RATIONALE
Clozapine is a unique medication with a potential role in the treatment of severe borderline personality disorder (BPD).
OBJECTIVES
The review examines the effectiveness of clozapine as a medication for management for severe BPD with high risk of suicide, violence or imprisonment, and aims to help guide clinical practice in managing severe BPD.
METHODS
A database search of the terms "Clozapine" AND "BPD"; "Antipsychotics" AND "BPD"; "Clozapine" AND "Borderline Personality Disorder"; and "Antipsychotics" AND "Borderline Personality Disorder" were performed in CINAHL, Cochrane Library, Embase, Medline, PsychINFO, PubMed, and Web of Science. Full-text articles of clinical clozapine use for BPD were included for review.
RESULTS
A total of 24 articles consisting of 1 randomised control trial, 10 non-controlled trials, and 13 case reports were identified. Most of the studies reported benefits from clozapine when used for severe BPD. Many of the studies focused on clozapine use in BPD patients at high risk of suicide. Results from these non-controlled and case reports support the use of clozapine in patients with severe BPD at high risk of suicide.
CONCLUSION
There may be a role for clozapine in treating severe treatment refractory BPD, especially for those patients at high risk of suicide and frequent hospitalisations.
Topics: Humans; Clozapine; Antipsychotic Agents; Suicide; Borderline Personality Disorder; Randomized Controlled Trials as Topic
PubMed: 37572113
DOI: 10.1007/s00213-023-06431-6 -
BMJ Open Nov 2023To assess the current evidence on the potential of digital health interventions (DHIs) to improve adherence to oral antipsychotics among patients with schizophrenia by... (Review)
Review
OBJECTIVES
To assess the current evidence on the potential of digital health interventions (DHIs) to improve adherence to oral antipsychotics among patients with schizophrenia by assessing the methodologies, feasibility and effectiveness of DHIs as well as the perceptions of relevant stakeholders.
DESIGN
The scoping review was conducted based on the methodologies outlined by Levac and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.
DATA SOURCES
PubMed, Embase, Web of Science, Scopus, CINAHL, PsycINFO and the Cochrane Library were searched in August 2023 to identify relevant publications from the previous decade.
ELIGIBILITY CRITERIA
Studies published in English focused on improving medication adherence among adult patients with schizophrenia or schizoaffective disorder via DHIs were selected. Protocols, editorials, comments, perspectives, reviews, correspondence and conference abstracts were excluded.
DATA EXTRACTION AND SYNTHESIS
The extracted data included general information about the study, framework, participants, features and strategies of DHIs, measurement tools for adherence used, and main findings.
RESULTS
In total, 64 studies were included in the qualitative synthesis. Features used in DHIs to improve medication adherence included phone calls, text messages, mobile apps, sensors, web-based platforms and electronic devices. Strategies included medication reminders and monitoring, providing medication-related information and suggestions, other illness management suggestions and individual support. Texting and mobile apps were commonly used as medication reminders and monitoring methods. Additionally, the use of sensors combined with other digital technologies has garnered significant attention. All the interventions were considered acceptable and feasible, and several were assessed in pilot trials. Preliminary findings suggest that DHIs could enhance medication adherence in patients with schizophrenia. However, further validation of their effectiveness is required.
CONCLUSION
DHIs are a promising approach to enhancing medication adherence among patients with schizophrenia. Future interventions should be interactive, focusing on user preference, experience and privacy.
Topics: Adult; Humans; Antipsychotic Agents; Schizophrenia; Text Messaging; Psychotic Disorders; Medication Adherence
PubMed: 37977861
DOI: 10.1136/bmjopen-2023-071984 -
International Journal of Nursing Studies Dec 2023This study aims to systematically assess the risk factors, the overall strength of association, and evidence quality related to delirium among adults hospitalized with... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study aims to systematically assess the risk factors, the overall strength of association, and evidence quality related to delirium among adults hospitalized with COVID-19.
METHODS
A comprehensive search was conducted in thirteen databases from inception to February 10, 2023. The included databases were thoroughly searched, including PubMed, Web of Science, Proquest, Ovid MEDLINE, CINAHL, Scopus, the Cochrane Library, FMRS, Wanfang Database, Chinese Biomedical Database (CBM), China Knowledge Resource Integrated Database (CNKI), Weipu Database (VIP), and Embase. The search was limited to articles published in English and Chinese. The selected studies were screened, data were extracted, and the quality was evaluated using the Newcastle-Ottawa Scale. Meta-analysis was performed using RevMan 5.4 software. The certainty of the evidence was assessed using the GRADE criteria.
RESULTS
A total of 22 cohort studies with a sample size of 11,957 individuals were included in the analysis. Among these studies, 20 were of high quality, while the remaining 2 were of moderate quality. The risk factors that showed the strongest association with delirium were prior cognitive impairment (including dementia), mechanical ventilation, and ICU admission. Age, frailty (Clinical Frailty Scale score > 5), antipsychotic use, benzodiazepine use, neutrophil-to-lymphocyte ratio, and vasopressor use were identified as moderate risk factors for delirium. According to the GRADE evaluation, ICU admission, benzodiazepine use, neutrophil-to-lymphocyte ratio, and vasopressor use had a high-quality body of evidence, while antipsychotic usage had an intermediate-quality body of evidence. All other risk factors had a low-quality body of evidence.
CONCLUSIONS
This systematic review and meta-analysis identified several medium- to high-intensity risk factors for delirium in hospitalized adults with COVID-19. ICU admission, benzodiazepine usage, neutrophil-to-lymphocyte ratio, antipsychotic use, and vasopressor use were associated with delirium and were supported by medium- to high-quality evidence. These findings provide healthcare professionals with an evidence-based basis for managing and treating delirium in hospitalized adults with COVID-19.
Topics: Humans; Adult; Antipsychotic Agents; Delirium; Frailty; COVID-19; Benzodiazepines; Cohort Studies; Risk Factors
PubMed: 37801933
DOI: 10.1016/j.ijnurstu.2023.104602 -
Journal of the American Academy of... Jul 2024Early-onset psychosis (EOP) refers to the development of psychosis before the age of 18 years. We aimed to summarize, for the first time, the meta-analytical evidence in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Early-onset psychosis (EOP) refers to the development of psychosis before the age of 18 years. We aimed to summarize, for the first time, the meta-analytical evidence in the field of this vulnerable population and to provide evidence-based recommendations.
METHOD
We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant, pre-registered (PROSPERO: CRD42022350868) systematic review of several databases and registers to identify meta-analyses of studies conducted in EOP individuals to conduct an umbrella review. Literature search, screening, data extraction, and quality assessment were carried out independently. Results were narratively reported, clustered across core domains. Quality assessment was performed with the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool.
RESULTS
A total of 30 meta-analyses were included (373 individual studies, 25,983 participants, mean age 15.1 years, 38.3% female). Individuals with EOP showed more cognitive impairments compared with controls and individuals with adult/late-onset psychosis. Abnormalities were observed meta-analytically in neuroimaging markers but not in oxidative stress and inflammatory response markers. In all, 60.1% of EOP individuals had a poor prognosis. Clozapine was the antipsychotic with the highest efficacy for overall, positive, and negative symptoms. Tolerance to medication varied among the evaluated antipsychotics. The risk of discontinuation of antipsychotics for any reason or side effects was low or equal compared to placebo.
CONCLUSION
EOP is associated with cognitive impairment, involuntary admissions, and poor prognosis. Antipsychotics can be efficacious in EOP, but tolerability and safety need to be taken into consideration. Clozapine should be considered in EOP individuals who are resistant to 2 non-clozapine antipsychotics. Further meta-analytical research is needed on response to psychological interventions and other prognostic factors.
PLAIN LANGUAGE SUMMARY
This umbrella review summarized the meta-analytical knowledge from 30 meta-analyses on early-onset psychosis. Early-onset psychosis refers to the development of psychosis before the age of 18 years and is associated with cognitive impairment, hospitalization, and poor prognosis. Individuals with early-onset psychosis show more cognitive impairments and abnormalities compared with controls. Clozapine was the antipsychotic with the highest efficacy for positive, negative, and overall symptoms and should be considered in individuals with early-onset psychosis.
STUDY PREREGISTRATION INFORMATION
Early Onset Psychosis: Umbrella Review on Diagnosis, Prognosis and Treatment factors; https://www.crd.york.ac.uk/PROSPERO/; CRD42022350868.
Topics: Humans; Psychotic Disorders; Adolescent; Age of Onset; Antipsychotic Agents; Meta-Analysis as Topic; Cognitive Dysfunction
PubMed: 38280414
DOI: 10.1016/j.jaac.2023.10.016 -
Schizophrenia Research Dec 2023Antipsychotic-induced catatonia (AIC) and neuroleptic malignant syndrome (NMS) are life-threatening adverse reactions to antipsychotic medication. We conducted a...
OBJECTIVES
Antipsychotic-induced catatonia (AIC) and neuroleptic malignant syndrome (NMS) are life-threatening adverse reactions to antipsychotic medication. We conducted a systematic review of literature following the PRISMA statement guidelines to obtain a description of these syndromes (population, context of occurrence, antipsychotic agents implicated) and draw conclusions about their links.
METHODS
We searched Medline and Web of science databases from January 1951 to May 2019 (further restricted from 2000 to 2019) using search terms including "catatonia", "neuroleptic malignant syndrome" and "antipsychotic agents" for case reports, case series and analytic studies. After screening 4082 records, 410 full-text articles (describing 555 events) were assessed for eligibility. We included events of AIC and/or NMS according to Diagnostic and Statistical Manual (DSM) criteria and extracted data about patients' characteristics, context of occurrence, antipsychotic agent(s) involved and treatment outcomes.
RESULTS
We included 165 events (16 AIC, 129 NMS and 20 AIC + NMS) from 144 case reports and case series. The most reported diagnosis was schizophrenia. Comorbid pre-existing conditions such as central nervous system diseases and acute medical events were common. Most of the events (63.3 %) occurred during antipsychotic monotherapy. Second-generation antipsychotics (SGAs, 63.8 %) were overall more implicated than first-generation antipsychotics (FGAs, 36.2 %).
DISCUSSION
Our findings highlight that any antipsychotic medication, even SGA monotherapy prescribed at recommended dose, is at risk for these side effects. FGAs and polypharmacy seem to represent risk factors for malignant catatonia in AIC. The clinical overlap observed between AIC and NMS events in our review suggests a clinical continuum between catatonia and NMS.
Topics: Humans; Antipsychotic Agents; Neuroleptic Malignant Syndrome; Catatonia; Schizophrenia; Treatment Outcome
PubMed: 37599139
DOI: 10.1016/j.schres.2023.08.003 -
Neuroscience and Biobehavioral Reviews May 2024The paucity of evidence regarding the safety of gestational antipsychotic exposure has led to treatment discontinuation in pregnant women with severe mental health... (Meta-Analysis)
Meta-Analysis Review
Association between prenatal antipsychotic exposure and the risk of attention-deficit/hyperactivity disorder and autism spectrum disorder: a systematic review and meta-analysis.
The paucity of evidence regarding the safety of gestational antipsychotic exposure has led to treatment discontinuation in pregnant women with severe mental health conditions. This systematic review and meta-analysis aimed to summarise the current evidence on the association between gestational antipsychotic exposure and attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children (Study protocol registered in PROSPERO:CRD42022311354). Five studies included in our meta-analysis with around 8.6 million pregnancy episodes in nine different countries/regions. Results from our meta-analysis indicate that the heightened risks of ASD and ADHD in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relationship with the antipsychotic exposure during pregnancy. The results underscore the importance of meticulously monitoring the neurodevelopment of children born to mothers with mental illnesses, which can facilitate early interventions and provide requisite support.
Topics: Child; Humans; Female; Pregnancy; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity; Antipsychotic Agents; Prenatal Exposure Delayed Effects; Mothers
PubMed: 38499117
DOI: 10.1016/j.neubiorev.2024.105635 -
Schizophrenia Research Feb 2024Type 2 diabetes (T2DM) is common in patients with schizophrenia and non-affective psychosis. These patients also have an increased prevalence of a family history of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Type 2 diabetes (T2DM) is common in patients with schizophrenia and non-affective psychosis. These patients also have an increased prevalence of a family history of T2DM. We performed a systematic review and meta-analysis of the association between a family history of T2DM and schizophrenia.
METHOD
We searched electronic databases from inception until July 2022 for studies of a family history of T2DM or gestational diabetes in patients with schizophrenia and controls. We performed random effects meta-analysis, calculating odds ratios (ORs) and 95 % confidence intervals (CI) and meta-regression analyses.
RESULTS
Nine studies were included, comprising 2953 patients with non-affective psychosis and 4484 controls. Schizophrenia was associated with an over two-fold increased odds of a family history of T2DM or gestational diabetes (OR = 2.18, 95 % CI 1.61-2.96, p < 0.01). In meta-regression analyses, age, sex, study quality score, and year of publication were all unrelated to the association.
CONCLUSION
We found that patients with schizophrenia had a 2.2-fold increased odds of a family history of T2DM versus controls. This association may be relevant to both the pathophysiology of schizophrenia and the reported increased risk of development of diabetes with antipsychotic treatment.
Topics: Pregnancy; Female; Humans; Diabetes Mellitus, Type 2; Schizophrenia; Diabetes, Gestational; Antipsychotic Agents; Prevalence
PubMed: 38118263
DOI: 10.1016/j.schres.2023.12.001 -
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 -
CNS Drugs Aug 2023Considering the improvement in adherence and convenience, once-monthly paliperidone palmitate (PP1M) has been increasingly used in the treatment of schizophrenia.... (Meta-Analysis)
Meta-Analysis
Effectiveness and Safety of Switching from Oral Antipsychotics to Once-Monthly Paliperidone Palmitate (PP1M) in the Management of Schizophrenia: A Systematic Review and Meta-Analysis.
BACKGROUND
Considering the improvement in adherence and convenience, once-monthly paliperidone palmitate (PP1M) has been increasingly used in the treatment of schizophrenia. However, the outcomes for patients who switch from oral antipsychotics (OAPs) to PP1M have not been reliably assessed. The objective of this systematic review and meta-analysis was to investigate the efficacy and safety of PP1M in the management of patients with schizophrenia with a prior history of OAP use.
METHODS
We conducted a systematic search in PubMed, EMBASE, and the Cochrane Library on 19 July 2022 to identify eligible studies. All studies that examined the effectiveness and safety of switching from OAPs to PP1M in patients with schizophrenia were included. The primary outcomes were relapse rate, hospitalisation rate, and the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score. The secondary outcomes included the changed number of inpatient visits, changed length of stay hospitalisation, change from baseline in the Clinical Global Impressions-Severity (CGI-S) score and the personal and social performance (PSP) total score, response rate, proportion of treatment discontinuation, and adverse events. We included randomised-controlled trials (RCTs), single-arm studies, and observational studies. Case reports, case series, and reviews were excluded. The quality assessment of included studies was performed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB2), the 9-point Newcastle-Ottawa Scale (NOS) instrument for non-randomised studies and cohort studies, and the 12-item National Institutes of Health (NIH) quality assessment tool for before-after (Pre-Post) study without control group. Follow-up times were reported as short- (≤ 13 weeks), medium- (14-26 weeks), and long term (≥ 27 weeks). Data were pooled using meta-analysis.
RESULTS
Fifteen studies with a total of 4740 patients were included. The long-term relapse rates and hospitalisation rates were 12% (95% CI 0.07-0.18) and 18% (95% CI 0.15-0.20), respectively. The short-, medium-, and long-term change in PANSS total score was - 21.69 (95% CI - 30.02 to -13.36), - 14.98 (95% CI - 21.45 to - 8.51) and - 17.88 (95% CI - 31.94 to -3.82), respectively. Approximately 50% of patients reported at least a 30% reduction in the PANSS score at the short-term follow-up. Improvements in CGI-S and PSP score were observed during various periods. There was a reduction in the length of stay hospitalisation and the number of inpatient visits at the medium- and long-term follow-ups. Low discontinuation and adverse event rates were reported.
CONCLUSION
Based on our findings, this study may support the efficacy and safety of switching from OAPs to PP1M for the treatment of patients with schizophrenia. Future large-scale studies are warranted to confirm our findings.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Schizophrenia; Administration, Oral; Recurrence; Chronic Disease
PubMed: 37490267
DOI: 10.1007/s40263-023-01028-1