OBJECTIVE: Olanzapine and risperidone have emerged as the most widely used drugs as short-term prescription in the treatment of behavioral disturbances in dementia. The present systematic review and meta-analysis was hence performed to investigate the effectiveness and safety profile of olanzapine and risperidone in the treatment of behavioral and psychological symptoms of dementia (BPSD), aiming to provide updated suggestion for clinical physicians and caregivers.
METHODS: Prospective controlled clinical studies were included, of which available data was extracted. Outcomes of BEHAVE-AD scores with the variation of grades, specific behaviors variables, as well as safety signals were pooled for the analysis by odds rates and weighted mean differences, respectively.
METHODS: Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang.
METHODS: Prospective, controlled clinical studies, conducted to compare the effectiveness and safety profile of olanzapine and risperidone in the treatment of BPSD.
METHODS: Interested data including baseline characteristics and necessary outcomes from the included studies were extracted independently by 2 investigators. BEHAVE-AD scale was adopted to assess the efficacy in the present study. All behaviors were evaluated at the time of the initiation of the treatment, as well as the completion of drugs courses. Adverse events were assessed with the criteria of Treatment Emergent Symptom Scale, or Coding Symbols for a Thesaurus of Adverse Reaction Terms dictionary. Weighted mean difference was used for the pooled analysis.
RESULTS: A total of 2427 participants were included in the present meta-analysis. Comparative OR on response rate, and remarkable response rate between olanzapine and risperidone was 0.65 (95% CI: 0.51-0.84; P = .0008), and 0.62 (95% CI: 0.50-0.78; P < .0001), respectively. There were statistical differences observed by olanzapine on the improvement of variables including delusions (WMD, -1.83, 95% CI, -3.20, -0.47), and nighttime behavior disturbances (WMD, -1.99, 95% CI, -3.60, -0.38) when compared to risperidone.
CONCLUSIONS: Our results suggested that olanzapine might be statistically superior to risperidone on the reduction of BPSD of Alzheimer\'s disease, especially in the relief of delusions and nighttime behavior disturbances. In addition, olanzapine was shown statistically lower risks of agitation, sleep disturbance, and extrapyramidal signs.

Among the pathophysiological correlates of schizophrenia, recent research suggests a potential role for the Hedgehog (Hh) signalling pathway, which has been traditionally studied in embryonic development and oncology. Its dysregulation may impact brain homeostasis, neuroplasticity, and potential involvement in neural processes. This systematic review provides an overview of the involvement of Hh signalling in the pathophysiology of schizophrenia and antipsychotic responses. We searched the PubMed and Scopus databases to identify peer-reviewed scientific studies focusing on Hh and schizophrenia, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, finally including eight studies, including three articles focused on patients with schizophrenia, two animal models of schizophrenia, two animal embryo studies, and one cellular differentiation study. The Hh pathway is crucial in the development of midbrain dopaminergic neurons, neuroplasticity mechanisms, regulating astrocyte phenotype and function, brain-derived neurotrophic factor expression, brain glutamatergic neural transmission, and responses to antipsychotics. Overall, results indicate an involvement of Hh in the pathophysiology of schizophrenia and antipsychotic responses, although an exiguity of studies characterises the literature. The heterogeneity between animal and human studies is another main limitation. Further research can lead to better comprehension and the development of novel personalised drug treatments and therapeutic interventions.

BACKGROUND: Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.
METHODS: We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.
CONCLUSIONS: Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.
BACKGROUND: PROSPERO-ID CRD42023410645.

Although the physical complications of gestational diabetes mellitus (GDM) are well known, emerging evidence suggests a significant link with psychiatric conditions such as schizophrenia (SCZ). This review aimed to explore the extent, nature, and implications of the association between GDM and SCZ, exploring how the 2 conditions may reciprocally influence each other. We conducted a comprehensive literature review and, analyzed clinical and mechanistic evidence supporting the mutual effects of GDM and SCZ. This review examined factors such as neurodevelopment and the impact of antipsychotics. The study found that Maternal GDM increases the risk of SCZ in offspring. Conversely, women with SCZ were more prone to hyperglycemic pregnancies. The research highlights significant regional variations in GDM prevalence, with the highest rate in the Middle East, North Africa, and South-East Asia regions. These regional variations may have an impact on the epidemiology of SCZ. Furthermore, this review identifies the potential biological and environmental mechanisms underlying these associations. There is a bidirectional relationship between GDM and SCZ, with each disorder potentially exacerbating the others. This relationship has significant implications for maternal and offspring health, particularly in regions with high GDM prevalence. These findings underline the need for integrated care approaches for women with SCZ during pregnancy and the importance of monitoring and managing GDM to mitigate the risk of SCZ in the offspring. Notably, this study recognizes the need for further research to fully understand these complex interactions and their implications for healthcare.

BACKGROUND: Many patients with schizophrenia have symptoms that do not respond to antipsychotics. This condition is called treatment-resistant schizophrenia and has not received specific attention as opposed to general schizophrenia. Psychological and psychosocial interventions as an add-on treatment to pharmacotherapy could be useful, but their role and comparative efficacy to each other and to standard care in this population are not known. We investigated the efficacy, acceptability, and tolerability of psychological and psychosocial interventions for patients with treatment-resistant schizophrenia.
METHODS: In this systematic review and network meta-analysis (NMA), we searched for published and unpublished randomised controlled trials (RCTs) through a systematic database search in BIOSIS, CINAHL, Embase, LILACS, MEDLINE, PsychInfo, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform for articles published from inception up to Jan 31, 2020. We also searched the Cochrane Schizophrenia Group registry for studies published from inception up to March 31, 2022, and PubMed and Cochrane CENTRAL for studies published from inception up to July 31, 2023. We included RCTs that included patients with treatment-resistant schizophrenia. The primary outcome was overall symptoms. We did random-effects pairwise meta-analyses and NMAs to calculate standardised mean differences (SMDs) or risk ratios with 95% CIs. No people with lived experience were involved throughout the research process. The study protocol was registered in PROSPERO, CRD42022358696.
RESULTS: We identified 30 326 records, excluding 24 526 by title and abstract screening. 5762 full-text articles were assessed for eligibility, of which 5540 were excluded for not meeting the eligibility criteria, and 222 reports corresponding to 60 studies were included in the qualitative synthesis. Of these, 52 RCTs with 5034 participants (1654 [33·2%] females and 3325 [66·8%] males with sex indicated) comparing 20 psychological and psychosocial interventions provided data for the NMA. Mean age of participants was 38·05 years (range 23·10-48·50). We aimed to collect ethnicity data, but they were scarcely reported. According to the quality of evidence, cognitive behavioural therapy for psychosis (CBTp; SMD -0·22, 95% CI -0·35 to -0·09, 35 trials), virtual reality intervention (SMD -0·41, -0·79 to -0·02, four trials), integrated intervention (SMD -0·70, -1·18 to -0·22, three trials), and music therapy (SMD -1·27, -1·83 to -0·70, one study) were more efficacious than standard care in reducing overall symptoms. No indication of publication bias was identified.
CONCLUSIONS: We provide robust findings that CBTp can reduce the overall symptoms of patients with treatment-resistant schizophrenia, and therefore clinicians can prioritise this intervention in their clinical practice. Other psychological and psychosocial interventions showed promising results but need further investigation.
BACKGROUND: DAAD-ASFE.

BACKGROUND: International guidelines discourage antipsychotic use for delirium; however, concerns persist about their continued use in clinical practice.
OBJECTIVE: We aimed to describe the prevalence and patterns of antipsychotic use in delirium management with regard to best-practice recommendations. Primary outcomes investigated were prevalence of use, antipsychotic type, dosage and clinical indication.
METHODS: Eligibility criteria: studies of any design that examined antipsychotic use to manage delirium in adults in critical care, acute care, palliative care, rehabilitation, and aged care were included. Studies of patients in acute psychiatric care, with psychiatric illness or pre-existing antipsychotic use were excluded.
METHODS: we searched five health databases on 16 August, 2023 (PubMed, CINAHL, Embase, APA PsycInfo, ProQuest Health and Medical Collection) using MeSH terms and relevant keywords, including \'delirium\' and \'antipsychotic\'. Risk of bias: as no included studies were randomised controlled trials, all studies were assessed for methodological quality using the Mixed Methods Appraisal Tool.
RESULTS: descriptive data were extracted in Covidence and synthesised in Microsoft Excel.
RESULTS: Included studies: 39 studies published between March 2004 and August 2023 from 13 countries (n = 1,359,519 patients). Most study designs were retrospective medical record audits (n = 16).
RESULTS: in 18 studies, participants\' mean age was ≥65 years (77.79, ±5.20). Palliative care had the highest average proportion of patients with delirium managed with antipsychotics (70.87%, ±33.81%); it was lower and varied little between intensive care unit (53.53%, ±19.73%) and non-intensive care unit settings [medical, surgical and any acute care wards] (56.93%, ±26.44%) and was lowest in in-patient rehabilitation (17.8%). Seventeen different antipsychotics were reported on. In patients aged ≥65 years, haloperidol was the most frequently used and at higher than recommended mean daily doses (2.75 mg, ±2.21 mg). Other antipsychotics commonly administered were olanzapine (mean 11 mg, ±8.54 mg), quetiapine (mean 64.23 mg, ±43.20 mg) and risperidone (mean 0.97 mg, ±0.64 mg).
CONCLUSIONS: The use of antipsychotics to manage delirium is strongly discouraged in international guidelines. Antipsychotic use in delirium care is a risk for adverse health outcomes and a longer duration of delirium, especially in older people. However, this study has provided evidence that clinicians continue to use antipsychotics for delirium management, the dose, frequency and duration of which are often outside evidence-based guideline recommendations. Clinicians continue to choose antipsychotics to manage delirium symptoms to settle agitation and maintain patient and staff safety, particularly in situations where workload pressures are high. Sustained efforts are needed at the individual, team and organisational levels to educate, train and support clinicians to prioritise non-pharmacological interventions early before deciding to use antipsychotics. This could prevent delirium and avert escalation in behavioural symptoms that often lead to antipsychotic use.

An association between psychiatric medications and falls and fractures in people taking them has been demonstrated, but which class or medication leads to the greatest risk of falls or fractures should be further investigated. The aim of this study was to compare and rank the magnitude of risk of falls and fractures due to different psychiatric medications. Eight databases were searched for this meta-analysis and evaluated using a frequency-based network meta-analysis. The results included a total of 28 papers with 14 medications from 5 major classes, involving 3,467,314 patients. The results showed that atypical antipsychotics were the class of medications with the highest risk of falls, and typical antipsychotics were the class of medications with the highest risk of resulting in fractures. Quetiapine ranked first in the category of 13 medications associated with risk of falls, and class Z drugs ranked first in the category of 6 medications associated with risk of fractures. The available evidence suggests that atypical antipsychotics and typical antipsychotics may be the drugs with the highest risk of falls and fractures, respectively. Quetiapine may be the medication with the highest risk of falls, and class Z drugs may be the medication with the highest risk of fractures.

BACKGROUND: Evidence suggests that inflammatory processes play a role in the pathophysiology of schizophrenia. Statins exert anti-inflammatory and antioxidant effects and may be effective in improving the symptoms of schizophrenia. This study explored whether statins, as an adjunctive therapy, can alleviate the symptoms of schizophrenia.
METHODS: PubMed, EMBASE, and the Cochrane Library were searched for articles published up to March 2023. The risk-of-bias tool for randomized trials was used to assess study quality. Two researchers independently assessed the risks of bias and extracted data. Pooled data on Positive and Negative Syndrome Scale (PANSS) scores were analyzed. A random-effects model was employed to calculate pooled effect sizes. Statistical heterogeneity across studies was assessed using the I2 statistic. All analyses were performed using RevMan5 and Comprehensive Meta-Analysis software.
RESULTS: Nine trials enrolling 533 patients in total were included. Add-on statin therapy was found to be associated with a significantly better total PANSS score [standardized mean difference (SMD) = -0.42, 95% confidence interval (CI) -0.75 to -0.09, I2 = 72%; P = 0.01] and PANSS negative subscale score (SMD = -0.26, 95% CI -0.45 to -0.07, I2 = 0%; P = 0.009) in comparison with placebo. However, add-on statin therapy did not appear to improve scores for the PANSS positive and general subscales at the study-defined endpoint (6-24 weeks).
CONCLUSIONS: Our meta-analysis indicates that adjunctive statin therapy may confer benefits in ameliorating PANSS negative and total scores. It needs more solid data to confirm the results are related to clinical improvement and functioning.

暂无摘要。

暂无摘要。