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Background: Schizophrenia is a debilitating condition that affects 1% of the global population. Understanding the prevalence and the factors predicting schizophrenia remission is crucial for healthcare providers. This study aimed to determine the prevalence of remission and factors affecting the remission. Cross-sectional study was conducted at the Amanuel Mental Specialized Hospital from 3 October, 2022, to 31 August, 2023, and included 271 participants. Remission was measured using Remission in Schizophrenia Working Group (RSWG) symptom severity-based criteria. Data analysis was done using SPSS V.25. Results: The mean age of participants was 34.2 with standard deviation (SD) of 10.5 years. Most were male (90%), unmarried (63.8%), lived with their relatives (91.9%), and were unemployed (56.5%). Fifty-two percent achieved symptomatic remission. Remission in patients with medication switched to SGAs increased by 1.9 times compared to patients without medication switch (AOR 1.9, 95% CI: 1.1, 1.2). Adherent patients had 2.7 times higher odds of symptomatic remission as compared to non-adherent patients (AOR 2.7, 95% CI: 1.5,4.9), and for each unit increase in body mass index (BMI), the odds of achieving symptomatic remission were increased by 13% (AOR 1.13, 95% CI: 1.04, 1.23). The odds of symptomatic remission decreased by 71% in patients experiencing moderate-to-severe side effects compared to their counterparts (AOR 0.29, 95% CI: 0.1, 0.6). Conclusions: Our study revealed a symptomatic remission was achieved in 141 (52%) of the subjects. There is a possibility to improve symptomatic remission with counseling on the importance of adherence, monitoring and managing side effects, and switching medication to either risperidone or olanzapine. Measuring remission using RSWG time-based criteria is recommended. [ABSTRACT FROM AUTHOR]

Background: Induced pluripotent stem cell (iPSC) based neuronal differentiation is valuable for studying neuropsychiatric disorders and pharmacological mechanisms at the cellular level. We aimed to examine the effects of typical and atypical antipsychotics on human iPSC-derived neural progenitor cells (NPCs). Methods: Proliferation and neurite outgrowth were measured by live cell imaging, and gene expression levels related to neuronal identity were analyzed by RT-QPCR and immunocytochemistry during differentiation into hippocampal dentate gyrus granule cells following treatment of low- and high-dose antipsychotics (haloperidol, olanzapine, and risperidone). Results: Antipsychotics did not modify the growth properties of NPCs after 3 days of treatment. However, the characteristics of neurite outgrowth changed significantly in response to haloperidol and olanzapine. After three weeks of differentiation, mRNA expression levels of the selected neuronal markers increased (except for MAP2), while antipsychotics caused only subtle changes. Additionally, we found no changes in MAP2 or GFAP protein expression levels as a result of antipsychotic treatment. Conclusions: Altogether, antipsychotic medications promoted neurogenesis in vitro by influencing neurite outgrowth rather than changing cell survival or gene expression. This study provides insights into the effects of antipsychotics on neuronal differentiation and highlights the importance of considering neurite outgrowth as a potential target of action. [ABSTRACT FROM AUTHOR]

• We provide the first network meta-analysis comparing long-acting injectable antipsychotics and their oral counterparts for the acute treatment of schizophrenia. • The efficacy of long-acting injectable and oral antipsychotics for acute schizophrenia is similar. • Some side-effects may be less frequent under LAIs, although this pattern is not consistent across outcomes and drugs. Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase. [ABSTRACT FROM AUTHOR]

Background: International guidelines discourage antipsychotic use for delirium; however, concerns persist about their continued use in clinical practice. Objectives: 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. Information sources: 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. Synthesis of 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). Synthesis of 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. [ABSTRACT FROM AUTHOR]

Background: Sudden unexplained death in individuals with mental health problems was described in 1960 and a link with antipsychotic drugs was postulated over 40 years ago. Down the years, a clear relation between electrocardiography (ECG) abnormalities and antipsychotic use was observed with special emphasis on QT prolongation. Various factors modulate the risk of QT prolongation including gender, age, race, and drug choice. An evaluation of antipsychotic use-induced QT changes in Eastern Indian population is the dire need of the hour. Aims and Objectives: The aim and objective are to study the effects of risperidone, olanzapine, and aripiprazole on QT interval after a period of 4 weeks of usage in previously drug-naïve Eastern Indian psychotic patients. Materials and Methods: A total of 78 drug-naïve patients fulfilling inclusion and exclusion criteria were randomly assigned to receive risperidone, olanzapine, and aripiprazole after a baseline ECG. A repeat ECG after 4 weeks of drug usage was done and compared using standard protocols with respect to QT interval. Findings were tabulated and statistical analysis was done using SPSS 25.0 to test for statistical significance at P<0.05. Results: Our study found significant rise in QT values after 4 weeks of using olanzapine and aripiprazole, but not with risperidone. However, none of the patients from either of the groups experienced any incidence of QT prolongation. Rise with olanzapine was significantly higher than that with risperidone. Conclusion: Caution is suggested in patients with risk factors for QT prolongation or a high value of QT during prescribing olanzapine. Studies with larger sample size can be carried out to find genetic predisposition of Indian population to anti-psychotic induced QT interval rise/prolongation. [ABSTRACT FROM AUTHOR]

Background: Quetiapine is commonly prescribed off-label to manage delirium in intensive care unit (ICU) patients. However, limited studies comparing its efficacy and safety to those of other antipsychotics exist in the literature. Method: A retrospective, single-center chart review study was conducted on adults admitted to the ICU between January 2017 and August 2022, who were diagnosed with delirium and treated with a single antipsychotic and had no neurological medical conditions, active alcohol withdrawal, or prior use of antipsychotics. Data were analyzed using SPSS software version 28, with p-values of <0.05 indicating statistical significance. Results: In total, 47 patients were included, of whom 22 (46.8%), 19 (40.4%), 4 (8.5%), and 2 (4.3%) were on quetiapine, haloperidol, risperidone, and olanzapine, respectively. The median number of hours needed to resolve delirium were 12 (21.5), 23 (28), 13 (13.75), and 36 (10) (p = 0.115) for quetiapine, haloperidol, risperidone, and olanzapine, respectively, with haloperidol being used for a significantly shorter median number of days than quetiapine (3 (2.5) days vs. 7.5 (11.5) days; p = 0.007). Of the medication groups, only quetiapine-treated patients received a significantly higher median maintenance compared to the initiation dose (50 (50) mg vs. 50 (43.75) mg; p = 0.039). For the length of stay in the ICU and hospital, delirium-free days, % of ICU time spent in delirium, ventilator-free days, the difference between the highest and baseline QTc intervals, and ICU and hospital mortalities, no significant difference was observed between the groups. Conclusions: Overall, the use of quetiapine in our retrospective study seems to not be advantageous over the other drugs in terms of efficacy and safety outcomes. [ABSTRACT FROM AUTHOR]

The standard pharmacological approach in psychiatric treatment, based on trial and error within a class of drug, often necessitates medication changes due to lack of efficacy or occurrence of adverse effects. The following case described how a more personalized pharmacogenetic approach could facilitate selection of effective treatment (Hudnik et al., 2024). [ABSTRACT FROM AUTHOR]

By meta-analysing pooled studies and available individual participant data, we aim to provide new insight on olanzapine therapeutic drug monitoring in schizophrenia. We conducted a computerized search of bibliographic databases (Pubmed, Cochrane library, Web of Science and PsycINFO) to identify studies that assessed the relationship between olanzapine plasma concentration and the change in patients' clinical scores. We investigated this relationship with olanzapine plasma level 12h00 post-intake using a random-effects model. 7 studies were included in the pooled data analysis (781 patients). We found no difference in oral dose between responders and non-responders but a significantly higher concentration of 4.50 µg/L in responders (p < 0.01). Olanzapine concentration above the thresholds identified in each study was associated with response (odd ratio = 3.50, p = 0.0007). We identified that non-responder patients showed greater inter-individual variability than responders. In the individual data analysis (159 patients), we found no relationship between dose and clinical response but an association between plasma level and response in the shape of a parabolic curve. The Receiver Operating Characteristic curve found a threshold of 22.07 µg/L to identify responders (96% sensitivity, 86% specificity) and a threshold of 56.47 µg/L to identify a decreased probability of response. In contrast to oral dose, our work confirmed that plasma olanzapine levels are associated with clinical response and should therefore be used to optimise treatment. We determined a treatment response threshold of 22.07 µg/L and suggest that a concentration above the therapeutic window may result in a decreased response. [Display omitted] [ABSTRACT FROM AUTHOR]