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Introduction: Managing body weight in patients with antipsychotic‐induced weight gain (AIWG) is challenging. Besides lifestyle interventions, pharmacological interventions may contribute to weight loss. This systematic review and meta‐analysis evaluated the effect on weight loss and adverse effects of glucagon‐like peptide‐1 (GLP‐1) agonists in patients with AIWG. Materials and Methods: Following PRISMA guidelines, we performed a meta‐analysis of blinded and open‐label randomised controlled trials (RCTs), non‐randomised controlled trials and cohort studies that evaluated treatment with GLP‐1 in patients with AIWG, regardless of psychiatric diagnosis. PubMed, Embase, PsycINFO and Cochrane Library databases were searched. Primary outcome measures were changes in body weight and BMI. Secondary outcomes were changes in adverse effects and severity of psychopathology due to GLP‐1 agonists. Results: Only data for exenatide and liraglutide could be included, that is, five RCTs and one cohort study. For exenatide the mean weight loss was −2.48 kg (95% Confidence Interval (CI) −5.12 to +0.64; p = 0.07), for liraglutide the mean weight loss was −4.70 kg (95% CI −4.85 to −4.56; p < 0.001). The mean change in BMI was −0.82 (95% CI −1.56 to −0.09; p = 0.03) in the exenatide groups and −1.52 (95% CI −1.83 to −1.22; p < 0.001) in the liraglutide groups. Exenatide and liraglutide did not adversely affect psychopathology. The most common adverse events were nausea, vomiting, and diarrhoea. Conclusion: The GLP‐1 agonists exenatide and liraglutide are promising drugs for inducing weight loss in patients with AIWG. The adverse effects are acceptable, and the addition of GLP‐1 does not increase the severity of psychopathology. However, more research is needed. [ABSTRACT FROM AUTHOR]

• What is the primary question addressed by this study? We aim to clarify and update the information on the efficacy and tolerability of long-acting antipsychotics in geriatric patients. • What is the main finding of this study? Compared to oral antipsychotics, long-acting antipsychotic use resulted in reduced hospitalization rates and reduced no-show rates, suggesting better engagement in treatment. Female patients had increased discontinuation rates of long-acting antipsychotics and patients with neurocognitive disorder trended in that direction. • What is the meaning of the finding? Long-acting antipsychotics appear to have good efficacy and tolerability in geriatric patients; some patients, however, particularly female patients and possibly patients with neurocognitive disorders, may not tolerate LAI as well as other patients, but more studies are needed on this topic. This study compares demographic, clinical characteristics, and outcomes in older adults on long-acting injectable antipsychotics (LAI-AP) vs. oral antipsychotics (PO-AP). This observational study with a retrospective cohort utilized the electronic medical record's search engine to review charts of geriatric patients on LAI-AP for a two-year period. A convenience sample on PO-AP formed the comparison group. LAI-AP patients were subcategorized into discontinuation and continuation groups. Conducted at an urban, psychiatric outpatient clinic, using charts from October 2020 to 2022. Patients at least 60 years-old with psychotic or mood disorders on antipsychotics for at least 3-months during the study period. Demographic and clinical variables, including diagnosis, medication type, side effects, medical comorbidities, neurocognitive status, and secondary medications, were collected for both PO-AP and LAI-AP groups. Outcome variables included missed appointments, psychiatric and medical hospitalizations, and emergency room visits. Correlates of discontinuation of LAI-AP were also assessed. LAI-AP had a higher proportion than PO-AP of primary psychotic disorders (87.8% vs. 64.3%). During the study, PO-AP had higher rates of missed appointments (median 18% vs. 13% for LAI-AP) and psychiatric admissions (mean 0.019/month vs. 0.006/month for LAI-AP;); Female sex was a risk factor for discontinuation of LAI-AP (86.7% of discontinuation group vs. 55.2% of continuation group). The LAI-AP group showed reduced hospitalizations, better treatment engagement, and comparable tolerability to PO-AP. Preliminary data suggests gender may influence LAI-AP discontinuation rates. This study adds to the sparse literature investigating the efficacy and tolerability of LAI-AP in geriatric patients. [ABSTRACT FROM AUTHOR]

Disorders manifested by both neurological and mental disorders belong to the neuropsychiatric diseases. This category includes Alzheimer's disease, Parkinson's disease, Wernicke–Korsakoff syndrome, delirium tremens, catatonia and anti-NMDA receptor encephalitis. The etiology of psychotic disorders in neuropsychiatric diseases probably differs from that in schizophrenia and other psychoses, which causes both inefficiency and adverse events when using antipsychotics in neuropsychiatry. In the absence of a therapeutic alternative, antipsychotics can be prescribed with caution for neurodegenerative disorders, whereas catatonia is a relative, and anti-NMDA receptor encephalitis is an absolute contraindication to their use.

Sex-related differences in psychopharmacology present unique challenges in both clinical and research settings. Recognition of sex differences in psychopharmacological treatment has increased in recent years, but a significant research gap regarding variations between men and women still exists. Biological factors, including hormonal fluctuations, genetic factors, and brain structure differences, contribute significantly to differential drug responses. Moreover, social determinants can influence the differential burden of psychiatric disorders between the sexes and may impact treatment plans. Incorporating sex as a key variable in personalized treatment programs and plans holds the potential to optimize efficacy and minimize adverse effects in psychopharmacology. Sex-related challenges in psychopharmacology necessitate a nuanced approach to treatment. Further research is needed to fully understand these differences and to develop guidelines for personalized medication management. By addressing these challenges, clinicians can improve treatment outcomes and enhance the quality of life of patients with psychiatric disorders.

Abstract Background Latinos are more likely than non-Latino Whites to develop dementia and be prescribed antipsychotics for dementia-related behavioral symptoms. Antipsychotics have significant risks yet are often overprescribed. Our understanding of how Latino caregivers of Latino older adults living with dementia perceive and address behavioral issues is limited, impeding our ability to address the root causes of antipsychotic overprescribing. Methods We interviewed Latino older adults’ caregivers and community-based organization workers serving older adults with cognitive impairment (key informants), focusing on the management of behavioral symptoms and experiences with health services. Results We interviewed 8 caregivers and 2 key informants. Caregivers were the spouses, children, or grandchildren of the older adult living with cognitive impairment; their ages ranged from 30 to 95. We identified three categories of how caregivers learned about, managed, and coped with behavioral symptoms: caregivers often faced shortcomings with dementia care in the medical system, receiving limited guidance and support; caregivers found community organizations and senior day centers to be lifelines, as they received relevant, timely advice and support, caregivers often devised their own creative strategies to manage behavioral symptoms. Conclusion In-depth interviews suggest that the healthcare system is failing to provide support for behavioral symptoms from dementia; caregivers of Latino older adults rely on community organizations instead.

Abstract Background Potentially inappropriate medications (PIMs) are prevalent in older adults with dementia and subsequent falls or fall-related injuries. The present study determined the risk of falls or fall-related injuries associated with PIM use in older adults with dementia. Methods The National Health Insurance Service-Elderly Cohort Database 2.0 (NHIS-ECDB 2.0) was used for this self-controlled case series (SCCS) study. This study included 1430 participants who went through exposure and non-exposure periods of PIM application among patients with dementia and experienced outcome events of falls or fall-related injuries between January 2016 and December 2019. The incidence of falls or fall-related injuries during the exposure and post-exposure periods was compared with that during the non-exposure period. Beers Criteria were used to define PIMs in patients with dementia. Negative binomial regression was conducted. The incidence rate ratio (IRR) was used to determine the risk of falls or fall-related injuries. Results During the exposure periods in which falls or fall-related injuries occurred, the mean number of PIMs among patients with dementia was 3.76 (SD = 2.99), and the most commonly used PIMs among patients with dementia were first-generation antihistamines (n = 283; 59.1%). Compared to the non-exposure period, the adjusted IRR during the exposure period was 1.57 (95% CI = 1.39–1.76). The risk of falls or fall-related injuries was increased when PIM use in patients with dementia was initiated (1–14 days: IRR = 2.76, 95% CI = 2.31–3.28; 15–28 days: IRR = 1.95, 95% CI = 1.48–2.56; ≥ 29 days: IRR = 1.17, 95% CI = 1.01–1.35). Especially, an increased risk of falls or fall-related injuries was associated with greater PIM use among patients with dementia. Conclusion Among older adults with dementia, PIMs significantly increase the risk of falls and fall-related injuries. Therefore, strategies should be developed to manage PIM prescriptions in patients with dementia to prevent falls.

BACKGROUND: Healthcare professionals who work in mental health institutions are more exposed to psychotropic medications than those in other healthcare institutions and are, therefore, more likely to self-prescribe. Self-prescription is a concerning phenomenon because of the potential for medication misuse, drug interaction, addiction, and other social, physical, and psychological consequences. This study investigated the prevalence of self-prescription of psychotropic medications and the most common self-prescribed psychotropic medications by healthcare professionals in mental health institutions in Saudi Arabia. It also aimed to determine the possible side effects and factors associated with self-prescription of psychotropic medications. MATERIALS AND METHODS: This was a cross-sectional study using an electronic survey consisting of a researcher-designed checklist, targeting healthcare professionals in mental health institutions in Saudi Arabia. The independent variables were sex, nationality, occupation, place of residence, place of work, previous diagnosis of mental illness, marital, and living status. Data were analyzed, using SPSS, and frequency distribution and percentages were calculated. Chi-square test was employed to determine association between self-prescription and various independent variables. RESULTS: The final sample size was 588; 9.5% healthcare professionals working at mental health institutions in Saudi Arabia admitted to self-prescription with psychotropic medications. Almost half of those who admitted to self-prescription (48.2%) and about 1/4 (23.2%) self-prescribed selective serotonin reuptake inhibitors and benzodiazepines, respectively. The most commonly reported side effects of self-prescription were gastrointestinal symptoms and drowsiness. The study also suggested that males were significantly more prone to self-prescribing than females (P < 0.001). CONCLUSION: To our knowledge, this is the first study in Saudi Arabia to assess the self-prescription of psychotropic medications by healthcare professionals at mental health institutions. This study is important for decision-makers in their planning and updating of prescription policies. It is also equally important to spread awareness among healthcare professionals about the consequences of self-prescription.

Abstract Background The risk of arrhythmia is usually assessed by the length of the corrected QT interval (QTc) when patients use antipsychotics. Prolonged QTc intervals are thought to increase the probability of malignant ventricular arrhythmias, and if we focus only on the QTc interval, we may be influenced by a single factor and make decisions that are not conducive to effective treatment. The index of cardiac electrophysiological balance (iCEB) is considered more valuable than the QTc for predicting drug-induced arrhythmias. It has been used in clinical practice, but no studies have observed changes in this index after the use of antipsychotics. Objective To investigate the changes in ventricular repolarization indices and the occurrence of arrhythmias in patients who have been using antipsychotic drugs for a long time, to compare the changes in iCEBc and QTc and to predict abnormal iCEBc values. Methods Patients with schizophrenia who had been hospitalized for more than 4 years and who were receiving atypical antipsychotics underwent a 12-lead synchronized electrocardiogram (ECG) every 2–4 weeks. The baseline data were measured at admission, defined as the baseline (time0), and the most obvious abnormal changes in ventricular depolarization and repolarization measured every 12 months were one-year follow-up (time1), two-year follow-up (time2), three-year follow-up (time3), and four-year follow-up (time4). Repeated measures analysis of variance was used for comparisons. The types and doses of drugs taken at 5 time points were recorded and converted into chlorpromazine equivalents for comparison. The incidence of arrhythmia during the observation cycle was recorded. Results The patients had been treated with antipsychotic medication for 4 years, and the duration of the QRS wave was longer in males than in females. TpTe, TpTe/QRS, TpTe/QT, TpTe/QTc, iCEB, and iCEBc increased significantly with hospital stay, while TpTe, TpTe/QRS, TpTe/QT, and TpTe/QTc exhibited more obvious changes in these indicators in female patients (P

Abstract Background Global antipsychotic usage, including off-label prescriptions, has increased in recent decades. However, trends in China, particularly for children and adolescents, remain unclear. This study explored these trends from 2016 to 2021 and identified factors associated with off-label prescriptions. Methods In this retrospective study, we analyzed on-label and off-label prescriptions based on drug information approved by the China National Medical Products Administration. To identify factors associated with off-label prescriptions, we conducted multivariate logistic regression analysis. Results Our study included 48,258 antipsychotic prescriptions, 52.4% (25,295) of which were prescriptions for males. Of these, 61.7% (29,813) were off-label. Over time, the number of antipsychotics and the percentage of off-label prescriptions for children and adolescents overall increased from 2016 to 2021. The use of atypical antipsychotics increased, whereas that of typical antipsychotics decreased. For off-label usage, all of the factors in our study were associated with off-label usage, including age, sex, year, region, department, reimbursement, antipsychotic type, drug expense, number of polypharmacy and diagnoses. Additionally, tiapride (15.8%) and aripiprazole (18.6%) were the most common typical and atypical antipsychotics, respectively. For pediatric diseases, common diagnoses included mood or affective disorders (31.7%) and behavioral and emotional disorders, with onset usually occurring in childhood and adolescence (29.1%). Furthermore, a depressive state was the most common diagnosis for which antipsychotic polypharmacy was used for treatment. Conclusion In this retrospective study, off-label antipsychotic prescriptions were common, with trends generally increasing among children and adolescents from 2016 to 2021. However, there is a lack of evidence supporting off-label usage, thus emphasizing the need for studies on the efficacy and safety of these treatments.

Abstract Background Female gynecological cancers represent a serious public health problem, with 1,398,601 new diagnoses and 671,875 deaths per year worldwide. Antipsychotics are often used in psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. It is estimated that the prescription of these drugs is linked to 1,800 deaths a year in the United States, but their association with cancer remains controversial. Methods We searched PubMed, Scopus, and Web of Science databases for studies reporting the correlation in the incidence risk of gynecological cancer by antipsychotic use. We used DerSimonian and Laird random-effect models to compute logit transformed odds ratio (OR) for the primary binary endpoint with 95% confidence interval (CI). Heterogeneity was assessed through effect size width along with I-squared and Tau-squared statistics. Review Manager 5.4.1. was used for statistical analyses. A p-value of

Abstract Neuroleptic malignant syndrome is a rare, life-threatening neurologic emergency characterized by fever, rigidity, autonomic instability, mental status changes, and an elevated creatine kinase level. It often occurs shortly after the initiation of neuroleptic treatment, or after a dose increase. The management of patients with NMS is based upon clinical severity and includes supportive care and withdrawal of antipsychotic agents and agents like bromocriptine and dantrolene. Complications include acute renal failure associated with rhabdomyolysis, respiratory failure, electrolyte imbalance, hepatic failure, seizures from hyperthermia, metabolic derangements, etc.

Background Methods Results Conclusions Federal policies targeting antipsychotic use among nursing home (NH) residents may have increased reporting of diagnoses for approved uses, including schizophrenia, Tourette's syndrome, and Huntington's Disease (called “exclusionary diagnoses” because they exclude residents from the antipsychotic quality metric). We assessed changes in new exclusionary diagnoses among long‐stay NH admissions specifically with dementia following federal policies.Retrospective, quarterly, interrupted time‐series analysis (2009–2018) of new long‐stay NH residents with dementia and no exclusionary diagnoses reported before NH admission. The National Partnership and the addition of facility level antipsychotic use to the Five Star Quality Rating system were key time exposures. Outcome was quarterly facility level predicted percentage of exclusionary diagnoses within 2 years of admission stratified by NH characteristics.For 264,095 long‐stay admissions, mean percentage of new exclusionary diagnoses was 2.2% before the Partnership. After the Partnership, there was an unadjusted increase in the percentage over time (slope change, 0.044, p = 0.018), but the percentage never exceeded 2.9%. The Partnership contributed to a one‐time decrease in diagnoses in NHs with an intermediate percentage of Black residents (−1.29%, p = 0.004). Before the Partnership, diagnoses were increasing among not‐for‐profit relative to for‐profit NHs (0.044; p = 0.012), but after the Partnership, the pattern reversed. For‐profit NHs saw an increase (+0.034, p = 0.002); not‐for‐profit NHs experienced a decrease (−0.014, p = 0.039). Quality Rating modifications had no significant effect.Exclusionary diagnosis reporting among long‐stay NH residents with dementia, the group most at risk from antipsychotics, did not increase in response to federal policies. Evaluation of reasons for the observed increase in exclusionary diagnoses among non‐dementia NH residents is warranted along with continued attention to how to incentivize the appropriate use of medications in residents with dementia that is crucial for high‐quality NH care. [ABSTRACT FROM AUTHOR]

Background: Potentially inappropriate medications (PIMs) are prevalent in older adults with dementia and subsequent falls or fall-related injuries. The present study determined the risk of falls or fall-related injuries associated with PIM use in older adults with dementia. Methods: The National Health Insurance Service-Elderly Cohort Database 2.0 (NHIS-ECDB 2.0) was used for this self-controlled case series (SCCS) study. This study included 1430 participants who went through exposure and non-exposure periods of PIM application among patients with dementia and experienced outcome events of falls or fall-related injuries between January 2016 and December 2019. The incidence of falls or fall-related injuries during the exposure and post-exposure periods was compared with that during the non-exposure period. Beers Criteria were used to define PIMs in patients with dementia. Negative binomial regression was conducted. The incidence rate ratio (IRR) was used to determine the risk of falls or fall-related injuries. Results: During the exposure periods in which falls or fall-related injuries occurred, the mean number of PIMs among patients with dementia was 3.76 (SD = 2.99), and the most commonly used PIMs among patients with dementia were first-generation antihistamines (n = 283; 59.1%). Compared to the non-exposure period, the adjusted IRR during the exposure period was 1.57 (95% CI = 1.39–1.76). The risk of falls or fall-related injuries was increased when PIM use in patients with dementia was initiated (1–14 days: IRR = 2.76, 95% CI = 2.31–3.28; 15–28 days: IRR = 1.95, 95% CI = 1.48–2.56; ≥ 29 days: IRR = 1.17, 95% CI = 1.01–1.35). Especially, an increased risk of falls or fall-related injuries was associated with greater PIM use among patients with dementia. Conclusion: Among older adults with dementia, PIMs significantly increase the risk of falls and fall-related injuries. Therefore, strategies should be developed to manage PIM prescriptions in patients with dementia to prevent falls. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Women may experience unique mental disorders due to hormone shifts. Rates of schizophrenia and bipolar disorder are similar between genders, but onset and symptoms may differ. Women tend to use more psychotropic drugs due to limited therapeutic options. This study was aimed to estimate the prevalence of psychotropic polypharmacy among females of childbearing potential and factors impacting prescribing patterns.This was a quantitative retrospective chart review for patients admitted to inpatient units at the Mental Health Hospital in Qatar. SPSS® Statistics was used for data analysis. In addition to descriptive statistics applied, linear regression and binary logistic regression models were used to examine the clinical and sociodemographic factors associated with polypharmacy and full therapeutic response upon discharge, respectively. An alpha value of 0.05 was used.Of the 347 patients, 52.7% of the patients received a prescription of at least two psychotropic drugs upon discharge. Around two‐thirds (63.1%) were prescribed at least one antipsychotic. Potential predictors of polypharmacy were age (p = 0.027), longer hospital stay (p = 0.003), family history (p < 0.001), absence of suicidal history (p = 0.005), and a diagnosis of a mood disorder (p = 0.009), or a diagnosis of a psychotic disorder (p = 0.015). A full response upon discharge was less likely to occur in patients with a longer stay (OR = 0.940; p = 0.029) and in those with a substance use disorder (OR = 0.166; p = 0.035).There is a notably high prevalence of total polypharmacy upon discharge. Some identified factors are modifiable. Evidence‐based prescription practices through hospital guidelines and education should be emphasized to avoid unreasonable polypharmacy. [ABSTRACT FROM AUTHOR]

This study aims to describe the patterns and trends in antipsychotic prescription among Dutch youth before and during the corona virus disease 2019 (COVID-19) pandemic (between 2017 and 2022). The study specifically aims to determine whether there has been an increase or decrease in antipsychotic prescription among this population, and whether there are any differences in prescription patterns among different age and sex groups. The study utilized the IADB database, which is a pharmacy prescription database containing dispensing data from approximately 120 community pharmacies in the Netherlands, to analyze the monthly prevalence and incidence rates of antipsychotic prescription among Dutch youth before and during the pandemic. The study also examined the prescribing patterns of the five most commonly used antipsychotics and conducted an autoregressive integrated moving average (ARIMA) analysis using data prior to the pandemic, to predict the expected prevalence rate during the pandemic. The prescription rate of antipsychotics for Dutch youth was slightly affected by the pandemic, with a monthly prevalence of 4.56 [4.50–4.62] per 1000 youths before COVID-19 pandemic and 4.64 [4.59–4.69] during the pandemic. A significant increase in prevalence was observed among adolescent girls aged 13–19 years. The monthly incidence rate remained stable overall, but rose for adolescent girls aged 13–19 years. Aripiprazole, and Quetiapine had higher monthly prevalence rates during the pandemic, while Risperidone and Pipamperon had lower rates. Similarly, the monthly incidence rates of Aripiprazole and Olanzapine went up, while Risperidone went down. Furthermore, the results from the ARIMA analysis revealed that despite the pandemic, the monthly prevalence rate of antipsychotic prescription was within expectation. The findings of this study suggest that there has been a moderate increase in antipsychotic prescription among Dutch youth during the COVID-19 pandemic, particularly in adolescent females aged 13–19 years. However, the study also suggests that factors beyond the pandemic may be contributing to the rise in antipsychotic prescription in Dutch youth. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) is a complex neuropsychiatric disorder associated with altered bioenergetic pathways and mitochondrial dysfunction. Antipsychotic medications, both first and second-generation, are commonly prescribed to manage SCZ symptoms, but their direct impact on mitochondrial function remains poorly understood. In this study, we investigated the effects of commonly prescribed antipsychotics on bioenergetic pathways in cultured neurons. We examined the impact of risperidone, aripiprazole, amisulpride, and clozapine on gene expression, mitochondrial bioenergetic profile, and targeted metabolomics after 24-h treatment, using RNA-seq, Seahorse XF24 Flux Analyser, and gas chromatography–mass spectrometry (GC–MS), respectively. Risperidone treatment reduced the expression of genes involved in oxidative phosphorylation, the tricarboxylic acid cycle, and glycolysis pathways, and it showed a tendency to decrease basal mitochondrial respiration. Aripiprazole led to dose-dependent reductions in various mitochondrial function parameters without significantly affecting gene expression. Aripiprazole, amisulpride and clozapine treatment showed an effect on the tricarboxylic acid cycle metabolism, leading to more abundant metabolite levels. Antipsychotic drug effects on mitochondrial function in SCZ are multifaceted. While some drugs have greater effects on gene expression, others appear to exert their effects through enzymatic post-translational or allosteric modification of enzymatic activity. Understanding these effects is crucial for optimising treatment strategies for SCZ. Novel therapeutic interventions targeting energy metabolism by post-transcriptional pathways might be more effective as these can more directly and efficiently regulate energy production. [ABSTRACT FROM AUTHOR]

Background: Compared with the general population, adults with an intellectual developmental disorder (IDD) are more likely to develop mental health problems and to receive high levels of psychotropic medication, particularly antipsychotics. The emotional development (ED) approach may help to better understand the nature of challenging behaviour (CB) and tailor treatment and support accordingly. The aim of this retrospective study was to investigate the impact of the ED approach on the prescription of psychotropic medication during inpatient psychiatric treatment. Methods: The clinical data of 1758 patients were analysed within a retrospective study design over a period of 12 years. ED level was assessed (1) for the first time (INITIAL‐SEO), (2) during a previous hospital stay (PAST‐SEO) or (3) not at all (NO‐SEO). The effects of the ED assessment and the respective intervention during the current admission on the number of psychotropics and the number and dosage of antipsychotics were analysed for the total sample, including those with CB, autism spectrum disorders and psychosis. Group differences were analysed by a chi‐square test and a one‐factorial analysis of variance. For analysing the impact of the application of the ED approach on psychotropic medication, a covariance model was applied. Changes between the subsamples were analysed by t‐tests for dependent samples. Results: The ED approach had a significant impact on reducing the overall amount of psychotropic medication and the dosage of antipsychotics in all patients with IDD. These effects were mainly attributable to those showing CB. In patients with autism spectrum disorders, the developmental approach reduced the number of antipsychotics. No effects could be observed in patients with psychosis; in this subsample, both the number and dosage of antipsychotics increased. Conclusions: The application of the ED approach in the current hospital stay reduced the number of psychotropic drugs and the number and dosage of antipsychotics, especially in those patients with IDD and CB, but also in those with autism spectrum disorders. [ABSTRACT FROM AUTHOR]

Certain antipsychotics elevate prolactin levels in patients with schizophrenia spectrum disorders (SSD), potentially affecting cognition, symptoms, and hormone levels. This study examines the association between prolactin, testosterone, and estrogen and cognition and symptoms in men with SSD, considering antipsychotic medication. This cross-sectional study included 128 men with SSD and 44 healthy men from two trials. Patients were divided into a prolactin-sparing (n = 53) and prolactin-raising group (n = 75) based on antipsychotic medication. We examined the association between hormones (testosterone, estrogen and prolactin), and cognition and symptoms using backward linear regression. Three domains of cognition were assessed including: processing speed, verbal fluency, and working memory, while symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Prolactin levels were highest in the prolactin-raising group, followed by the control group, and lowest in the prolactin-sparing group (H = 45.279, p <.001). Testosterone and estrogen levels did not differ significantly between groups. In the prolactin-raising group, prolactin negatively correlated with testosterone (r (73) = −0.32, p =.005). Higher testosterone predicted better cognitive functioning (working memory: β = 0.20, p =.007, verbal fluency: β = 0.30, p =.001) and lower symptom scores (total: β = −0.21, p =.001; negative: β = −0.24, p =.002) in men with SSD. Conversely, higher estrogen levels related to slower processing speed (β = −0.22, p <.001) and higher symptoms scores (β = 0.23, p =.010) in men with SSD. The results suggest positive associations between testosterone and cognition and symptoms in men with SSD, while suggesting that high prolactin levels could relate to lower testosterone levels, possibly worsening cognition and symptoms in men with SSD. [ABSTRACT FROM AUTHOR]

The striatum is thought to play a critical role in the pathophysiology and antipsychotic treatment of schizophrenia. Previous studies have revealed abnormal functional connectivity (FC) of the striatum in early-onset schizophrenia (EOS) patients. However, no prior studies have examined post-treatment changes of striatal FC in EOS patients. We recruited 49 first-episode drug-naïve EOS patients to have resting-state functional magnetic resonance imaging scans at baseline and after 8 weeks of treatment with antipsychotics, along with baseline scanning of 34 healthy controls (HCs) for comparison purposes. We examined the FC values between each seed in striatal subregion and the rest of the brain. The Positive and Negative Syndrome Scale (PANSS) was applied to measure psychiatric symptoms in patients. Compared with HCs at baseline, EOS patients exhibited weaker FC of striatal subregions with several brain regions of the salience network and default mode network. Meanwhile, FC between the dorsal caudal putamen (DCP) and left supplementary motor area, as well as between the DCP and right postcentral gyrus, was negatively correlated with PANSS negative scores. Furthermore, after 8 weeks of treatment, EOS patients showed decreased FC between subregions of the putamen and the triangular part of inferior frontal gyrus, middle frontal gyrus, supramarginal gyrus and inferior parietal lobule. Decreased striatal FC is evident, even in the early stages of schizophrenia, and enhance our understanding of the neurodevelopmental abnormalities in schizophrenia. The findings also demonstrate that reduced striatal FC occurs after antipsychotic therapy, indicating that antipsychotic effects need to be accounted for when considering striatal FC abnormalities in schizophrenia. [ABSTRACT FROM AUTHOR]

Good adherence to antipsychotic therapy helps prevent relapses in first-episode psychosis (FEP). We used data from the FEP-CAUSAL Collaboration, an international consortium of observational cohorts, to emulate a target trial comparing antipsychotics, with treatment discontinuation as the primary outcome. Other outcomes included all-cause hospitalization. We benchmarked our results to estimates from the European First Episode Schizophrenia Trial, a randomized trial conducted in the 2000s. We included 1097 patients with a psychotic disorder and less than 2 years since psychosis onset. Inverse-probability weighting was used to control for confounding. The estimated 12-month risks of discontinuation for aripiprazole, first-generation agents, olanzapine, paliperidone, quetiapine, and risperidone were 61.5% (95% CI, 52.5-70.6), 73.5% (95% CI, 60.5-84.9), 76.8% (95% CI, 67.2-85.3), 58.4% (95% CI, 40.4-77.4), 76.5% (95% CI, 62.1-88.5), and 74.4% (95% CI, 67.0-81.2), respectively. Compared with aripiprazole, the 12-month risk differences were -15.3% (95% CI, -30.0 to 0.0) for olanzapine, -12.8% (95% CI, -25.7 to -1.0) for risperidone, and 3.0% (95% CI, -21.5 to 30.8) for paliperidone. The 12-month risks of hospitalization were similar between agents. Our estimates support use of aripiprazole and paliperidone as first-line therapies for FEP. Benchmarking yielded similar results for discontinuation and absolute risks of hospitalization as in the original trial, suggesting that data from the FEP-CAUSAL Collaboration sufficed to remove confounding for these clinical questions. This article is part of a Special Collection on Mental Health. [ABSTRACT FROM AUTHOR]

Objective: Akathisia, a common side effect of psychotropic medications, poses a significant challenge in neuropsychiatry, affecting up to 30% of patients on antipsychotics. Despite its prevalence, akathisia remains poorly understood, with difficulties in diagnosis, patient reporting, and treatment efficacy. This research aimed to shed light on effective interventions to improve akathisia management. Methods: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted, encompassing controlled trials in English and Italian languages. Databases, such asPubMed, Scopus, and EMBASE, were searched until July 9, 2023. Treatment effectiveness was assessed using standardized mean differences (SMDs) in post-treatment akathisia scores. Results: Thirteen studies involving 446 individuals met the inclusion criteria. Benzodiazepines, beta-blockers, and NaSSA demonstrated significant efficacy as compared with placebo. Anticholinergic, anticonvulsant, triptan, and other treatments did not show significant differences. Benzodiazepines ranked highest in P -scores (0.8186), followed by beta-blockers and NaSSA. Conclusions: Effective management of akathisia is crucial, with benzodiazepines, beta-blockers, and NaSSA offering evidence-based options. Treatment rankings provide guidance for clinicians. Future research should prioritize larger, more robust studies to address limitations associated with small sample sizes and publication bias. This research enhances our understanding of interventions for akathisia, offering promising options to improve patient quality of life and prevent complications related to non-adherence and mismanagement. [ABSTRACT FROM AUTHOR]

Objective: Globally, rates of metabolic disorders continue to climb, leading to significant disease morbidity and mortality. Individuals with mental illness are particularly prone to obesity, and some medications, such as antipsychotics, may increase the risk for metabolic disorders. The American Psychiatric Association and the American Diabetes Association recommend that patients taking antipsychotic medications receive regular screening for metabolic disorders. This study examined hospital and community factors associated with screening these patients for such disorders. Methods: The authors combined Centers for Medicare and Medicaid Services (CMS) hospital-level data on screening for metabolic disorders among patients with an antipsychotic prescription with community data, including urbanization classification, social vulnerability, and metabolic disease presence and risk factors. Data were merged at the county level and evaluated with a nonparametric multivariate regression model. Results: The CMS data set included 1,497 U.S. hospitals with data on screening for metabolic disorders among patients with an antipsychotic prescription. Screening rates varied by type of facility; acute care and critical access hospitals outperformed freestanding psychiatric facilities (p<0.001). No other variables examined in the multivariate model were associated with screening for metabolic disorders. Conclusions: Despite common resource limitations, screening for metabolic disorders may be driven more by logistics and less by time, finances, or a community's primary care network. Identifying the specific logistical challenges of freestanding psychiatric facilities could aid in the development of targeted interventions to improve the rates of screening for and treatment of not only metabolic disorders but also other common comorbid conditions. [ABSTRACT FROM AUTHOR]

Objective: Previous research has suggested that demographic factors affect the likelihood of a patient with schizophrenia receiving a clozapine prescription. The authors aimed to determine the impact of race, social determinants of health, gender, rurality, and care patterns on clozapine prescription rates. Methods: This cross-sectional observational study used structured electronic health records data from 3,160 adult patients diagnosed as having schizophrenia between October 1, 2015, and November 30, 2021, in a multifacility health system. The social vulnerability index (SVI) was used to quantify social determinants of health. Descriptive data analysis, logistic regression, and sensitivity analysis were conducted to identify differences between patients with schizophrenia who received a clozapine prescription and those who received antipsychotic medications other than clozapine. Results: Overall, 401 patients with schizophrenia were given a clozapine prescription during the study period, and 2,456 received antipsychotics other than clozapine. Results of the logistic regression indicated that White race (OR=1.71, compared with Black race), community minority status and language SVI score (OR=2.97), and increased treatment duration (OR=1.36) were significantly associated with a higher likelihood of clozapine prescription; gender, rurality, age at first diagnosis, and ethnicity did not influence the likelihood of receiving clozapine. Conclusions: Black patients with schizophrenia had a lower likelihood of receiving a clozapine prescription compared with White patients, even after analyses accounted for demographic variables, social determinants of health, and care access patterns. Given the effectiveness of clozapine in managing treatment-resistant schizophrenia, it is crucial for future research to better understand the factors contributing to this treatment disparity. [ABSTRACT FROM AUTHOR]

Dementia is a disease most prevalent in the older adult population. The cognitive symptoms of dementia include impairments in problem-solving, memory, and language. Some patients experience noncognitive symptoms in addition to the cognitive symptoms of dementia. These noncognitive symptoms are called behavioral and psychological symptoms of dementia or BPSD. The primary objective of our study was to examine the therapeutic options, guidelines, and clinical considerations for the management of BPSD. The existing literature about BPSD was reviewed with searches in PubMed, MEDLINE, and online search platforms. Dysregulation of neurotransmission involving acetylcholine, dopamine, and serotonin has been shown to cause behavioral and psychological symptoms of Alzheimer's disease. BPSD can include hallucinations, agitation, delusions, anxiety, apathy, abnormal body movements, irritability, depression, disinhibition, and sleep or appetite changes. Pharmacologic therapies used in the treatment of BPSD include antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Treatment can be tailored to the specific noncognitive symptoms that are experienced. The use of these agents may be limited based on recommendations from the Beers Criteria®, STOPP criteria, treatment guidelines, and FDA warnings. [ABSTRACT FROM AUTHOR]

Introduction: Schizophrenia (SCZ) and autism spectrum disorder (ASD) are neurodevelopmental diseases characterized by different psychopathological manifestations and divergent clinical trajectories. Various alterations at glutamatergic synapses have been reported in both disorders, including abnormal NMDA and metabotropic receptor signaling. Methods: We conducted a bicentric study to assess the blood serum levels of NMDA receptors-related glutamatergic amino acids and their precursors, including L-glutamate, L-glutamine, D-aspartate, L-aspartate, L-asparagine, Dserine, L-serine and glycine, in ASD, SCZ patients and their respective control subjects. Specifically, the SCZ patients were subdivided into treatment-resistant and non-treatment-resistant SCZ patients, based on their responsivity to conventional antipsychotics. Results: D-serine and D-aspartate serum reductions were found in SCZ patients compared to controls. Conversely, no significant differences between cases and controls were found in amino acid concentrations in the two ASD cohorts analyzed. Discussion: This result further encourages future research to evaluate the predictive role of selected D-amino acids as peripheral markers for SCZ pathophysiology and diagnosis. [ABSTRACT FROM AUTHOR]

Background: Neuropsychopharmacological compounds may exert complex brain-wide effects due to an anatomically and genetically broad expression of their molecular targets and indirect effects via interconnected brain circuits. Electrophysiological measurements in multiple brain regions using electroencephalography (EEG) or local field potential (LFP) depth-electrodes may record fingerprints of such pharmacologically-induced changes in local activity and interregional connectivity (pEEG/pLFP). However, in order to reveal such patterns comprehensively and potentially derive mechanisms of therapeutic pharmacological effects, both activity and connectivity have to be estimated for many brain regions. This entails the problem that hundreds of electrophysiological parameters are derived from a typically small number of subjects, making frequentist statistics ill-suited for their analysis. Methods: We here present an optimized interpretable machine-learning (ML) approach which relies on predictive power in individual recording sequences to extract and quantify the robustness of compound-induced neural changes from multi-site recordings using Shapley additive explanations (SHAP) values. To evaluate this approach, we recorded LFPs in mediodorsal thalamus (MD), prefrontal cortex (PFC), dorsal hippocampus (CA1 and CA3), and ventral hippocampus (vHC) of mice after application of amphetamine or of the dopaminergic antagonists clozapine, raclopride, or SCH23390, for which effects on directed neural communication between those brain structures were so far unknown. Results: Our approach identified complex patterns of neurophysiological changes induced by each of these compounds, which were reproducible across time intervals, doses (where tested), and ML algorithms. We found, for example, that the action of clozapine in the analysed cortico-thalamohippocampal network entails a larger share of D1--as opposed to D2-receptor induced effects, and that the D2-antagonist raclopride reconfigures connectivity in the delta-frequency band. Furthermore, the effects of amphetamine and clozapine were surprisingly similar in terms of decreasing thalamic input to PFC and vHC, and vHC activity, whereas an increase of dorsal-hippocampal communication and of thalamic activity distinguished amphetamine from all tested anti-dopaminergic drugs. Conclusion: Our study suggests that communication from the dorsal hippocampus scales proportionally with dopamine receptor activation and demonstrates, more generally, the high complexity of neuropharmacological effects on the circuit level. We envision that the presented approach can aid in the standardization and improved data extraction in pEEG/pLFP-studies. [ABSTRACT FROM AUTHOR]

Background Evidence suggests that cannabis may be a causal factor for development of schizophrenia. We aimed to investigate whether use of antipsychotic medication, benzodiazepines, and psychiatric service use differs among patients with schizophrenia depending on whether psychosis was precipitated by a diagnosis of cannabis use disorder (CUD). Methods We utilized the nationwide Danish registries to identify all individuals with an incident diagnosis of schizophrenia from 1995 to 2016. We also collected information on whether first CUD diagnosis preceded schizophrenia and thus defined a group of potentially cannabis-related schizophrenia. We compared the cannabis-related schizophrenia group both with all non-cannabis-related patients with schizophrenia and with non-cannabis-related patients with schizophrenia that were propensity-score matched to cases using a range of potentially confounding variables. Results We included 35 714 people with incident schizophrenia, including 4116 (11.5%) that were cannabis-related. In the unmatched-comparison analyses, there were no clear differences over time in use of antipsychotics and benzodiazepines related to whether the diagnosis of schizophrenia was cannabis-related. After propensity-score matching, use of antipsychotics and benzodiazepines was significantly lower among cannabis-related cases of schizophrenia. In the unmatched comparison, the cannabis-related group had significantly more days admitted than the non-cannabis-related group. This was markedly attenuated after propensity-score matching. Conclusions Our findings indicate the importance of considering cannabis-related cases of schizophrenia as a potentially distinct disorder in terms of prognosis. It is unclear, however, if these differences are due to different biological types of schizophrenia being compared or if they rather indicate behavioral differences such as reduced adherence and treatment-seeking. [ABSTRACT FROM AUTHOR]

Background: The risk of arrhythmia is usually assessed by the length of the corrected QT interval (QTc) when patients use antipsychotics. Prolonged QTc intervals are thought to increase the probability of malignant ventricular arrhythmias, and if we focus only on the QTc interval, we may be influenced by a single factor and make decisions that are not conducive to effective treatment. The index of cardiac electrophysiological balance (iCEB) is considered more valuable than the QTc for predicting drug-induced arrhythmias. It has been used in clinical practice, but no studies have observed changes in this index after the use of antipsychotics. Objective: To investigate the changes in ventricular repolarization indices and the occurrence of arrhythmias in patients who have been using antipsychotic drugs for a long time, to compare the changes in iCEBc and QTc and to predict abnormal iCEBc values. Methods: Patients with schizophrenia who had been hospitalized for more than 4 years and who were receiving atypical antipsychotics underwent a 12-lead synchronized electrocardiogram (ECG) every 2–4 weeks. The baseline data were measured at admission, defined as the baseline (time0), and the most obvious abnormal changes in ventricular depolarization and repolarization measured every 12 months were one-year follow-up (time1), two-year follow-up (time2), three-year follow-up (time3), and four-year follow-up (time4). Repeated measures analysis of variance was used for comparisons. The types and doses of drugs taken at 5 time points were recorded and converted into chlorpromazine equivalents for comparison. The incidence of arrhythmia during the observation cycle was recorded. Results: The patients had been treated with antipsychotic medication for 4 years, and the duration of the QRS wave was longer in males than in females. TpTe, TpTe/QRS, TpTe/QT, TpTe/QTc, iCEB, and iCEBc increased significantly with hospital stay, while TpTe, TpTe/QRS, TpTe/QT, and TpTe/QTc exhibited more obvious changes in these indicators in female patients (P < 0.01). The changes in iCEB and iCEBc were more significant in males (P < 0.01). The incidences of arrhythmia (arrhythmic events included premature ventricular beats and premature atrial beats) within 5 time points were 2.5%, 6.25%, 6.25%, 6.25% and 5%, respectively. More than 90% of patients treated with antipsychotics did not have any arrhythmias. No TdP syncope or other cardiovascular symptoms were found in any of the patients. Conclusion: After long-term use of antipsychotics, the ventricular repolarization index gradually increased with time. The new ventricular repolarization indices iCEB and iCEBc were more sensitive than the QTc at predicting arrhythmia. According to the abnormal QTc values in men and women, we predict that the abnormal value of the iCEBc in males is 4.528 and that in females is 5.315. [ABSTRACT FROM AUTHOR]

Background: Treatment with different antipsychotics can lead to various metabolic side effects in patients with psychosis, impacting long-term prognosis. This study aimed to compare the changes and clinical efficacy of insulin resistance in patients treated with olanzapine and ziprasidone. Method: A retrospective analysis was conducted on the clinical data of 80 patients with schizophrenia. The patients were divided into olanzapine treatment group and ziprasidone treatment group. Parameters including body weight, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin resistance index, and Positive and Negative Syndrome Scale (PANSS) scores were recorded and compared before and after treatment. Results: BMI, FPG, FPI, homeostatic model assessment of insulin resistance (HOMA-IR), CHO, TG and LDL in both groups were significantly higher than before treatment (p < 0.05). These parameters were significantly higher in the olanzapine group than in the ziprasidone group (p < 0.05). The level of HDL in both groups was significantly decreased after treatment, and the level of HDL in the olanzapine group was significantly lower than that in the ziprasidone group after treatment (p < 0.05). After treatment, the total score and score of PANSS in both groups were significantly lower than before treatment (p < 0.05). After treatment, there was no significant difference in total score and PANSS score between both groups (p > 0.05). The incidence of insulin resistance (IR) was significantly higher in the olanzapine group compared to the ziprasidone group (χ² = 4.021, p < 0.05). In the IR group, BMI, FPG, FPI, TG, and LDL levels were higher than in the non-IR group (p < 0.05). Multivariate analysis indicated that BMI, FPG, FPI, TG, and LDL were independent risk factors for IR (odd ratio (OR) >1, p < 0.05). Conclusions: Treatment with olanzapine and ziprasidone improves clinical symptoms in patients with schizophrenia, but increases the risk of insulin resistance. The metabolic side effects of olanzapine are more pronounced. [ABSTRACT FROM AUTHOR]

SUMMARY: Antipsychotics are commonly prescribed to manage the behavioural and psychological symptoms of dementia (BPSD) despite their modest efficacy and significant adverse effects. Psychosocial interventions are recommended as the first-line approach in treating BPSD before considering pharmacological options. A Cochrane Review by Lühnen et al (2023) evaluated the effects of psychosocial interventions on reducing antipsychotic prescription in care homes, and found that no generalisable recommendations can be made based on the currently available evidence. This commentary attempts to critically appraise and add context to the review. [ABSTRACT FROM AUTHOR]

Antipsychotics with weight gain as side effect and vitamin D receptor dysfunction associated with single nucleotide polymorphisms (VDR SNPs) may have different effects on vitamin D status. Hence, present study aimed to investigate the relationship between vitamin D with body mass index (BMI), antipsychotics and VDR SNPs (rs2228570, rs1544410, rs7975232 and rs731236) in Malaysian patients with schizophrenia. Serum vitamin D level was measured using competitive enzyme–linked immunosorbent assay kit. VDR SNPs were analyzed using polymerase chain reaction–restriction fragment length polymorphism. We found significantly lower serum vitamin D level in patients with schizophrenia (p < 0.01), especially those taking atypical antipsychotics (p = 0.02) and combined antipsychotics (p = 0.02) and obese (BMI ≥27.5 kg/m2) patients (p = 0.04) after adjustment for covariates. For VDR SNPs, the CT genotype of rs1544410, CA genotype of rs7975232, and AA and AG genotypes of rs731236 may contribute to the significant decreased serum vitamin D level in patients (p < 0.05). Nevertheless, these relationships may differ by populations or medical conditions. The hypotheses of volumetric dilution and sequestration of vitamin D may explain the lower vitamin D level in obese patients. In addition, lifestyle factors such as poor diet and lack of physical activity with less sunlight exposure may cause reduced vitamin D level among patients. As patients in present study were prescribed with various antipsychotics, the effect of each antipsychotic on vitamin D level could not be determined. Thus, future studies should investigate the effect of different types of antipsychotics and obesity on vitamin D level in schizophrenia. • Patients with schizophrenia were having significant reduced serum vitamin D level. • Atypical and combined antipsychotics may be linked with decreased vitamin D level. • Obese patients were having lower vitamin D level after covariate adjustment. • Certain genotypes of VDR SNPs may contribute to lower vitamin D level in patients. [ABSTRACT FROM AUTHOR]

To improve understanding of Capgras syndrome (CS) in the pediatric population, this study investigates its clinical features and discerns similarities and differences compared to CS in adults. We conducted a descriptive systematic review of case reports following PRISMA guidelines, including cases of pediatric patients with CS. Patient demographics, medical and psychiatric history, imposter identity, underlying diagnosis, clinical manifestation, treatments, and outcomes were extracted and analyzed. We included 37 articles comprising 38 cases. The median age of patients was 15, with 23 (60.5%) being male. The most prevalent underlying diagnoses were schizophrenia spectrum and other psychotic disorders (47.3%). Imposter identity involved parents in 32 cases (84.2%). Associated symptoms included persecutory delusions (63.1%), auditory hallucinations (42.1%), aggression (31.5%), and depression (21.0%). There is a significant gap in our understanding of CS, particularly in pediatric patients. This is the first systematic review of CS in pediatric patients, encompassing all cases found in English literature since 1923. [ABSTRACT FROM AUTHOR]

Gene expression alterations in postmortem schizophrenia tissue are well-documented and are influenced by genetic, medication, and epigenetic factors. The Wingless/Integrated (WNT) signaling pathway, critical for cell growth and development, is involved in various cellular processes including neurodevelopment and synaptic plasticity. Despite its importance, WNT signaling remains understudied in schizophrenia, a disorder characterized by metabolic and bioenergetic defects in cortical regions. In this study, we examined the gene expression of 10 key WNT signaling pathway transcripts: IQGAP1, CTNNβ1, GSK3β, FOXO1, LRP6, MGEA5, TCF4, βTRC, PPP1Cβ, and DVL2 in the dorsolateral prefrontal cortex (DLPFC) using postmortem tissue from schizophrenia subjects (n = 20, 10 males, 10 females) compared to age, pH, and postmortem interval (PMI)-matched controls (n = 20, 10 males, 10 females). Employing the R-shiny application Kaleidoscope, we conducted in silico "lookup" studies from published transcriptomic datasets to examine cell- and region-level expression of these WNT genes. In addition, we investigated the impact of antipsychotics on the mRNA expression of the WNT genes of interest in rodent brain transcriptomic datasets. Our findings revealed no significant changes in region-level WNT transcript expression; however, analyses of previously published cell-level datasets indicated alterations in WNT transcript expression and antipsychotic-specific modulation of certain genes. These results suggest that WNT signaling transcripts may be variably expressed at the cellular level and influenced by antipsychotic treatment, providing novel insights into the role of WNT signaling in the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]

Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia (TRS). Although a large body of evidence supports its efficacy and favorable risk-benefit ratio in individuals who have failed two or more antipsychotics, clozapine remains underused. However, variations in clozapine utilization across geographic and clinical settings suggest that it could be possible to improve its use. In this narrative review and expert opinion, we summarized information available in the literature on the mechanisms of action, effectiveness, and potential adverse events of clozapine. We identified barriers leading to discouragement in clozapine prescription internationally, and we proposed practical solutions to overcome each barrier. One of the main obstacles identified to the use of clozapine is the lack of appropriate training for physicians: we highlighted the need to develop specific professional programs to train clinicians, both practicing and in residency, on the relevance and efficacy of clozapine in TRS treatment, initiation, maintenance, and management of potential adverse events. This approach would facilitate physicians to identify eligible patients and offer clozapine as a treatment option in the early stage of the disease. We also noted that increasing awareness of the benefits of clozapine among healthcare professionals, people with TRS, and their caregivers can help promote the use of clozapine. Educational material, such as leaflets or videos, could be developed and distributed to achieve this goal. The information provided in this article may be useful to improve disease burden and support healthcare professionals, patients, and caregivers navigating the complex pathways to TRS management. [ABSTRACT FROM AUTHOR]

Antipsychotic drug efficacy may vary in placebo-controlled and active-controlled trials. The study aims to investigate the performance of antipsychotics in these two different study designs using single-arm meta-analysis. We included randomized controlled trials (RCTs) comparing second-generation antipsychotics with placebo or other antipsychotics from our previous systematic reviews and updated the results with the search on Cochrane Schizophrenia Group register until March 06, 2022. The outcomes were the differences in the change of overall, positive and negative symptoms of schizophrenia, and the difference in study discontinuation between placebo-controlled and head-to-head trials. Random-effects single-arm meta-analysis and subgroup test were conducted to examine the differences in each outcome. A total of 208 RCTs (n = 42,159) were included in the analysis. Of these, 85 trials with 17,056 participants were placebo-controlled, while the remaining were head-to-head trials. Antipsychotics in head-to-head trials demonstrated a significantly greater improvement in overall symptoms (MC −23.58; 95 % CI −25.33, −21.83) compared to antipsychotics in placebo-controlled trials (MC −16.74; 95 % CI −17.80, −15.69; p < 0.0001). Similar findings were observed for positive symptoms, negative symptoms, study discontinuation and sensitivity analyses. Notably, when assessing antipsychotics individually, the same antipsychotic consistently demonstrated superior performance in head-to-head trials compared to placebo-controlled trials. In conclusion, antipsychotics in head-to-head trials presented a considerable efficacy superiority compared to those in placebo-controlled trials. Moreover, the efficacy of the same antipsychotics varied depending on the study design. Future trials should carefully consider the methodology and employ strategies to mitigate the potential for overestimation or underestimation of treatment efficacy. [ABSTRACT FROM AUTHOR]

A pharmacokinetic (PK) bridging approach was successfully employed to support the dosing regimen and approval of brexpiprazole in pediatric patients aged 13‐17 years with schizophrenia. Brexpiprazole was approved in 2015 for the treatment of schizophrenia and the adjunctive treatment of major depressive disorder in adults based on efficacy and safety data from clinical trials. On January 13, 2020, the US Food and Drug Administration issued a general advice letter to sponsors highlighting the acceptance of efficacy extrapolation of certain atypical antipsychotics from adult patients to pediatric patients considering the similarity in disease and exposure–response relationships. Brexpiprazole is the first atypical antipsychotic approved in pediatrics using this approach. The PK data available from pediatric patients aged 13‐17 years have shown high variability due to the limited number of PK evaluable subjects, which limits a robust estimation of differences between adult and pediatric patients. The PK model‐based approach was thus utilized to evaluate the appropriateness of the dosing regimen by comparing PK exposures in pediatric patients aged 13‐17 years with exposures achieved in adults at the approved doses. In addition to exposure matching, safety data from a long‐term open‐label clinical study in pediatric patients informed the safety profile in pediatric patients. This report illustrates the potential of leveraging previously collected efficacy, safety, and PK data in adult patients to make a regulatory decision in pediatric patients for the indication of schizophrenia. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms. On the contrary, the support for utilizing quetiapine is not as substantial as other antipsychotics because research studies specifically investigating its application are still emerging and relatively recent. The broad mechanisms of action of AAPs, involving dopamine and serotonin receptors, provide improved outcomes and fewer side effects than typical antipsychotics. Conversely, other antipsychotics, including risperidone, olanzapine, aripiprazole, ziprasidone, and lurasidone, have been found to worsen motor symptoms and are generally not recommended for PDP. While AAPs offer favorable benefits, they are associated with specific adverse effects. Extrapyramidal symptoms, somnolence, hypotension, constipation, and cognitive impairment are commonly observed with AAP use. Clozapine, in particular, carries a risk of agranulocytosis, necessitating close monitoring of blood counts. Pimavanserin, a selective serotonin inverse agonist, avoids receptor-related side effects but has been linked to corrected QT (QTc) interval prolongation, while quetiapine has been reported to be associated with an increased risk of mortality. This review aims to analyze the benefits, risks, and mechanisms of action of antipsychotic medications to assist clinicians in making informed decisions and enhance patient care. [ABSTRACT FROM AUTHOR]

Key content: The perinatal period confers an elevated risk of both relapses and new onset of mental illness. Suboptimal treatment can have a profound impact on maternal mortality and morbidity, neonatal outcomes and longer term child development.Most psychotropic medication can be used safely in pregnancy, with some notable exceptions.While decisions on the use of psychotropic medications in pregnancy are often complex and should be multidisciplinary, it is imperative that obstetricians and gynaecologists familiarise themselves with current literature to provide evidence‐based counselling and care.Existing guidelines on the use of psychotropic medication are largely aimed at psychiatrists, and to date there has been a lack of concise, digestible information with a focus on core knowledge for obstetricians and gynaecologists.We summarise existing evidence on the use of antidepressants, antipsychotics, mood stabilisers and sedatives in the perinatal period. For each drug class we describe the teratogenicity, impact on pregnancy, breastfeeding and the newborn. Learning objectives: To be familiar with common psychotropic medication used in pregnancy and the postpartum period.To understand key evidence on the safety profile of psychiatric medication in the perinatal period and apply this to individualised counselling. [ABSTRACT FROM AUTHOR]

Predictive processing is a computational framework that aims to explain how the brain processes sensory information by making predictions about the environment and minimizing prediction errors. It can also be used to explain some of the key symptoms of psychotic disorders such as schizophrenia. In recent years, substantial advances have been made in our understanding of the neuronal circuitry that underlies predictive processing in cortex. In this review, we summarize these findings and how they might relate to psychosis and to observed cell type–specific effects of antipsychotic drugs. We argue that quantifying the effects of antipsychotic drugs on specific neuronal circuit elements is a promising approach to understanding not only the mechanism of action of antipsychotic drugs but also psychosis. Finally, we outline some of the key experiments that should be done. The aims of this review are to provide an overview of the current circuit-based approaches to psychosis and to encourage further research in this direction. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To conduct a systematic review and meta-analysis assessing whether the use of antipsychotic medications in critically ill adult patients with delirium impacts patient-important outcomes. DATA SOURCES: A medical librarian searched Ovid MEDLINE, EMBASE, APA PsycInfo, and Wiley's Cochrane Library as well as clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform up to November 2023. STUDY SELECTION: Independently and in duplicate, reviewers screened abstracts and titles for eligibility, then full text of qualifying studies. We included parallel-group randomized controlled trials (RCTs) that included critically ill adult patients with delirium. The intervention group was required to receive antipsychotic medications at any dose, whereas the control group received usual care or placebo. DATA EXTRACTION: Reviewers extracted data independently and in duplicate using a piloted abstraction form. Statistical analyses were conducted using RevMan software (version 5.4). DATA SYNTHESIS: Five RCTs (n = 1750) met eligibility criteria. The use of antipsychotic medications compared with placebo did not increase the number of delirium- or coma-free days (mean difference 0.90 d; 95% CI, -0.32 to 2.12; moderate certainty), nor did it result in a difference in mortality, duration of mechanical ventilation, ICU, or hospital length of stay. The use of antipsychotics did not result in an increased risk of adverse events (risk ratio 1.27; 95% CI, 0.71-2.30; high certainty). Subgroup analysis of typical versus atypical antipsychotics did not identify any subgroup effect for any outcome. CONCLUSIONS: In conclusion, our systematic review and meta-analysis demonstrated with moderate certainty that there is no difference in delirium- or coma-free days when delirious critically ill adults are treated with antipsychotic medications. Further studies in the subset of patients with hyperactive delirium may be of benefit. [ABSTRACT FROM AUTHOR]

Antipsychotics are frequently used for inpatients with alcohol withdrawal syndromes (AWS). While there is evidence on the effects of these medications in other settings there is little data on the mortality rate associated with these drugs for the treatment of AWS) We utilized the national COSMOS Epic database to identify inpatients with AWS. We then assessed the mortality rate for adult patients with or without the use of anti-psychotics along with subsets of patients based on age, gender, race, and ethnicity. We identified 233,821 patients of whom 26% received antipsychotic agents. The mortality rate was 1.5%. Patients aged 60 or over and those who received typical antipsychotic agents had a higher mortality rate. The use of typical antipsychotic agents is associated with a higher mortality rate. The use of any antipsychotic agent in patients aged 60 or over is associated with an increased mortality rate. Further study of this effect is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Literature on antipsychotic medication adherence in early psychosis primarily assessed adherence behaviors and focused on young patients. There is a paucity of research investigating negative medication attitude and its determinants in the early illness course, particularly in older-aged sample. We aimed to examine prevalence and correlates of medication non-adherence behaviors and negative medication attitudes separately in adult patients with early psychosis. Methods: One hundred ninety-nine Chinese early psychosis patients aged 26–55 years who had received three-year treatment for first psychotic episode in Hong Kong were examined. Assessments encompassing socio-demographics, premorbid adjustment, clinical and treatment profiles, self-stigma and therapeutic alliance were conducted. Patients were evaluated with Medication Compliance Questionnaire, which is a modified Chinese-translated version of Medication Adherence Rating Scale and includes items measuring adherence behaviors and attitudes towards medications. Results: Rates of medication non-adherence and negative attitude towards medications were 38.7% and 50.8%, respectively. Multivariate regression analysis showed that more severe positive symptoms, greater self-stigma and negative medication attitude were independently associated with medication non-adherence. Negative attitude towards medications was significantly associated with younger age, higher educational attainment, diagnosis of other psychotic disorders, poorer insight, greater self-stigma and less satisfaction with communication with healthcare staff, which represented an index reflecting suboptimal therapeutic alliance. Conclusion: Antipsychotic non-adherence and negative medication attitudes are frequently observed in adult early psychosis patients. Our findings indicate that poor insight, elevated self-stigma and suboptimal therapeutic alliance may constitute potential treatment targets for promoting medication adherence and rectifying negative medication attitudes in the early illness stage. [ABSTRACT FROM AUTHOR]

Several studies indicate the impact of antipsychotics like risperidone and paliperidone on oxidative stress parameters, yet data remain inconsistent. We investigated the link between these medications, hyperprolactinemia (HPRL), and oxidative stress. This study was conducted at the Psychiatry Clinic, University Clinical Center, Kragujevac, between November 2022 and August 2023. Inclusion criteria comprised diagnosed psychotic disorders from the ICD-10-based F20-F29 spectrum and clinical stability on risperidone/paliperidone for ≥12 weeks with no recent dose adjustments. Exclusion criteria included pregnancy, breastfeeding, relevant medical conditions, or co-therapy with prolactin-secreting drugs. Data encompassed drug choice, administration method, therapy duration, and daily dose. Prolactin (PRL) levels, oxidative stress parameters (TBARS, H2O2, O2−, NO2−), and antioxidant system (CAT, GSH, SOD) were assessed. Of 155 subjects, women exhibited significantly higher PRL levels (p < 0.001) and symptomatic HPRL (p < 0.001). Drug choice and regimen significantly influenced TBARS (p < 0.001), NO2− (p < 0.001), O2− (p = 0.002), CAT (p = 0.04), and GSH (p < 0.001) levels. NO2− levels were affected by drug dose (p = 0.038). TBARS (p < 0.001), O2− (p < 0.001), and SOD (p = 0.022) inversely correlated with PRL levels, suggesting PRL's protective role against oxidative stress. The female sex association with higher PRL levels implies additional factors influencing PRL's antioxidant role. Antipsychotic choice and dosage impact PRL and oxidative stress markers, necessitating further exploration. [ABSTRACT FROM AUTHOR]

Olanzapine is an atypical antipsychotic drug and a potent muscarinic M3 receptor (M3R) antagonist. Olanzapine has been reported to cause metabolic disorders, including dyslipidemia. Anaplastic lymphoma kinase (Alk), a tyrosine kinase receptor well known in the pathogenesis of cancer, has been recently identified as a key gene in the regulation of thinness via the regulation of adipose tissue lipolysis. This project aimed to investigate whether Olanzapine could modulate the hepatic Alk pathway and lipid metabolism via M3R. Female rats were treated with Olanzapine and/or Cevimeline (an M3R agonist) for 9 weeks. Lipid metabolism and hepatic Alk signaling were analyzed. Nine weeks' treatment of Olanzapine caused metabolic disturbance including increased body mass index (BMI), fat mass accumulation, and abnormal lipid metabolism. Olanzapine treatment also led to an upregulation of Chrm3, Alk, and its regulator Ptprz1, and a downregulation of Lmo4, a transcriptional repressor of Alk in the liver. Moreover, there were positive correlations between Alk and Chrm3, Alk and Ptprz1, and a negative correlation between Alk and Lmo4. However, cotreatment with Cevimeline significantly reversed the lipid metabolic disturbance and adipose tissue accumulation, as well as the upregulation of the hepatic Alk signaling caused by Olanzapine. This study demonstrates evidence that Olanzapine may cause metabolic disturbance by modulating hepatic Alk signaling via M3R, which provides novel insight for modulating the hepatic Alk signaling and potential interventions for targeting metabolic disorders. [ABSTRACT FROM AUTHOR]

Data on reproductive safety of recently approved newer antipsychotics are limited. Here, we report a case vignette of a patient with schizophrenia treated with cariprazine during pregnancy. The patient became pregnant unexpectedly while taking medication. As a result of shared decision-making, the patient and her psychiatrist decided to continue the treatment, which proved to be protective against relapse and had no adverse effect either on the course of pregnancy or on the health of the newborn. Cariprazine maintenance treatment during pregnancy was found to be safe in our case. [ABSTRACT FROM AUTHOR]

Background: Global antipsychotic usage, including off-label prescriptions, has increased in recent decades. However, trends in China, particularly for children and adolescents, remain unclear. This study explored these trends from 2016 to 2021 and identified factors associated with off-label prescriptions. Methods: In this retrospective study, we analyzed on-label and off-label prescriptions based on drug information approved by the China National Medical Products Administration. To identify factors associated with off-label prescriptions, we conducted multivariate logistic regression analysis. Results: Our study included 48,258 antipsychotic prescriptions, 52.4% (25,295) of which were prescriptions for males. Of these, 61.7% (29,813) were off-label. Over time, the number of antipsychotics and the percentage of off-label prescriptions for children and adolescents overall increased from 2016 to 2021. The use of atypical antipsychotics increased, whereas that of typical antipsychotics decreased. For off-label usage, all of the factors in our study were associated with off-label usage, including age, sex, year, region, department, reimbursement, antipsychotic type, drug expense, number of polypharmacy and diagnoses. Additionally, tiapride (15.8%) and aripiprazole (18.6%) were the most common typical and atypical antipsychotics, respectively. For pediatric diseases, common diagnoses included mood or affective disorders (31.7%) and behavioral and emotional disorders, with onset usually occurring in childhood and adolescence (29.1%). Furthermore, a depressive state was the most common diagnosis for which antipsychotic polypharmacy was used for treatment. Conclusion: In this retrospective study, off-label antipsychotic prescriptions were common, with trends generally increasing among children and adolescents from 2016 to 2021. However, there is a lack of evidence supporting off-label usage, thus emphasizing the need for studies on the efficacy and safety of these treatments. [ABSTRACT FROM AUTHOR]

This document is a compilation of scientific articles and studies that explore the role of glycine transporters in schizophrenia and other psychiatric disorders. The articles discuss the mechanisms of glycine release and the potential therapeutic targets for treating schizophrenia. They also examine the effects of glycine augmentation on symptoms and explore the use of glycine transporter inhibitors as potential treatments for cognitive impairment and negative symptoms associated with schizophrenia. [Extracted from the article]

Neuroleptic malignant syndrome is a rare, life-threatening neurologic emergency characterized by fever, rigidity, autonomic instability, mental status changes, and an elevated creatine kinase level. It often occurs shortly after the initiation of neuroleptic treatment, or after a dose increase. The management of patients with NMS is based upon clinical severity and includes supportive care and withdrawal of antipsychotic agents and agents like bromocriptine and dantrolene. Complications include acute renal failure associated with rhabdomyolysis, respiratory failure, electrolyte imbalance, hepatic failure, seizures from hyperthermia, metabolic derangements, etc. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring (TDM) is a specific method for monitoring therapy by measuring the plasma concentration of a drug, followed by interpretation by a qualified expert and acceptance by the clinician. It is a significant aid for personalized medicine in the area of dose individualization, as it allows for rational therapy with minimal occurrence of adverse effects, reduced mortality and morbidity, and reduced overall treatment costs. After excluding noncompliance; genetic and exogenous influences affecting plasma drug levels (so-called pseudopharmacoresistance) are the most likely causes of pharmacological resistance. It has been demonstrated that there is a large interindividual variability in drug pharmacokinetics among patients receiving the same dose. Due to the development of new analytical methods, TDM has become an important tool in the system of ensuring the quality of pharmacotherapy. It should be noted that TDM includes not only measurement of drug concentrations, but also clinical interpretation of the results, which requires knowledge of pharmacokinetics, time of sample collection, drug history, knowledge of the patient's clinical condition, and specific laboratory values corresponding to biomarkers. The aim of this article is to contribute to raising awareness of the necessity of TDM in specific clinical situations. [ABSTRACT FROM AUTHOR]