Chlorpromazine Equivalent Dose Research Articles

Unidentified CYP2D6 genotype does not affect pharmacological treatment for patients with first episode psychosis.

Research on the pharmacogenetic influence of hepatic CYP450 enzyme 2D6 (CYP2D6) on metabolism of drugs for psychosis and associated outcome has been inconclusive. Some results suggest increased risk of adverse reactions in poor and intermediate metabolizers, while others find no relationship. However, retrospective designs may fail to account for the long-term pharmacological treatment of patients. Previous studies found that clinicians adapted risperidone dose successfully without knowledge of patient CYP2D6 phenotype. Here, we aimed to replicate the results of those studies in a Dutch cohort of patients with psychosis (N = 418) on pharmacological treatment. We compared chlorpromazine-equivalent dose between CYP2D6 metabolizer phenotypes and investigated which factors were associated with dosage. This was repeated in two smaller subsets; patients prescribed pharmacogenetics-actionable drugs according to published guidelines, and risperidone-only as done previously. We found no relationship between chlorpromazine-equivalent dose and phenotype in any sample (complete sample: p = 0.3, actionable-subset: p = 0.82, risperidone-only: p = 0.34). Only clozapine dose was weakly associated with CYP2D6 phenotype (p = 0.03). Clinicians were thus not intuitively adapting dose to CYP2D6 activity in this sample, nor was CYP2D6 activity associated with prescribed dose. Although the previous studies could not be replicated, this study may provide support for existing and future pharmacogenetic research.

Characterization of Pain and Somatization and its Relationship with Psychopathology in Early Onset Psychosis

Early onset psychosis (EOP) frequently presents with a severe clinical phenotype and poor long-term prognosis. Clinical experience suggests that individuals with EOP have abnormal pain and somatosensory processing, yet relative to adult-onset psychosis, pain and somatic sensory processing in EOP have rarely been studied. The history of two characteristic patients is described to illustrate clinical presentations of pain in EOP patients. Furthermore, 31 patients with EOP were studied with self-reported questionnaires informing on pain severity, pain catastrophizing, central sensitization, and somatization. Structured clinical interviews were administered to confirm Diagnostic and Statistical Manual of Mental Disorders-5 EOP diagnosis and the patient's dimensions of psychopathology were measured by the Brief Psychiatric Rating Scale (BPRS). Out of 31 EOP patients, 22 reported distressing pain, where higher pain severity corresponded with greater BPRS total and affectivity and resistance subscale scores. The degree of psychopathology was associated (N=31; p<0.05, FDR-corrected) with the magnitude of pain catastrophizing, central sensitization, and somatization. Multivariate analysis revealed relationships (N=31; p<0.05, FDR-corrected) between BPRS subscale (negative symptoms and activation) scores with somatization severity. The observed associations occurred independent of antipsychotic medication usage as quantified by chlorpromazine equivalent doses. Pain and somatosensory symptoms could be a frequent cause of distress in patients with EOP and their severity associated with the degree of psychopathology. Future studies should determine if treating pain and somatic symptoms in EOP patients can lead to better control of psychosis as well as improve quality of life.

Predictors of continuation for asenapine from real-world data in patients with schizophrenia

BackgroundThe continuation rates of pharmacotherapy in schizophrenia exhibit variability, a phenomenon influenced by the specific antipsychotic agent prescribed and patient-related factors such as age and duration of illness. In this context, our study aims to elucidate the predictors of medication continuation for asenapine sublingual tablets, characterized by unique formulation properties.MethodsOur investigation leveraged real-world data collected through post-marketing surveillance in Japan, comprising 3236 cases. Utilizing multivariate logistic regression analysis, we identified patient-related factors associated with medication continuation as the primary outcome measure, subsequently employing survival analysis for further evaluation. Additionally, adverse event occurrence was assessed as a secondary outcome measure.ResultsMultivariate logistic regression analysis unveiled significant predictors of asenapine continuation, notably including patient-related factors such as a chlorpromazine equivalent dose exceeding 600 mg/day and an illness duration of 25 years or more. While the overall continuation rate stood at 40.6%, patients exhibiting factors such as a chlorpromazine equivalent dose surpassing 600 mg/day or an illness duration exceeding 25 years demonstrated continuation rates of 46.3% and 47.9%, respectively. Remarkably, patients presenting both factors showcased the highest continuation rate at 52.5%.ConclusionsOur findings shed light on distinct patient-related predictors of asenapine continuation, deviating from those observed with other antipsychotic medications. This underscores the necessity of recognizing that predictive factors for antipsychotic medication continuation vary across different agents. Moving forward, elucidating these predictive factors for various antipsychotic medications holds paramount importance in schizophrenia treatment, facilitating the delivery of tailored therapeutic interventions for individual patients.

Associations between constipation risk and lifestyle, medication use, and affective symptoms in patients with schizophrenia: a multicenter cross-sectional study.

To investigate the association between lifestyle and atypical antipsychotic drug use in patients with schizophrenia and the risk of constipation and to assess the impact of anxiety and depressive symptoms on constipation risk. Cross-sectional convenience sampling was employed, and 271 participants aged 20-65 were enrolled. Data were collected via a structured questionnaire comprising participants' demographic data, medication information, dietary behavior assessment, and the Baecke Physical Activity Questionnaire, Beck Depression Inventory-II, and Beck Anxiety Inventory. IBM SPSS 24.0 with multivariate logistic regression was used for data analysis. We performed a subgroup analysis of anticholinergic drugs via multivariate logistic regression. In total, 180 participants had functional constipation; risk factors included female sex, anxiety symptoms, depressive symptoms, and quetiapine and aripiprazole use. Patients who drank more than 3,000cc of water daily or used risperidone were less likely to have functional constipation. Depressive and anxiety symptoms were risk factors even after adjusting for sex, use of anticholinergics and laxatives, consuming two servings of fruit, consuming three servings of vegetables, consuming more than 3,000cc of water daily, physical activity, medical comorbidity, chlorpromazine equivalent dose, and atypical antipsychotic use. Similar associations were found for two affective symptoms and functional constipation in the subgroup analysis of anticholinergic drugs. The prevalence of functional constipation in patients with schizophrenia was 66.4%. The risk factors included female sex, anticholinergics, aripiprazole, quetiapine, and depressive and anxiety symptoms. Risperidone users and those who drank 3000cc of water daily were less likely to have constipation.

Assessing regional intracortical myelination in schizophrenia spectrum and bipolar disorders using the optimized T1w/T2w-ratio.

Dysmyelination could be part of the pathophysiology of schizophrenia spectrum (SCZ) and bipolar disorders (BPD), yet few studies have examined myelination of the cerebral cortex. The ratio of T1- and T2-weighted magnetic resonance images (MRI) correlates with intracortical myelin. We investigated the T1w/T2w-ratio and its age trajectories in patients and healthy controls (CTR) and explored associations with antipsychotic medication use and psychotic symptoms. Patients with SCZ (n = 64; mean age = 30.4 years, s.d. = 9.8), BPD (n = 91; mean age 31.0 years, s.d. = 10.2), and CTR (n = 155; mean age = 31.9 years, s.d. = 9.1) who participated in the TOP study (NORMENT, University of Oslo, Norway) were clinically assessed and scanned using a General Electric 3 T MRI system. T1w/T2w-ratio images were computed using an optimized pipeline with intensity normalization and field inhomogeneity correction. Vertex-wise regression models were used to compare groups and examine group × age interactions. In regions showing significant differences, we explored associations with antipsychotic medication use and psychotic symptoms. No main effect of diagnosis was found. However, age slopes of the T1w/T2w-ratio differed significantly between SCZ and CTR, predominantly in frontal and temporal lobe regions: Lower T1w/T2w-ratio values with higher age were found in CTR, but not in SCZ. Follow-up analyses revealed a more positive age slope in patients who were using antipsychotics and patients using higher chlorpromazine-equivalent doses. While we found no evidence of reduced intracortical myelin in SCZ or BPD relative to CTR, different regional age trajectories in SCZ may suggest a promyelinating effect of antipsychotic medication.

Short-chain fatty acids in schizophrenia: are they affected by a depressive state?

IntroductionShort-chain fatty acids (SCFA) are bacterial metabolites that, within microbiome-gut-brain axis, make a promising research line on etiopathology of mental diseases like schizophrenia (SZ) and major depression disorder. Besides, depressive symptoms are frequent clinical features of SZ.Objectives-Describe fecal SCFA concentrations in SZ patients.-Analyze differences in SCFA depending on:-Depression.- Clinical severity, antipsychotics and antidepressants, comorbidities (pro-inflammatory state/obesity/metabolic syndrome [MetS]), lifestyle. MethodsCross-sectional study of 67 outpatients [mean age=43.52±12.42, range=22-67; males=40 (59.7%)] with diagnosis (DSM-5) of SZ recruited from their mental health clinics in Oviedo (Spain). -Assessment:-Fecal SCFA (gas chromatography;μg/mL).-Plasmatic C-reactive protein (CPR;mg/dL).-PANSS, Calgary Depression (CDS), International Physical Activity (IPAQ), Mediterranean Diet Adherence (MEDAS).-Toxic habits (alcohol use/smoking/cannabis).-Chlorpromazine equivalent doses (CPZ-ED), use of antidepressants.-MetS (ATP-III), body mass index (BMI; kg/cm2).-Statistics: Spearman correlation, U Mann-Whitney, ANCOVA. Results14 patients showed clinical depression (CDS≥5). There were no differences in age or sex between groups. 36 patients (53.7%) showed systemic low-grade inflammation (CPR≥0.3mg/dL) and 32 (30.8%) MetS.Table 1 shows fecal SCFA levels by depressive state. Means (SD) are ahown. Table 1CDS≤4CDS≥5TotalU Mann-Whitney (p-value)Acetate21.449(12.823)12.911(7.189)19.665(12.328)221.000(0.021)Propanoate9.170(6.819)6.848(6.036)8.685(6.687)268.500(0.114)Butyrate8.529(6.436)7.875(8.232)8.392(6.787)320.000(0.432)Total SCFA39.148(23.770)31.415(24.526)36.742(23.549)250.000(0.062)Correlations were found in Age with Butyrate (r=-0.248,p=0.043) and weekly alcohol units with Propanoate (r=0.250,p=0.041) plus trend to significance with Butyrate (r=0.232,p=0.059). It also showed a trend towards statistical relation for CPZ-ED with Propanoate (r=-0.253,p=0.039) and Total SCFA (r=-0.253,p=0.039). We found no correlation in SCFA with MetS, CGI, PANSS-N, BMI, IPAQ, MEDAS and other toxic habits.ANCOVA was performed to Acetate and Total SCFA using depression state as independent variable and Age and CPZ-ED as covariates. There was a trend towards statistical significance for Acetate (F=3.937,p=0.052,η2=0.059) whereas Total SCFA showed no difference (F=1.350,p=2.250,η2=0.021).Conclusions There seems to be lower levels of fecal Acetate in SZ patients with depressive symptoms, considering age and antipsychotic intake. In our sample there was no relation between SFCA and clinical severity, lifestyle, comorbidities or antidepressant use.Disclosure of InterestNone Declared

Widespread cortical and subcortical gray matter loss and an increase of globus pallidus volume in treatment-resistant schizophrenia

Introduction It is still being discussed whether treatment-resistant schizophrenia (TRS) is a biological subtype which differs from non-treatment-resistant schizophrenia or is it a more severe condition that affects brain worse than non-treatment-resistant schizophrenia. However, there are few and heterogeneous studies and the etiology of TRS remains quite unclear.ObjectivesThis study aimed to explore cortical and subcortical morphometric characteristics in TRS patients and its associations with the clinical features. The pilot stage comprises the comparison to the mentally healthy subjects.Methods 21 right-handed male patients (mean age 28.99 ± 8.08 years) fulfilling TRS criteria and 21 matched healthy controls (mean age 29.35 ± 7.41 years) underwent T1-weighted structural MRI at 3T Philips scanner and clinical examination. Images were processed using FreeSurfer 7.1.1. Cortical thickness and area, volumes of subcortical structures and separately volumes of the amygdala nuclei and hippocampal subregions were compared between groups. The morphometry data, PANSS (Positive and Negative Syndrome Scale), CDSS (Calgary Depression Scale for Schizophrenia) and daily chlorpromazine equivalent doses of antipsychotics were included in correlational analysis. Results were considered significant if they retained significance after correction for multiple comparisons.Results Compared to healthy controls, TRS patients showed decreased gray matter thickness in frontal, temporal, parietal, occipital, cingulate and insular regions (Figure 1). The temporal lobe showed the most prominent thinning of the cortex. The volumes of the amygdala, hippocampus (Figure 2) and nucleus accumbens, a number of amygdala nuclei and hippocampal subregions bilaterally were also decreased in TRS patients. The volume of the right globus pallidus, on the contrary, was increased (Figure 2). No correlations between altered cortical thickness, PANSS (positive, negative, general psychopathology scales and total score), CDSS and chlorpromazine equivalent doses of antipsychotics were found.Image:Image 2:Conclusions The widespread gray matter cortical and subcortical loss in TRS finds confirmation in the literature. The increased globus pallidus volume is an unexpected and intriguing result. Other studies demonstrated conflicting results on that point. Some studies reported possible therapy influence, others suggested possible associations with symptoms. We did not find any correlations with psychometric or therapy characteristics. It is possible that there are non-linear relationships or relationships that exist only at a certain stage of the disease. As for therapy, patients took individual medication, consisting of various antipsychotics and drugs from other pharmacological groups, and such heterogeneity could affect the results of the study. Further research is going to be carried out.Disclosure of InterestNone Declared

Concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer: A multicenter, retrospective, observational study.

There is concern that hydroxyzine exacerbates delirium, but a recent preliminary study suggested that the combination of haloperidol and hydroxyzine was effective against delirium. This study examined whether the concomitant use of hydroxyzine and haloperidol worsened delirium in patients with cancer. This retrospective, observational study was conducted at 2 general hospitals in Japan. The medical records of patients with cancer who received haloperidol for delirium from July to December 2020 were reviewed. The treatments for delirium included haloperidol alone or haloperidol combined with hydroxyzine. The primary outcome was the duration from the first day of haloperidol administration to the resolution of delirium, defined as its absence for 2 consecutive days. The time to delirium resolution was analyzed to compare the haloperidol group and hydroxyzine combination group using the log-rank test with the Kaplan-Meier method. Secondary outcomes were (1) the total dose of antipsychotic medications, including those other than haloperidol (measured in chlorpromazine-equivalent doses), and (2) the frequencies of detrimental incidents during delirium, specifically falls and self-removal of drip infusion lines. The unpaired t-test and Fisher's exact test were used to analyze secondary outcomes. Of 497 patients who received haloperidol, 118 (23.7%) also received hydroxyzine. No significant difference in time to delirium resolution was found between the haloperidol group and the hydroxyzine combination group (log-rank test, P = 0.631). No significant difference between groups was found in either chlorpromazine-equivalent doses or the frequency of detrimental incidents. This study showed that the concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer.

Efficacy of Long-Acting Injectable Antipsychotics Versus Oral Antipsychotics in Preventing Psychiatric Rehospitalizations.

Schizophrenia is a chronic, debilitating mental illness that incurs a large economic burden. Decreasing hospital readmissions is a priority in health care to improve patient quality of life and decrease health care costs. Determining ways to prevent readmissions such as improving access to long-acting injectable (LAI) antipsychotics is important to assess. A single-center retrospective review was conducted comparing readmission rates of patients diagnosed with schizophrenia or schizoaffective disorder discharged on LAI or oral antipsychotics between August 1, 2019, and June 30, 2022. The primary outcome was the 30-day psychiatric readmission rate. Secondary outcomes included chlorpromazine equivalent doses and use of anticholinergic medications. The 30-day readmission rate was 1.9% for the LAI antipsychotic group and 8.3% for the oral antipsychotic group ( P = 0.03; 95% confidence interval, 1.05-20.02). The average chlorpromazine equivalent antipsychotic dose of patients discharged on LAI versus oral antipsychotic medications was 477.3 and 278.6 mg/d, respectively ( P < 0.001). In addition, the prevalence of medications used to treat extrapyramidal symptom was 22.3% (n = 23) for the LAI antipsychotic group and 30.8% (n = 74) for the oral antipsychotic group ( P = 0.12). Sixty-four percent of LAI antipsychotics utilized were obtained from pharmaceutical company hospital inpatient free trial programs. Long-acting injectable antipsychotics showed a statistically significant reduction in 30-day rehospitalizations as compared with oral antipsychotics and hospital inpatient free trial programs aided in LAI antipsychotic acquisition.

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study

IntroductionRegional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.Methods15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables.ResultsCompared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges’ g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses.ConclusionEOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.

Factors Associated With Physical Restraints in a Psychiatric Unit in Japan: a Retrospective Study.

To identify factors associated with the use and duration of physical restraint (PR) in a psychiatric unit in Japan. Medical records of 1308 patients admitted first time to the psychiatric emergency unit of Showa University Northern Yokohama Hospital between 1 January 2014 and 31 December 2021 were retrospectively reviewed. Data collected included patient age, sex, outpatient treatment, living arrangements, disability pension status, diagnosis (based on ICD-10), and psychotropic medication use at admission (chlorpromazine equivalent dose, imipramine equivalent dose, diazepam equivalent dose, and number of mood stabilisers administered). Logistic regression analysis and multiple regression analysis were used to identify factors associated with the use and duration of PR, respectively. Of 1308 patients, 399 (30.5%) were subjected to PR and 909 (69.5%) were not. Among the 399 patients subjected to PR, 54 were excluded from the multiple regression analysis for duration of PR as they remained subject to PR on the day of discharge. The remaining 345 patients were subject to PR for a median of 10 days. PR utilisation was associated with male sex (odds ratio [OR] = 1.420), treatment at our hospital (OR = 0.260), treatment at other hospitals (OR = 0.645), F3 diagnosis (depression) [OR = 0.290], F4-9 diagnosis (OR = 0.309), and imipramine equivalent dose at admission (unit OR = 0.994). The log-transformed duration of PR was independently associated with the age group of 50 to 69 years (β = 0.248), the age group of ≥70 years (β = 0.274), receiving a disability pension (β = 0.153), an F1 diagnosis (β = -0.187), an F4-9 diagnosis (β = -0.182), chlorpromazine equivalent dose at admission (β = 0.0004), and number of mood stabilisers administered at admission (β = -0.270). Identifying factors associated with the use and duration of PR may lead to reduction in the use and duration of PR.

Deep Learning-based Brain Age Prediction in Patients With Schizophrenia Spectrum Disorders.

The brain-predicted age difference (brain-PAD) may serve as a biomarker for neurodegeneration. We investigated the brain-PAD in patients with schizophrenia (SCZ), first-episode schizophrenia spectrum disorders (FE-SSDs), and treatment-resistant schizophrenia (TRS) using structural magnetic resonance imaging (sMRI). We employed a convolutional network-based regression (SFCNR), and compared its performance with models based on three machine learning (ML) algorithms. We pretrained the SFCNR with sMRI data of 7590 healthy controls (HCs) selected from the UK Biobank. The parameters of the pretrained model were transferred to the next training phase with a new set of HCs (n = 541). The brain-PAD was analyzed in independent HCs (n = 209) and patients (n = 233). Correlations between the brain-PAD and clinical measures were investigated. The SFCNR model outperformed three commonly used ML models. Advanced brain aging was observed in patients with SCZ, FE-SSDs, and TRS compared to HCs. A significant difference in brain-PAD was observed between FE-SSDs and TRS with ridge regression but not with the SFCNR model. Chlorpromazine equivalent dose and cognitive function were correlated with the brain-PAD in SCZ and FE-SSDs. Our findings indicate that there is advanced brain aging in patients with SCZ and higher brain-PAD in SCZ can be used as a surrogate marker for cognitive dysfunction. These findings warrant further investigations on the causes of advanced brain age in SCZ. In addition, possible psychosocial and pharmacological interventions targeting brain health should be considered in early-stage SCZ patients with advanced brain age.

Impact of long-acting injectable aripiprazole on the concomitant medication and antipsychotic polypharmacy: a retrospective, observational study of 127 patients with psychosis.

Antipsychotic polypharmacy (APP) has become prevalent over the years, but several concerns have been raised over APP. Accumulating evidence suggests that aripiprazole long-acting injectable (LAI) may reduce the rate of APP, but the association remains speculative. This retrospective observational study included 127 patients with psychosis and observed them for 1.8 ± 1.3 years, up to 4 years. Prescription data of antipsychotics (APs), mood stabilisers, benzodiazepines, and anti-extrapyramidal side effect medications were obtained at baseline and the last observation. Daily chlorpromazine equivalent (CPZ) dose of APs decreased from 124.40 ± 235.35 mg to 77.95 ± 210.36 mg ( P = 0.027). The daily dose of anticholinergics and beta-blockers also significantly decreased after introducing aripiprazole LAI. Among the patients having APP, the number of concurrent APs along with daily CPZ dose of APs decreased after initiation of aripiprazole LAI from 1.28 ± 0.62 to 0.85 ± 0.73 ( P < 0.001) and 298.33 ± 308.70 mg to 155.43 ± 280.53 mg ( P = 0.004), respectively. Treatment with aripiprazole LAI for up to 4 years in patients with psychosis was associated with a reduced number of prescribed APs in patients having an APP and a reduced dose of APs and concurrent psychotropic medications.

Evaluation of Arterial Stiffness in Depression Patients.

It has been known that there is a significant correlation between depression and cardiovascular diseases. However, the reasons behind this correlation that could affect mortality and morbidity were not fully identified. The present study aimed to analyze arterial stiffness diagnosed with ultrasonography, which could be associated with cardiovascular disease risks in depression patients, and to compare the findings with those of healthy controls. The study was conducted with 35 depression patients and 35 healthy individuals. Routine complete blood and biochemistry tests were requested for all patients, and their weight and height, waist circumference, and diastolic and systolic arterial blood pressure were measured. Femoral and carotid artery intima-media thickness and other arterial stiffness parameters were determined with Doppler ultrasonography. It was determined that the systolic pressure (P = .028) was higher in the patient group (P = .028). Also, the carotid elastic modulus (P = .048) was significantly higher in the patient group. A negative and significant correlation was determined between femoral compliance and chlorpromazine equivalent dose (P = .021, r = -0.389). It was determined that the systolic blood pressure and carotid elastic modulus arterial stiffness parameters were significantly higher in depression patients. Measurable arterial stiffness parameters should be investigated in depression patients as cardiovascular risk markers. Furthermore, the determination of the effects of psychotropic drugs employed in arterial stiffness treatment could play an important role in the determination of cardiovascular disease risk in these patients.

Impact of on-site pharmacists in residential aged care facilities on the quality of medicines use: a cluster randomised controlled trial (PiRACF study)

Residents of residential aged care facilities (RACFs) have a high prevalence of use of potentially inappropriate medications (PIMs) and resultant medicines-related harm. This study investigated the effect of an on-site pharmacist model on PIMs use and other medication outcomes for residents in RACFs. A multi-facility, non-blind, cluster randomised controlled trial, with randomisation at the facility level, was conducted. Fifteen facilities enrolled and participated in the study, 7 facilities (560 residents) were allocated to the intervention arm and 8 facilities (737 residents) were allocated to the control arm. Each facility in the intervention arm employed an on-site pharmacist for 12 months to perform medication management activities as part of an interdisciplinary care team. The primary outcome was the proportion of residents taking at least one PIM according to the 2019 Beers® Criteria. Using generalised linear mixed-effects models, accounting for confounders and clustering, there was a significant reduction in the proportion of residents prescribed at least one PIM (odds ratio 0.50, 95% confidence interval, 0.335–0.750; p = 0.001) in the intervention arm. There were also significant decreases in the Anticholinergic Cognitive Burden scale and chlorpromazine equivalent daily dose of antipsychotics. The on-site pharmacist intervention significantly improved the appropriateness of medicines use in RACFs.

Correlates of severity in a clinical staging model of schizophrenia: a cross-sectional study among 158 subjects

BackgroundClinical staging has been widely used to predict and optimize the treatment of medical disorders. Different models have been proposed to map the development, progression, and extension of psychiatric disorders over time, mainly for schizophrenia. The primary objective of this study was to classify patients with psychosis according to the McGorry staging model and compare factors between the different stages.MethodsThis was a cross-sectional study, collecting data from 158 patients hospitalized for schizophrenia/psychosis. The survey included the Mini International Neuropsychiatric Interview (MINI), Positive and Negative Symptom Scale (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Yong Mania Rating Scale (YMRS), Clinical Global Impression (CGI) scale, and the McGorry staging model.ResultsPatients have been classified into three clinical stages: relapse of psychotic disorder (43%), multiple relapses (47.5%), and persistent and severe illness (9.5%). A higher mean duration of hospitalization, psychotic symptoms (PANSS total scale and subscales), chlorpromazine equivalent dose, and number of antipsychotic treatments were found among participants in Stage 4 as compared to the other groups. However, a significantly higher mean GAF scale was found among participants in stage 3b as compared to the other groups.ConclusionEach stage in the McGorry staging model of schizophrenia is associated with well-defined clinical presentations, which help decide the appropriate treatment. Using such models in psychiatry can improve the diagnostic process and potential therapeutic interventions for patients suffering from mental disorders.

Differential effects of parental socioeconomic status on cortical thickness in patients with schizophrenia spectrum disorders and healthy controls

ObjectivesWidespread changes in cortical thickness (CT) have been repeatedly reported in schizophrenia (SZ). The nature of the pathophysiologic process underlying such changes remains to be elucidated. The aims of the present study were to measure the CT; evaluate parent socioeconomic status (pSES), childhood trauma (ChT) and premorbid adjustment (PA) in patients with schizophrenia spectrum disorders (SSDs); and investigate group differences in CT (i.e., SSD vs. healthy controls (HCs)), pSES, PA, and/or ChT, as well as the interactions among these factors. Methods164 patients with SSD and 245 age-, sex- and education-matched healthy controls have participated. The pSES, ChT and PA were evaluated using Korean version of Polyenvironmental Risk Score, Early Trauma Inventory Self Report-Short Form and Premorbid Adjustment Scale, respectively. Vertex-wise measure of CT was estimated using the FreeSurfer. To investigate the main effects and interactions, multilevel regression was employed. ResultsWe found widespread cortical thinning in patients with SSDs compared to HCs. The cortical thinning was associated with ChT, symptom severity and chlorpromazine equivalent dose and duration of illness in patients. In multilevel regression, main effects of group and pSES and interaction between group and pSES were found whereas a significant interaction between ChT and CPZ equivalent was found in patients. ConclusionOur findings indicate that compared to HCs, patients with SSDs have cortical structural abnormalities, and that group and pSES interaction determines CT. Further studies are needed to explore the effects of psychosocial factors on brain structural and functional abnormalities in SZ.

Decreased insight, but not self-stigma or belief about medicine, is associated with greater severity of delusions in a sample of long-stay patients with schizophrenia: a cross-sectional study

BackgroundThere are, to date, limited and inconsistent findings concerning the relationship between insight and psychotic symptoms, despite some evidence in favor of the clinical and therapeutic relevance of the insight construct. We aimed to add to the pool of the available data in this area, by examining the correlations between the severity of insight and positive psychotic symptoms (delusions and auditory hallucinations), while accounting for self-stigma and attitudes towards medication, in a sample of long-stay inpatients with schizophrenia.MethodsA cross-sectional study was conducted at the Psychiatric Hospital of the Cross, between July and October 2021. A total of 82 patients diagnosed with schizophrenia (aged 55.55 ± 10.21 years, 54.9% males) were enrolled. The semi-structured psychotic symptom rating scales, the Birchwood Insight Scale, the Belief About Medicine Questionnaire, and the Internalized Stigma of Mental Illness were used.ResultsThe mean duration of illness in years was 30.15 ± 11.73, and the mean duration of hospitalization in years was 17.56 ± 9.24. Sixteen out of the 82 patients (19.5%) were considered as having poor insight. Bivariate analyses showed that higher chlorpromazine equivalent dose was significantly associated with more delusions, whereas higher insight was significantly associated with lower delusions. Multivariable analyses revealed that Higher chlorpromazine equivalent dose (Beta = 0.004) was significantly associated with more delusions, whereas higher insight (Beta = − 0.89) was significantly associated with less delusions. No significant associations were found between insight, self-stigma and hallucinations.ConclusionOur results imply that more impaired insight is associated with greater severity of delusions, above and beyond the effects of self-stigma and medication doses. These findings are valuable to aid clinicians and researchers improve their understanding of the relationship insight-psychotic symptoms, and could help personalize prevention and early intervention strategies in schizophrenia.

Prevalence of Treatment Resistant Psychoses in a Complete National Forensic Mental Health Service: A Dundrum Forensic Redevelopment Evaluation Study (D-FOREST)

IntroductionTreatment resistant schizophrenia and other treatment resistant psychotic disorders are believed to be over-represented in forensic patient clusters. The true rates of treatment resistant psychoses in secure forensic hospitals remain unexplored.ObjectivesThis study aimed to ascertain the prevalence of treatment resistant psychoses within a complete national forensic mental health service. In addition, the study sought to examine the relationships between treatment resistance for psychotic symptoms and treatment resistance in other domains, such as offending behaviour.MethodsThis is a cross-sectional study of a complete cohort of patients admitted to the National Forensic Mental Health Service in Ireland during the period 01/11/2021 to 31/01/2022. All inpatients at the time of the study were included. Demographic details, data appertaining to diagnosis, medication, measures of risk (HCR-20), recovery (DUNDRUM toolkit), functioning (GAF), and symptoms (PANSS) were collated. Data were gathered as part of the Dundrum Forensic Redevelopment Evaluation Study (D-FOREST).ResultsThe sample consisted of 170 patients. Majority (n=162) 95.3% were male. The majority (n=116), 68.2%, were admitted from prisons, while a smaller number (n=35), 20.6%, were admitted from other psychiatric facilities. The insanity defense (n=94) 55.3% was the most common legal status, followed by unfit to plead (n=16) 9.4%. The commonest diagnosis was schizophrenia (n=97) 57.1%, followed by schizoaffective disorder (n=27) 15.9% and autism spectrum disorder (n=5) 2.9%. The mean age at admission was 35.52 years and the median age was 34.37 ± 9.43 SD.Of the total sample, 25.9% of patients were on more than 1000 mg per day chlorpromazine equivalent (CPZE) doses. Those whose psychotic symptoms required treatment with CPZE doses over 1000 mg per day scored poorly on DUNDRUM-3 programme completion, DUNDRUM-4 recovery scale, HCR-20 historical, HCR-20 clinical, HCR-20 risk, HCR-20 dynamic, and had poorer overall functioning (all P&lt;0.001) than those who required lower antipsychotic doses. On binary logistic regression, correcting for age and gender, the only variable that remained significant was GAF (adjusted odds ratio = 0.979, 95% CI 0.962-0.996, P=0.014). In forward entry model regression, only the DUNDRUM-4 recovery scale (odds ratio = 1.13, 95% CI 1.07-1.19, P&lt;0.001) and GAF (adjusted odds ratio = 0.979, 95% CI 0.962-0.996, P&lt;0.001) were significant. This model had a robust forward and backward likelihood ratio.ConclusionsRates of treatment resistant psychoses in forensic hospital groups are indeed elevated. Overall functioning on GAF and recovery across a wide range of components in the DUNDRUM-4 scale are the best predictors of treatment resistant psychosis.Disclosure of InterestNone Declared

Effects of antipsychotic and anticholinergic medications on cognition in chronic patients with schizophrenia

BackgroundPatients with psychosis frequently use a variety of psychotropic medicines, many of which have anticholinergic effects that can impair cognition. Therefore, this study aimed to evaluate whether there is an association between medications used for neuropsychological disorders/symptoms and cognition in patients with schizophrenia, focusing on their anticholinergic load and antipsychotic doses.Study designA cross-sectional study between July 2019 and Mars 2020 at the Psychiatric Hospital of the Cross-Lebanon enrolled 120 inpatients diagnosed with schizophrenia. The total anticholinergic burden was calculated based on the Anticholinergic Drug Scale (ADS), and the chlorpromazine equivalent dose was calculated using the Andreasen method to assess the relative antipsychotic dose. Also, the objective cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) tool.Study results.A significantly higher BACS total score (r = -0.33, p < 0.001), higher verbal memory (r = -0.26, p = 0.004), higher working memory (r = -0.20, p = 0.03), higher motor speed (r = -0.36, p < 0.001), and higher attention and speed of information processing (r = -0.27, p = 0.003) were significantly associated with lower chlorpromazine equivalent dose. Higher ADS (Standardized Beta (SB) = -.22; p = .028), higher chlorpromazine equivalent dose (SB = -.30; p = .001), and taking mood stabilizer medications (SB = -.24; p = .004) were significantly associated with lower cognition.ConclusionThis study confirms that the cognitive functions of chronic patients with schizophrenia may be affected by medications and their anticholinergic burden. More studies are needed to explain the role of cholinergic neurotransmission and general neurochemical mechanisms in the cognitive impairment of patients with schizophrenia.