Antipsychotic Dose Research Articles

The liminal space of first-episode psychosis and its treatment: A qualitative study exploring the experience of young people participating in an antipsychotic dose reduction randomized controlled trial.

The current guidelines recommend continuation of antipsychotic medication for a minimum of at least 1 year following a first episode of psychosis (FEP). There have been several trials investigating whether early dose reduction or cessation leads to improved functional outcomes. The aim of this study was to explore the experience of consenting to and participating in a randomized controlled trial (RCT) of antipsychotic medication cessation. Five participants in the Reduce trial-an RCT evaluating early antipsychotic medication dose reduction/cessation following FEP-aged 22-24 years completed a semistructured qualitative interview following the RCT. Interpretive phenomenological analysis was undertaken to understand the key themes. A superordinate theme was derived from interviews: the Liminal Space of FEP and treatment. Themes within the Liminal Space included: rejection versus identification with psychosis, medication as symbolic of illness versus wellness, embodiment of wellness and illness with medication, medication as symbolic of independence versus dependence, discovery of independence when autonomously choosing medication, the Reduce trial offered safety to navigate the liminal space, and self-exploration versus altruism. The experience and treatment of FEP involves young people feeling torn between multiple, competing perspectives, demands, and priorities. Participation in an RCT exploring dose reduction provided additional supports contributing to the perception of greater safety to navigate their own experiences of treatment that was appropriate for them. When treatment is experienced as collaborative, involves shared decision making and support, other than medication, young people feel more equipped to navigate the liminal space. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for Monitoring Momentary Subjective Well-Being and Psychotic Experiences During Antipsychotic Dose Reduction: Two Single-Case Time Series Experience Sampling Method Pilot Study

Supplemental Material for Monitoring Momentary Subjective Well-Being and Psychotic Experiences During Antipsychotic Dose Reduction: Two Single-Case Time Series Experience Sampling Method Pilot Study

Increased antipsychotic drug concentration in hospitalized patients with mental disorders following COVID-19 infection: a call for attention.

Examine the alterations in antipsychotic concentrations following coronavirus disease-2019 (COVID-19) infection among hospitalized patients with mental disorders and conduct an analysis of the factors influencing these changes. Data were collected from inpatients at Beijing Huilongguan Hospital between December 12, 2022, and January 11, 2023, pre- and post-COVID-19. Based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, 329 inpatients with mental disorders were included (3 with incomplete data excluded). Primary outcomes assessed changes in antipsychotic concentrations pre- and post-COVID-19, while secondary outcomes examined factors linked to concentration increases and antipsychotic dose adjustments. Clozapine (P < 0.001), aripiprazole (P < 0.001), quetiapine (P = 0.005), olanzapine (P < 0.001), risperidone (P < 0.001), and paliperidone (P < 0.001) concentrations increased post-COVID-19 in patients with mental disorders. Notably, clozapine concentration surpassing pre-infection levels was highest. Clozapine users were more likely to adjust their dose (50.4%) compared to olanzapine (17.5%) and otherantipsychotics. Moreover, traditional Chinese patent medicines and antibiotics during COVID-19 infection were associated with antipsychotic reduction or withdrawal (OR = 2.06, P = 0.0247; OR = 7.53, P = 0.0024, respectively). Antipsychotic concentrations in hospitalized patients with mental disorders increased after COVID-19 infection, that may be related not only to COVID-19, but also to the use of Chinese patent medicines during infection. The pre-infection concentration and types of antipsychotics, patient's gender, and combination of traditional Chinese medicine or antibiotics, were factors found to correlate with increased drug concentrations and necessitate dose adjustments.

Multivariate associations between neuroanatomy and cognition in unmedicated and medicated individuals with schizophrenia

Previous studies that focused on univariate correlations between neuroanatomy and cognition in schizophrenia identified some inconsistent findings. Moreover, antipsychotic medication may impact the brain-behavior profiles in affected individuals. It remains unclear whether unmedicated and medicated individuals with schizophrenia would share common neuroanatomy-cognition associations. Therefore, we aimed to investigate multivariate neuroanatomy-cognition relationships in both groups. A sample of 59 drug-naïve individuals with first-episode schizophrenia (FES) and a sample of 115 antipsychotic-treated individuals with schizophrenia were finally included. Multivariate modeling was conducted in the two patient samples between multiple cognitive domains and neuroanatomic features, such as cortical thickness (CT), cortical surface area (CSA), and subcortical volume (SV). We observed distinct multivariate correlational patterns between the two samples of individuals with schizophrenia. In the FES sample, better performance in token motor, symbol coding, and verbal fluency tests was associated with greater thalamic volumes but lower CT in the prefrontal and anterior cingulate cortices. Two significant multivariate correlations were identified in antipsychotic-treated individuals: 1) worse verbal memory performance was related to smaller volumes for the most subcortical structures and smaller CSA mainly in the temporal regions and inferior parietal lobule; 2) a lower symbol coding test score was correlated with smaller CSA in the right parahippocampal gyrus but greater volume in the right caudate. These multivariate patterns were sample-specific and not confounded by imaging quality, illness duration, antipsychotic dose, or psychopathological symptoms. Our findings may help to understand the neurobiological basis of cognitive impairments and the development of cognition-targeted interventions.

Living systematic review and meta-analysis of plasma-concentrations of antipsychotic drugs in carriers and non-carriers of variant CYP450 genotypes: Living systematic review protocol

Introduction Carriers of variant alleles of genes that encode liver CYP450 and UGT enzymes may experience abnormal plasma levels of antipsychotics and, consequently, worse efficacy or tolerability. Although pharmacogenomics is a rapidly developing field, current guidelines often rely on limited, underpowered evidence. We have previously demonstrated that meta-analysis is a viable strategy for overcoming this problem. Here, we propose a project that will expand our previous work and create a living systematic review and meta-analysis of drug plasma level differences between carriers and non-carriers of variant genotype-predicted phenotypes for every pharmacokinetic drug-gene interaction relevant to commonly used antipsychotic drugs. Protocol First, a baseline systematic review and meta-analysis will be conducted by searching for observational pharmacogenomics-pharmacokinetic studies. Data on dose-adjusted drug plasma levels will be extracted, and participants will be grouped based on their genotype for each drug-gene pair separately. Differences in plasma drug levels between different phenotypes will be compared using a random-effect ratio-of-means meta-analysis. The risk of bias will be assessed using ROBINS-I, and the certainty of evidence will be assessed using GRADE. Following the establishment of baseline results, the literature search will be re-run at least once every six months, and the baseline data will be updated and re-evaluated as new evidence is published. A freely available website will be designated to present up-to-date results and conclusions. Discussion This systematic review will provide evidence-based results that are continuously updated with evidence as it emerges in the rapidly developing field of pharmacogenomics. These results may help psychiatrists in their decision-making, as clinicians are becoming increasingly aware of the patients’ genetic data as testing becomes more widespread and cheaper. In addition, the results may serve as a scientific basis for the development of evidence-based pharmacogenomics algorithms for personalized dosing of antipsychotics to mitigate potentially harmful drug-gene interactions.

Rash caused by lurasidone in old chinese patient with bipolar disorder: case-based review

BackgroundRash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone.Case presentationA 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic.ConclusionsIn conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

Effect of esketamine combined with dexmedetomidine on delirium in sedation for mechanically ventilated ICU patients: protocol for a nested substudy within a randomized controlled trial

BackgroundUse of sedatives and analgesics is associated with the occurrence of delirium in critically ill patients receiving mechanical ventilation. Dexmedetomidine reduces the occurrence of delirium but may cause hypotension, bradycardia, and insufficient sedation. This substudy aims to determine whether the combination of esketamine with dexmedetomidine can reduce the side effects and risk of delirium than dexmedetomidine alone in mechanically ventilated patients.MethodsThis single-center, randomized, active-controlled, superiority trial will be conducted at The First Affiliated Hospital of Nanjing Medical University. A total of 134 mechanically ventilated patients will be recruited and randomized to receive either dexmedetomidine alone or esketamine combined with dexmedetomidine, until extubation or for a maximum of 14 days. The primary outcome is the occurrence of delirium, while the second outcomes include the number of delirium-free days; subtype, severity, and duration of delirium; time to first onset of delirium; total dose of vasopressors and antipsychotics; duration of mechanical ventilation; ICU and hospital length of stay (LOS); accidental extubation, re-intubation, re-admission; and mortality in the ICU at 14 and 28 days.DiscussionThere is an urgent need for a new combination regimen of dexmedetomidine due to its evident side effects. The combination of esketamine and dexmedetomidine has been applied throughout the perioperative period. However, there is still a lack of evidence on the effects of this regimen on delirium in mechanically ventilated ICU patients. This substudy will evaluate the effects of the combination of esketamine and dexmedetomidine in reducing the risk of delirium for mechanically ventilated patients in ICU, thus providing evidence of this combination to improve the short-term prognosis. The study protocol has obtained approval from the Medical Ethics Committee (ID: 2022-SR-450).Trial registrationClinicalTrials.gov: NCT05466708, registered on 20 July 2022.

Divergent thinking as a predictor of life skills in patients with schizophrenia: Evidence from the modified Tinkertoy Test.

Patients with schizophrenia often exhibit poor life skills, posing significant clinical challenges. Life skills comprise cognitive functions crucial for planning daily activities, including divergent thinking. However, the cognitive deficits contributing to these diminished skills among patients with schizophrenia are underexplored. This study introduces a modified Tinkertoy Test (m-TTT) to investigate the correlation between life skills, divergent thinking, and psychological assessment tools in patients with schizophrenia. Fifty-two patients with schizophrenia, alongside a control group, matched for sex, age, and education, were evaluated using psychological assessment tools. For the patient group, the Life Skills Profile (LSP) and Positive and Negative Syndrome Scale were administered to measure functional abilities and psychiatric symptoms, respectively. Additionally, duration of disease and antipsychotic daily dosage levels were assessed exclusively in the patient group. Both groups were evaluated with the m-TTT, Idea Fluency Test (IFT), Design Fluency Test (DFT), and Brief Assessment of Cognition in Schizophrenia (BACS) to comprehensively assess cognitive functions. A stepwise multiple regression model was conducted to identify significant correlates of LSP total score among the patient group. The schizophrenia group scored notably lower than the neurotypical controls on the m-TTT, IFT, DFT, and BACS. Our stepwise multiple regression analysis highlighted that the LSP total score was significantly correlated with the total m-TTT score and presence of negative symptoms. Divergent thinking could be a crucial factor in the life skills of individuals with schizophrenia. Rehabilitation programs based on this cognitive function might enhance their daily living capabilities.

Protective Effect of Hyperprolactinemia on Oxidative Stress in Patients with Psychotic Disorder on Atypical Antipsychotics Risperidone and Paliperidone: A Cross-Sectional Study.

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.

A Trajectory of Long-Term Antipsychotic Medication Dosage in Inpatients with Severe Behavioral and Psychological Symptoms of Dementia: A Retrospective Study.

While antipsychotics are often prescribed for behavioral and psychological symptoms of dementia (BPSD), typically on an off-label basis, these medications have serious adverse effects. This study investigated the long-term use of antipsychotics among inpatients with dementia displaying severe BPSD, focusing on how prescriptions change over time. Medical charts at Kusakabe Memorial Hospital were retrospectively reviewed from October 2012 to September 2021. The study included patients diagnosed with dementia, admitted for BPSD, and were continuing antipsychotics at 3 months of their admission. Antipsychotic dosages were categorized as high (≥300 mg/d), medium (100-300 mg/d), and low (<100 mg/d) based on chlorpromazine equivalents and tracked until 15 months during hospitalization. Binary logistic regression was used to identify factors associated with dosage reductions between months 3 and 6. This study involved 188 patients, with an average age of 81.2 years, 67% of whom were diagnosed with Alzheimer&apos;s dementia. At 3 months, 15.4% were taking high, 44.1% on medium, and 40.4% on low dosages of antipsychotics. The highest average dosage was observed at 3 months, with a subsequent decrease over time. By the 12th month, 20-30% of patients in all dosage categories had stopped their antipsychotic medication. Significant factors for dosage reduction included higher initial doses (OR 1.003, 95%Cl: 1.001-1.006, P=0.01) and male gender (OR 2.481, 95%Cl: 1.251-4.918, P=0.009). A trajectory of antipsychotic dosage in inpatients with severe BPSD has rarely been reported. This research emphasizes the need for personalized strategies in managing long-term pharmacotherapy for this vulnerable group of patients.

Analysis of Antipsychotic Dosage in Patients With Tardive Dyskinesia: A Case-Control Study Using the Claims Database of the Corporate Health Insurance Association.

This study aimed to assess the association between antipsychotic doses and the risk of tardive dyskinesia (TD) in clinical practice using a Japanese claims database from 2010 to 2020. The study population included patients 15 years or older with a diagnosis record of schizophrenia, depression, or bipolar disorder who were prescribed antipsychotics. Using a case-control design, we categorized patients newly diagnosed with TD as cases, with corresponding 1:10 matching in the control group. The primary endpoint was the relative risk of TD in the >median dose and ≤median dose groups, as determined using conditional logistic regression analysis adjusted for age. The analysis population included 58,452 patients, and the median daily antipsychotic dose was 75 mg/d of chlorpromazine equivalent (CPZE). Of these, 80 were identified as TD cases, and doses >75 mg/d were associated with a significantly increased risk of TD at the last prescription and the maximum dose, respectively, before the date of the first diagnosis of TD. Post-hoc analysis further showed a significant association between doses ≥300 mg/d and the risk of TD compared to doses ≤75 mg/d and doses >75 to <300 mg/d. Comparing ≥300 mg/d versus >75 to <300 mg/d, the odd ratios at the last prescription and maximum dose before the first diagnosis of TD were 3.40 and 3.50, respectively. In the Japanese medical claims database of patients receiving relatively low doses of antipsychotics, doses >75 mg/d were associated with an increased risk of TD in a dose-dependent manner.

Central Nervous System Medications: Pharmacokinetic and Pharmacodynamic Considerations for Older Adults.

Most drugs have not been evaluated in the older population. Recognizing physiological alterations associated with changes in drug disposition and with the ultimate effect, especially in central nervous system-acting drugs, is fundamental. While considering pharmacokinetics, it should be noted that the absorption of most drugs from the gastrointestinal tract does not change in advanced age. There are only few data about the effect of age on the transdermal absorption of medications such as fentanyl. Absorption from an intramuscular injection may be similar in older adults as in younger patients. The distribution of lipophilic drugs (such as diazepam) is increased owing to a relative increase in the percentage of body fat, causing drug accumulation and prolonged drug elimination following cessation. Phase I drug biotransformation is variably decreased in aging, impacting elimination, and hepatic drug clearance has been shown to decrease in older individuals by 10-40% for most drugs studied. Lower doses of phenothiazines, butyrophenones, atypical antipsychotics, antidepressants (citalopram, mirtazapine, and tricyclic antidepressants), and benzodiazepines (such as diazepam) achieve the same extent of exposure. For renally cleared drugs with no prior metabolism (such as gabapentin), the glomerular filtration rate appropriately estimates drug clearance. Important pharmacodynamic changes in older adults include an increased sedative effect of benzodiazepines at a given drug exposure, and a higher sensitivity to mu opiate receptor agonists and to opioid adverse effects. Artificial intelligence, physiologically based pharmacokinetic modeling and simulation, and concentration-effect modeling enabling a differentiation between the pharmacokinetic and the pharmacodynamic effects of aging might help to close some of the gaps in knowledge.

Determinants/Predictors of QT Abnormalities in Patients on Psychotropic Medications in a Nigerian Tertiary Hospital.

Cardiovascular disease is a major global burden and a leading cause of premature death among patients with severe mental illness. Over time, research and clinical practice have paid increased attention to the impact of psychiatric medications on cardiac repolarization. In a resource-limited setting, it is common for psychotropic medications to be initiated and maintained in an outpatient setting without baseline or follow up ECG. This study evaluated the determinants and predictors of QT abnormalities among patient taking psychotropic drugs. We conducted a cross-sectional study in a population of 150 psychiatric patients on psychotropics and 75 controls. We studied the effects of various psychotropic drugs on QT dispersion (QTd) and corrected QT interval (QTc) as well as correlation with the types and dosages of psychotropic drugs used. All the subjects had detailed clinical examination and resting electrocardiogram (ECG) at 25mm/sec done. QTc was determined using Bazett formula and QTd was determined by subtracting shortest from longest QT in 12-lead ECG. The prevalence of prolonged QTc and QTd as well as the mean QTc and QTd were significantly higher in patients than the control group. The mean QTc was significantly higher in patient on typical antipsychotics compared to those on atypical antipsychotics. Age, heart rate and antipsychotic dose in chlorpromazine equivalent were predictors of QTc with the heart rate being the most powerful predictor among them. Psychotropic drugs use is associated with QTc and QTd prolongation with age, heart rate and antipsychotic dose as predictors of QTc.

Psychotropic medications and mortality from cardiovascular disease and suicide for individuals with depression in Taiwan

BackgroundPolypharmacy for treatment of depression has been increasing in Taiwan. MethodsIndividuals having depressive disorders were identified in a national database for healthcare services and followed up for 5 years. The mean dosage of antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics was calculated; the associations between the exposure dosage to different psychotropic medications and patients’ overall death and death due to cardiovascular diseases (CVD) and suicide were examined. ResultsA total of 400,042 individuals with depressive disorders (63.8% women) were identified. Compared with those with no exposure to antidepressants, patients prescribed antidepressants had decreased mortality. Use of antipsychotics had a dose-related increase in overall mortality risk compared to no exposure group. Contrarily, depressed patients taking sedative-hypnotics had decreased overall and CVD mortality compared to no exposure group, with the most prominent decrease in CVD mortality of up to 54.9% for those in the moderate exposure group (hazard ratio: 0.451, 95% confidence interval: 0.405–0.503). A moderate or high dose of antidepressants or sedative-hypnotics was shown to be associated with a significantly increased mortality for suicide compared to those with no exposure. ConclusionsAntidepressant and sedative-hypnotic use was associated with decreased all-cause and CVD-related mortality and use of antipsychotics was associated with a dose-related increase in mortality risk. Future studies are needed to further clarify the involved mechanisms and benefits and risks should be carefully weighed when prescribing psychotropic medications in patients with depressive disorders.

Antipsychotic Medication Continuation vs Taper and Discontinuation in Patients With Schizophrenia and Other Nonaffective Psychotic Disorders.

Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.

Sex Differences Between Female and Male Individuals in Antipsychotic Efficacy and Adverse Effects in the Treatment of Schizophrenia.

Antipsychotics are core treatments for people living with psychotic disorders. Understanding individualised factors that influence both efficacy and adverse responses will improve outcomes. The objective of this study was to examine sex differences in antipsychotic-related efficacy and tolerability. This was a secondary analysis of data from phase 1 and 1a of Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE); participants with schizophrenia were randomly assigned to double-blinded treatment with oral olanzapine, quetiapine, risperidone, ziprasidone or perphenazine. Measures included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale and Calgary Depression Rating Scale, as well as self-reported side effects, medication compliance, dosage, weight measurements and various blood parameters. There were 1460 participants including 380 female and 1080 male individuals. Very few differences existed between male and female participants in response, adverse reactions, compliance or antipsychotic dosage. However, significantly more female participants than male participants reported constipation (28% vs 16%), dry mouth (50% vs 38%), gynecomastia/galactorrhea (11% vs 3%), incontinence/nocturia (16% vs 8%) and self reportedweight gain (37% vs 24%) [all p < 0.001]. Within the risperidone treatment group, there was a significantly greater increase in prolactin levels (p < 0.001) among female participants (n = 61) than male participants (n = 159). No overall differences in clinician-rated measures, weight gain or otherlaboratory indicators were found. While overall sex differences were limited across efficacy and tolerability for antipsychotic treatment, there were some specific findings with risperidone. Further examination of sex differences within antipsychotic trials will be important to improve efficacy and reduce adverse responses across as well as individualising care for people with schizophrenia.

Living systematic review and meta-analysis of plasma-concentrations of antipsychotic drugs in carriers and non-carriers of variant CYP450 genotypes: Living systematic review protocol.

Carriers of variant alleles of genes that encode liver CYP450 and UGT enzymes may experience abnormal plasma levels of antipsychotics and, consequently, worse efficacy or tolerability. Although pharmacogenomics is a rapidly developing field, current guidelines often rely on limited, underpowered evidence. We have previously demonstrated that meta-analysis is a viable strategy for overcoming this problem. Here, we propose a project that will expand our previous work and create a living systematic review and meta-analysis of drug plasma level differences between carriers and non-carriers of variant genotype-predicted phenotypes for every pharmacokinetic drug-gene interaction relevant to commonly used antipsychotic drugs. First, a baseline systematic review and meta-analysis will be conducted by searching for observational pharmacogenomics-pharmacokinetic studies. Data on dose-adjusted drug plasma levels will be extracted, and participants will be grouped based on their genotype for each drug-gene pair separately. Differences in plasma drug levels between different phenotypes will be compared using a random-effect ratio-of-means meta-analysis. The risk of bias will be assessed using ROBINS-I, and the certainty of evidence will be assessed using GRADE. Following the establishment of baseline results, the literature search will be re-run at least once every six months, and the baseline data will be updated and re-evaluated as new evidence is published. A freely available website will be designated to present up-to-date results and conclusions. This systematic review will provide evidence-based results that are continuously updated with evidence as it emerges in the rapidly developing field of pharmacogenomics. These results may help psychiatrists in their decision-making, as clinicians are becoming increasingly aware of the patients' genetic data as testing becomes more widespread and cheaper. In addition, the results may serve as a scientific basis for the development of evidence-based pharmacogenomics algorithms for personalized dosing of antipsychotics to mitigate potentially harmful drug-gene interactions.

D-serine and D-amino acid oxidase levels in patients with schizophrenia spectrum disorders in the first episode and 6-month follow-up

BackgroundD-serine and the D-amino acid oxidase (DAO) enzyme, which breaks down d-amino acids, may be involved in the pathophysiology of schizophrenia by affecting the N-methyl-D-aspartate (NMDA) receptor. The exact role of D-serine and DAO, as well as the consequences of increased DAO activity in patients with schizophrenia, remain unclear. We aimed to investigate D-serine and DAO levels in patients with first-episode schizophrenia spectrum disorders before treatment and after six months of treatment. MethodComparisons for the serum levels of D-serine and DAO were made between 81 healthy controls and 89 patients with first-episode schizophrenia spectrum disorders without a history of treatment. Further comparisons were made after 6 months for changes in these levels in the 41 patients in follow-up. The Positive and Negative Syndrome Scale (PANNS), Calgary Scale for Depression in Schizophrenia (CDSS), Montreal Cognitive Assessment Scale (MoCA), Global Assessment Scale (GAS), and Clinical Global Impression Scale (CGI) were used to evaluate the symptom severity and functionality. Secondary results included comparisons related to antipsychotic equivalent doses. ResultsBefore treatment, patients had significantly lower levels of D-serine, DAO, and D-serine/DAO ratio compared to healthy individuals (p < 0.001; p < 0.001; p = 0.004). DAO and D-serine levels of the patients were higher after six months of treatment (p = 0.025; p = 0.001). There was correlation of DAO levels with antipsychotic dosage and with PANSS negative and total subscale scores (rho = 0.421, p = 0.01; rho = 0.280, p = 0.008; rho = 0.371, p = 0.000). No correlation was found between serum D-serine level, DAO level, and the D-serine/DAO ratio with cognitive function. ConclusionsThe results suggest that D-serine and DAO may play a role that is sensitive to treatment effects in schizophrenia spectrum disorders. To gain a more comprehensive understanding of the impact antipsychotic drugs have on NMDA receptor dysfunction, there is a requirement for studies that directly evaluates the activity of the DAO enzyme.

Aberrant salience mediates the interplay between emotional abuse and positive symptoms in schizophrenia

IntroductionChildhood trauma and adversities (CTA) and aberrant salience (AS) have a pivotal role in schizophrenia development, but their interplay with psychotic symptoms remains vague. We explored the mediation performed by AS between CTA and psychotic symptomatology in schizophrenia. MethodsWe approached 241 adults suffering from schizophrenia spectrum disorders (SSDs), who have been in the unit for at least 12 consecutive months, excluding the diagnosis of dementia, and recent substance abuse disorder, and cross-sectional evaluated through the Aberrant Salience Inventory (ASI), Childhood Trauma Questionnaire Short-Form (CTQ-SF), and Positive and Negative Symptom Scale (PANSS). We tested a path-diagram where AS mediated the relationship between CTA and psychosis, after verifying each measure one-dimensionality through confirmatory factor analysis. ResultsThe final sample comprised 222 patients (36.9% female), with a mean age of 42.4 (± 13.3) years and an average antipsychotic dose of 453.6 (± 184.2) mg/day (chlorpromazine equivalents). The mean duration of untreated psychosis was 1.8 (± 2.0) years while the mean onset age was 23.9 (± 8.2) years. Significant paths were found from emotional abuse to ASI total score (β = 0.39; p < .001) and from ASI total score to PANSS positive (β = 0.17; p = .019). Finally, a statistically significant indirect association was found from emotional abuse to PANSS positive mediated by ASI total score (β = 0.06; p = .041; CI 95% [0.01, 0.13]). ConclusionEmotional abuse has an AS-mediated effect on positive psychotic symptomatology. AS evaluation could allow a better characterization of psychosis as well as explain the presence of positive symptoms in adults with SSDs who experienced CTA.

Results from the open-label, single-center, clinical study assessing the efficacy and safety of a group cognitive stimulation therapy in Russian-speaking patients with the moderate dementia stage of Alzheimer's disease

Introduction. Cognitive stimulation therapy (CST) used worldwide to treat cognitive impairment has recently attracted interest of Russian medical and scientific minds. However, when applied to Russian-speaking patients with dementia, CST requires adaptation. Aim. To evaluate the effectiveness and safety of the Russian-language version of CST for Russian-speaking patients with Alzheimer’s disease at the stage of moderate dementia.Materials and мethods. 8 participants involved into the trial were residents of social care center ZILANT diagnosed as dementia patients with Alzheimer’s, aged 76 ± 10.8 years, with the median MMSE score identified 17 ± 5.0. Before implementing the main course of CST developed by E. Spector et al we translated and localized it for Russian patients. The patients undergoing CST were assessed for the state of cognitive functions, everyday activity, mental symptoms, as well as enjoyment and involvement. One of the recruited patients was excluded due to restlessness and anxiety.Results. Seven patients had significantly improved on ADAS-Cog scale (p = 0.002), Lowton&amp;Brody and ADCS-ADL. The NPI scale indicated a reduction in symptoms of delirium and apathy which contributed to a reduction in antipsychotic dosages and a corresponding decrease in caregiver’s distress. The most striking indicator of CST effectiveness was improvements in the patient’s mood and satisfaction, which we view significant in everyday life and as an indicator of CST safety.Conclusion. The Russian-language version of CST proved effective and safe for moderate dementia patients with Alzheimer’s and can be recommended for implementing in clinical practice. This opens up prospects for studying CST as part of various drug strategies in treatment of dementia of various origins.