Use Of Atypical Antipsychotics Research Articles

Aripiprazole, but Not Olanzapine, Alters the Response to Oxidative Stress in Fao Cells by Reducing the Activation of Mitogen-Activated Protein Kinases (MAPKs) and Promoting Cell Survival.

Prolonged use of atypical antipsychotics (AAPs) is commonly associated with increased cardiovascular disease risk. While weight gain and related health issues are generally considered the primary contributors to this risk, direct interference with mitochondrial bioenergetics, particularly in the liver where these drugs are metabolized, is emerging as an additional contributing factor. Here, we compared the effects of two AAPs with disparate metabolic profiles on the response of Fao hepatoma cells to oxidative stress: olanzapine (OLA), which is obesogenic, and aripiprazole (ARI), which is not. Results showed that cells treated with ARI exhibited resistance to H2O2-induced oxidative stress, while OLA treatment had the opposite effect. Despite enhanced survival, ARI-treated cells exhibited higher apoptotic rates than OLA-treated cells when exposed to H2O2. Gene expression analysis of pro- and anti-apoptotic factors revealed that ARI-treated cells had a generally blunted response to H2O2, contrasting with a heightened response in OLA-treated cells. This was further supported by the reduced activation of MAPKs and STAT3 in ARI-treated cells in response to H2O2, whereas OLA pre-treatment enhanced their activation. The loss of stress response in ARI-treated cells was consistent with the observed increase in the mitochondrial production of O2•-, a known desensitizing factor. The physiological relevance of O2•- in ARI-treated cells was demonstrated by the increase in mitophagy flux, likely related to mitochondrial damage. Notably, OLA treatment protected proteasome activity in Fao cells exposed to H2O2, possibly due to the better preservation of stress signaling and mitochondrial function. In conclusion, this study highlights the underlying changes in cell physiology and mitochondrial function by AAPs. ARI de-sensitizes Fao cells to stress signaling, while OLA has the opposite effect. These findings contribute to our understanding of the metabolic risks associated with prolonged AAP use and may inform future therapeutic strategies.

Risk of renal impairment in atypical antipsychotics: a systematic review and meta-analysis.

Atypical antipsychotics are associated with several adverse effects including metabolic syndrome, weight gain, QTc interval prolongation, and extrapyramidal effects. This study aims to investigate the risk of renal impairment in patients receiving atypical antipsychotics. A systematic literature search was conducted via PubMed and Ovid SP and Web of Science to retrieve studies reporting the risk of renal impairment in patients receiving atypical antipsychotic treatment. The pooled risk ratio (RR) of renal impairment and the subgroup analysis was calculated using the random-effects generic inverse variance method in Cochrane Review Manager. A total of 4 studies involving 514,710 patients (221, 873 patients on atypical antipsychotics/CKD and 292, 837 controls) were included in this meta-analysis. Patients on atypical antipsychotics exhibited an increased risk of renal impairment, with a pooled risk ratio of 1.34 (95%CI 1.23-1.47). Subgroup analysis demonstrated that atypical antipsychotic use was associated with an increased risk of both acute kidney injury (AKI) (RR 1.51, 95%CI 1.34-1.71) and chronic kidney disease (CKD) (RR: 1.23, 95%CI 1.12-1.35). Patients receiving atypical antipsychotics have an increased risk of renal impairment. Quetiapine carries the highest risk of renal impairment encompassing both AKI and CKD.

Analysis of Atypical Antipsychotics-Induced Adverse Events Related to Diabetes Mellitus in Patients With Dementia Using the Japanese Adverse Drug Event Report Database.

Patients with dementia are prescribed low-dose atypical antipsychotics (AAPs) to treat psycho-behavioral symptoms. Although AAPs are known to cause diabetes mellitus-related adverse events (DMAEs), information regarding AAPs-induced DMAEs experienced by patients with dementia is lacking. To use the Japan Adverse Drug Event Report (JADER) database to assess the onset tendencies and patterns of DMAEs attributable to AAPs prescribed to patients with dementia. We performed an analysis using dementia cases from the JADER database that were registered from April 2004 to December 2022. Data in the JADER database are completely anonymized; thus, we did not require institutional review board approval for using the JADER database in our study. The reporting odds ratio and proportional reporting ratio (PRR) were used to assess the onset tendencies of DMAEs with AAPs. In addition, Weibull shape parameters were used to assess the patterns of DMAEs that occur with the use of AAPs. We identified AAPs associated with DMAEs. In particular, low doses of quetiapine showed the potential to induce DMAEs. An analysis of the onset of DMAEs showed the early failure patterns for AAPs (median onset = 38 days). The AAPs may cause DMAEs in patients with dementia. Low doses of quetiapine may induce DMAEs. Health care workers should focus on the development of DMAEs during the early administration period of AAPs. These results may assist with the safe management of patients with dementia who use AAPs.

TREATMENT OF SCHIZOPHRENIA IN ELDERLY PATIENTS

Introduction: The treatment of schizophrenia in elderly patients presents a significant clinical challenge due to the disease's particularities in this age group. Schizophrenia is a chronic mental disorder characterized by profound disturbances in thought, emotions, and behavior. In elderly patients, the condition may manifest in a more complex manner, with exacerbation of psychotic symptoms and cognitive decline that negatively impacts quality of life. The interplay between aging and schizophrenia requires a therapeutic approach tailored to the specific needs of the elderly, considering comorbidities, polypharmacy, and adverse effects of treatments. Objective: The objective of the systematic review was to evaluate treatment strategies for schizophrenia in elderly patients, examining the effectiveness and safety of available therapeutic interventions, as well as the specific clinical management issues within this population. Methodology: The systematic review was conducted based on the PRISMA checklist, utilizing the databases PubMed, Scielo, and Web of Science. Five main descriptors were used: "schizophrenia," "elderly," "treatment," "antipsychotic therapy," and "effectiveness." Articles published in the last 10 years were included. Inclusion criteria were: studies focused on patients aged 65 and older diagnosed with schizophrenia, articles addressing specific therapeutic interventions, and studies reporting quantifiable clinical outcomes. Exclusion criteria were: articles that did not differentiate the age group of participants, studies without original data or that did not include elderly patients, and publications that did not directly address schizophrenia treatment. Results: The results indicated that treatment for schizophrenia in the elderly frequently involved the use of atypical antipsychotics, which are preferred due to their more favorable side effect profile compared to typical antipsychotics. However, the effectiveness of these medications may be reduced in the elderly due to altered pharmacokinetics and increased risk of adverse effects. The combination of psychosocial therapy and support proved beneficial in improving treatment adherence and quality of life for patients. The need for individualized management and consideration of comorbidities were also highlighted. Conclusion: Treatment of schizophrenia in elderly patients requires a personalized approach that accounts for the complexities associated with aging. Medication choices should be made cautiously, prioritizing those with a lower risk of adverse effects. Additionally, integrating psychosocial strategies can significantly improve clinical outcomes and quality of life for these patients. Ongoing review of practices and guidelines is crucial for optimizing care and addressing the needs of this aging population.

Clinical characteristics and treatment of psychosis in Parkinson's disease: A narrative review.

Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disorder whose clinical presentation consists of motor and non-motor signs and symptoms. Among the non-motor symptoms, psychosis can occur in the later stages of the disease. Psychosis in PD (PDP) is a common, complex, and significantly disabling disorder associated with poorer quality of life, accelerated cognitive decline, need for hospitalization or institutionalization, and mortality. Hallucinations are a significant symptom of PDP, sporadic at first but more frequent in the later course of the disease, and significantly disrupt daily activities. Appropriate and timely screening of psychotic manifestations is necessary for adequate therapeutic procedures. After the exclusion of comorbid conditions as a possible cause of psychosis, correction of antiparkinsonian therapy may be required, and if necessary, the introduction of antipsychotics. The latest therapeutic recommendations include the use of pimavanserin, if available, otherwise second-generation or atypical antipsychotics. Although PDP has long been recognized as a possible complication in the course of the disease, further clinical studies are needed to fully understand its etiopathogenesis and pathophysiological mechanisms.

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.

The atypical antipsychotics and sexual dysfunction: a pharmacovigilance-pharmacodynamic study.

Atypical antipsychotics (AAPs)-induced sexual dysfunction (SD) is a frequent issue in clinical practice, often underestimated by clinicians and not extensively researched. The current study aimed to quantify the strength of association between the use of different AAPs and SD using real-world data from the FDA Adverse Event Reporting System (FAERS), as well as investigate the receptor mechanisms that are involved. Data from the FAERS database from the first quarter of 2004 to the third quarter of 2023 were queried through OpenVigil 2.1. Disproportionality analysis was estimated using the reporting odds ratio (ROR) and information component (IC) methods, and linear regression was used to investigate the relationship between ROR and receptor occupancy which was estimated using in vitro receptor binding profiles. Our analysis yielded 4839 reports that co-mentioned AAP and SD events, and the findings revealed statistical associations between 12 AAPs and SD. The highest signal value was identified for iloperidone reporting retrograde ejaculation with iloperidone (ROR = 832.09, ROR025 = 552.77; IC = 9.58, IC025 = 6.36), followed by compulsive sexual behavior with aripiprazole (ROR = 533.02, ROR025 = 435.90; IC = 7.30, IC025 = 5.97), and psychosexual disorder for aripiprazole (ROR = 145.80, ROR025 = 109.57; IC025 = 6.47, IC025 = 4.86). Different characteristics of the SD side effects in each AAPs were discovered after further data mining. Regression analysis revealed potential effects for receptor occupancy of D2, D3, and 5-HT1A receptors on ROR. However, no significant correlation persisted following sensitivity analyses. This is the first study to investigate the AAP-SD associations by using FAERS. In this study, we report for the first time a significant association between aripiprazole and SD based on real-world data. The study suggests that different AAPs have varying levels of association with SD, and the D2, D3, and 5-HT1A receptor occupancy may contribute to potential mechanisms. The findings of this study warrant further validation of more studies and clinical causality assessment.

Trends and off-label utilization of antipsychotics in children and adolescents from 2016 to 2021 in China: a real-world study

BackgroundGlobal 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.MethodsIn 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.ResultsOur 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.ConclusionIn 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.

Влияние атипичных антипсихотиков на развитие сахарного диабета 2-го типа

Atypical antipsychotics (novell atypical generation antipsychotics) have entered clinical practice recently, but despite this, they have already managed to occupy one of the leading positions in modern therapy of mental disorders such as schizophrenia and bipolar affective disorder. It is known that treatment with antipsychotics of both generations is associated with a number of side effects. When using atypical antipsychotics, metabolic disorders, including carbohydrate metabolism, occupy a leading place. A number of scientific studies, the analysis of which we are conducting in this review, describe the mechanisms of development of such changes in glucose homeostasis as hyperglycemia and insulin resistance in patients receiving therapy with second-generation antipsychotics (atypical). Another proven side effect is an increase in appetite and an increase in body weight. It is obvious that such metabolic changes have the potential to lead to the development of type 2 diabetes mellitus in the long term. The relevance of the study lies in the fact that the use of atypical antipsychotics is not always among the causes of drug-induced diabetes mellitus. In this regard, not all internists, endocrinologists, general practitioners, and sometimes even psychiatrists consider patients receiving treatment with these drugs to be at increased risk. Consequently, primary and secondary prevention of diabetes mellitus among such patients may not be carried out or may be insufficient. In this review, through meta-analysis, we summarized data on the effect of the main representatives of atypical antipsychotics on the possibility of developing type 2 diabetes mellitus, and also examined in more depth the pathogenesis of carbohydrate metabolism disorders in patients receiving therapy with these drugs.

Barriers to long-acting injectable atypical antipsychotic use in Japan: Insights from a comparative psychiatrist survey.

To investigate the negative attitudes of Japanese psychiatrists toward atypical long-acting injectable (LAI) antipsychotics, which are the current mainstream LAIs in Japan. We surveyed 69 Japanese psychiatrists using a 5-point Likert scale to assess their attitudes toward atypical LAI antipsychotics. Our assessment referenced concerns identified in a study conducted in Japan a decade ago, which found significant differences when compared with a survey of German psychiatrists. We also identified the factors influencing these negative attitudes. Additionally, the results were compared with those of previous Japanese and German studies. More than 50% of Japanese psychiatrists expressed negative attitudes toward atypical LAI antipsychotics in various areas. These concerns included apprehensions about cost, reluctance to recommend them initially, pain from injections, complexity of switching to LAI, usage in first-episode cases, and sufficient medication adherence with oral drugs. In all three studies, cost and adequate adherence to oral medication were concerns that exceeded the average of the three negative comments. Age and experience in psychiatry influenced the psychiatrists' attitudes toward using these drugs in first-episode cases. These findings shed light on the reasons for the underutilization of atypical LAI antipsychotics and suggest opportunities to enhance their appropriate use in clinical settings.

Clearing the Fog: A Review of Antipsychotics for Parkinson's-Related Hallucinations: A Focus on Pimavanserin, Quetiapine and Clozapine.

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.

Evidence-Informed Approach to De-Prescribing of Atypical Antipsychotics (AAP) in the Management of Behavioral Expressions (BE) in Advanced Neurocognitive Disorders (NCD): Results of a Retrospective Study

IntroductionDiagnosis of behaviors in advanced neurocognitive disorders (aNCD) is one of exclusion, and the framework has been laid out in DSM-V. However, clinical assessments in aNCD become increasingly unreliable, and commonly used psychometric tools for clinical assessments lack reliability and validity, thereby making outcomes unreliable. Consequently, the syndromic and symptom management approaches for behaviors in aNCD behaviors have yielded poor results. To address this, the focus has shifted towards understanding the ‘meaning’ of behaviors in aNCD, recognizing them as a ‘mode of communication’. To date, there are no existing frameworks to ascribe ‘meaning’ to behaviors in aNCD.ObjectivesLuBAIR™ paradigm is the first step in offering such a framework for understanding the ‘purpose’ and ‘meaning’ of behaviors in NCD. The ‘meaning’ ascribed to each behavioral category was used to guide the use of atypical antipsychotics in their management. De-prescribing was attempted on patients who qualified to enter this retrospective study. De-prescribing was defined as successful if individuals were completely withdrawn from AAP and remained off them for 60 days without the re-emergence of behaviors.MethodsThe data collected on the second occasion, in the successful and failed de-prescribed groups, were compared in this retrospective study. MANOVA, Chi-Square paired t-test statistical analyses were used to detect the differences in the behavioral categories between the two cohorts. Cohen d was used to measure effect size.ResultsPatients who did not have Mis-Identification and Goal-Directed Expressions were more likely to successfully de-prescribe: X2 (1, N = 40) = 29.119 p < 0.0001 and X2 (1, N = 40) = 32.374, p < 0.0001, respectively. Alternatively, the same behavioral categories were more likely present in patients who failed de-prescribing: MANOVA and paired t-test (p < 0.0001). Atypical antipsychotics, in their role as an antipsychotic and mood stabilizer, may be used to manage Mis-Identification and Goal-Directed Expressions, respectively.ConclusionsLuBAIR paradigm has the potential to guide the development of specific behavioral care plans and the use of AAP in managing individual behavioral categories. AAP use can be justified for managing Misidentification and Goal-Directed Expressions. Vocal expressions may warrant the use of AAP, pending further study. The LuBAIR paradigm offers guidance for de-prescribing AAP for all other behavioral categories in the LuBAIR Inventory. This study is also a preliminary step in validating the psychological theories used to support the individual categories. This workshop will educate the participants on the LuBAIR paradigm and its application in developing person-centered interventions for behaviors in a NCD.Disclosure of InterestNone Declared

Quetiapine Versus Haloperidol in the Management of Hyperactive Delirium: Randomized Controlled Trial

BackgroundIn the population of patients in the intensive care unit (ICU), most studies compared the use of atypical antipsychotics, such as quetiapine, with the use of traditional haloperidol in patients with delirium of various forms and etiologies. The role of such agents in patients with hyperactive delirium is not fully understood. This study compares the effectiveness of quetiapine with haloperidol in treating the hyperactive form of delirium in terms of their effects on the Delirium Rating Scale-Revised-98 (DRS-R-98), length of stay in the ICU, and mortality in critically ill patients.MethodsOne hundred adult patients diagnosed with hyperactive delirium were randomly assigned to receive either oral quetiapine (25–50 mg/day) or haloperidol (1–2 mg/day). The response, defined as “a DRS-R-98 severity score reduction from baseline of 50% or more” and a DRS-R-98 severity score of 12 or less without relapse, was the primary outcome.ResultsThe mean age of all patients was 68 ± 6 years. The study population’s overall response rate was 92%. Response rates for the two groups were remarkably equal (p = 0.609). Secondary outcomes were comparable in both groups, such as ICU mortality (p = 0.496), in-hospital mortality (p = 0.321), in-hospital stay (p = 0.310), and the need for mechanical ventilation (p > 0.99). But the quetiapine group showed a statistically reduced mean ICU stay (10.1 ± 2.0 vs. 11.7 ± 2.6 days, p = 0.018) and increased sleeping hours per night (p = 0.001).ConclusionsQuetiapine may be equally as effective as haloperidol in treating the symptoms of hyperactive delirium in critically ill patients, with no mortality benefit.

Are antipsychotics carcinogenic?: A review of the literature

IntroductionAntipsychotics are currently widely prescribed for various mental disorders. A presumption of a potential carcinogenic effect of antipsychotics was raised by certain studies. There are few data in the literature on this subject.ObjectivesStudy the relationship between the use of antipsychotics and the risk of cancer.MethodsA systematic literature review was carried out on PubMed looking for articles in English, published during the last decade (2013-2023), using the keywords “Antipsychotics” and “Cancer”. We included all articles studying the relationship between antipsychotics use and cancer risk.Results Nine articles were included in our study, the majority of which focused on breast cancer. The results regarding breast cancer were discordant: although three studies did not show an association between the administration of antipsychotics and breast cancer, more recent studies have proven the opposite. Indeed, chronic exposure to antipsychotics, particularly those raising prolactinemia, was significantly associated with an accumulated risk of breast cancer, especially with positive estrogen receptors, whereas prolactin-sparing antipsychotics were not associated with it. Regarding hematologic malignancies, unlike other antipsychotics, long-term use of clozapine was associated with a high risk of malignancy, and had a greater effect on mortality from lymphoma and leukemia than to agranulocytosis. On the other hand, it has been proven that the use of atypical antipsychotics is associated with a reduced risk of lung cancer.ConclusionsData from the literature regarding the carcinogenic potential of antipsychotics remain discordant and inconclusive. The most recent studies are worrying and highlight in particular an association between the use of antipsychotics and the increased risk of breast cancer. If these data are confirmed in future studies, this will undoubtedly impact the benefit-risk balance when making therapeutic decisions.Disclosure of InterestNone Declared

The role of Galacto-oligosaccharides (GOS) in the recovery from dysbiosis in patients on long-term atypical antipsychotic treatment

Introduction Atypical antipsychotic (AAP) drugs are the gold-standard treatment for psychotic patients but are nowadays also widely prescribed among people with other mental disorders. Notwithstanding the benefits of AAP in terms of symptom improvement, there are severe adverse effects including the metabolic syndrome. A novel hypothesis is that part of these undesirable effects of antipsychotics could be mediated by their deleterious effects on the microbiome. This may result in dysbiosis, the disruption of bacterial species of the gut microbiota. Recently, dysbiosis has been linked to poor quality of life, depression and anxiety through the gut-brain axis. Mounting evidence proposes that prebiotic consumption may be helpful in the recovery of dysbiosis, although this effect is unclear among long-term antipsychotic users.ObjectivesThe main objective of this study is to assess the potential beneficial effects of the prebiotic Galacto-oligosaccharides (GOS) in combination with 2′-fucosyllactose (2’-FL) on the gut microbiota, by showing a relative increase in Bifidobacteria in fecal samples following intervention. The secondary objective is to assess the effects of GOS on mental wellbeing, sleep, and metabolic parameters. We hypothesize that GOS+2’FL supplementation will improve gut health, mental wellbeing, sleep, and metabolic parameters. Data will be collected 4 weeks prior to the start of the intervention during an observation only phase [t0], at baseline [t1], and after 2 [t2] and 6 [t3] weeks of GOS+2’FL intake. A follow-up will take place at week 10, 4 weeks after the intervention [t4]. Other outcomes that are assessed include the FiberScreen tool, the form of human faeces (Bristol Stool Chart), side effects and the defined daily dosis (DDD) of antipsychotic medication.MethodsThe study is a single-arm pilot study (non-randomized and non-blinded). We aim to include 30 psychiatric patients on long-term atypical antipsychotic use, irrespective of their specific psychiatric disorder, with a BMI > 25 kg/m2. Following a run-in period of 4 weeks (no intervention but all other aspects of the study), the participants will consume GOSplus (7.0 g BiotisTMGOS + 0.7 g 2’-FL) daily during the first consumption moment of the day (preferably in the morning) for 42 days. The GOSplus powder has a slightly sweet flavour. The primary endpoint is the change in Bifidobacteria in fecal samples from week 0 to week 6.ResultsThe study started recruiting participants in October 2023.ConclusionsConclusions are expected by the end of 2024.Disclosure of InterestNone Declared

Prolactin level changes according to atypical antipsychotics use: a study based on Clinical Data Warehouse

IntroductionAntipsychotics are associated with increased serum prolactin. It depends on the type of the antipsychotics and gender. There are previous studies, but it is necessary to compare them including new drugs.ObjectivesAntipsychotic drugs are known as the major cause of non-neoplastic hyperprolactinemia. This study aimed to investigate the levels of serum prolactin elevation depending on the use of antipsychotic drugs in patients through the Clinical Data WarehouseMethodsOur study included 118 subjects who were all diagnosed according to ICD-10 for schizophrenia, schizotypal and delusional disorders, manic episodes, and bipolar affective disorders. All the subjects were taking one of risperidone, blonanserin, amisulpride, and olanzapine. They had prolactin blood tests collected retrospectively through CDW.Results Among the 118 subjects included in the analysis, the mean serum prolactin level was 65.1± 54.7ng/ml. Serum prolactin levels were significantly higher in subjects taking risperidone or amisulpride compared to blonanserin and olanzapine. The female subjects who took amisulpride or olanzapine had significantly higher prolactin levels, but there was no difference in prolactin levels between the sex in the subjects who took risperidone or blonanserin.ConclusionsThis study suggests the need for regular monitoring of serum prolactin levels in patients who are taking antipsychotics, especially in female patients. Further studies on the subjects with controlled confounding variables and larger sample groups are needed.Disclosure of InterestNone Declared

Impact of formulary-related pharmacy claim rejections of cariprazine on health care utilization and treatment patterns among patients with bipolar I disorder.

Formulary restrictions, intended to limit inappropriate medication use and decrease pharmacy costs, may prevent or delay patients with bipolar I disorder from initiating cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5HT1A receptor partial agonist that is approved to treat manic/mixed or depressive episodes associated with bipolar I disorder. Little is known about the downstream consequences of formulary-related cariprazine prescription rejections. To evaluate the impact of formulary-related cariprazine claim rejections on health care resource utilization (HCRU) and treatment patterns among patients newly prescribed cariprazine for bipolar I disorder. Symphony Health Integrated Dataverse was used to identify commercially insured adults (aged ≥18 years) with bipolar I disorder and at least 1 pharmacy claim for cariprazine (rejected because of formulary restrictions or approved; date of the first claim is the index date) from March 2015 through October 2020. Formulary-related rejection reasons included noncoverage, prior authorization requirement, and step therapy requirement. Baseline characteristics were evaluated during the 12 months pre-index and balanced between rejected and approved cohorts using 1:2 propensity score matching. HCRU outcomes included all-cause and mental health (MH)-related hospitalizations, emergency department (ED) visits, and outpatient visits. Treatment patterns were analyzed descriptively and included treatment delay and atypical antipsychotic use. HCRU was reported per patient-year and compared between cohorts using rate ratios; 95% CIs and P values were calculated using nonparametric bootstrap procedures. The matched rejected and approved cohorts comprised 1,554 and 3,108 patients, respectively. The rejected cohort had 22% more all-cause and 24% more MH-related hospitalizations per patient-year vs the approved cohort (rate ratio [95% CI], all-cause: 1.22 [1.01-1.48], P = 0.024; MH-related: 1.24 [1.01-1.55], P = 0.044). ED and outpatient visits were numerically, but not significantly, greater in the rejected cohort. Of patients in the rejected cohort, 34.7% never received an atypical antipsychotic and 76.8% never received cariprazine. For those who later received cariprazine or another atypical antipsychotic, the average treatment delay was approximately 6 months (188 days) and approximately 4 months (123 days) after the initial rejection, respectively. Patients with bipolar I disorder and formulary-related cariprazine claim rejections experienced significantly more hospitalizations than patients whose initial claim was approved; ED and outpatient visits were similar between cohorts. Less than a quarter of patients whose initial claim was rejected later received cariprazine, and more than one-third never received any atypical antipsychotic. To our knowledge, this is the first study to evaluate the impact of formulary-related rejections of cariprazine on HCRU and treatment patterns in patients with bipolar I disorder.

Antipsychotics-related hyperprolactinaemia among patients with schizophrenia in Maiduguri.

Hyperprolactinaemia among patients on antipsychotic medications is generally overlooked due to lack of outwardly visible symptoms, patient resistance to reporting because the symptoms are perceived as shameful, or to clinician's insufficient knowledge. The study aimed to evaluate the patterns and correlates of hyperprolactinemia among patients with schizophrenia on antipsychotic medications. The study was conducted in a psychiatric facility in Maiduguri, Northeastern Nigeria. A total of 209 patients with schizophrenia were evaluated through a cross-sectional design and assayed for serum prolactin with ELISA Kits. Frequencies and percentages were tabulated for categorical variables. Variables with significant associations with hyperprolactinaemia on chi-square (p < 0.05) were subjected to logistic regression analysis. The prevalence of hyperprolactinaemia was 45.9% in all patients on antipsychotic medication. The prevalence because of the use of typical and atypical antipsychotics was 51.5% and 25.0%, respectively. Hyperprolactinaemia was significantly associated with typical antipsychotics (β = 0314, p = 0.002), high overall drug dosage (β = 2.340, p = 0.003), high-dose typical antipsychotics (β = 3.228, p = 0.000), twice daily dosing frequency (β = 2.751, p = 0.001) and polypharmacy (β = 1.828, p = 0.0024). The findings support that patients on typical, high-dose antipsychotic medications and polypharmacy have a high prevalence of hyperprolactinaemia. As hyperprolactinaemia is often undetectable, screening and patient psycho-education on the significance of the signs and symptoms of hyperprolactinaemia is required for necessary clinical intervention. The study provides evidence for the rational use of antipsychotic medications in sub-Saharan Africa.

Atypical antipsychotics in the treatment of depression in affective disorders and schizophrenia (using the aripiprazole model)

The review discusses aspects of the use of atypical antipsychotics in the treatment of depression in affective disorders and schizophrenia using the model of aripiprazole, a partial agonist of dopamine receptors. According to numerous studies, aripiprazole is the drug of choice for augmentative therapy of major depressive disorder, as well as for relieving and long-term maintenance monotherapy and combination therapy of various affective episodes of bipolar affective disorder and depression in schizophrenia.

Risk of long-term care admissions among Medicare beneficiaries treated with pimavanserin or quetiapine for Parkinson's disease psychosis in USA: a retrospective administrative claims database analysis.

Aim: Risk of long-term care (LTC) admission (LTCA) associated with atypical antipsychotic (AAP) use among patients with Parkinson's disease psychosis (PDP) is a major concern. However, no comparative studies have examined the differences in risk of LTC admissions between pimavanserin (PIM), the only FDA-approved AAP for PDP, and other off-label AAPs including quetiapine (QUE). Objective: To examine all-cause LTCA rates and risk among PDP patients treated with AAPs such as QUE or PIM. Methods: Analysis of Parts A, Band D claims (100% Medicare sample; 2013-2019) of Medicare beneficiaries with PDP that initiate ≥12-month continuous PIM or QUE monotherapy from 1 January 2014 to31 December 2018 (i.e., index date) without any AAP use in the 12-month pre-index period was conducted. Outcome assessments among 1:1 propensity score-matched (31 variables - age, sex, race, region and 27 Elixhauser comorbidities) beneficiaries on PIM versus QUE included risk of all-cause skilled nursing facility stays (SNF-stays), LTC-stays, and overall LTCA (i.e., SNF-stays or LTC-stays). All-cause LTCA rates and LTCA risk were compared using logistic regression and cox proportional hazards models, respectively, controlling for demographics, comorbidities and co-existing-dementia or insomnia. Results: Of the matched sample (n=842 for each group) from total sample (n=9652), overall all-cause LTCA and SNF-stay rates were 23.2 and 20.2% for PIM versus 33.8 and 31.4% for QUE, respectively (p<0.05, for each). Hazard ratio (95% CI) for risk of SNF-stay and overall LTCA was 0.78 (0.61, 0.98) and 0.80 (0.66, 0.97), respectively, for PIM versus QUE beneficiaries (p<0.05, for each). Conclusion: The 20% lower risk of LTCA (i.e., greater delay) with PIM versus QUE in this analysis may suggest that PIM should be started early for the treatment of PDP.