Effects Of Atypical Antipsychotics Research Articles

Exposure-Response Modeling in Adults and Adolescents With Schizophrenia to Support the Extrapolation of Brexpiprazole Efficacy to Adolescents.

In order to accelerate drug development and avoid unnecessary drug trials in vulnerable pediatric populations, the US Food and Drug Administration (FDA) released a general advice letter to sponsors permitting the effectiveness of atypical antipsychotics for the treatment of schizophrenia in adults to be extrapolated to adolescents. Extrapolation is based on the evidence-based assumptions that (1) disease characteristics and (2) response to therapy, are similar in adults and adolescents. Whereas the FDA validated the extrapolation approach using data from multiple drug development programs, aripiprazole data are the most relevant to confirm the validity of the extrapolation approach for brexpiprazole, since aripiprazole and brexpiprazole both modulate dopaminergic and serotonergic signaling in the brain. The aims of this analysis were (1) to quantitatively assess the aripiprazole exposure (average steady-state concentration)-response (Positive and Negative Syndrome Scale total score change from baseline) similarity between adults and adolescents with schizophrenia, (2) to extend the aripiprazole exposure-response modeling to brexpiprazole using adult data, and (3) to use the brexpiprazole model to predict schizophrenia symptom response in adolescents. Disease-drug-dropout models were developed using patient-level data from clinical studies of aripiprazole (1007 adults, 294 adolescents) and brexpiprazole (1235 adults) in schizophrenia. The aripiprazole model demonstrated similar exposure-response between adults and adolescents with schizophrenia, validating the extrapolation approach. Extrapolation of the brexpiprazole adult exposure-response model to adolescents predicted the efficacy of brexpiprazole in adolescents aged 13-17 years with schizophrenia.

Comparative effectiveness of clozapine and non-clozapine atypical antipsychotics provided by the Brazilian National Health System in adults with schizophrenia.

Currently, 21 million people live with the disease, mostly in low to middle-income countries. We aimed to assess the survival of patients with schizophrenia using clozapine compared with non-clozapine atypical antipsychotics provided by the Brazilian National Health System using real-world data. This is an open retrospective cohort study of patients diagnosed with schizophrenia to whom atypical antipsychotics were dispensed by the Brazilian National Health System between 2000 and 2015, based on deterministic-probabilistic pairing of administrative data records. The Kaplan-Meier method was used to estimate the cumulative probability of survival and the Cox proportional hazards model was adjusted to assess the risk factors for survival via the hazard ratio (HR). Participants were 375,352 adults with schizophrenia, with an overall survival rate of 76.0% (95%CI 75.0-76.0) at the end of the cohort. Multivariate analysis indicated a greater risk of death for men (HR=1.30; 95%CI 1.27-1.32), older adults (HR=17.05; 95%CI 16.52-17.60), and in the Southeast region of Brazil (HR=1.20; 95%CI 1.17-1.23). Patients who used non-clozapine atypical antipsychotics had a 21% greater risk of death when compared to those taking clozapine (HR=1.21; 95%CI 1.14-1.29). Additionally, a history of hospitalization for pneumonia (HR=2.17; 95%CI 2.11-2.23) was the main clinical variable associated with increased risk of death, followed by hospitalization for lung cancer (HR=1.82; 95%CI 1.58-2.08), cardiovascular diseases (HR=1.44; 95%CI 1.40-1.49) and any type of neoplasia (HR=1.29; 95%CI 1.19-1.40). This is the first published Brazilian cohort study that evaluated survival in people with schizophrenia, highlighting the impact of atypical antipsychotics. In this real-world analysis, the use of clozapine had a protective effect on survival when compared to olanzapine, risperidone, quetiapine, and ziprasidone.

Haloperidol, Olanzapine, and Risperidone Induce Morphological Changes in an In Vitro Model of Human Hippocampal Neurogenesis.

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

Effect of Atypical Anti-psychotics on Cognition in Schizophrenia

Effect of Atypical Anti-psychotics on Cognition in Schizophrenia

Evaluation of antipsychotic side effects on schizophrenia patients at Dr Radjiman Wediodiningrat Hospital, Indonesia

Background: Schizophrenia is the most common mental illness with a poor prognosis. Antipsychotics are the major treatment for Schizophrenia. Objective: This study examines schizophrenia patients' side effects and antipsychotic medication. Method: A retrospective study with cross-sectional observational analysis was conducted in June 2023, with only the data from schizophrenia patients in Dr. Radjiman Wediodiningrat Hospital, Indonesia. Data were collected from the prescription records of schizophrenia inpatients from January to June 2023. The Chi-square test was used to analyse and measure the relationship between the incidence of adverse events with antipsychotics in schizophrenia patients. Result: Schizophrenia inpatients were majority male (74.7%) and the age 18-35 years was 41%. This study showed that the pattern of prescription of antipsychotics is atypical monotherapy (37.6%) and combinations (24.9%) were the most antipsychotics prescribed. Most of the schizophrenia outpatients have extrapyramidal syndrome side effects (31.9%), such as rigidity (12.2%), tremor (3.5%), dystonia (6.6%), and other side effects (11.8%). Conclusion: This study highlighted that atypical antipsychotics were the most common choice for treatment in the inpatient setting. Atypical have a lower risk of extrapyramidal side effects than typical. The negative effects of atypical antipsychotics, including metabolic syndrome, have not been identified. Thus, more research is required.

The Effect of Antipsychotics on Cognition in Schizophrenia-A Current Narrative Review.

The majority of schizophrenia-affected individuals display deficiencies in multiple cognitive domains such as attention, working memory, long-term memory, and learning, deficiencies that are stable throughout the disease. The purpose of this narrative review was to examine the effect of antipsychotics on several cognitive domains affected by schizophrenia. Methods: We searched MEDLINE, Elsevier, Scopus, and DOAJ databases for randomized controlled trials and other studies investigating the effects of typical and atypical antipsychotics on cognition in patients with schizophrenia in studies conducted in the last decade. Results: The majority of studies included in this review showed that antipsychotics (especially SGAs) have positive effects on both cognition and general psychopathology of schizophrenia. We mention that treatment with antipsychotic substances represents an ongoing effort of the researchers, who are constantly searching for the best approach to meet the mental health needs of schizophrenia patients. Conclusions: Even with those positive results, it should be noted that more studies are needed in order to fully observe the various effects of certain antipsychotic substances on cognition.

Safety of Atypical Antipsychotics in a Child and Adolescent Inpatient Setting: A Naturalistic Study.

This study's objective was to investigate the adverse effects of atypical antipsychotics (AAPs) on the metabolic, hematological, and endocrinological systems in the inpatient environment for children and adolescents with diverse psychiatric disorders. A retrospective assessment of 208 children's and adolescents' medical records was conducted. All patients were on AAP monotherapy. At baseline and after treatment, measurements of body weight, height, body mass index (BMI), BMI z-score, fasting blood glucose (FBG), total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol, complete blood count, liver functions, thyroid functions, and prolactin levels were made. Scores from the Children's Global Assessment Scale (CGAS) and the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) were preserved. The overall patient population had a mean age of 14.50 ± 2.32 years, 139 girls, and 69 boys. Of the patients, 63 (30.29%) were on risperidone (RIS), 69(33.17%) were on aripiprazole (ARI), 32 (15.39%) were on quetiapine (QUE), 42 (20.19%) were on olanzapine (OLA), and 2 (0.96%) were on clozapine (CLO). In the OLA group, the BMI and BMI z-score increased more than in the RIS, QUE, and ARI groups (P = .030, P = .014, and P = .001, respectively) (P = .001). The mean difference in CGAS and HoNOSCA between the start of antipsychotic medication and hospital discharge was statistically different for all four groups (P = .001 for all). The mean FBG levels in the OLA group increased statistically significantly (P = .013, P = .021) in contrast to the RIS group. In addition, a statistically significant difference in triglycerides across the groups was found (P = .003). According to the findings of our study, children and adolescents appear to be at a significant risk for psychotropic-induced PRL increase, weight gain, metabolic, and hematological consequences. To prevent serious health problems, a meticulous risk-benefit assessment for AAPs treatment should be done between clinicians and patients and their families.

Atypical Antipsychotics and Sexual Functions in Schizophrenia: A Cross-sectional Study

Abstract Background: Antipsychotics are associated with sexual dysfunction. However, studies selectively exploring the sexual impact of atypical antipsychotics in a standardized male population are limited, and further more in the Indian context. Thus, a need was felt to understand, explore and assess the impact of atypical antipsychotics on sexual wellness in a standardized male population suffering from Schizophrenia. Objective: To study the effect of Atypical Antipsychotics on Sexual functions in sexually active male patients of Schizophrenia treated with Atypical Antipsychotics. Materials and Methods: 150 sexually active freshly diagnosed treatment naïve males with Schizophrenia were administered atypical antipsychotics. Their sexual functions were assessed after 1 month using Arizona Sexual Experience Questionnaire (ASEX). Results: Olanzapine, risperidone, and clozapine had maximum incidence of sexual dysfunction (SD) while quetiapine and aripiprazole were having the least. 54% had one or more SD, prominent ones being low sexual desire (54%), dissatisfaction with their sexual drive (41.3%), dissatisfaction with orgasm (39.3%) and inability to reach orgasm (32%). Conclusion: SD rates are higher among patients of Schizophrenia treated with Atypical Antipsychotics. All the domains of sexual functioning are affected. Clinicians should routinely assess the sexual functioning in patients on treatment with antipsychotics and should incorporate sexual health as a dimension in their treatment plan.

Metabolic effects of atypical antipsychotics: Molecular targets.

Atypical antipsychotics (AAPs) are commonly prescribed drugs in the treatment of schizophrenia, bipolar disorder and other mental diseases with psychotic traits. Although the use of AAPs is associated with beneficial effects in these patients, they are also associated with undesired metabolic side effects, including metabolic syndrome (MetS). MeS is defined by the presence of metabolic abnormalities such as large waist circumference, dyslipidemia, fasting hyperglycemia and elevated blood pressure, which predispose to type 2 diabetes (T2D) and cardiovascular disease. In this review, the molecular and cellular mechanisms involved in these undesired metabolic abnormalities induced by AAPs are described. These mechanisms are complex as AAPs have multiple cellular targets which significantly affect the activities of several hormones and neuromodulators. Additionally, AAPs affect all the relevant metabolic organs, namely the liver, pancreas, adipose tissue, skeletal muscle and intestine, and the central and peripheral nervous system as well. A better understanding of the molecular targets linking AAPs with MetS and of the mechanisms responsible for clinically different side effects of distinct AAPs is needed. This knowledge will help in the development of novel AAPs with less adverse effects as well as of adjuvant therapies to patients receiving AAPs.

Putative neural mechanisms underlying release-mode-specific abnormalities in dopamine neural activity in a schizophrenia-like model: The distinct roles of glutamate and serotonin in the impaired regulation of dopamine neurons.

Abnormalities in dopamine function might be related to psychiatric disorders such as schizophrenia. Even at the same concentration, dopamine exerts opposite effects on information processing in the prefrontal cortex depending on independent dopamine release modes known as tonic and phasic releases. This duality of dopamine prevents a blanket interpretation of the implications of dopamine abnormalities for diseases on the basis of absolute dopamine levels. Moreover, the mechanisms underlying the mode-specific dopamine abnormalities are not clearly understood. Here, I show that the two modes of dopamine release in the prefrontal cortex of a schizophrenia-like model are disrupted by different mechanisms. In the schizophrenia-like model established by perinatal exposure to inflammatory cytokine, epidermal growth factor, tonic release was enhanced and phasic release was decreased in the prefrontal cortex. I examined the activity of dopamine neurons in the ventral tegmental area (VTA), which sends dopamine projections to the prefrontal cortex, under anaesthesia. The activation of VTA dopamine neurons during excitatory stimulation (local application of glutamate or N-methyl-d-aspartic acid [NMDA]), which is associated with phasic activity, was blunt in this model. Dopaminergic neuronal activity in the resting state related to tonic release was increased by disinhibition of the dopamine neurons due to the impairment of 5HT2 (5HT2A) receptor-regulated GABAergic inputs. Moreover, chronic administration of risperidone ameliorated this disinhibition of dopaminergic neurons. These results provide an idea about the mechanism of dopamine disturbance in schizophrenia and may be informative in explaining the effects of atypical antipsychotics as distinct from those of typical drugs.

Population Pharmacokinetic Analysis of Brexpiprazole to Support its Indication and Dose Selection in Adolescents With Schizophrenia.

Due to the customary delay between medication approvals in adult and adolescent populations, adolescents with schizophrenia may receive off-label antipsychotic treatment, without empirically justified dosing recommendations. In order to accelerate pediatric drug development, the US Food and Drug Administration (FDA) released a general advice letter to sponsors permitting the effectiveness of atypical antipsychotics for the treatment of schizophrenia in adults to be extrapolated to adolescents based on a pharmacokinetic (PK) analysis to support dose selection, plus a safety study. The aim of the present article is to describe the population PK analysis that was submitted to the FDA to inform brexpiprazole dose selection in adolescents with schizophrenia. Using a population PK model with brexpiprazole clearance and volume of distribution allometrically scaled by body weight, PK simulations showed comparable brexpiprazole dose-exposure between adults and adolescents aged 13-17years following oral daily doses of brexpiprazole 1-4mg, indicating that the target brexpiprazole dose of 2-4mg/day in adults with schizophrenia is also suitable for adolescents. Based on this population PK analysis, together with a safety study in adolescents, the FDA approved brexpiprazole for the treatment of schizophrenia in adolescents aged 13-17years, via extrapolation of the efficacy of brexpiprazole from adults to adolescents.

Magnetic resonance imaging detects white adipose tissue beiging in mice following PDE10A inhibitor treatment

Weight gain is a common harmful side effect of atypical antipsychotics used for schizophrenia treatment. Conversely, treatment with the novel phosphodiesterase-10A (PDE10A) inhibitor MK-8189 in clinical trials led to significant weight reduction, especially in patients with obesity. This study aimed to understand and describe the mechanism underlying this observation, which is essential to guide clinical decisions. We hypothesized that PDE10A inhibition causes beiging of white adipose tissue (WAT), leading to weight loss. Magnetic resonance imaging (MRI) methods were developed, validated, and applied in a diet-induced obesity mouse model treated with a PDE10A inhibitor THPP-6 or vehicle for measurement of fat content and vascularization of adipose tissue. Treated mice showed significantly lower fat fraction in white and brown adipose tissue, and increased perfusion and vascular density in WAT versus vehicle, confirming the hypothesis, and matching the effect of CL-316,243, a compound known to cause adipose tissue beiging. The in vivo findings were validated by qPCR revealing upregulation of Ucp1 and Pcg1-α genes, known markers of WAT beiging, and angiogenesis marker VegfA in the THPP-6 group. This work provides a detailed understanding of the mechanism of action of PDE10A inhibitor treatment on adipose tissue and body weight and will be valuable to guide both the use of MK-8189 in schizophrenia and the potential application of the target for weight loss indication.

Evaluation of the Effect of Barberry Root (Berberis Vulgaris) on the Prevention of Metabolic Syndrome Caused by Atypical Antipsychotic Drugs in Patients with Schizophrenia: A Three-Blind Placebo-Controlled Clinical Trial.

Objective: Metabolic syndrome is a potential side effect of atypical antipsychotics which are the current standard treatment for schizophrenia. Therefore, we aimed to examine the effect of barberry root (Berberis vulgaris) on the prevention of metabolic syndrome caused by atypical antipsychotic drugs in patients with schizophrenia. Method : Our research was a three-blind randomized clinical trial. The participants included all patients who were diagnosed with schizophrenia through the SCID-5 questionnaire and based on the DSM-5-TR criteria by two psychiatric experts. These patients were randomly divided into intervention and placebo groups. During a three-month treatment period, the intervention group received three 500 mg capsules of barberry root extract daily, whereas the placebo group received the same capsules containing 500 mg of starch powder. Metabolic syndrome variables including fasting blood glucose, serum lipids (triglyceride and cholesterol), blood pressure, weight and waist circumference were measured before and after the treatment as outcome measure. Chi-square and t-tests were used for data analysis using SPSS-22 software. Results: At the beginning of the study, there was no significant difference between the intervention group (n = 41) and the placebo group (n = 47) in terms of demographic factors, and pre-treatment assessments including weight, waist size, fasting blood HDL, fasting blood triglycerides and systolic and diastolic blood pressure and fasting blood glucose (P > 0.05). Within group analysis showed that some metabolic factors significantly increased in both groups after the treatment (P < 0.05). Indeed, in both groups, metabolic syndrome measures worsened after the three-month treatment period. The parameters of weight and waist size were significantly higher in the intervention group than the placebo group after treatment (P < 0.05). Conclusion: Barberry root extract was not able to control the Effects of antipsychotic drugs on metabolic syndrome in schizophrenia.

Pharmacotherapies for Treatment-Resistant Depression: How Antipsychotics Fit in the Rapidly Evolving Therapeutic Landscape.

One in three adults with major depressive disorder (MDD) do not experience clinically significant improvement after multiple sequential courses of antidepressants and have treatment-resistant depression (TRD). The presence of TRD contributes to the morbidity and excess mortality associated with MDD and has been linked to significantly increased health care expenses. In the absence of a consensus definition of TRD, this report takes a broad approach by considering inadequate response to one or more courses of antidepressants and focuses on atypical antipsychotics that are approved by the U.S. Food and Drug Administration for treatment of depression (aripiprazole, brexpiprazole, cariprazine, extended-release quetiapine, and olanzapine-fluoxetine combination). While multiple acute-phase studies have demonstrated the efficacy of these medications in improving depressive symptoms, clinically meaningful improvement (i.e., remission) remains limited, with significant concerns about side effects (including weight gain, metabolic dysfunction, extrapyramidal symptoms, and tardive dyskinesia), especially with long-term use. With the rapidly evolving landscape of antidepressant treatments over the past few years, which has witnessed approval of rapid-acting antidepressants (e.g., esketamine nasal spray and dextromethorphan-bupropion combination) and several more in the late-stage pipeline (e.g., zuranolone and psilocybin), it remains to be seen whether the use of atypical antipsychotics will go the way of the older and rarely prescribed antidepressants (such as tricyclics and monoamine oxidase inhibitors). Pragmatic clinical trials are needed to compare the effectiveness of atypical antipsychotics with TRD-specific pharmacotherapies and neuromodulation treatments and to identify the optimal sequencing of these varied approaches for patients with MDD. When using atypical antipsychotics, clinicians and patients are encouraged to use a shared decision-making approach by personalizing treatment selection based on anticipated side effects, tolerability, cost, and feasibility.

Co-prescription of aripiprazole on prolactin levels in long-term hospitalized chronic schizophrenic patients with co-morbid type 2 diabetes: A retrospective clinical study.

One of the most frequent side effects of atypical antipsychotics is hyperprolactinemia (HPRL), and metformin or aripiprazole co-prescription is regarded as an effective therapy option for reducing prolactin (PRL) levels. However, whether either of the two drugs can reduce PRL levels in patients with long-term hospitalized chronic schizophrenia with co-morbid type 2 diabetes (T2DM) has not been adequately reported. In our study, long-term hospitalized chronic schizophrenia patients with co-T2DM who were prescribed olanzapine or risperidone as the primary antipsychotic medication were enrolled. A total of 197 of these cases with co-prescribed aripiprazole were set up as the study group (co-Ari group), and the other 204 cases without co-prescribed aripiprazole were set up as the control group (non-Ari group). The two groups' variations in each target parameter were compared, and the variables affecting PRL levels were examined. Compared to the non-Ari group, fasting blood glucose (FBG), blood uric acid (UA), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in the co-Ari group, but there was no difference in PRL levels. Co-prescribing aripiprazole had no impact on PRL levels in all patients with co-T2DM, and aripiprazole dose had no impact on PRL levels in the clinical subgroup of the co-Ari group. Aripiprazole not only worsened the severity of index disturbances associated to metabolism in long-term hospitalized chronic schizophrenia patients with co-T2DM on metformin-based hypoglycemic medications but also failed to lower PRL levels.

Seborrheic Dermatitis: A Case of an Atypical Side Effect of Atypical Antipsychotics.

Seborrheic Dermatitis: A Case of an Atypical Side Effect of Atypical Antipsychotics.

Beneficial effects of atypical antipsychotics on object recognition deficits after adolescent toluene exposure in mice: involvement of 5-HT1A receptors

ABSTRACT Background: Inhalant (e.g. toluene) misuse by adolescents has been linked to psychosis and persistent cognitive deficits. Identifying effective strategies to improve cognitive deficits following chronic toluene misuse is critical. 5-HT1A receptor has been proposed as a target for the treatment of cognitive deficits. Objectives: We compared the effects of antipsychotics on recognition deficits after adolescent toluene exposure in mice and elucidated the role of 5-HT1A receptors in the cognition-improving effects of antipsychotics. Methods: Male NMRI mice (n = 279) received one injection per day of either toluene (750 mg/kg) or corn oil at postnatal days 35–39 and 42–46. Thereafter, the acute and subchronic effects of haloperidol, aripiprazole, or clozapine on toluene-induced recognition deficits were evaluated by novel object recognition test. Results: Acute administration of aripiprazole (p < .05) and clozapine (p < .01), but not haloperidol, significantly attenuated the toluene-induced recognition deficits. Pretreatment with 5-HT1A receptor antagonist WAY -100,635 (p < .05) blocked their beneficial effects. Moreover, 5-HT1A receptor agonist buspirone (p < .01) ameliorated the toluene-induced recognition deficits, which was reversed by WAY -100,635 (p < .001). Finally, after repeated treatment with clozapine, aripiprazole, and buspirone daily for 14 days, the impaired object recognition in toluene-exposed mice was significantly improved (p < .05) and the beneficial effects lasted for at least 2 weeks (p < .05). Conclusions: The results indicate that clozapine and aripiprazole, which display 5-HT1A agonist properties, restored cognitive deficits in mice induced by adolescent toluene exposure. These findings suggest that these antipsychotics should be further explored as a potential treatment option for cognitive deficits in patients with psychosis associated with toluene exposure.

National trends in metabolic risk of psychiatric inpatients in the United States during the atypical antipsychotic era

Although the cardiometabolic effects of atypical antipsychotics have been well-described in clinical samples, less is known about the longer-term impacts of these treatments. We report rates of metabolic syndrome in a nationally representative sample of U.S. adult inpatients 1993–2018 admitted for schizophrenia-spectrum disorders (n = 1,785,314), any mental health disorder (n = 8,378,773), or neither (n = 14,458,616) during a period of widespread atypical antipsychotic use. Metabolic syndrome, derived from additional diagnoses, was defined as three or more of hypertension, dyslipidemia, type II diabetes, hyperglycemia, and overweight or obese. Using an ecological age and period design, a 4-level period variable was constructed to proxy for atypical antipsychotic exposure as the minimum of age minus 20 years or the calendar year minus 1997 in accord with the disease course for schizophrenia-spectrum illness and the market share of atypical antipsychotics in the U.S. Logistic regression models, adjusted for age, year, and exposure main effects, estimated odds ratios (ORs) of metabolic syndrome. Relative to other mental health or other discharges, schizophrenia-spectrum discharges had an elevated risk for metabolic syndrome regardless of potential atypical antipsychotic exposure (OR = 1.46; 95 % CI, 1.30–1.64). For schizophrenia-spectrum discharges, periods of potential atypical antipsychotic exposure conferred additional metabolic syndrome risk OR = 1.21; 95 % CI, 1.04–1.41 for exposures of 1–2 years, OR = 1.29; 95 % CI, 1.13–1.46 for 3–7 years, OR = 1.27; 95 % CI, 1.12–1.44 for 8–12 years, and OR = 1.10; 95 % CI 0.98–1.24 for >12 years. In summary, cardiometabolic disease and related risks were elevated among a nationally representative sample of adult inpatients with schizophrenia-spectrum disorders during a period of pervasive atypical antipsychotic use.

Schizophrenia And Polycystic Ovary Syndrome: A Case Report

IntroductionPatients with Polycystic ovary syndrome (PCOS) have increased vulnerability to psychiatric disorders, particularly a tendency to depression and anxiety, as well as schizophrenia. The association between PCOS and psychiatric disorders is a topic of research given the possibility of common potential mechanisms as well as the clinical similarity between the adverse effects of atypical antipsychotics and the symptoms of PCOS.ObjectivesWe proposed to investigate the etiopathogenic relationship between schizophrenia and PCOS as well as the therapeutic particularities.MethodsWe report a case of schizophrenia occurring in a patient with PCOS. Then, we conducted a literature review using “PubMed” database and keywords “psychosis”, “schizophrenia”, “Polycystic ovary syndrome” and “antipsychotic drugs”.ResultsShe was an 18-year-old patient, diagnosed with PCOS since 2018. She has been followed in the psychiatry outpatient department since 8 months for psychotic symptoms (hallucinatory syndrome with thoughts of self-aggressiveness, delusional syndrome with mental automatism…). She was prescribed olanzapine (5 then 10 mg/day). However, after a weight gain (4 kg per month), this drug was switched by Risperidone (2 then 4 mg/day). The evolution was marked by the appearance of galactorrhea. Thus, the Risperidone was switched to Aripiprazole. Then, we noted a significant improvement on the psychiatric features and a better clinical tolerance.ConclusionsFor women with PCOS and psychosis, treatment with antipsychotic drugs can worsen PCOS symptomatology and lead to negative consequences for a woman’s reproductive potential and her quality of life. Therefore, the psychosis management must take these particularities into account, in order to improve the prognosis of both diseases.DisclosureNo significant relationships.

Does clozapine affect the discriminative stimulus effects of food deprivation in rats trained to discriminate between 2 and 22 hours food deprivation?

In humans, weight gain is a side effect of several atypical antipsychotics. Previous research with rodents indicates clozapine may increase food consumption for the first 2‐4 hours after injection (Antelman et al. 1977; Benvenga &amp; Leander 1997; Lee &amp; Clifton 2002) as well as increase motivation to acquire food under a progressive ratio schedule (Abela et al. 2020; Loh et al. 1992; Mobini et al. 2000). In other studies, however, clozapine has been shown to reduce response rates in lever pressing operant procedures (Ford et al., 1997; Kaempf &amp; Porter, 1997; Varvel et al., 2002; Wiley et al., 1994; Abela 2020) and decrease food intake in rodents (Baptista et al., 1993). The current study investigated if clozapine would affect the discriminative stimulus effects of food deprivation. Male, Sprague‐Dawley rats (n = 11) were trained to discriminate 22 hrs of food deprivation from 2 hrs of food deprivation in a two‐lever, operant choice task. Rats were trained to respond on the right lever after 2 hrs of food deprivation to earn a 45 mg food pellet under an FR 15 schedule. Left lever presses were punished with 8 seconds of darkness. Under 22 hr deprivation conditions, the contingencies were reversed (left lever presses were reinforced with food delivery and right lever presses resulted in 8 seconds of darkness). Training sessions lasted until subjects earned 10 reinforcers or 15 minutes elapsed. Acquisition of discrimination was defined as 80% or greater condition appropriate responding both before the first reinforcer was earned and for the entire session for 8 out of 10 consecutive days. After acquiring the discrimination, subjects were food deprived for 2 or 22 hrs and administered clozapine (1.0 ‐ 5.6 mg/kg, s.c.). or vehicle (30% DMSO; 1.0 ml/kg, s.c.). During test sessions, responses toward either lever were reinforced under the FR 15. The session lasted until subjects earned 5 reinforcers or 5 minutes elapsed, whichever occurred first. The discriminative stimulus effects of food deprivation and response rates were assessed every 15 min for the succeeding 2 hrs. After test sessions, each subjects’ food intake was recorded for 1 hour. Clozapine had no effect on the discriminative stimulus effects of 2 hr deprivation, however, clozapine (1.0 ‐ 5.6 mg/kg) significantly decreased response rates. After 22 hrs food deprivation, clozapine (1.0 ‐ 5.6 mg/kg) significantly decreased % 22 hr deprivation‐appropriate responding. Response rates were significantly increased by 1.0 mg/kg clozapine, whereas response rates were decreased by 5.6 mg/kg clozapine compared to rates of responding following 30% DMSO. Clozapine (3.2 ‐ 5.6 mg/kg) decreased food intake in rats under both food deprivation conditions. These data provide further support for the notion that clozapine decreases feeding‐related behaviors in rats.