Side Effects Of Antipsychotics Research Articles

Early Intervention in Psychosis and Management of First Episode Psychosis in Low- and Lower-Middle-Income Countries: A Systematic Review.

People with first-episode psychosis (FEP) in low- and lower-middle-income countries (LMIC) experience delays in receiving treatment, resulting in poorer outcomes and higher mortality. There is robust evidence for effective and cost-effective early intervention in psychosis (EIP) services for FEP, but the evidence for EIP in LMIC has not been reviewed. We aim to review the evidence on early intervention for the management of FEP in LMIC. We searched 4 electronic databases (Medline, Embase, PsycINFO, and CINAHL) to identify studies describing EIP services and interventions to treat FEP in LMIC published from 1980 onward. The bibliography of relevant articles was hand-searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The search strategy produced 5074 records; we included 18 studies with 2294 participants from 6 LMIC countries. Thirteen studies (1553 participants) described different approaches for EIP. Pharmacological intervention studies (n = 4; 433 participants) found a high prevalence of metabolic syndrome among FEP receiving antipsychotics (P ≤ .005). One study found a better quality of life in patients using injectables compared to oral antipsychotics (P = .023). Among the non-pharmacological interventions (n = 3; 308 participants), SMS reminders improved treatment engagement (OR = 1.80, CI = 1.02-3.19). The methodological quality of studies evidence was relatively low. The limited evidence showed that EIP can be provided in LMIC with adaptations for cultural factors and limited resources. Adaptations included collaboration with traditional healers, involving nonspecialist healthcare professionals, using mobile technology, considering the optimum use of long-acting antipsychotics, and monitoring antipsychotic side effects.

A Possible Role of Akkermansia muciniphila in the Treatment of Olanzapine-Induced Weight Gain.

Second-generation antipsychotics are mainly used in both acute and long-term treatment of major psychiatric disorders. Although better tolerated than first-generation antipsychotic drugs, they can frequently induce weight gain and metabolic disorders, of these, olanzapine is one of the drugs more likely to induce these side effects. There is consistent evidence of the role of gut microbiota in modulating the gut-brain axis with complex crosstalk with the host involving satiety signaling pathways, food intake behavior, and weight and metabolic regulation. Second-generation antipsychotics induce important gut microbiota modification thus contributing together with the central and peripheral receptors blockade mechanism to weight gain induction and metabolic impairment. These drugs can alter the composition of gut microbiota and induce dysbiosis, often reducing the concentration of Akkermansia muciniphila, a bacterium that is also decreased in patients with diabetes, obesity, metabolic syndrome, or chronic inflammatory diseases. Probiotic administration can be a safe and well-tolerated approach to modulate microbiotaandoffer an integrative strategy in psychiatric patients suffering antipsychotic side effects. Multiple strain probiotics and Akkermansia muciniphila alone have been administered both in mice models and in clinical populations demonstrating efficacy on antipsychotic-induced metabolic impairment and showing a contribution in reducing induced weight gain.Akkermansia muciniphila can improve several parameters altered by olanzapine administration, such as weight gain, insulin resistance, hyperglycemia, liver function, systemic inflammation, and gut barrier function. Although we do not have jet trials in the psychiatric population, this probiotic may be a complementary approach to treating olanzapine-induced weight gain and metabolic side effects.

Mechanisms of adverse mammary effect induced by olanzapine and therapeutic interventions in rat model.

BackgroundOlanzapine antagonizes dopamine receptors and is prescribed to treat multiple psychiatric conditions. The main side effect of concern for olanzapine is weight gain and metabolic syndrome. Olanzapine induces hyperprolactinemia, however its effect on the mammary gland is poorly documented. MethodsRats received olanzapine by gavage or in drinking water at 1, 3, and 6 mg/kg/day for 5–40 days or 100 days, with and without coadministration of bromocriptine or aripiprazole and using once daily or continuous administration strategies. Histomorphology of the mammary gland, concentrations of prolactin, estradiol, progesterone, and olanzapine in serum, mammary gland and adipose tissue, and mRNA and protein expressions of prolactin receptors were analyzed. ResultsIn adult and prepubescent female rats and male rats, olanzapine induced significant development of mammary glands in dose- and time-dependent manners, with histopathological hyperplasia of mammary ducts and alveoli with lumen dilation and secretion, marked increase of mammary prolactin receptor expression, a marker of breast tissue, and with mild increase of circulating prolactin. This side effect can be reversed after medication withdrawal, but long-term olanzapine treatment for 100 days implicated tumorigenic potentials indicated by usual ductal epithelial hyperplasia. Olanzapine induced mammary development was prevented with the coaddition of the dopamine agonist bromocriptine or partial agonist aripiprazole, or by continuous administration of medication instead of a once daily regimen. ConclusionsThese results shed light on the previously overlooked effect of olanzapine on mammary development and present experimental evidence to support current clinical management strategies of antipsychotic induced side effects in the breast.

Medication adherence and related psychosocial and clinical factors among schizophrenic patients: a cross - sectional analytical study in National Psychiatric Hospital 2, Vietnam

Background and Aims: Schizophrenia is a chronic and severe mental disorder. Treatment by antipsychotic medication is one of the main therapies to control the symptoms. Medication non/poor adherence is a one of the key factors leading to relapse and declined social and occupational function in patients. However, prevalence of schizophrenic patients with non/poor adherence to medication was quite high in previous studies. Therefore, this study aimed to identify the prevalence of medication non/poor adherence and its related psychosocial and clinical factors among schizophrenic patients. Subjects and Method: a cross - sectional analytical study of 126 schizophrenic patients at National Psychiatric Hospital 2 were conducted to evaluate the rate of medication non-adherence by Morisky Medication Adherence Scale 8 item (MMAS - 8). Data were collected on patients’ sociodemographic factors such as sex, age, marital and economic status, level of education and clinical factors including duration of schizophrenia, clinical symptoms evaluated by Positive and Negative syndrome scale (PANSS), type, and side effects of medication. Logistic regression was used to analyze the factors associated with medication non-adherence among schizophrenic patients. Results: Rate of poor medication adherence among participants was 78.57% by using MMAS – 8. The associated factors with poor medication adherence among schizophrenic patients were level of education under high school; unstable job/unemployment; poor insight about schizophrenia, poor family care/support, high scores of negative PANSS and general PANSS scale, duration of schizophrenia above 5 years, treated by typical antipsychotics and having more than two side effects of antipsychotics. Conclusion: The rate of poor medication adherence/ non - adherence among schizophrenic patients is high. Mental health staff should be aware of this risk and screening individuals for relevant risk factors is highly recommended Key words: medication adherence, schizophrenia, social - psycho - clinical factors.

Influence of Lifestyle Factors on Metabolic Syndrome in Psychiatric Patients Attending a Community Mental Health Setting: A Cross-sectional Study

Background: Metabolic syndrome (MetS) is a concern in psychiatric patients. We aimed to study the influence of the modifiable lifestyle factors on MetS in adult psychiatric patients along with associated clinical factors and quality of life. Methods: Factors such as diet (Healthy Eating Index), exercise, substance use, cardiovascular risk (QRISK), illness severity (Clinical Global Impression), medications, adverse events (Systematic Monitoring of Adverse Events Related to Treatments), and quality of life (Recovering Quality of Life Scale) were assessed along with clinical components for MetS in 323 psychiatric patients receiving routine care and monitoring in a Community Mental Health Team. Results: MetS was present in 50.5% (95% CI: 45.0–55.9). It was significantly associated with higher age, duration of mental illness, body mass index (BMI), QTc, QRISK, and antipsychotic drugs. In logistic regression, age, QTc, QRISK, and BMI remained significantly linked to MetS. Patients with or without MetS were comparable in their lifestyle factors such as diet, exercise, and substance use, along with the family history of metabolic disorders, age at onset of mental illness, duration of antipsychotic medication, side effects, psychiatric diagnoses, and quality of life. However, many patients with or without MetS had poorer diet and physical inactivity, indicating scope for interventions. Conclusions: Around half of the psychiatric patients had MetS, and modifiable lifestyle factors did not differentiate individuals with or without MetS. The need for further research on the prevention and management of MetS in psychiatric patients is highlighted.

Clarification of Psychiatric Nurses' Intentions and Analysis Contents in Observing Schizophrenia Patient.

The purpose of this study was to clarify what psychiatric nurses intended to observe when observing schizophrenia patient and what they analyzed from their observations. Twenty-one experienced nurses were included in the study. Data were collected through semi-structured interviews, and content analysis was conducted. The results were as follows:Nurses' intentions in observing patient were [Observation of psychiatric symptoms], [Observation of normality or abnormality], [Possibility of self-harm or harming others], [Side effects of antipsychotics], [Degree of communication disorder], [Degree of self-care], [Observation of nutritional status], [Effects of external stimuli on patient], and [Less importance of observing doctor]. Nurses' analysis contents were [Analysis of psychiatric symptoms], [No risk of self-harm or harming others], [Effects of antipsychotics], [Presence of communication disorder], [Lack of trust in doctor], [Problems in daily life], [Consideration of future nursing intervention], [Assessment of normality or abnormality], [Unhealthy physical state], and [Unnecessary analysis]. The results of this study revealed the nurses' observational process. J. Med. Invest. 71 : 54-61, February, 2024.

Treatment of schizophrenia evaluated via the pharmacopsychometric triangle—An integrative approach with emphasis on well-being and functioning

Quantification of treatment response is crucial to optimize outcomes for patients with schizophrenia. In this study, we evaluated the relationship between quantitative measures of clinician-rated symptom severity and self-rated side effects, well-being, and functioning among inpatients with schizophrenia using the six-item version of the Positive and Negative Syndrome Scale (PANSS-6), the Glasgow Antipsychotic Side-effect Scale (GASS), the WHO-Five Well-being Index (WHO-5), and the Sheehan Disability Scale (SDS). All measurements were conducted as close to admission and discharge as possible. Well-being and functioning were found to be most strongly associated with the additive effect of symptoms and side effects, while changes in side effects, well-being, and functioning appeared to be relatively independent from changes in symptom severity. The use of both symptom and side effect measures should inform clinical decision-making in the treatment of schizophrenia, as it has the potential to optimize functioning and well-being.

The association of lower urinary tract symptoms with schizophrenia and its treatments: A narrative review.

A higher incidence of lower urinary tract symptoms (LUTS) in people with schizophrenia compared to the general population is often suggested. However, it is not clear whether this is a genuine association, and whether it is a direct result of schizophrenia itself, or a side-effect of certain antipsychotics. We undertook a narrative review evaluating how the published literature reports the relationship between LUTS and schizophrenia and its treatments. We searched Embase, Ovid Emcare, and Ovid MEDLINE(R) ALL to August 2022, limited to the English language. We selected the following search terms: schizophrenia, schizophrenic, LUTS, overactive bladder, urinary urgency, urinary incontinence, overactive bladder, enuresis, nocturnal enuresis, and voiding dysregulation. We identified seven domains for assessment in advance of commencing the review. These were the categorization, description, and treatment status of schizophrenia; evaluation of LUTS; categorization of LUTS confounders; recapturing of the disease states of both schizophrenia and LUTS after therapies; assessment of the association between LUTS and schizophrenia and/or antipsychotics. The association between LUTS and schizophrenia was poorly described. The evidence was low quality and focused predominantly on urinary incontinence as an antipsychotic side effect, neglecting other LUTS. The status of schizophrenia was often incompletely characterized, and no papers made use of a bladder diary or LUTS-specific questionnaires to assess symptoms. No papers collected information about LUTS in patients not on antipsychotics, nor did any thoroughly evaluate the influence of confounding variables. Despite the tendency of symptoms and severity of both conditions to fluctuate over time, no studies fully assessed the status of both schizophrenia and LUTS at baseline, therapy initiation, and follow-up. It is not possible to state whether there is an association between LUTS and schizophrenia or its treatments. This review highlights the need to improve research and clinical management of the urinary tract in schizophrenia, with meticulously designed longitudinal studies.

Knowledge of antipsychotic medication and their side effects among psychiatric nurses at a tertiary hospital in Lesotho

Factors that impede the physical health monitoring of patients with severe mental illness are multidimensional, and healthcare providers’ knowledge and expertise regarding antipsychotic medication and side effects remain key determinants of the frequency and quality of screening a patient shall be subjected to. This challenge transcends the monitoring of patients treated with antipsychotics, where scholars have determined a lack of knowledge about screening for adverse effects, resulting in poor clinical assessments among patients prescribed antipsychotics. This study aimed to describe nurses’ knowledge regarding antipsychotic medications and their side effects at the psychiatric hospital in Lesotho. To guide the research process, a quantitative, non-experimental, descriptive approach was employed with 40 nurses out of 44 nurses as respondents, who were selected using convenience sampling, and respondents rated their knowledge regarding the side effects of antipsychotic medication using a Likert scale on a structured research questionnaire. The data were collected using a self-administered questionnaire, analysed using SPSS (version 28), and displayed using tables, frequencies, standard deviations, and means. This study's female respondents comprised 30 (75.0%) and 10 (25.0%) males. The mean age was 39.05 (SD 8.9), with eight years of psychiatry experience. A total of 29 (72.0%) had sufficient antipsychotic knowledge (t = 36.38, df = 39, p < .000), 31 (78.3%) and had adequate knowledge of the side effects of antipsychotic drugs (t = 34.00375, df = 39, p < .000). In conclusion, this study reveals a positive trend in nursing knowledge about antipsychotic medications and associated side effects, highlighting the importance of ongoing professional development to maintain and enhance this expertise.

Antidepressant and antipsychotic side-effects and personalised prescribing: a systematic review and digital tool development

Side-effects of psychiatric medication impair quality of life and functioning. Furthermore, they contribute to morbidity, mortality, stigma, and poor treatment concordance resulting in relapse of psychiatric illness. Guidelines recommend discussing side-effects with patients when making treatment decisions, but a synthesis of antidepressant and antipsychotic side-effects to guide this process is missing, and considering all side-effects is a complex, multidimensional process. We aimed to create comprehensive databases of antipsychotic and antidepressant side-effects, and a digital tool to support database navigation. To create the databases, we did an umbrella review of Embase, PsycINFO, and MEDLINE from database inception to June 26, 2023. We included meta-analyses of randomised controlled trials examining antipsychotic monotherapy in the treatment of schizophrenia or antidepressant monotherapy in the treatment of major depressive disorder. We included meta-analyses in adults (aged ≥18 years) that assessed drugs with a common comparator. The search was complemented by a review of national and international guidelines and consensus statements for the treatment of major depressive disorder and schizophrenia in adults. Effect sizes for antipsychotic and antidepressant side-effects were extracted from meta-analyses examining the largest number of drugs. In cases of incomplete meta-analytic coverage, data were imputed on the basis of guideline-derived ordinal rankings or, if imputation was not possible, ordinal scores were extracted. Both meta-analytic and ordinal outcomes were normalised to provide values between 0 and 1. We then constructed a digital tool, the Psymatik Treatment Optimizer, to combine the side-effect databases with side-effect concerns of an individual user, to enable users to select side-effects of concern and the relative degree of concern for each side-effect. Concern weightings and the side-effect databases are synthesised via a multicriteria decision analysis method (technique for order of preference by similarity to ideal situation, or TOPSIS). Of 3724 citations, 14 articles containing 68 meta-analyses of individual side-effects met inclusion criteria. After review of 19 guidelines, seven provided ordinal data. Antipsychotic data were extracted from five studies (11 meta-analyses, n=65 594 patients) and four guidelines, and antidepressant data were extracted from three guidelines. The resultant databases included data on 32 antipsychotics (14 side-effects) and 37 antidepressants (nine side-effects). The databases highlighted the clinical dilemma associated with balancing side-effects, with avoidance of one side-effect (eg, weight gain for antipsychotics) increasing the risk of others (eg, akathisia). To aid with this dilemma, the Psymatik Treatment Optimizer synthesises the side-effect databases with individual user-defined concern weights. After computing up to 5851 pairwise comparisons for antidepressants and 5142 pairwise comparisons for antipsychotics, Psymatik ranks treatments in order of preference for the individual user, with the output presented in a heatmap. By facilitating collaborative, personalised, and evidence-based prescribing decisions, the side-effect databases and digital application supports care delivery that is consistent with international regulatory guidance for the treatment of schizophrenia and depression, and it therefore has promise for informing psychiatric practice and improving outcomes. National Institute for Health and Care Research, Maudsley Charity, Wellcome Trust, Medical Research Council.

THE EFFECT OF HYDROXYZINE ON AKATHISIA AND OTHER NEUROLOGICAL SIDE EFFECTS OF ANTIPSYCHOTICS IN THE TREATMENT OF PARANOID SCHIZOPHRENIA

Side effects of antipsychotic drugs are the most urgent problem in the pharmacotherapy of schizophrenia. Medications used to correct side effects of various pharmacological groups, including correctors of cholinolytics, tranquilizers-benzodiazepines, have severe side effects, which justifies the search for no less effective and at the same time safer alternatives. The aim of the study was to evaluate the corrective effect of Hydroxyzine on akathisia and other neurological disorders that develop as side effects of antipsychotic therapy. Materials and methods. The study analyzed the severity of side effects in 43 patients suffering from paranoid schizophrenia receiving monotherapy with antipsychotics, before their administration, on the 7th and 21st day after the start of taking Hydroxyzine. The severity of side effects was assessed by the ESRS scales and the scale of evaluating drug-induced akathisia. Results. A significant corrective effect of Hydroxyzine on akathisia and other neurological side effects of antipsychotics was shown on the 7th day of Hydroxyzine therapy, the severity of Parkinsonism, dyskinesia, akathisia and tremor significantly decreased. Patients noted an improvement in general well-being, a decrease in the level of anxiety associated with the disease, staying in a psychiatric hospital, side effects of psychopharmacotherapy. Hydroxyzine significantly reduced the severity of akathisia, assessed both objectively and subjectively by patients. There was a decrease in the need of patients to move, to change the position of the body, improved sleep, reduced emotional stress. In general, Hydroxyzine had a positive effect in the form of a decrease in pathological motor activity and a decrease in the severity of emotional manifestations associated with the side effect of antipsychotics, which persisted on the 21st day of Hydroxyzine therapy in the absence of clinically significant undesirable side effects. Conclusions. The results of the study show the effectiveness of Hydroxyzine for correcting neurological side effects of antipsychotics along with good tolerability and substantiate the possibility of expanding its use in the complex therapy of paranoid schizophrenia.

Urdu Translation and Adaptation of Glasgow Antipsychotic Side-Effect Scale (GASS)

The main objective of the study was “Urdu translation and cultural adaptation” of Glasgow Anti-psychotic Side-effect Scale (GASS). The study comprised two phases and employed a combined methods design. Multiple Forward Translation Method was used to translate and adapt GASS, and a pre-clinical version was administered to 58 indoor patients. Later, psychometric properties and gender patterns of side effects were assessed. The pre-final version of the tool had good content validity with S-CVI of .94 and I-CVIs of .8 to .1. The Cronbach alpha for men indicated good internal consistency and reliability, while it was low for women. Both men and women exhibited mild to moderate severity of symptoms. This study provides a tool to assess side effects of SGAs in our setting.

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.

Exploring Personal Recovery in Schizophrenia: The Role of Mentalization.

Recovery is a broadly debated concept in the field of psychiatry research and in schizophrenia. Our study aims to understand the correlation between personal recovery from schizophrenia and factors such as mentalization, disability, quality of life, and antipsychotic side effects; Methods: Participants with schizophrenia (according to DSM-5 criteria) were consecutively recruited from the Psychiatry Unit of the University of Catania, Italy. Participants were assessed with the Recovery Assessment Scale (RAS), the Multidimensional Mentalizing Questionnaire (MMQ), the brief version of the WHO Disability Assessment Schedule (WHO-DAS), the EuroQoL-5 dimensions-5 levels, the Insight Orientation Scale (IOS) and the Glasgow Antipsychotic Side Effect Scale (GASS); Results: 81 patients were included. Our findings showed a positive correlation between RAS total scores and MMQ scores, especially in "good mentalizing" subdomains. IOS scores also had a positive association with RAS and MMQ scores. In contrast, poor mentalizing abilities negatively correlated with WHO-DAS 2.0 scores. While antipsychotic side effects influenced functioning, they did not impact perceived recovery. Conclusions: The study's results identified potential predictors of personal recovery from schizophrenia. These findings could contribute to creating tailored interventions to facilitate the recovery process.

A transdiagnostic approach to negative symptoms: exploring factor structure and negative symptoms in bipolar disorders.

Negative symptoms are increasingly recognized as transdiagnostic phenomena, linked to reduced quality of life and functioning, and often caused or worsened by amendable external factors such as depression, social deprivation, side-effects of antipsychotics or substance use. The structure of negative symptoms fits into two dimensions: diminished expression and apathy. These may differ in association with external factors that influence their severity and may thus require different treatment approaches. The dimensions are comprehensively established in non-affective psychotic disorders but are understudied in bipolar disorders. We conducted exploratory and confirmatory factor analyses in a sample of 584 individuals with bipolar disorder to assess the latent factor structure of negative symptoms as measured by the Positive and Negative Syndrome Scale (PANSS), and performed correlational analyses and multiple hierarchical regression analyses to investigate links between the two dimensions of negative symptoms and clinical and sociodemographic correlates. The latent factor structure of negative symptoms fits into two dimensions, i.e., diminished expression and apathy. A diagnosis of bipolar type I or a history of psychotic episodes predicted more severe levels of diminished expression. Depressive symptoms were associated with more severe negative symptoms across dimensions, yet 26.3% of euthymic individuals still displayed at least one mild or more severe negative symptom (PANSS score ≥ 3). The two-dimensional structure of negative symptoms seen in non-affective psychotic disorders reproduces in bipolar disorders indicating similarities in their phenomenology. Diminished expression was associated with a history of psychotic episodes and a diagnosis of BD-I, which may infer closer connections to psychosis liability. We found significantly less severe negative symptoms in euthymic than depressed participants. Nevertheless, more than a quarter of the euthymic individuals had at least one mild negative symptom, demonstrating some degree of persistence beyond depressed states.

Prescribing and deprescribing trends in schizophrenia: An overview of inpatients in Belgium and in the Canadian province of Québec.

Although switching to antipsychotic monotherapy improves patient outcomes in schizophrenia, antipsychotic deprescribing is rarely performed, and its use varies between countries, as do psychotropic prescribing patterns. This study aimed to determine factors associated with antipsychotic deprescribing at discharge after a psychiatric hospitalization and to compare psychotropic prescribing patterns between Belgium and Québec, Canada. Data on adult inpatients with schizophrenia were collected retrospectively in seven hospitals. At discharge, the number of antipsychotics had decreased in 22.2% of the 63 Canadian patients and 9.9% of the 516 Belgian patients. A number of factors increased the likelihood of antipsychotic deprescribing: a hospitalization in the Canadian hospital (aOR = 4.13, 95% CI 1.48-11.5), living in a residential facility (aOR = 2.51, 95% CI 1.05-4.39), ≥2 previous antipsychotic trials (aOR = 15.38, 95% CI 3.62-65.36), having an antipsychotic side effect (aOR = 1.86, 95% CI 1.01-3.44) and being in a general hospital (aOR = 2.28, 95% CI 1.09-4.75). Patients on a long-acting injectable antipsychotic (aOR = 0.51, 95% CI 0.26-0.98), with prior clozapine use (aOR = 0.36, 95% CI 0.13-0.95), greater antipsychotic exposure (aOR = 0.35, 95% CI 0.2-0.61) and more hypno-sedatives (aOR = 0.65, 95% CI 0.43-0.98), were less likely to be deprescribed. Specific deprescribing interventions could target patients who are less likely to be deprescribed.

Schizophrenia and cardiometabolic abnormalities: A Mendelian randomization study.

Background: Individuals with a diagnosis of schizophrenia are known to be at high risk of premature mortality due to poor physical health, especially cardiovascular disease, diabetes, and obesity. The reasons for these physical health outcomes within this patient population are complex. Despite well-documented cardiometabolic adverse effects of certain antipsychotic drugs and lifestyle factors, schizophrenia may have an independent effect. Aims: To investigate if there is evidence that schizophrenia is causally related to cardiometabolic traits (blood lipids, anthropometric traits, glycaemic traits, blood pressure) and vice versa using bi-directional two-sample Mendelian randomization (MR) analysis. Methods: We used 185 genetic variants associated with schizophrenia from the latest Psychiatric Genomics Consortium GWAS (n = 130,644) in the forward analysis (schizophrenia to cardiometabolic traits) and genetic variants associated with the cardiometabolic traits from various consortia in the reverse analysis (cardiometabolic traits to schizophrenia), both at genome-wide significance (5 × 10-8). The primary method was inverse-variance weighted MR, supported by supplementary methods such as MR-Egger, as well as median and mode-based methods. Results: In the forward analysis, schizophrenia was associated with slightly higher low-density lipoprotein (LDL) cholesterol levels (0.013 SD change in LDL per log odds increase in schizophrenia risk, 95% CI, 0.001-0.024 SD; p = 0.027) and total cholesterol levels (0.013 SD change in total cholesterol per log odds increase in schizophrenia risk, 95% CI, 0.002-0.025 SD; p = 0.023). However, these associations did not survive multiple testing corrections. There was no evidence of a causal effect of cardiometabolic traits on schizophrenia in the reverse analysis. Discussion: Dyslipidemia and obesity in schizophrenia patients are unlikely to be driven primarily by schizophrenia itself. Therefore, lifestyle, diet, antipsychotic drugs side effects, as well as shared mechanisms for metabolic dysfunction and schizophrenia such as low-grade systemic inflammation could be possible reasons for the apparent increased risk of metabolic disease in people with schizophrenia. Further research is needed to examine the shared immune mechanism hypothesis.

Histone deacetylase 1 regulates haloperidol-induced motor side effects in aged mice

BackgroundAntipsychotic drugs prescribed to elderly patients with neuropsychiatric disorders often experience severe extrapyramidal side effects. Previous studies from our group suggest that changes in histone modifications during aging increase the risk for antipsychotic drug side effects, because co-administration of antipsychotics with class 1 histone deacetylase (HDAC) inhibitors could mitigate the severity of motor side effects in aged mice. However, which HDAC subtype contributes to the age-related sensitivity to antipsychotic drug side effects is unknown. MethodsIn this study, we overexpressed histone deacetylase type 1(HDAC1) in the striatum of 3-month-old mice and knocked down HDAC 1 in the striatum of 21-month-old mice by microinjection of AAV9-HDAC1-GFP or AAV9-CRISPR/Cas9-HDAC1-GFP vectors. Four weeks after the viral-vector delivery, the typical antipsychotic drug haloperidol was administered daily for 14 days, followed by motor function assessments through the open field, rotarod, and catalepsy behavioral tests. ResultsYoung mice with overexpressed HDAC1 showed increased cataleptic behavior induced by haloperidol administration, which is associated with the increased HDAC1 level in the striatum. In contrast, aged mice with HDAC1 knocked down rescued locomotor activity, motor coordination, and decreased cataleptic behavior induced by haloperidol administration, which is associated with decreased HDAC1 level in the striatum. ConclusionsOur results suggest that HDAC1 is a critical regulator in haloperidol-induced severe motor side effects in aged mice. Repression of HDAC1 expression in the striatum of aged mice could mitigate typical antipsychotic drug-induced motor side effects.

Rhabdomyolysis Caused by a Behavioral Manifestation of Acute Mania

AbstractIntroductionWhile seen in patients with bipolar disorder due to NMS, antipsychotic side effects, or substance use, rhabdomyolysis resulting from behaviors seen in mania has not been reported in recent literature. We present a case of a patient with rhabdomyolysis due to exertion during a manic episode.CaseA 29-year-old male with a history of bipolar disorder type 1 was brought to the ED in June 2022 after he was found on the roof of a local theater sharing excerpts from a book he had written. Temperatures outside were 100–102 Fahrenheit. On presentation, the patient had rapid, pressured speech and demonstrated flight of ideas. He was religiously preoccupied. He had been previously admitted to Psychiatric Emergency Services in April 2022 for mania and was discharged with lithium and lamotrigine. He had been titrating these medications with his outpatient psychiatrist.The patient’s labs showed an elevated creatinine of 1.49, up from his baseline of 1.09. Further workup revealed an elevated CK of 3,538. Additional abnormalities included an AST of 70, calcium of 10.6, total bilirubin of 1.6, and WBC of 15.5. He was afebrile, oriented, and had no obvious signs of infection. The patient received 2 liters of Lactated Ringers (LR) and was admitted to Internal Medicine. Later, he was agitated overnight and received 10mg olanzapine and 2mg lorazepam. Lithium level following fluid resuscitation was 0.6.On interview the next day, the patient described working on a creative religious piece that he wanted to share with others, leading to him climbing on the roof. He had been hyper-focused on this work, with 1–4 hours of sleep nightly. He also had been frequently doing gymnastics, walking long distances, and climbing other buildings. He endorsed diffuse muscle pain, but this was not reproducible on exam.150mL/hr of LR was started, and PO fluid intake was encouraged. He agreed to resume his medications and was started on lithium 900mg and lamotrigine 50mg. His CK continued to downtrend. WBC count decreased and was 12.9 at discharge. Lamotrigine was titrated up to home dose of 100mg. His mania improved, and he was ultimately discharged home with outpatient follow-up.ConclusionRhabdomyolysis results from the release of toxic cellular compounds from muscle fibers. Complications include acute renal failure, hyperkalemia, and compartment syndrome. Causes include substance use, medications, trauma, seizures, ischemia, overexertion, and dehydration. Recently reported cases of mania-associated rhabdomyolysis involve iatrogenic causes, such as neuromuscular malignant syndrome (NMS) and non-NMS antipsychotic side effects.Other causes include high-risk drug use during mania. Rhabdomyolysis due to behavioral manifestations of mania have been documented more rarely in older reports, similarly, addressing excessive exercise and dehydration. Therefore, our case represents a reminder of the medical sequalae resulting from actions undertaken during acute mania. This highlights the importance of implementing effective treatment to prevent such episodes.FundingNo Funding