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The Senior Care Pharmacist Jul 2024In older inpatients, anticholinergic medications can increase the risk of complications that may increase length of stay (LOS). Cyclobenzaprine is an anticholinergic...
In older inpatients, anticholinergic medications can increase the risk of complications that may increase length of stay (LOS). Cyclobenzaprine is an anticholinergic medication associated with mental status changes, falls, and injuries in older patients. The purpose of this study is to determine whether use of a lower cyclobenzaprine dose (5 mg) compared with higher dosing (10 mg) will affect LOS, 30-day readmission rates, and need for injectable psychotropic agents in inpatients 65 years of age and older. This was a retrospective cohort analysis comparing outcomes in patients 65 years of age and older who received either a 5 mg or 10 mg cyclobenzaprine dose during their inpatient admission over a 2.5-year period. The primary outcome was hospital LOS, adjusted using multivariate linear regression. Secondary outcomes included 30-day readmission rate adjusted using logistic regression and use of injectable antipsychotics or benzodiazepines. A sub-analysis evaluated the impact of the institution's implementation of a geriatric prescribing context (GEM-CON) on cyclobenzaprine dose selection. The adjusted LOS was 32.7% longer (95% CI 25.9%-39.9%) for patients exposed to higher-dose cyclobenzaprine. Use of injectable antipsychotics or benzodiazepines was also significantly greater in the higher-dose group ( < 0.001; = 0.025). Cyclobenzaprine dose was not significantly associated with readmission on multivariate analysis (OR = 0.93, 95% CI 0.45-1.93). After GEM-CON implementation, there was a significant increase in use of the recommended lower cyclobenzaprine dose ( < 0.001). Use of lower cyclobenzaprine dosing in older inpatients is associated with reduced hospital LOS and need for injectable antipsychotics and benzodiazepines.
Topics: Humans; Aged; Retrospective Studies; Male; Female; Aged, 80 and over; Length of Stay; Patient Readmission; Amitriptyline; Dose-Response Relationship, Drug; Inpatients; Cholinergic Antagonists; Cohort Studies; Antipsychotic Agents
PubMed: 38937891
DOI: 10.4140/TCP.n.2024.249 -
BMC Pulmonary Medicine Jun 2024Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between...
BACKGROUND
Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between female and male PE patients. This paper aimed to compare the sex-specific differences in clinical characteristics and laboratory indicators in psychotic patients with PE.
METHODS
This retrospective study enrolled psychiatric patients with PE from June 2018 to June 2022 at Shenzhen Kangning Hospital (Shenzhen Mental Health Center). Demographic characteristics, factors associated with PE, and laboratory indices were collected to assess sex-specific differences.
RESULTS
Of the 168 patients, 87 (51.8%) were female and 81 (48.2%) were male, with a mean age of 58 years for females and 46 years for male patients. The male group had higher ratio of hyperprolactinemia, more patients using antipsychotic medications, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation than the female group (p < 0.05). Female patients were significantly older, exhibited a higher prevalence of diabetes, and had a greater number of patients taking antidepressants and hypnotics/sedatives than male patients (p < 0.05). Schizophrenia spectrum disorders were more prevalent in male patients, while female patients had a higher incidence of mood disorders (p < 0.05). Among patients aged < 45 years, the male group had higher D-dimer levels at PE onset and greater D-dimer difference (p < 0.05). Among all 112 patients aged ≥ 45 years, male patients were more likely than female patients to have respiratory tract infections, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation (p < 0.05). The multiple linear regression analysis indicated that hyperprolactinemia and the use of first-generation antipsychotics (FGAs) were associated with D-dimer levels at PE onset in male patients, while the time of PE onset and protective restraints were associated with D-dimer levels at PE onset in female patients (p < 0.05).
CONCLUSION
PE-associated clinical features differ between male and female patients. These differences may imply that the processes and mechanisms of PE onset are sex specific. Male patients are more likely to have respiratory tract infections and higher D-dimer levels at PE onset than female patients. The use of FGAs may be associated with increased D-dimer in male psychiatric patients, while protective restraints may be associated with increased D-dimer in female psychiatric patients.
Topics: Humans; Male; Female; Pulmonary Embolism; Retrospective Studies; Middle Aged; Fibrin Fibrinogen Degradation Products; Sex Factors; Adult; Aged; China; Antipsychotic Agents; Risk Factors; Mental Disorders; Hyperprolactinemia; Prevalence
PubMed: 38937698
DOI: 10.1186/s12890-024-03122-6 -
Journal of Clinical Psychopharmacology
Topics: Humans; Bipolar Disorder; Female; Pregnancy; Pregnancy Complications; Antimanic Agents; Antipsychotic Agents; Adult
PubMed: 38935569
DOI: 10.1097/JCP.0000000000001887 -
Medicina (Kaunas, Lithuania) Jun 2024Hyperprolactinemia, as a potential side-effect of some antipsychotic medications, is associated with decreased bone density and an increased risk of fractures. This...
Hyperprolactinemia, as a potential side-effect of some antipsychotic medications, is associated with decreased bone density and an increased risk of fractures. This study investigates whether calcium and vitamin D supplementation affects prolactin receptor ( gene expression in the duodenum, vertebrae, and kidneys of female rats with sulpiride-induced hyperprolactinemia. Twenty-one-week-old female Wistar rats were assigned to three groups: Group S consisted of ten rats who received sulpiride injections (10 mg/kg) twice daily for 6 weeks; Group D (10 rats) received daily supplementation of 50 mg calcium and 500 IU vitamin D along with sulpiride for the last 3 weeks; and Group C consisting of seven age-matched nulliparous rats serving as a control group. Real-time PCR was used to assess gene expression in the duodenum, vertebrae, and kidneys. In Group S, Prlr gene expression was notably decreased in the duodenum ( < 0.01) but elevated in the vertebrae and kidneys compared to Group C. Conversely, Group D exhibited significantly increased Prlr expression in the duodenum ( < 0.01) alongside elevated expression in the vertebrae and kidneys. In sulpiride-induced hyperprolactinemia, decreased Prlr gene expression in the duodenum may lead to reduced intestinal calcium absorption. Consequently, prolactin may draw calcium from the skeletal system to maintain calcium balance, facilitated by increased Prlr gene expression in the vertebrae. However, vitamin D supplementation in sulpiride-induced hyperprolactinemia notably enhances Prlr gene expression in the duodenum, potentially ameliorating intestinal calcium absorption and mitigating adverse effects on bone health.
Topics: Animals; Hyperprolactinemia; Sulpiride; Rats, Wistar; Female; Vitamin D; Rats; Calcium; Duodenum; Receptors, Prolactin; Gene Expression
PubMed: 38929559
DOI: 10.3390/medicina60060942 -
International Journal of Molecular... Jun 2024Understanding the transport mechanism is crucial for developing inhibitors that block allergen absorption and transport and prevent allergic reactions. However, the...
Understanding the transport mechanism is crucial for developing inhibitors that block allergen absorption and transport and prevent allergic reactions. However, the process of how beta-conglycinin, the primary allergen in soybeans, crosses the intestinal mucosal barrier remains unclear. The present study indicated that the transport of beta-conglycinin hydrolysates by IPEC-J2 monolayers occurred in a time- and quantity-dependent manner. The beta-conglycinin hydrolysates were absorbed into the cytoplasm of IPEC-J2 monolayers, while none were detected in the intercellular spaces. Furthermore, inhibitors such as methyl-beta-cyclodextrin (MβCD) and chlorpromazine (CPZ) significantly suppressed the absorption and transport of beta-conglycinin hydrolysates. Of particular interest, sodium cromoglycate (SCG) exhibited a quantity-dependent nonlinear suppression model on the absorption and transport of beta-conglycinin hydrolysates. In conclusion, beta-conglycinin crossed the IPEC-J2 monolayers through a transcellular pathway, involving both clathrin-mediated and caveolae-dependent endocytosis mechanisms. SCG suppressed the absorption and transport of beta-conglycinin hydrolysates by the IPEC-J2 monolayers by a quantity-dependent nonlinear model via clathrin-mediated and caveolae-dependent endocytosis. These findings provide promising targets for both the prevention and treatment of soybean allergies.
Topics: Globulins; Seed Storage Proteins; Antigens, Plant; Soybean Proteins; Animals; Cromolyn Sodium; Chlorpromazine; Endocytosis; beta-Cyclodextrins; Cell Line; Biological Transport; Glycine max; Intestinal Mucosa; Swine
PubMed: 38928351
DOI: 10.3390/ijms25126636 -
International Journal of Molecular... Jun 2024Schizophrenia spectrum disorders (SSD) are a group of diseases characterized by one or more abnormal features in perception, thought processing and behavior. Patients...
Schizophrenia spectrum disorders (SSD) are a group of diseases characterized by one or more abnormal features in perception, thought processing and behavior. Patients suffering from SSD are at risk of developing life-threatening complications. Pharmacogenetic studies have shown promising results on personalized treatment of psychosis. In the current study, 103 patients diagnosed with SSD treated with risperidone as antipsychotic monotherapy were enrolled. Socio-demographics and clinical data were recorded, and laboratory tests and genotyping standard procedure for cytochrome P450 (CYP) 2D6*4 were performed. Patients were evaluated by the Positive and Negative Syndrome Scale (PANSS) on admission and at discharge. Based on the reduction in the PANSS total score, subjects were divided into non-responders, partial responders and full responders. Only 11 subjects had a full response to risperidone (10.67%), 53 subjects (51.45%) had a partial response, and 39 participants (37.86%) were non-responders. Patients at first episode psychosis showed significantly higher levels of blood glucose and prolactin levels, while chronic patients showed significantly higher LDL levels. Adverse drug reactions (ADR) such as tremor and stiffness significantly correlated with genetic phenotypes ( = 0.0145). While CYP2D6 showed no impact on treatment response, ADR were significantly more frequent among poor and intermediate metabolizers.
Topics: Humans; Cytochrome P-450 CYP2D6; Risperidone; Male; Female; Schizophrenia; Adult; Antipsychotic Agents; Middle Aged; Genotype; Young Adult
PubMed: 38928058
DOI: 10.3390/ijms25126350 -
Biomolecules Jun 2024Induced pluripotent stem cell (iPSC) based neuronal differentiation is valuable for studying neuropsychiatric disorders and pharmacological mechanisms at the cellular...
BACKGROUND
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).
METHODS
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).
RESULTS
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.
CONCLUSIONS
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.
Topics: Humans; Olanzapine; Risperidone; Neurogenesis; Hippocampus; Haloperidol; Antipsychotic Agents; Induced Pluripotent Stem Cells; Neural Stem Cells; Cell Differentiation; Cell Proliferation; Cells, Cultured; Neuronal Outgrowth
PubMed: 38927091
DOI: 10.3390/biom14060688 -
JAMA Psychiatry Jun 2024Antipsychotic drugs (particularly clozapine) have been associated with pneumonia in observational studies. Despite studies of the associations between antipsychotic use...
IMPORTANCE
Antipsychotic drugs (particularly clozapine) have been associated with pneumonia in observational studies. Despite studies of the associations between antipsychotic use and incident pneumonia, it remains unclear to what degree antipsychotic use is associated with increased risk of pneumonia, whether dose-response associations exist, and what agents are specifically associated with incident pneumonia.
OBJECTIVE
To estimate pneumonia risk associated with specific antipsychotics and examine whether polytherapy, dosing, and receptor binding properties are associated with pneumonia in patients with schizophrenia.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study identified patients with schizophrenia or schizoaffective disorder (hereafter, schizophrenia) aged 16 years or older from nationwide Finnish registers from 1972 to 2014. Data on diagnoses, inpatient care, and specialized outpatient care were obtained from the Hospital Discharge Register. Information on outpatient medication dispensing was obtained from the Prescription Register. Study follow-up was from 1996 to 2017. Data were analyzed from November 4, 2022, to December 5, 2023.
EXPOSURES
Use of specific antipsychotic monotherapies; antipsychotics modeled by dosage as low (<0.6 of the World Health Organization defined daily dose [DDD] per day), medium (0.6 to <1.1 DDDs per day), or high dose (≥1.1 DDDs per day); antipsychotic polypharmacy; and antipsychotics categorized according to their anticholinergic burden as low, medium, and high.
MAIN OUTCOMES AND MEASURES
The primary outcome was hospitalization for incident pneumonia. Pneumonia risk was analyzed using adjusted, within-individual Cox proportional hazards regression models, with no antipsychotic use as the reference.
RESULTS
The study included 61 889 persons with schizophrenia (mean [SD] age, 46.2 [16.0] years; 31 104 men [50.3%]). During 22 years of follow-up, 8917 patients (14.4%) had 1 or more hospitalizations for pneumonia and 1137 (12.8%) died within 30 days of admission. Compared with no antipsychotic use, any antipsychotic use overall was not associated with pneumonia (adjusted hazard ratio [AHR], 1.12; 95% CI, 0.99-1.26). Monotherapy use was associated with increased pneumonia risk compared with no antipsychotic use (AHR, 1.15 [95% CI, 1.02-1.30]; P = .03) in a dose-dependent manner, but polytherapy use was not. When categorized by anticholinergic burden, only the use of antipsychotics with a high anticholinergic burden was associated with pneumonia (AHR, 1.26 [95% CI, 1.10-1.45]; P < .001). Of specific drugs, high-dose quetiapine (AHR, 1.78 [95% CI, 1.22-2.60]; P = .003), high- and medium-dose clozapine (AHR, 1.44 [95% CI, 1.22-1.71]; P < .001 and AHR, 1.43 [95% CI, 1.18-1.74]; P < .001, respectively), and high-dose olanzapine (AHR, 1.29 [95% CI, 1.05-1.58]; P = .02) were associated with increased pneumonia risk.
CONCLUSIONS AND RELEVANCE
Results of this cohort study suggest that in patients with schizophrenia, antipsychotic agents associated with pneumonia include not only clozapine (at dosages ≥180 mg/d) but also quetiapine (≥440 mg/d) and olanzapine (≥11 mg/d). Moreover, monotherapy antipsychotics and antipsychotics with high anticholinergic burden are associated with increased pneumonia risk in a dose-dependent manner. These findings call for prevention strategies aimed at patients with schizophrenia requiring high-risk antipsychotics.
PubMed: 38922592
DOI: 10.1001/jamapsychiatry.2024.1441 -
Current Issues in Molecular Biology May 2024Among the pathophysiological correlates of schizophrenia, recent research suggests a potential role for the Hedgehog (Hh) signalling pathway, which has been... (Review)
Review
Is the Hedgehog Pathway Involved in the Pathophysiology of Schizophrenia? A Systematic Review of Current Evidence of Neural Molecular Correlates and Perspectives on Drug Development.
Among the pathophysiological correlates of schizophrenia, recent research suggests a potential role for the Hedgehog (Hh) signalling pathway, which has been traditionally studied in embryonic development and oncology. Its dysregulation may impact brain homeostasis, neuroplasticity, and potential involvement in neural processes. This systematic review provides an overview of the involvement of Hh signalling in the pathophysiology of schizophrenia and antipsychotic responses. We searched the PubMed and Scopus databases to identify peer-reviewed scientific studies focusing on Hh and schizophrenia, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, finally including eight studies, including three articles focused on patients with schizophrenia, two animal models of schizophrenia, two animal embryo studies, and one cellular differentiation study. The Hh pathway is crucial in the development of midbrain dopaminergic neurons, neuroplasticity mechanisms, regulating astrocyte phenotype and function, brain-derived neurotrophic factor expression, brain glutamatergic neural transmission, and responses to antipsychotics. Overall, results indicate an involvement of Hh in the pathophysiology of schizophrenia and antipsychotic responses, although an exiguity of studies characterises the literature. The heterogeneity between animal and human studies is another main limitation. Further research can lead to better comprehension and the development of novel personalised drug treatments and therapeutic interventions.
PubMed: 38920990
DOI: 10.3390/cimb46060318 -
Systematic Reviews Jun 2024Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a...
BACKGROUND
Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.
METHODS
We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.
DISCUSSION
Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-ID CRD42023410645.
Topics: Humans; Systematic Reviews as Topic; Network Meta-Analysis; Schizophrenia, Treatment-Resistant; Transcranial Direct Current Stimulation; Antipsychotic Agents; Transcranial Magnetic Stimulation; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 38915121
DOI: 10.1186/s13643-024-02585-2