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Naunyn-Schmiedeberg's Archives of... Jun 2024Clozapine has been considered the "gold standard" in the treatment of schizophrenia for many years. Clozapine has a superior effect, particularly in the treatment of...
Clozapine has been considered the "gold standard" in the treatment of schizophrenia for many years. Clozapine has a superior effect, particularly in the treatment of negative symptoms and suicidal behaviour. However, due to its numerous adverse reactions, clozapine is mainly used for treatment-resistant schizophrenia. The aim of this paper is to analyze the results of clinical studies on clozapine from 2012-2022. PubMed was used as the database. Sixty-four studies were included and categorised by topic. The pharmacokinetic properties of clozapine tablets and a clozapine suspension solution did not differ markedly. Clozapine was superior to olanzapine and risperidone in reducing aggression and depression. A long-term study showed that metabolic parameters changed comparably with olanzapine and clozapine after 8 years. Risperidone and ziprasidone can be used as an alternative to clozapine. Scopolamine, atropine drops, and metoclopramide are effective in the treatment of clozapine-induced hypersalivation. Eight drugs, including liraglutide, exenatide, metformin, and orlistat, are potentially effective in the treatment of clozapine-induced weight gain. Ziprasidone, haloperidol, and aripiprazole showed a positive effect on symptoms when added to clozapine. No investigated drug was superior to clozapine for the treatment of schizophrenia. Ziprasidone and risperidone can also be used well for the treatment of schizophrenia. In the treatment of clozapine-induced hypersalivation and weight gain, some drugs proved to be effective.
PubMed: 38918233
DOI: 10.1007/s00210-024-03209-1 -
Drugs - Real World Outcomes Jun 2024Reducing falls and fractures remains an important clinical goal in managing older residents with Parkinson's disease psychosis (PDP) in long-term care/nursing home...
Falls and Fractures among Nursing Home Residents Treated with Pimavanserin versus Other Atypical Antipsychotics: Analysis of Medicare Beneficiaries with Parkinson's Disease Psychosis.
BACKGROUND
Reducing falls and fractures remains an important clinical goal in managing older residents with Parkinson's disease psychosis (PDP) in long-term care/nursing home (LTC/NH) settings.
OBJECTIVES
This analysis examined risk of all-cause falls or fractures among PDP residents on continuous monotherapy with pimavanserin (PIM) versus (i) other atypical antipsychotics (AAPs) [quetiapine (QUE), risperidone (RIS), olanzapine (OLA), aripiprazole (ARI)] and (ii) QUE.
METHODS
A retrospective analysis of parts A, B, and D claims from a 100% Medicare sample (2013-2019) in LTC/NH settings was conducted. LTC/NH residents in the USA initiating continuous monotherapy (PIM versus other AAPs; PIM versus QUE) for ≥ 6 months between 01 January 2014 and 31 December 2018 were 1:1 propensity score matched (PSM) on 31 variables (age, sex, race, region, and 27 Elixhauser comorbidities). Outcomes included three measures: risks of falls only, fractures only, and falls/fractures during 6-months follow-up. Demographic characteristics were described using chi-square and t-tests. Generalized linear models were used to assess difference in risks of falls/fractures.
RESULTS
Of 7187 residents, 47.59% (n = 3420) were female and mean age was 78.8 (± 7.75) years. In total, 14% (n = 1005) were on PIM and 86% (n = 6182) were on other AAPs. After PSM, falls only among PIM residents (n = 1005) was 4.58% (n = 46) versus 7.66% (n = 77) for other AAPs (n = 1005) [relative risk (RR) = 0.63 (0.46, 0.86), p < 0.05] and 8.26% (n = 83) for QUE (n = 1005) residents (p < 0.05). Fractures only among PIM residents was 1.39% (n = 14) compared with 2.09% (n = 21) for other AAPs (p = 0.31) and 1.89% (n = 19) for QUE (p = 0.49), respectively. Taken together, falls/fractures among PIM residents were 5.67% (n = 57) versus 9.05% (n = 91) for other AAPs [RR = 0.63 (0.46, 0.86), p < 0.05] and 9.55% (n = 96) for QUE (p < 0.05), respectively.
CONCLUSIONS
In this analysis of LTC/NH residents with PDP, PIM had a 37% and 41% lower risk of all-cause falls/fractures versus other AAPs and versus QUE, respectively.
PubMed: 38914856
DOI: 10.1007/s40801-024-00433-2 -
International Journal of General... 2024Dementia is a common neurogenerative disease among older adults. Therefore, they are more prone to potentially inappropriate medication (PIM), which is medication that...
BACKGROUND
Dementia is a common neurogenerative disease among older adults. Therefore, they are more prone to potentially inappropriate medication (PIM), which is medication that causes more harm rather than protecting the health of an individual. Hence, the American Geriatrics Society (AGS) has recognized the risk of certain medication classes on this population and released PIM according to Beers criteria, which is a helpful guide for clinicians to ensure the safety of medication before it is prescribed. The aim of this study is to assess the prevalence of PIM use among older adults with dementia as a risk factor in comparison to other older adults without dementia.
METHODS
A retrospective study was conducted in an outpatient setting in a tertiary hospital targeting elderly patients aged 65 years old or over from January 2020 to September 2022. A total of 598 patients were screened, and 270 patients met the inclusion criteria. The eligible patients were then divided into two groups: 168 were in a non-dementia group and 102 were in a dementia group.
RESULTS
PIM use was reported in patients with and without dementia. The most inappropriate medication that was prescribed comprised atypical antipsychotics PIM for both patients with and without dementia. However, the prevalence was higher in the dementia group for quetiapine (75% vs 24% respectively), olanzapine (82% vs 17% respectively) or risperidone (92% vs 7%, respectively). Anticholinergics were highly prescribed in older adult without dementia as compared to dementia patient and was statistically significant for solifenacin (96% vs.3.6% respectively) and amitriptyline (88% vs 11% respectively).
CONCLUSION
Among elderly patients in outpatient care settings, the prevalence of PIM use is considered high in dementia patients for antipsychotics, while a higher use of benzodiazepine and anticholinergics was found in non-dementia patients.
PubMed: 38912331
DOI: 10.2147/IJGM.S456091 -
International Immunopharmacology Jun 2024The accumulation of amyloid-β (Aβ) in the brain is the first pathological mechanism to initiate Alzheimer's disease (AD) pathogenesis. However, the precise role of Aβ...
The accumulation of amyloid-β (Aβ) in the brain is the first pathological mechanism to initiate Alzheimer's disease (AD) pathogenesis. However, the precise role of Aβ in the disease progression remains unclear. Through decades of research, prolonged inflammation has emerged as an important core pathology in AD. Previously, a study has demonstrated the neurotoxic effect of Aβ-induced neuroinflammation in neuron-glia co-culture at 72 h. Here, we hypothesise that initial stage Aβ may trigger microglial inflammation, synergistically contributing to the progression of neurite lesions relevant to AD progression. In the present study, we aimed to determine whether olanzapine, an antipsychotic drug possessing anti-inflammatory properties, can ameliorate Aβ-induced progressive neurite lesions. Our study reports that Aβ induces neurite lesions with or without inflammatory microglial cells in vitro. More intriguingly, the present study revealed that Aβ exacerbates neurite lesions in synergy with microglia. Moreover, the time course study revealed that Aβ promotes microglia-mediated neurite lesions by eliciting the secretion of pro-inflammatory cytokines. Furthermore, our study shows that olanzapine at lower doses prevents Aβ-induced microglia-mediated progressive neurite lesions. The increase in pro-inflammatory cytokines induced by Aβ is attenuated by olanzapine administration, associated with a reduction in microglial inflammation. Finally, this study reports that microglial senescence induced by Aβ was rescued by olanzapine. Thus, our study provides the first evidence that 1 µM to 5 µM of olanzapine can effectively prevent Aβ-induced microglia-mediated progressive neurite lesions by modulating microglial inflammation. These observations reinforce the potential of targeting microglial remodelling to slow disease progression in AD.
PubMed: 38908083
DOI: 10.1016/j.intimp.2024.112469 -
Journal of Huntington's Disease Jun 2024Huntington's disease (HD) is an autosomal dominant disorder that affects the basal ganglia, caused by CAG repeats in the huntingtin gene. Delusional infestation (DI)...
Huntington's disease (HD) is an autosomal dominant disorder that affects the basal ganglia, caused by CAG repeats in the huntingtin gene. Delusional infestation (DI) is a rare psychotic manifestation of the disease. This report presents two cases of HD patients with DI, both middle-aged females. The first patient achieved remission of DI with olanzapine, later cross-tapered to risperidone, but had spontaneous relapses. The second experienced gradual resolution of DI with risperidone in the setting of iron repletion and amantadine discontinuation, although her other psychotic symptoms remained. These cases shed light on an uncommon condition and may help guide understanding of the most effective treatment for it.
PubMed: 38905053
DOI: 10.3233/JHD-240013 -
Indian Journal of Anaesthesia Jun 2024Post-discharge nausea and vomiting (PDNV) is a pertinent problem in patients undergoing ambulatory surgery. The objective of this study was to assess the efficacy of the...
Olanzapine versus standard antiemetic prophylaxis for the prevention of post-discharge nausea and vomiting after propofol-based general anaesthesia: A randomised controlled trial.
BACKGROUND AND AIMS
Post-discharge nausea and vomiting (PDNV) is a pertinent problem in patients undergoing ambulatory surgery. The objective of this study was to assess the efficacy of the novel drug olanzapine, which has proved its efficiency in patients undergoing highly emetogenic chemotherapy for PDNV prevention.
METHODS
This randomised controlled trial recruited 106 adult patients (18-65 years) undergoing highly emetogenic daycare surgeries with propofol-based general anaesthesia (GA). Group O received preoperative oral olanzapine 10 mg, and Group C, acting as a control, received 8 mg of intravenous dexamethasone and 4 mg of ondansetron intraoperatively. The primary outcome was nausea (numeric rating scale >3) and/or vomiting 24 h after discharge. Secondary outcomes included nausea and vomiting in the post-anaesthesia care unit (PACU), severe nausea, vomiting and side effects. Normality was assessed using the Shapiro-Wilk test, and the independent samples -test or the Mann-Whitney test was used to compare continuous variables. Fisher's exact test was used to assess any non-random associations between the categorical variables.
RESULTS
The incidence and severity of postoperative nausea and vomiting were similar in both groups within PACU (four patients experienced nausea and vomiting, three had severe symptoms in Group O, = 0.057) and in the post-discharge period (three patients in Group O had nausea and vomiting compared to five patients in Group C, of which four were severe, = 0.484). The side effects (sedation, dizziness, and light-headedness) were comparable between the two groups.
CONCLUSION
A single preoperative oral olanzapine can be an effective alternative to standard antiemetic prophylaxis involving dexamethasone and ondansetron for preventing PDNV in highly emetogenic daycare surgeries with propofol-based GA.
PubMed: 38903258
DOI: 10.4103/ija.ija_1162_23 -
Psychiatry Research Jun 2024The risk of fatal choking for people with schizophrenia and associations with antipsychotic medication are largely unknown. Therefore, we calculated the choking-related...
The risk of fatal choking for people with schizophrenia and associations with antipsychotic medication are largely unknown. Therefore, we calculated the choking-related standardized mortality ratio for schizophrenia relative to the general population (SMR). We also computed adjusted hazard ratios (aHR) of choking-related mortality for antipsychotics in a nationwide cohort of patients with schizophrenia (N = 59,916). SMR was 20.5 (95 % confidence interval (CI)=17.1-23.9). The aHR was 1.74 (95 %CI=1.19-2.55) for strong dopamine 2-antagonists. For other antipsychotics, CIs included 1. Importantly, aHRs were particularly high for high dose categories of strong dopamine D2 receptor (D2R) antagonists. In conclusion, a schizophrenia diagnosis is associated with a 20-fold risk of death due to choking. This risk is elevated during use of strong D2R antagonist antipsychotics, particularly when prescribed in high dosages.
PubMed: 38901365
DOI: 10.1016/j.psychres.2024.116012 -
Journal of Nippon Medical School =... Jun 2024Schizophrenia develops during adolescence. Maternal infections during the fetal period increase the incidence of schizophrenia in children, which suggests that the...
Schizophrenia develops during adolescence. Maternal infections during the fetal period increase the incidence of schizophrenia in children, which suggests that the pathogenesis involves neuroinflammation. Here, we report a case of new-onset schizophrenia in a 16-year-old boy after COVID-19. After developing COVID-19, he entered a catatonic state 4 days later and was hospitalized. Benzodiazepines alleviated his catatonia, but hallucinations and delusions persisted. Encephalitis and epilepsy were excluded by magnetic resonance imaging (MRI), encephalography, and cerebrospinal fluid examination. Psychosis persisted after the virus titer declined and the inflammatory response subsided. Moreover, the patient exhibited delusions of control-a Schneider's first-rank symptom. Schizophrenia was diagnosed, and olanzapine improved his symptoms. He had a brief history of insomnia before COVID-19 but his symptoms did not satisfy the ultra-high-risk criteria. However, COVID-19 may have facilitated development of schizophrenia through neuroinflammation and volume reduction in the gray matter of the right medial temporal lobe. This case demonstrates that infectious diseases in adolescents should be carefully managed, to prevent schizophrenia.
PubMed: 38897947
DOI: 10.1272/jnms.JNMS.2025_92-301 -
The Lancet. Child & Adolescent Health Jul 2024The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
The degree of physiological responses to individual antipsychotic drugs is unclear in children and adolescents. With network meta-analysis, we aimed to investigate the effects of various antipsychotic medications on physiological variables in children and adolescents with neuropsychiatric and neurodevelopmental conditions.
METHODS
For this network meta-analysis, we searched Medline, EMBASE, PsycINFO, Web of Science, and Scopus from database inception until Dec 22, 2023, and included randomised controlled trials comparing antipsychotics with placebo in children or adolescents younger than 18 years with any neuropsychiatric and neurodevelopmental condition. Primary outcomes were mean change from baseline to end of acute treatment in bodyweight, BMI, fasting glucose, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, prolactin, heart rate, systolic blood pressure (SBP), and QT interval corrected for heart rate (QTc) for patients receiving either active treatment or placebo. For multigroup trials reporting several doses, we calculated a summary value for each physiological variable for all doses. After transitivity assessment, we fitted frequentist random-effects network meta-analyses for all comparisons in the network. A Kilim plot was used to summarise the results for all treatments and outcomes, providing information regarding the strength of the statistical evidence of treatment effects, using p values. Network heterogeneity was assessed with τ, risk of bias of individual trials was assessed with the Cochrane Collaboration's Tool for Assessing Risk of Bias, and the credibility of findings from each network meta-analysis was assessed with the Confidence in Network Meta-Analysis (CINEMA) app. This study is registered on PROSPERO (CRD42021274393).
FINDINGS
Of 6676 studies screened, 47 randomised controlled trials were included, which included 6500 children (mean age 13·29 years, SD 2·14) who received treatment for a median of 7 weeks (IQR 6-8) with either placebo (n=2134) or one of aripiprazole, asenapine, blonanserin, clozapine, haloperidol, lurasidone, molindone, olanzapine, paliperidone, pimozide, quetiapine, risperidone, or ziprasidone (n=4366). Mean differences for bodyweight change gain compared with placebo ranged from -2·00 kg (95% CI -3·61 to -0·39) with molindone to 5·60 kg (0·27 to 10·94) with haloperidol; BMI -0·70 kg/m (-1·21 to -0·19) with molindone to 2·03 kg/m (0·51 to 3·55) with quetiapine; total cholesterol -0·04 mmol/L (-0·39 to 0·31) with blonanserin to 0·35 mmol/L (0·17 to 0·53) with quetiapine; LDL cholesterol -0·12 mmol/L (-0·31 to 0·07) with risperidone or paliperidone to 0·17 mmol/L (-0·06 to 0·40) with olanzapine; HDL cholesterol 0·05 mmol/L (-0·19 to 0·30) with quetiapine to 0·48 mmol/L (0·18 to 0·78) with risperidone or paliperidone; triglycerides -0·03 mmol/L (-0·12 to 0·06) with lurasidone to 0·29 mmol/L (0·14 to 0·44) with olanzapine; fasting glucose from -0·09 mmol/L (-1·45 to 1·28) with blonanserin to 0·74 mmol/L (0·04 to 1·43) with quetiapine; prolactin from -2·83 ng/mL (-8·42 to 2·75) with aripiprazole to 26·40 ng/mL (21·13 to 31·67) with risperidone or paliperidone; heart rate from -0·20 bpm (-8·11 to 7·71) with ziprasidone to 12·42 bpm (3·83 to 21·01) with quetiapine; SBP from -3·40 mm Hg (-6·25 to -0·55) with ziprasidone to 10·04 mm Hg (5·56 to 14·51) with quetiapine; QTc from -0·61 ms (-1·47 to 0·26) with pimozide to 0·30 ms (-0·05 to 0·65) with ziprasidone.
INTERPRETATION
Children and adolescents show varied but clinically significant physiological responses to individual antipsychotic drugs. Treatment guidelines for children and adolescents with a range of neuropsychiatric and neurodevelopmental conditions should be updated to reflect each antipsychotic drug's distinct profile for associated metabolic changes, alterations in prolactin, and haemodynamic alterations.
FUNDING
UK Academy of Medical Sciences, Brain and Behaviour Research Foundation, UK National Institute of Health Research, Maudsley Charity, the Wellcome Trust, Medical Research Council, National Institute of Health and Care Research Biomedical Centre at King's College London and South London and Maudsley NHS Foundation Trust, the Italian Ministry of University and Research, the Italian National Recovery and Resilience Plan, and Swiss National Science Foundation.
Topics: Humans; Antipsychotic Agents; Child; Adolescent; Network Meta-Analysis; Randomized Controlled Trials as Topic; Mental Disorders; Heart Rate; Blood Pressure
PubMed: 38897716
DOI: 10.1016/S2352-4642(24)00098-1 -
Cureus May 2024Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like...
Prevalence, Attributes, and Risk Factors of QT-Interval-Prolonging Drugs and Potential Drug-Drug Interactions in Cancer Patients: A Prospective Study in a Tertiary Care Hospital.
Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like antiemetics, antidepressants, analgesics, and antimicrobials), there is a heightened risk for possible QT interval prolongation. There is a dearth of evidence in the literature regarding the usage of QT-prolonging anticancer drugs and associated risk factors that have the propensity to prolong QT interval. The purpose was to explore the extent of the use of QT-interval-prolonging drugs and potential QT-prolonging drug-drug interactions (QT-DDIs) in cancer patients attending OPD in a tertiary-care hospital. Methods This was a hospital-based, cross-sectional, observational study. Risk stratification of QT-prolonging drugs for torsades de pointes (TdP) was done by the Arizona Center for Education and Research on Therapeutics (AzCERT)/CredibleMeds-lists, and potential QT-DDIs were determined with four online DDI-checker-software. Results In 1331 cancer patients, the overall prevalence of potential QT-prolonging drug utilization was 97.3%. Ondansetron, pantoprazole, domperidone, and olanzapine were the most frequent QT-prolonging drugs in cancer patients. The top six antineoplastics with potential QT-prolonging and torsadogenic actions were capecitabine, oxaliplatin, imatinib, bortezomib, 5-fluorouracil, and bendamustine. Evidence-based pragmatic QTc interval prolongation risk assessment tools are imperative for cancer patients. Conclusion This study revealed a high prevalence of QT-prolonging drugs and QT-DDIs among cancer patients who are treated with anticancer and non-anticancer drugs. As a result, it's critical to take precautions, stay vigilant, and avoid QT-prolonging in clinical situations. Evidence-based pragmatic QTc interval prolongation risk assessment tools are needed for cancer patients.
PubMed: 38882995
DOI: 10.7759/cureus.60492