Use Of Antipsychotics Research Articles

Making Sense of Recovery From First Psychosis With Antipsychotic Medication: A Qualitative Phenomenological Study.

Recovering from a first psychosis is a highly individual process and requires the person to make sense of their experiences. Clinicians, in turn, need to comprehend these first-person perspectives, creating a mutual sense-making dynamic. Antipsychotic medication is a substantial part of psychosis treatment. Providing insight in the lived experience of recovery with antipsychotics could improve the mutual understanding and help bridge the gap between the perspective of the clinician and that of the person recovering from psychosis. 14 persons in recovery from a first psychosis with the use of antipsychotics were interviewed. Their narratives were analyzed using Interpretative Phenomenological Analysis (IPA). Five overarching themes were found, representing important and meaningful experiences in recovering with antipsychotic medication. Theme 1: antipsychotics as external dampening (4 subthemes); Theme 2: shifting of realities; Theme 3: pace of recovery; Theme 4: antipsychotics' influence on identity; and Theme 5: is it truly the antipsychotics? Our findings show that recovery from psychosis with antipsychotics is an all-encompassing, multi-faceted, and ambivalent experience. The themes found in this research could inspire clinicians to discuss less obvious aspects of the experience of recovering with antipsychotics. Even more so, paying attention to the first-person perspective could lead to a more thorough understanding and benefit therapeutic relationships.

Sex differences in prolactin levels and clinical outcomes in patients with a first psychotic episode

AimTo analyze the clinical, neurocognitive, and functional impact of prolactin levels according to sex in patients with a First Episode Psychosis (FEP). MethodsWe measured prolactin levels in 221 non-affective FEP patients treated with antipsychotics (AP) and 224 healthy controls, at baseline and 2-year follow-up. We examined whether the relationships between clinical and functional variables were mediated by prolactin, controlling for antipsychotic use, according to sex. ResultsProlactin levels were higher in patients when compared to controls at both time points. Baseline factors associated with prolactin were chlorpromazine equivalents, attention, and executive functioning. In the FEP group, prolactin levels were associated with functioning and diminished expression in males, and with working memory in females. Prolactin levels (p=0.0134) played a role as a mediator between negative symptomatology (p=0.086) and functional outcome (p=0.008) only in FEP male patients at baseline. ConclusionsProlactin plays a role in the functionality and clinical symptomatology of FEP patients. Our results suggest that pharmacological counselling in patients with hyperprolactinemia at baseline and negative symptomatology might improve their functional and clinical outcomes.

Antipsychotic-induced prolactin elevation in premenopausal women with schizophrenia: associations with estrogen, disease severity and cognition.

Antipsychotic-induced prolactin elevation may impede protective effects of estrogens in women with schizophrenia-spectrum disorders (SSD). Our study sought to confirm whether the use of prolactin-raising antipsychotics is associated with lower estrogen levels, and to investigate how estrogen and prolactin levels relate to symptom severity and cognition in premenopausal women with SSD. This cross-sectional study included 79 premenopausal women, divided in three groups of women with SSD treated with prolactin-sparing antipsychotics (n = 21) or prolactin-raising antipsychotics (n = 27), and age-matched women without SSD (n = 31). Circulating 17β-estradiol was compared among groups. In patients, we assessed the relationship between prolactin and 17β-estradiol, and the relationships of these hormones to symptom severity and cognition, using correlation analyses and backward regression models. In women receiving prolactin-raising antipsychotics, 17β-estradiol levels were lower as compared to both other groups (H(2) = 8.34; p = 0.015), and prolactin was inversely correlated with 17β-estradiol (r=-0.42, p = 0.030). In the prolactin-raising group, 17β-estradiol correlated positively with verbal fluency (r = 0.52, p = 0.009), and 17β-estradiol and prolactin together explained 29% of the variation in processing speed (β17β-estradiol = 0.24, βprolactin=-0.45, F(2,25) = 5.98, p = 0.008). In the prolactin-sparing group, 17β-estradiol correlated negatively with depression/anxiety (r=-0.57, p = 0.014), and together with prolactin explained 26% of the variation in total symptoms (β17β-estradiol=-0.41, βprolactin = 0.32, F(2,18) = 4.44, p = 0.027). In women with SSD, antipsychotic-induced prolactin elevation was related to lower estrogen levels. Further, estrogens negatively correlated with symptom severity and positively with cognition, whereas prolactin levels correlated negatively with cognition. Our findings stress the clinical importance of maintaining healthy levels of prolactin and estrogens in women with SSD.

A comparison of clinical characteristics and course predictors in early- and childhood-onset schizophrenia.

The aim of this study was to compare the clinical characteristics of childhood-onset schizophrenia (COS) and early-onset schizophrenia (EOS) during the first- episode psychosis and the stable period, to examine psychopharmacological treatment approaches, and to investigate potential predictive factors for prognosis. Demographic, clinical, and psychopharmacological therapy data for 31 patients diagnosed with COS and 66 with EOS were retrieved from the file records in this multicenter study. Symptom distribution and disease severity and course were evaluated twice, in the acute psychotic stage and in the latest stable phase, during follow-up using the positive and negative syndrome scale (PANSS) and clinical global impression (CGI) scales. A statistically significant difference was observed between the groups' CGI improvement rates and median last stable stage PANSS positive, negative, and general psychopathology symptom scores (p = .005, p = .031, p = .005, and p = .012, respectively). Premorbid neurodevelopmental disorder and obsessive-compulsive disorder and comorbidities were more common in the COS group (p = .025 and p = .030, respectively), and treatment required greater multiple antipsychotic use in that group (p = .013). When the independent variables affecting the difference between pre- and post-treatment PANSS scores were examined using linear regression analysis, the model established was found to be statistically significant (F = 5.393; p = .001), and the group variable (p = .024), initial disease severity (p = .001), and socioeconomic level (p = .022; p = .007) emerged as predictive factors for the disease course. Although early diagnosis and treatment is an important factor in improving prognosis in schizophrenia, more specific predictors for schizophrenia need to be identified. Additionally, preventive programs and pharmacological methods need to be developed in children with neurodevelopmental problems, particularly those from low socioeconomic status families.

Rash caused by lurasidone in old chinese patient with bipolar disorder: case-based review

BackgroundRash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone.Case presentationA 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic.ConclusionsIn conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

Prescription medication use in the 10 years prior to diagnosis of young onset Alzheimer’s disease: a nationwide nested case-control study

BackgroundPatients with young onset Alzheimer’s disease (YOAD) face long diagnostic delays. Prescription medication use may provide insights into early signs and symptoms, which may help facilitate timely diagnosis.MethodsIn a register-based nested case-control study, we examined medication use for everyone diagnosed with YOAD in a Danish memory clinic during 2016–2020 compared to cognitively healthy controls. Prescription medication use were grouped into 13 overall categories (alimentary tract and metabolism, blood and blood forming organs, cardiovascular system, dermatologicals, genitourinary system and sex hormones, systemic hormonal preparations, antiinfectives for systemic use, antineoplastic and immunomodulating agents, musculo-skeletal system, nervous system, antiparasitic products, respiratory system, and sensory organs). Further stratifications were done for predetermined subcategories with a use-prevalence of at least 5% in the study population. Conditional logistic regression produced odds ratios, which given the use of incidence-density matching is interpretable as incidence rate ratios (IRRs). The association between prescription medication use and subsequent YOAD diagnosis was examined in the entire 10-year study period and in three time-intervals.ResultsThe study included 1745 YOAD cases and 5235 controls. In the main analysis, several overall categories showed significant associations with YOAD in one or more time-intervals, namely blood and blood forming organs and nervous system. Prescription medication use in the nervous system category was increased for YOAD cases compared to controls already 10->5 years prior to diagnosis (IRR 1.17, 95% CI 1.05–1.31), increasing to 1.57 (95% CI 1.39–1.78) in the year preceding diagnosis. This was largely driven by antidepressant and antipsychotic use, and especially prominent for first-time users.ConclusionsIn this study, medication use in several categories was associated with YOAD. Onset of treatment-requiring psychiatric symptoms such as depression or psychosis in mid-life may serve as potential early indicators of YOAD.

Distribution of neuropsychiatric profiles and comorbid diseases in dementia subtypes

Objectives: Alzheimer’s disease (AH) is the most prevalent cause of dementia, followed closely by vascular dementia. Mixed vascular-Alzheimer’s dementia (MVAD) is more evident in individuals aged 80 and above. Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after AH. Vascular risk factors play important role in the pathogenesis of dementia syndromes. Behavioral and psychological symptoms represent a significant portion of the non-cognitive manifestations in dementia patients. This study aimed to evaluate the distribution of chronic diseases, behavioral disorders, psychiatric findings, and medication use in patients followed with different dementia diagnoses. Methods: Prevalance of chronic diseases, behavioral disorders, psychiatric findings as well as the usage of antidepressant and antipsychotic medications among patients followed up in dementia outpatient clinics with the diagnosis of AD, mild cognitive impairment (MCI), vascular dementia (VaD), FTD, and MVAD were investigated. Neuropsychiatric inventory (NPI) was applied to the patients. Results: Four hundred and fifty-five patients were accepted in the study. The patients were distributed as follows: AD (n=303, female/male: 187/115, age = 78±8 years), MCI (n=53, female/male: 31/22, age = 69±10 years), VaD (n=31, female/male: 18/13, age = 68±9 years), FTD (n=32, female/male: 17/15, age = 68±9 years), and MVAD (n=36, female/male: 16/20, age = 76±10 years). Both AD and MVAD groups were significantly older than the other groups (F = 23.2, P<0.0001). The ratio of comorbid chronic diseases was 80% in the AD group, 72% in the MCI group, 91% in the VaD group, 59% in the FTD group, and 93% in the MVAD group. In the whole group, antipsychotic drug use was 27.5% and antidepressant drug use was 28.9%. The mean NPI score was 32.9±28 in antipsychotic users and 16±19 in non-users (P<0.0001). The mean NPI of antidepressant users was 17.6±19 and 21.9±25 (P=0.055) in non-users. Conclusion: There is a comorbid chronic disease burden in all dementia subtypes, although at varying intensities, and as the chronic disease burden increases, behavioral disorders and psychotic findings increase, and accordingly, the use of antipsychotics also increases.

Predicting Alzheimer’s disease from cognitive footprints in mid and late life: How much can register data and machine learning help?

BackgroundReal-world data with decades-long medical records are increasingly available alongside the growing adoption of machine learning in healthcare research. We evaluated the performance of machine learning models in predicting the risk of Alzheimer’s disease (AD) using data from the Finnish national registers. MethodsWe conducted a case-control study using data from the Finnish MEDALZ (Medication use and Alzheimer’s disease) study. Altogether 56,741 individuals with incident AD diagnosis (age ≥ 65 years at diagnosis and born after 1922) and their 1:1 age-, sex-, and region of residence-matched controls were included. The association of risk factors, evaluated at different age periods (45–54, 55–64, 65+), and AD were assessed with logistic regression. Predictive accuracies of logistic regressions were compared with seven machine learning models (L1-regularized logistic regression, Naive bayes, Decision tree, Random Forest, Multilayer perceptron, XGBoost, and LightGBM). Findings63.5 % of cases and controls were females and the mean age was 79.1 (SD = 5.1). The strongest associations with AD were observed for head injuries at age 55–64 (OR, 95 % CI 1.33, 1.19–1.48) and 65+ (1.31, 1.23–1.40), followed by antidepressant use (1.30, 1.22–1.38) at 55–64 and antipsychotic use (1.27, 1.19–1.35) at 65+. The predictive accuracies of all models were low, with the best performance (AUC 0.603) observed in Random Forest for predicting AD onset at age 65–69. InterpretationAlthough significant associations were identified between many risk factors and AD, the low predictive accuracies suggest that specialised healthcare diagnosis data is not sufficient for predicting AD and linkage with other data sources is needed.

Antipsychotic drug use in individuals with dementia: risks and alternatives

Sarah Jane Palmer looks at the risks associated with prescribing antipsychotic drugs to people with dementia and what other options could be used instead.

Utilization of Lower-Dose Cyclobenzaprine in the Older Inpatient.

Background 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. Objective 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. Methods 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. Results 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 (P < 0.001; P = 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 (P < 0.001). Conclusion Use of lower cyclobenzaprine dosing in older inpatients is associated with reduced hospital LOS and need for injectable antipsychotics and benzodiazepines.

Psychopharmacology Review for Eating Disorders Among Children, Adolescents, and Adults.

This article reviews the latest research on pharmacological management of eating disorders, including anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), and avoidant/restrictive food intake disorder. Recent literature for both youth and adult populations obtained through a PubMed search was included. American Psychiatric Association guidelines, National Institute for Health and Care Excellence guidelines, Canadian practice guidelines, and World Federation of Societies of Biological Psychiatry guidelines were also included. First-line recommendations were focused on therapy because the evidence for medication management of eating disorders continues to be limited. Some limited evidence was found for antipsychotic use for AN, selective serotonin reuptake inhibitors and topiramate use for BN, and stimulant and topiramate use for BED. Further medication trials are needed to help with complex eating disorder presentations in adults and youth.

A Comprehensive Guide to Long-Acting Injectable Antipsychotics for Primary Care Clinicians.

We propose a paper that provides education on commonly used long-acting injectable antipsychotics (LAIs) to improve primary care based mental health interventions in patients with severe mental illnesses (SMIs) such as schizophrenia, schizoaffective disorder, and bipolar disorders. With the expanding interface of primary care and psychiatry across all healthcare settings, it has become increasingly important for primary care clinicians to have a broader understanding of common psychiatric treatments, including LAIs. Long-acting injectable antipsychotics have been shown to be helpful in significantly improving treatment adherence, preventing disease progression, improving treatment response, decreasing readmission rates, and reducing social impairment. We discuss evidence-based indications and guidelines for use of long-acting injectable antipsychotics. We provide an overview of the treatment of SMI with LAIs, mainly focusing on the most commonly used long-acting injectable antipsychotics, advantages and disadvantages of each, along with outlining important clinical pearls for ease of practical application. Equipped with increased familiarity and understanding of these essential therapies, primary care clinicians can better facilitate early engagement with psychiatric care, promote more widespread use, and thus significantly improve the wellbeing and quality of life of patients with severe mental illness.

Early-life risperidone alters locomotor responses to apomorphine and quinpirole in adulthood

An escalating trend of antipsychotic drug use in children with ADHD, disruptive behavior disorder, or mood disorders has raised concerns about the impact of these drugs on brain development. Since antipsychotics chiefly target dopamine receptors, it is important to assay the function of these receptors after early-life antipsychotic administration. Using rats as a model, we examined the effects of early-life risperidone, the most prescribed antipsychotic drug in children, on locomotor responses to the dopamine D1/D2 receptor agonist, apomorphine, and the D2/D3 receptor agonist, quinpirole. Female and male Long-Evans rats received daily subcutaneous injections of risperidone (1.0 and 3.0 mg/kg) or vehicle from postnatal day 14–42. Locomotor responses to one of three doses (0.03, 0.1, and 0.3 mg/kg) of apomorphine or quinpirole were tested once a week for four weeks beginning on postnatal day 76 and 147 for each respective drug. The locomotor activity elicited by the two lower doses of apomorphine was significantly greater in adult rats, especially females, administered risperidone early in life. Adult rats administered risperidone early in life also showed more locomotor activity after the low dose of quinpirole. Overall, female rats were more sensitive to the locomotor effects of each agonist. In a separate group of rats administered risperidone early in life, autoradiography of forebrain D2 receptors at postnatal day 62 revealed a modest increase in D2 receptor density in the medial caudate. These results provide evidence that early-life risperidone administration can produce long-lasting changes in dopamine receptor function and density.

The use of psychotropic drugs in oncological diseases (review)

Background: It is estimated that at least 25-30% of cancer patients experience mental disorders. Due to the high prevalence of these disorders among this patient population, psychotropic drugs have been successfully utilized in oncology for an extended period of time. The use of psychotropic drugs enables targeted symptom management to improve the quality of life of cancer patients. However, it is essential to carefully evaluate the risks of drug interactions and potential side effects when prescribing any psychotropic medication. The aim of the study: The aim of this study was to analyze the utilization of psychopharmacotherapy in oncology practice for treating comorbid mental disorders and symptoms related to oncological diseases. An evaluation of the side effects and drug interactions of psychopharmacological and oncological drugs was conducted. Materials and methods: The eLibrary, PubMed, and Google Scholar databases were searched using the keywords “psychooncology” and “psychopharmacotherapy”. Reviews, meta-analyses, and therapy recommendations were selected from the obtained results, which provided the most comprehensive coverage of the current scientific data on this topic. Results: Anxiety disorders and depressive reactions are prevalent in cancer patients and can be successfully treated with psychopharmacological intervention. Additionally, symptoms associated with the oncological process or side effects of treatment such as anorexia, pain, and nausea can be alleviated through the use of antidepressants and antipsychotics. However, it is crucial to carefully evaluate the risks of drug interactions when prescribing any psychotropic drugs. For instance, strong cytochrome CYP2D6 inhibitors can lead to a decrease in the concentration of the active metabolite tamoxifen, while the combination of antidepressants and tramadol increases the risk of serotonin syndrome. Conclusion: The application of psychotropic drugs in the treatment of cancer can greatly enhance the patients' quality of life. However, potential side effects and drug interactions must be carefully evaluated.

Sex-specific differences in the clinical profile among psychiatric patients with pulmonary Embolism: a hospital-based retrospective study

BackgroundPulmonary 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.MethodsThis 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.ResultsOf 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).ConclusionPE-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.

Pneumonia Risk, Antipsychotic Dosing, and Anticholinergic Burden in Schizophrenia

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. 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. 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. 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. 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. 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. 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.

Antipsychotic Discontinuation and New Trazodone Use in Ontario Nursing Homes: Evidence of Medication Substitution

ObjectivesAn unintended consequence of efforts to reduce antipsychotic medications in nursing homes is the increase in use of other psychotropic medications; however, evidence of substitution remains limited. Our objective was to measure individual-level prescribing patterns consistent with substitution of trazodone for antipsychotics. DesignRetrospective cohort study. Setting and ParticipantsResidents of Ontario nursing homes aged 66–105 years with an admission assessment between April 1, 2010, and March 31, 2019, who were receiving an antipsychotic and had no antidepressant medication use at admission to the nursing home. MethodsWe used linked health administrative data to examine changes in medication use over three quarterly assessments following admission. Antipsychotic and trazodone use were measured at each assessment. The rate of trazodone initiation was compared between residents no longer dispensed an antipsychotic (discontinued) and those with an ongoing antipsychotic (continued) using discrete time survival analysis, controlling for baseline resident characteristics. ResultsWe identified 13,306 residents dispensed an antipsychotic with no antidepressant use at admission (mean age 84 years, 61.5% women, 82.8% with dementia). As of the first quarterly assessment, nearly 20% of residents no longer received an antipsychotic and 9% received a new trazodone medication. Over time, residents who discontinued antipsychotics had a rate of trazodone initiation that was 82% higher compared to residents who continued (adjusted hazard ratio 1.82, 95% CI 1.66–2.00). Conclusions and ImplicationsResidents admitted to a nursing home with antipsychotic use had a higher rate of trazodone initiation if they discontinued (vs continued) an antipsychotic. These findings suggest antipsychotic substitution with trazodone after entering a nursing home.

Development of a simultaneous LC–MS/MS analytical method for plasma: 16 antipsychotics approved in Japan and 4 drug metabolites

The increased risk of adverse drug reactions due to the concomitant use of antipsychotics is problematic in the treatment of schizophrenia. Therefore, the simultaneous analysis of their plasma concentrations is required. In this study, we developed a simultaneous liquid chromatography/tandem mass spectrometry (LC–MS/MS) method for analyzing plasma antipsychotics approved in Japan for therapeutic drug monitoring (TDM) applications. First, we counted the prescriptions for 16 antipsychotics and concomitant drugs used at the Tohoku University Hospital. LC–MS/MS was used for the simultaneous analysis of 16 antipsychotics and four drug metabolites. This analysis was conducted using a combination of selected reaction monitoring mode and reversed-phase chromatography. Following the examination of the MS/MS and LC conditions, an analytical method validation test was conducted. The developed method was used to analyze plasma antipsychotic levels in patients with schizophrenia. One-third of the patients received treatment with multiple antipsychotics. Under LC–MS/MS conditions, LC separation was performed using a combination of a C18 column and ammonium formate-based mobile phases with a gradient flow. The calibration curves were optimized by adjusting the ion abundance, and 11 compounds met the criteria for intra- and inter-day reproducibility tests. Some stability test results did not meet these criteria; therefore, further investigation is required. The developed method permitted the measurement of all the plasma parameters, including concentrations above the therapeutic range. Therefore, this method may be useful in the daily TDM practice of antipsychotics.Graphical abstract

A Trajectory of Long-Term Antipsychotic Medication Dosage in Inpatients with Severe Behavioral and Psychological Symptoms of Dementia: A Retrospective Study.

While antipsychotics are often prescribed for behavioral and psychological symptoms of dementia (BPSD), typically on an off-label basis, these medications have serious adverse effects. This study investigated the long-term use of antipsychotics among inpatients with dementia displaying severe BPSD, focusing on how prescriptions change over time. Medical charts at Kusakabe Memorial Hospital were retrospectively reviewed from October 2012 to September 2021. The study included patients diagnosed with dementia, admitted for BPSD, and were continuing antipsychotics at 3 months of their admission. Antipsychotic dosages were categorized as high (≥300 mg/d), medium (100-300 mg/d), and low (<100 mg/d) based on chlorpromazine equivalents and tracked until 15 months during hospitalization. Binary logistic regression was used to identify factors associated with dosage reductions between months 3 and 6. This study involved 188 patients, with an average age of 81.2 years, 67% of whom were diagnosed with Alzheimer&apos;s dementia. At 3 months, 15.4% were taking high, 44.1% on medium, and 40.4% on low dosages of antipsychotics. The highest average dosage was observed at 3 months, with a subsequent decrease over time. By the 12th month, 20-30% of patients in all dosage categories had stopped their antipsychotic medication. Significant factors for dosage reduction included higher initial doses (OR 1.003, 95%Cl: 1.001-1.006, P=0.01) and male gender (OR 2.481, 95%Cl: 1.251-4.918, P=0.009). A trajectory of antipsychotic dosage in inpatients with severe BPSD has rarely been reported. This research emphasizes the need for personalized strategies in managing long-term pharmacotherapy for this vulnerable group of patients.

Lessons learned from CMS's National Partnership to Improve Dementia Care: a thematic synthesis of multiple stakeholder-engaged studies.

Antipsychotic prescribing in United States nursing homes (NHs) has decreased since the Center for Medicare & Medicaid Service debuted the National Partnership to Improve Dementia Care in Nursing Homes (NP); however, reductions have stalled. To help explain persistent antipsychotic use despite the NP's reduction efforts, the perspectives of diverse NP stakeholders were qualitatively assessed. This study aimed to re-evaluate these individual perspectives in combined thematic synthesis to discover NP improvement opportunities undetectable in single stakeholder assessments. Thematic synthesis. Through immersive crystallisation, original source coding results were organised into related descriptive themes. Similarities and differences were identified, and descriptive themes were regrouped into new, increasingly abstract, analytical themes. This cycle continued until variances were resolved and analytic themes sufficiently described and explained all initial descriptive themes. Three analytic themes emerged regarding NP improvement opportunities. The NP's positive impacts would be augmented by: (i) a deeper and expanded appreciation of stakeholder perspectives; (ii) more urgent and rapid adaptation to unintended adverse outcomes; and (iii) greater recognition of the contextual and environmental factors influencing decisions to prescribe or not prescribe antipsychotic medications. Stakeholder groups described: perspectives they perceived as inadequately considered by the NP; insufficient NP engagement with the stakeholders capable of creating evidenced, affordable, and available non-pharmacologic therapies for dementia symptoms; recognition that dementia interventions effective for a specific individual at a specific time in a specific community may not generalise; and diverse ongoing undesirable outcomes from NP policies that could be mitigated by NP modifications. The NP has done much to advance dementia care in NHs. Notwithstanding, these results suggest the NP would only be improved through increasingly comprehensive inclusion of stakeholder perspectives, enhanced incorporation of individual contextual factors, and a more decisive mechanism for ongoing and continual adaptation.