Use Of Atypical Antipsychotics Research Articles

Barriers to long-acting injectable atypical antipsychotic use in Japan: Insights from a comparative psychiatrist survey.

To investigate the negative attitudes of Japanese psychiatrists toward atypical long-acting injectable (LAI) antipsychotics, which are the current mainstream LAIs in Japan. We surveyed 69 Japanese psychiatrists using a 5-point Likert scale to assess their attitudes toward atypical LAI antipsychotics. Our assessment referenced concerns identified in a study conducted in Japan a decade ago, which found significant differences when compared with a survey of German psychiatrists. We also identified the factors influencing these negative attitudes. Additionally, the results were compared with those of previous Japanese and German studies. More than 50% of Japanese psychiatrists expressed negative attitudes toward atypical LAI antipsychotics in various areas. These concerns included apprehensions about cost, reluctance to recommend them initially, pain from injections, complexity of switching to LAI, usage in first-episode cases, and sufficient medication adherence with oral drugs. In all three studies, cost and adequate adherence to oral medication were concerns that exceeded the average of the three negative comments. Age and experience in psychiatry influenced the psychiatrists' attitudes toward using these drugs in first-episode cases. These findings shed light on the reasons for the underutilization of atypical LAI antipsychotics and suggest opportunities to enhance their appropriate use in clinical settings.

Clearing the Fog: A Review of Antipsychotics for Parkinson's-Related Hallucinations: A Focus on Pimavanserin, Quetiapine and Clozapine.

Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms. On the contrary, the support for utilizing quetiapine is not as substantial as other antipsychotics because research studies specifically investigating its application are still emerging and relatively recent. The broad mechanisms of action of AAPs, involving dopamine and serotonin receptors, provide improved outcomes and fewer side effects than typical antipsychotics. Conversely, other antipsychotics, including risperidone, olanzapine, aripiprazole, ziprasidone, and lurasidone, have been found to worsen motor symptoms and are generally not recommended for PDP. While AAPs offer favorable benefits, they are associated with specific adverse effects. Extrapyramidal symptoms, somnolence, hypotension, constipation, and cognitive impairment are commonly observed with AAP use. Clozapine, in particular, carries a risk of agranulocytosis, necessitating close monitoring of blood counts. Pimavanserin, a selective serotonin inverse agonist, avoids receptor-related side effects but has been linked to corrected QT (QTc) interval prolongation, while quetiapine has been reported to be associated with an increased risk of mortality. This review aims to analyze the benefits, risks, and mechanisms of action of antipsychotic medications to assist clinicians in making informed decisions and enhance patient care.

Quetiapine Versus Haloperidol in the Management of Hyperactive Delirium: Randomized Controlled Trial.

In the population of patients in the intensive care unit (ICU), most studies compared the use of atypical antipsychotics, such as quetiapine, with the use of traditional haloperidol in patients with delirium of various forms and etiologies. The role of such agents in patients with hyperactive delirium is not fully understood. This study compares the effectiveness of quetiapine with haloperidol in treating the hyperactive form of delirium in terms of their effects on the Delirium Rating Scale-Revised-98 (DRS-R-98), length of stay in the ICU, and mortality in critically ill patients. One hundred adult patients diagnosed with hyperactive delirium were randomly assigned to receive either oral quetiapine (25-50mg/day) or haloperidol (1-2mg/day). The response, defined as "a DRS-R-98 severity score reduction from baseline of 50% or more" and a DRS-R-98 severity score of 12 or less without relapse, was the primary outcome. The mean age of all patients was 68 ± 6years. The study population's overall response rate was 92%. Response rates for the two groups were remarkably equal (p = 0.609). Secondary outcomes were comparable in both groups, such as ICU mortality (p = 0.496), in-hospital mortality (p = 0.321), in-hospital stay (p = 0.310), and the need for mechanical ventilation (p > 0.99). But the quetiapine group showed a statistically reduced mean ICU stay (10.1 ± 2.0 vs. 11.7 ± 2.6days, p = 0.018) and increased sleeping hours per night (p = 0.001). Quetiapine may be equally as effective as haloperidol in treating the symptoms of hyperactive delirium in critically ill patients, with no mortality benefit.

Impact of formulary-related pharmacy claim rejections of cariprazine on health care utilization and treatment patterns among patients with bipolar I disorder.

Formulary restrictions, intended to limit inappropriate medication use and decrease pharmacy costs, may prevent or delay patients with bipolar I disorder from initiating cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5HT1A receptor partial agonist that is approved to treat manic/mixed or depressive episodes associated with bipolar I disorder. Little is known about the downstream consequences of formulary-related cariprazine prescription rejections. To evaluate the impact of formulary-related cariprazine claim rejections on health care resource utilization (HCRU) and treatment patterns among patients newly prescribed cariprazine for bipolar I disorder. Symphony Health Integrated Dataverse was used to identify commercially insured adults (aged ≥18 years) with bipolar I disorder and at least 1 pharmacy claim for cariprazine (rejected because of formulary restrictions or approved; date of the first claim is the index date) from March 2015 through October 2020. Formulary-related rejection reasons included noncoverage, prior authorization requirement, and step therapy requirement. Baseline characteristics were evaluated during the 12 months pre-index and balanced between rejected and approved cohorts using 1:2 propensity score matching. HCRU outcomes included all-cause and mental health (MH)-related hospitalizations, emergency department (ED) visits, and outpatient visits. Treatment patterns were analyzed descriptively and included treatment delay and atypical antipsychotic use. HCRU was reported per patient-year and compared between cohorts using rate ratios; 95% CIs and P values were calculated using nonparametric bootstrap procedures. The matched rejected and approved cohorts comprised 1,554 and 3,108 patients, respectively. The rejected cohort had 22% more all-cause and 24% more MH-related hospitalizations per patient-year vs the approved cohort (rate ratio [95% CI], all-cause: 1.22 [1.01-1.48], P = 0.024; MH-related: 1.24 [1.01-1.55], P = 0.044). ED and outpatient visits were numerically, but not significantly, greater in the rejected cohort. Of patients in the rejected cohort, 34.7% never received an atypical antipsychotic and 76.8% never received cariprazine. For those who later received cariprazine or another atypical antipsychotic, the average treatment delay was approximately 6 months (188 days) and approximately 4 months (123 days) after the initial rejection, respectively. Patients with bipolar I disorder and formulary-related cariprazine claim rejections experienced significantly more hospitalizations than patients whose initial claim was approved; ED and outpatient visits were similar between cohorts. Less than a quarter of patients whose initial claim was rejected later received cariprazine, and more than one-third never received any atypical antipsychotic. To our knowledge, this is the first study to evaluate the impact of formulary-related rejections of cariprazine on HCRU and treatment patterns in patients with bipolar I disorder.

Antipsychotics-related hyperprolactinaemia among patients with schizophrenia in Maiduguri.

Hyperprolactinaemia among patients on antipsychotic medications is generally overlooked due to lack of outwardly visible symptoms, patient resistance to reporting because the symptoms are perceived as shameful, or to clinician's insufficient knowledge. The study aimed to evaluate the patterns and correlates of hyperprolactinemia among patients with schizophrenia on antipsychotic medications. The study was conducted in a psychiatric facility in Maiduguri, Northeastern Nigeria. A total of 209 patients with schizophrenia were evaluated through a cross-sectional design and assayed for serum prolactin with ELISA Kits. Frequencies and percentages were tabulated for categorical variables. Variables with significant associations with hyperprolactinaemia on chi-square (p < 0.05) were subjected to logistic regression analysis. The prevalence of hyperprolactinaemia was 45.9% in all patients on antipsychotic medication. The prevalence because of the use of typical and atypical antipsychotics was 51.5% and 25.0%, respectively. Hyperprolactinaemia was significantly associated with typical antipsychotics (β = 0314, p = 0.002), high overall drug dosage (β = 2.340, p = 0.003), high-dose typical antipsychotics (β = 3.228, p = 0.000), twice daily dosing frequency (β = 2.751, p = 0.001) and polypharmacy (β = 1.828, p = 0.0024). The findings support that patients on typical, high-dose antipsychotic medications and polypharmacy have a high prevalence of hyperprolactinaemia. As hyperprolactinaemia is often undetectable, screening and patient psycho-education on the significance of the signs and symptoms of hyperprolactinaemia is required for necessary clinical intervention. The study provides evidence for the rational use of antipsychotic medications in sub-Saharan Africa.

Atypical antipsychotics in the treatment of depression in affective disorders and schizophrenia (using the aripiprazole model)

The review discusses aspects of the use of atypical antipsychotics in the treatment of depression in affective disorders and schizophrenia using the model of aripiprazole, a partial agonist of dopamine receptors. According to numerous studies, aripiprazole is the drug of choice for augmentative therapy of major depressive disorder, as well as for relieving and long-term maintenance monotherapy and combination therapy of various affective episodes of bipolar affective disorder and depression in schizophrenia.

Risk of long-term care admissions among Medicare beneficiaries treated with pimavanserin or quetiapine for Parkinson's disease psychosis in USA: a retrospective administrative claims database analysis.

Aim: Risk of long-term care (LTC) admission (LTCA) associated with atypical antipsychotic (AAP) use among patients with Parkinson's disease psychosis (PDP) is a major concern. However, no comparative studies have examined the differences in risk of LTC admissions between pimavanserin (PIM), the only FDA-approved AAP for PDP, and other off-label AAPs including quetiapine (QUE). Objective: To examine all-cause LTCA rates and risk among PDP patients treated with AAPs such as QUE or PIM. Methods: Analysis of Parts A, Band D claims (100% Medicare sample; 2013-2019) of Medicare beneficiaries with PDP that initiate ≥12-month continuous PIM or QUE monotherapy from 1 January 2014 to31 December 2018 (i.e., index date) without any AAP use in the 12-month pre-index period was conducted. Outcome assessments among 1:1 propensity score-matched (31 variables - age, sex, race, region and 27 Elixhauser comorbidities) beneficiaries on PIM versus QUE included risk of all-cause skilled nursing facility stays (SNF-stays), LTC-stays, and overall LTCA (i.e., SNF-stays or LTC-stays). All-cause LTCA rates and LTCA risk were compared using logistic regression and cox proportional hazards models, respectively, controlling for demographics, comorbidities and co-existing-dementia or insomnia. Results: Of the matched sample (n=842 for each group) from total sample (n=9652), overall all-cause LTCA and SNF-stay rates were 23.2 and 20.2% for PIM versus 33.8 and 31.4% for QUE, respectively (p<0.05, for each). Hazard ratio (95% CI) for risk of SNF-stay and overall LTCA was 0.78 (0.61, 0.98) and 0.80 (0.66, 0.97), respectively, for PIM versus QUE beneficiaries (p<0.05, for each). Conclusion: The 20% lower risk of LTCA (i.e., greater delay) with PIM versus QUE in this analysis may suggest that PIM should be started early for the treatment of PDP.

Atypical antipsychotic use does not impact weight gain for individuals with extreme anorexia nervosa: a retrospective case–control study

BackgroundThere are no U.S. Food and Drug Administration (FDA)-approved medications for the treatment of anorexia nervosa (AN). Various medication classes have been evaluated for benefits in this population, including antipsychotics. Studies focused on use of antipsychotics for assistance with weight restoration in AN produced conflicting results. While current evidence does not suggest that antipsychotic medications can be generally recommended for persons with AN, some individuals might benefit from an antipsychotic medication for anxiety, mood, and the cognitive distortions that accompany the illness. It is well-established that atypical antipsychotics can cause weight gain when taken by other psychiatric populations. This published data can understandably limit the willingness of persons with AN to trial these medications. Given the conflicting results of studies examining antipsychotic-related weight gain in AN, it is currently hypothesized that individuals with extreme anorexia nervosa, restricting type, do not experience the weight gain seen in other psychiatric populations utilizing atypical antipsychotics.MethodsTwo hundred seventy-six individuals with extreme AN were enrolled in this retrospective, case–control study between April 1, 2016 and June 30, 2022 utilizing study-specific inclusion and exclusion criteria. Clinical and demographic data, including use of atypical antipsychotics and weights, were retrospectively obtained from chart review. Variables were assessed for normality using univariate statistics. Continuous variables were described using means (M) and standard deviations (SD) or medians and interquartile ranges (IQR) based on normality. Differences in weight gain between cohorts was ascertained via independent samples t-test. P values of < 0.05 were considered statistically significant, and all analyses were completed using SAS Enterprise Guide software version 7.1 (SAS Institute, Cary, NC) and R version 4.3.1 (R Core Team, 2023).ResultsUse of antipsychotics in this population of individuals with extreme AN did not impact the rate of weight gain (M: 1.7 kg/week, SD: 0.9 and 0.8, for cases and controls respectively).ConclusionsWeight gain is often cited by individuals with AN as a feared side effect of antipsychotic medications. In this study, there was no difference in weight trends for individuals taking atypical antipsychotic medications during the refeeding process compared with individuals who were not.

Workshop I: Evidence-informed approach to prescribing of atypical antipsychotics to manage behaviors in Neurocognitive disorders: Results of a pilot study

Background:The LuBAIR™ Paradigm is a novel approach to ascribe meaning to behavioral expressions in advanced neurocognitive disorders when the reliability of a clinical assessment is limited. The meaning ascribed to each behavioral category was used to identify those who are likely to respond to the use of atypical antipsychotics in their management. De-prescribing was attempted on patients who qualified to enter this retrospective study. De-prescribing was defined as successful if individuals were completely withdrawn from AAP and remained off them for 60 days without the re-emergence of behaviors.Methods:The LuBAIR™ Inventory was filled on two occasions. The data collected on the second occasion, in the successful and failed de-prescribed groups, were compared in this retrospective study. MANOVA, Chi-Square paired t-test statistical analyses were used to detect the differences in the behavioral categories between the two cohorts. Cohen d was used to measure effect size.Results:Patients who did not have Mis-Identification and Goal-Directed Expressions were more likely to successfully de-prescribe: X2 (1, N = 40) = 29.119 p &lt; 0.0001 and X2 (1, N = 40) = 32.374, p &lt; 0.0001, respectively. Alternatively, the same behavioral categories were more likely to be present in patients who failed de-prescribing: MANOVA and paired t-test (p &lt; 0.0001).Conclusion:Atypical antipsychotics, in their role as an antipsychotic and mood stabilizer, may be used to manage Mis-Identification and Goal-Directed Expressions, respectively.

YOD Symposium Part 2

Objectives:LuBAIR™ Paradigm, a novel approach to ascribing meaning for behavioral expression in advanced neurocognitive disorder, was used to identify behavioral categories that are likely to respond to the use of atypical antipsychotics in their management.Design:A retrospective study.Setting:St. Peter’s Hospital (SPH), Hamilton, Ontario, Canada.Participants:Forty patients qualified for the study.Intervention:LuBAIR™ Inventory populated on all recruited patients on two separate occasions. The first time was within two weeks of admission and the second time was after sixty days, if they successfully de-prescribed off the AAP, or sooner, if they failed de-prescribing.Measurements:Chi-Square paired t-test and Cohen d Statistical tests were used to detect the difference in the behavioral categories between the two cohorts.Results:Seventeen patients were successfully de-prescribed, and twenty-three failed de-prescribing. Results on the LuBAIR™ Inventory, filled on the second occasion, in the successful de-prescribed and the failed de-prescribed groups compared using the Chi-Square Statistical test to detect the difference in the behavioral categories the two cohorts. Patients who did not have Mis-Identification Expressions (MiE) and Goal-Directed Expressions (GDE), amongst the cluster of behavioral categories in their clinical presentation, were more likely to successfully de-prescribe of AAP: X2 (1, N = 40) = 29.119 p&lt;.0001 and X2 (1, N = 40) = 32.374, p&lt;.0001, respectively. Alternatively, the same behavioral categories were more likely to be present in patients who failed de-prescribing: paired t-test and Cohen-d (P&lt;0.0001).Conclusion:The MIE and GDE were statistically significant, suggesting that these behaviors were more present in patients who failed de-prescribing. Atypical antipsychotics, in their role as an antipsychotic and mood stabilizer, may be used to manage Mis-Identification and Goal-Directed Expressions, respectively.

Oculogyric crisis symptoms related to risperidone treatment: a case report

BackgroundOculogyric crisis (OGC) is a rare focal dystonia of the ocular muscles that not only interferes with patients’ medication adherence but also negatively affects the course and prognosis of the primary disease. Early detection and treatment of OGC can improve patients’ medication adherence and quality of life.Case presentationThis paper reports a case of a 19-year-old Asian female with a diagnosis of schizophrenia who was treated intermittently with atypical antipsychotics aripiprazole or risperidone for 2 years, with improvement of psychotic symptoms during the course of medication, and then developed double eye rolling and staring with irritability when treated with risperidone 4 mg/d or 6 mg/d. Then, we changed the medication to clozapine, and the patient’s psychotic symptoms were controlled and stable. The symptoms of double eye rolling and gaze disappeared.ConclusionOculogyric crisis (OGC) is a rare focal dystonia of the oculogyric muscle. This case provides clinicians with a basis for the early recognition and management of oculogyric crisis during the use of atypical antipsychotics (risperidone).

Analysis of Atypical Antipsychotics-Induced Adverse Events Related to Diabetes Mellitus in Patients With Dementia Using the Japanese Adverse Drug Event Report Database.

Patients with dementia are prescribed low-dose atypical antipsychotics (AAPs) to treat psycho-behavioral symptoms. Although AAPs are known to cause diabetes mellitus-related adverse events (DMAEs), information regarding AAPs-induced DMAEs experienced by patients with dementia is lacking. To use the Japan Adverse Drug Event Report (JADER) database to assess the onset tendencies and patterns of DMAEs attributable to AAPs prescribed to patients with dementia. We performed an analysis using dementia cases from the JADER database that were registered from April 2004 to December 2022. Data in the JADER database are completely anonymized; thus, we did not require institutional review board approval for using the JADER database in our study. The reporting odds ratio and proportional reporting ratio (PRR) were used to assess the onset tendencies of DMAEs with AAPs. In addition, Weibull shape parameters were used to assess the patterns of DMAEs that occur with the use of AAPs. We identified AAPs associated with DMAEs. In particular, low doses of quetiapine showed the potential to induce DMAEs. An analysis of the onset of DMAEs showed the early failure patterns for AAPs (median onset = 38 days). The AAPs may cause DMAEs in patients with dementia. Low doses of quetiapine may induce DMAEs. Health care workers should focus on the development of DMAEs during the early administration period of AAPs. These results may assist with the safe management of patients with dementia who use AAPs.

Atypical antipsychotics and the risk of sudden cardiac death among individuals receiving maintenance hemodialysis

ObjectiveIndividuals receiving hemodialysis have high rates of sudden cardiac death (SCD). This study characterized oral atypical antipsychotic use and compared the cardiac safety of atypical antipsychotics with QT prolongation FDA warnings to that of atypical antipsychotics without such warnings among outpatients receiving hemodialysis. MethodsData for this active-comparator, new-user cohort study were obtained from the U.S. Renal Data System (2007–2019). The primary outcome was 1-year SCD risk. Fine and Gray proportional subdistribution hazard models with inverse probability of treatment weighting were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). ResultsThe quetiapine vs. atypical antipsychotics without QT prolongation warnings cohort included 18,943 quetiapine new-users and 19,571 non-warning atypical antipsychotic new-users. When compared to new-use of atypical antipsychotics without QT prolongation warnings, quetiapine new-use was not associated with the risk of SCD (aHR (95% CI) = 1.00 (0.93, 1.07)) or broader cardiac outcomes. Comparisons of all atypical antipsychotics with QT prolongation warnings vs. atypical antipsychotics without warnings generated similar results. ConclusionsQuetiapine, which carries an FDA warning for QT prolongation, did not associate with cardiac risk compared to atypical antipsychotics without warnings among hemodialysis outpatients. Findings may inform prescriber selection of atypical antipsychotics in this population.

Metabolic effects of atypical antipsychotics: Molecular targets.

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

Risk of developing avascular necrosis of the femoral head and neck among patients with bipolar disorder: A nationwide cohort study

Background and objectivesThe association between bipolar disorder (BD) and avascular necrosis of the femoral head and neck (AVNHNF) remains unclear. We aimed to investigate the risk of AVNHNF among different polarity of BD. MethodsBetween 2001 and 2010, patients with BD were selected from the Taiwan National Health Research Database. The controls were individuals without severe mental disorder who were matched for demographic, medical and psychiatric comorbidities. Cox regression analysis was used to estimate the risk of AVNHNF, with adjustments for demographics, comorbidities, exposure to corticosteroids, and all-cause clinical visits. ResultsA total of 84,721 patients with BD and 169,442 controls were included. Patients with BD demonstrated a 1.92-fold (95% of confidence interval: 1.21–3.04) higher risk of AVNHNF compared with the controls. The risk was increased to 7.91-fold (4.32–14.49) in patients with severe BD compared with the controls. Importantly, patients with severe bipolar depression were associated with a 14.23-fold higher risk of AVNHNF compared with the controls, while those with sever bipolar mania were associated with a 3.55-fold higher risk. Compared with the controls with alcohol use disorder (AUD), patients with BD and comorbid AUD were associated with a 2.0-fold higher risk of AVNHNF. Finally, long-term use of atypical antipsychotics was associated with a decreased risk of AVNHNF). ConclusionClinicians should be aware of the increased risk of AVNHNF among patients with BD. This increased risk was associated with disorder severity, polarity, and comorbidity with AUD, and attenuated by long-term atypical antipsychotic treatment.

Trends in use of antipsychotics and psychoactive drugs in older patients after major surgery.

Professional society guidelines recommend limiting the use of antipsychotics in older patients with postoperative delirium. How these recommendations affected the use of antipsychotics and other psychoactive drugs in the postoperative period has not been studied. This retrospective cohort study included patients 65 years or older without psychiatric diagnoses who underwent major surgery in community hospitals (CHs) and academic medical centers (AMCs) in the United States. The outcome was the rate of hospital days exposed to antipsychotics, antidepressants, antiepileptics, benzodiazepines, hypnotics, and selective alpha-2 receptor agonist dexmedetomidine in the postoperative period by hospital type. The study included 4,098,431 surgical admissions from CHs (mean age 75.0 [standard deviation, 7.1] years; 50.8% female) during 2008-2018 and 2,310,529 surgical admissions from AMCs (75.0 [7.4] years; 49.4% female) during 2009-2018. In the intensive care unit (ICU) setting, the number of exposed days per 1000 hospital-days declined for haloperidol (CHs: 33-21 days [p < 0.01]; AMCs: 24-15 days [p < 0.01]) and benzodiazepines (CHs: 261-136 days [p < 0.01]; AMCs: 150-77 days [p < 0.01]). The use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine increased, while hypnotic use varied by the hospital type. In the non-ICU setting, the rate declined for haloperidol in CHs but not in AMCs (CHs: 10-6 days [p < 0.01]; AMCs: 4-3 days [p = 0.52]) and for benzodiazepines in both settings (CHs: 126-56 days [p < 0.01]; AMCs: 30-27 days [p < 0.01]). The use of antiepileptics and antidepressants increased, while the use of atypical antipsychotics and hypnotics varied by the hospital type. The use of haloperidol and benzodiazepines in the postoperative period declined at both CHs and AMCs. These trends coincided with the increasing use of other psychoactive drugs.

Comparative Safety Analysis of Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery : A Nationwide Cohort Study.

Antipsychotics are commonly used to manage postoperative delirium. Recent studies reported that haloperidol use has declined, and atypical antipsychotic use has increased over time. To compare the risk for in-hospital adverse events associated with oral haloperidol, olanzapine, quetiapine, and risperidone in older patients after major surgery. Retrospective cohort study. U.S. hospitals in the Premier Healthcare Database. 17 115 patients aged 65 years and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018. Haloperidol (≤4 mg on the day of initiation), olanzapine (≤10 mg), quetiapine (≤150 mg), and risperidone (≤4 mg). The risk ratios (RRs) for in-hospital death, cardiac arrhythmia events, pneumonia, and stroke or transient ischemic attack (TIA) were estimated after propensity score overlap weighting. The weighted population had a mean age of 79.6 years, was 60.5% female, and had in-hospital death of 3.1%. Among the 4 antipsychotics, quetiapine was the most prescribed (53.0% of total exposure). There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%, reference group), olanzapine (2.8%; RR, 0.74 [95% CI, 0.42 to 1.27]), quetiapine (2.6%; RR, 0.70 [CI, 0.47 to 1.04]), and risperidone (3.3%; RR, 0.90 [CI, 0.53 to 1.41]). The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or TIA, with no statistically significant differences by treatment group. Residual confounding by delirium severity; lack of untreated group; restriction to oral low-to-moderate dose treatment. These results suggest that atypical antipsychotics and haloperidol have similar rates of in-hospital adverse clinical events in older patients with postoperative delirium who receive an oral low-to-moderate dose antipsychotic drug. National Institute on Aging.

Treatment patterns, health care resource utilization, and costs associated with use of atypical antipsychotics as first vs subsequent adjunctive treatment in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent mental health condition associated with substantial economic burden. Inadequate response to first-line antidepressant monotherapy is common, with most patients requiring 1 or more changes in their treatment regimen. Adjunctive treatment with atypical antipsychotics (AAs) is a guideline-recommended treatment option in patients with inadequate response. However, patients often cycle through multiple treatments before receiving adjunctive AAs, and the economic impact of this delay is unknown. OBJECTIVE: To describe adjunctive treatment patterns among patients with MDD and compare health care resource utilization (HCRU) and costs between patients whose first adjunctive therapy included an AA and those who received an AA after other adjunctive treatments. METHODS: The Merative MarketScan Commercial Database (January 1, 2014, to June 30, 2019) was used to identify patients with administrative claims meeting the following inclusion criteria: adults with newly diagnosed MDD (first observed MDD diagnosis = index diagnosis date); continuous health insurance for at least 6 months pre-index and at least 3 months post-index; and initiation of MDD treatment within 60 days post-index. Lines of therapy (LOTs), HCRU, and costs were analyzed in patients who received AA adjunctive therapy, including those who initiated AAs as the first adjunctive treatment and those who initiated AAs as subsequent adjunctive treatment. RESULTS: Of 508,830 patients meeting inclusion criteria, 121,060 (24%) received adjunctive treatment and 20,797 (4%) received an AA as adjunctive therapy. Mean time to adjunctive therapy initiation was approximately 7.3 months for AA adjunctive therapy. Patients who initiated an AA as their first adjunctive therapy compared with patients who initiated an AA as their subsequent adjunctive therapy had fewer LOTs on average (0.9 LOTs vs 3.9 LOTs) and shorter time between index diagnosis date and initiation of an AA (5 months vs 12 months). Subsequent AA initiators had significantly greater HCRU than first AA initiators (driven primarily by outpatient visits) and incurred significantly higher total health care costs, with mean all-cause and mental health-related health care cost differences per patient per year of $2,441 and $1,762, respectively (both P < 0.05). CONCLUSIONS: Less than 5% of patients in this study received an adjunctive AA as part of their MDD treatment regimen, suggesting underutilization of this recommended therapeutic approach. Patients who received an AA as their first adjunctive treatment regimen had lower HCRU and health care costs than subsequent AA initiators. Along with published evidence of clinical benefits, this potential impact on economic burden should be considered when making treatment choices for patients with inadequate response to antidepressants.

Assessing the relationship between antipsychotic drug use and prolidase enzyme activity and oxidative stress in schizophrenia patients: a case-control study.

The relationship between proline, its association with oxidative stress, and its connection to schizophrenia is a subject that has not been sufficiently investigated. The aim of this study is to evaluate the possible effects of atypical and combined (typical and atypical) antipsychotic use on serum prolidase enzyme activity (SPEA) and serum oxidative stress parameters, and to assess the relationship between SPEA and oxidative stress in patients with schizophrenia. A total of 57 patients with schizophrenia, of which 34 were using atypical (AAPG) and 23 were using combined (typical and atypical) (CAPG) antipsychotic therapy, and 28 healthy volunteers (control group) were included in this case-control study. SPEA levels of AAPG and CAPG were significantly lower than that of control group ( P = 0.003). The oxidative stress index (OSI) value of AAPG was significantly higher than the other two groups ( P = 0.001). SPEA (<1860 U/l) and OSI (≥0.54) could discriminate schizophrenia patients with antipsychotic therapy from control groups ( P = 0.001 and P = 0.007, respectively). Lower SPEA levels were associated with antipsychotic use ( P = 0.007). The SPEA values of patients with schizophrenia on antipsychotics were significantly lower compared to controls. OSI values were significantly higher in atypical antipsychotic recipients compared to those on combined antipsychotics and healthy controls.

Evaluation of Atypical Antipsychotics for the Facilitation of Weaning Sedation in Mechanically Ventilated Critically Ill Patients.

Sedatives and analgesics are commonly utilized as continuous infusions in the ICU but have complications, including an increase in mechanical ventilation days, ICU length of stay, and delirium. Atypical antipsychotics (AAPs) affect several receptors including muscarinic, histamine, and α-1 adrenergic receptors, which may allow them to act as adjunctive agents to facilitate weaning of continuous infusions. To determine if there is a decrease in sedatives/analgesics requirements with the use of quetiapine and olanzapine in mechanically ventilated critically ill patients. A single-center, retrospective study conducted at Brigham and Women's Hospital from 1/1/2018 to 12/31/2019. Patients were included if they were mechanically ventilated for at least 48 hours before and following AAP initiation, were receiving at least one sedative/analgesic by continuous infusion and received AAP for at least 48 hours. The major endpoint was the percentage of patients with ≥20% reduction in the cumulative dose (CD) of midazolam, propofol, or opioids using morphine mg equivalent (MME), 48 hours from AAP initiation. Minor endpoints included median changes in CD at 24 and 48 hours, and Richmond Agitation-Sedation Scale (RASS), and Critical Care Pain Observation Tool (CPOT) changes at 48 hours. A total of 1177 encounters were screened and 107 were included. Within the 48 hours after AAP initiation, 77.6% had ≥20% reduction in the CD of a sedative/analgesic. There was a significant reduction in propofol, no change in MME, and significant increase in dexmedetomidine median CD at 48 hours from AAP start. No difference was found in pain scores, but patients had significantly lighter sedation scores in the 48 hours after AAP initiation. A multivariate analysis showed that earlier initiation of antipsychotics was associated with a higher likelihood of achieving a 20% reduction in a sedative/analgesic. AAP use was associated with a significant reduction in sedatives/analgesics doses. Future studies are warranted to confirm the results.