Antipsychotic Initiation Research Articles

Patterns of medicine use in the year prior to death by suicide: an Australian population-based case series study

Prescribed medicines are commonly used to treat mental health conditions but are also often implicated in suicide death by poisoning. This was a descriptive study quantifying changes in dispensing and initiation of antidepressants, benzodiazepines, and antipsychotics in the year prior to death by suicide. In this Australian population-based case series, we used national coronial data linked with dispensing claims for all people ≥10 years who died by suicide (2013-2019). Our primary outcome was change in aggregate weekly medicine dispensing the year before death, quantified using piecewise linear regression stratified by cause of death (medicine poisoning vs other causes). Our secondary outcome was change in medicine initiation rates. This study was performed between June 2021 and July2023. Our study included 14,207 people (24% female, median age 44 years). In the year prior to death, we observed higher rates of nervous system medicine use in people who died by medicine poisoning compared with those that did not: antidepressants (62.4% vs 42.9%), benzodiazepines (51.4% vs 29.0%), antipsychotics (25.6% vs 17.1%), opioids (43.8% vs 23.4%). For benzodiazepines, among people who died by medicine poisoning the slope (rate of increase) changed from 0.18 (95% CI-0.01, 0.37) to 4.12 (95% CI 0.98, 7.26) dispensings per 1000 people per week at 8 weeks prior to death. Among people who died of other causes, the slope changed from 0.18 (95% CI 0.14, 0.22) to 2.41 (95% CI 1.90, 2.91) also at 8 weeks prior to death. For antidepressants, among people who died of medicine poisoning we observed no change in the slope. Among people who died of other causes, the slope increased from 0.18 (95% CI 0.09, 0.28) to 1.68 (95% CI 1.20, 2.15) at 14 weeks prior to death. Dispensing of antidepressants and benzodiazepines increased more rapidly closer to date of death, regardless of medicine involvement in death. This suggests these changes may reflect worsening symptoms or increased help seeking and that the method of death by suicide may be due to greater means access. However, findings need to be interpreted with caution as our analyses were performed on aggregate data and may not reflect person-level changes. This study is funded by a grant from the Australian National Health and Medical Research Council (NHMRC) and the Translational Australian Clinical Toxicology Research (TACT) Group.

Olanzapine Versus Quetiapine: Corrected QT Changes in Critically Ill Patients.

Olanzapine and quetiapine are frequently administered atypical antipsychotic medications and their effects on the corrected QT (QTc) in the critically ill population remain understudied. The objective of this study was to compare the impact of olanzapine and quetiapine on QTc changes in critically ill patients. This was a single-center, retrospective analysis. Adult patients admitted to the intensive care unit (ICU) from January 2023 through July 2023 were included if they received ≥2 doses of either olanzapine or quetiapine within a 48-hour period and had one QTc evaluated within 48 hours of antipsychotic initiation. The major endpoint was a composite of the incidence of QTc prolongation (defined as QTc > 500 ms or QTc > 60 ms above baseline) following antipsychotic initiation. Univariable and multivariable analyses were performed to identify risk factors for QTc prolongation. There was no statistical difference in the major composite endpoint between patients in the olanzapine and quetiapine groups (8/83 [9.6%] vs 19/129 [14.7%]; P = .28). The incidence of QTc > 500 ms (7/244 [2.9%] vs 20/427 [4.7%]; P = .25) and change from baseline >60 ms (5/244 [2.0%] vs 17/427 [4.0%]; P = .26) were not statistically different between the olanzapine and quetiapine groups, respectively. There were no occurrences of Torsades de Pointes or extrapyramidal symptoms in either group. The results of this study suggest olanzapine and quetiapine may have similar impact on QTc prolongation in critically ill patients. These findings could contribute to safer prescribing practices in the ICU.

The risk of diabetes and HbA1c deterioration during antipsychotic drug treatment: A Danish two-cohort study among patients with first-episode schizophrenia.

Antipsychotics increase the risk of developing diabetes, but clinical trials are not generalizable with short follow-up, while observational studies often lack important information, particularly hemoglobin A1c (HbA1c). We followed two Danish cohorts with schizophrenia. First, using Danish nationwide registers, we identified all individuals diagnosed with first-episode schizophrenia (FES) between 1999 and 2019 (n = 31,856). Exposure was a redeemed prescription for an antipsychotic, and the outcome was diabetes, defined via hospital-based diagnosis and redeemed prescriptions for glucose-lowering drugs. Adjusted Cox regression calculated hazard rate ratios (HRR). Second, using data from the Central Denmark Region, we identified all individuals diagnosed with FES from October 2016 to September 2022 (n = 2671). Using a within-subject design, we analyzed the change in HbA1c during the 2 years after initiation of specific antipsychotics compared to the 2 years before. In the nationwide cohort, 2543 (8.0%) individuals developed diabetes (incidence rate = 9.39 [95% CI = 9.03-9.76] per 1000 person-years). Antipsychotics, compared to periods without, were associated with an increased risk of developing diabetes (HRR = 2.04, 95% CI = 1.75-2.38). We found a dose-response association, particularly for second-generation antipsychotics, and different risk rates for specific antipsychotics. In the Central Denmark Region cohort, a total of 9.2% developed diabetes but mean HbA1c levels remained stable at 37 mmol/mol during the 2 years after initiation of antipsychotic medication. This comprehensive real-world two-cohort study emphasizes that diabetes affects almost 10% of patients with FES. Antipsychotics increase this risk, while HbA1c deterioration requires longer treatment. These findings are important for clinicians and young patients with FES.

Initiation and Persistence of Antipsychotic Medications at Hospital Discharge Among Community-Dwelling Veterans With Dementia

ObjectivesAdults with dementia are frequently prescribed antipsychotic medications despite concerns that risks outweigh benefits. Understanding conditions where antipsychotics are initially prescribed, such as hospitalization, may offer insights into reducing inappropriate use. Design, Setting, ParticipantsRetrospective cohort study of community-dwelling veterans with dementia aged ≥68 with VA hospitalizations in 2014, using Veterans Health Administration (VA) and Medicare data. MeasurementsThe primary outcome was new outpatient antipsychotic prescription at hospital discharge. We used generalized estimating equations to study associations between antipsychotic initiation and patient, hospitalization, and facility characteristics. Among veterans with antipsychotic initiation, we used a cumulative incidence function to evaluate discontinuation in the year following hospitalization, accounting for competing risks. Results4,719 community-dwelling veterans with dementia had VA hospitalizations in 2014; 264 (5.6%) filled new antipsychotic prescriptions at discharge. Antipsychotic initiation was associated with discharge unit (surgical vs medical, OR 0.41, 95% CI 0.19–0.87; psychiatric vs medical, OR 6.58, 95% CI 4.48–9.67), length of stay (OR 1.03/day, 95% CI 1.02–1.05), and delirium diagnosis (OR 2.61, 95% CI 1.78–3.83), but not demographic or facility characteristics. Among veterans with antipsychotic initiation, the 1-year cumulative incidence of discontinuation was 18.2% (n = 47); 15.9% (n = 42) of those who were alive and not censored remained on antipsychotics at 1 year. ConclusionsAntipsychotic initiation at hospital discharge was uncommon among community-dwelling veterans with dementia; however, once initiated, antipsychotic persistence at 1 year was common among those who remained community-dwelling. Hospitalization is a contributor to potentially-inappropriate medications in the community, suggesting an opportunity for medication review after hospitalization.

Long-Acting Injectable Antipsychotic Initiation in Child and Adolescent Patients with Psychiatric Disorders.

Objectives: There are currently no long-acting injectable antipsychotics (LAIAs) that are approved by the Food and Drug Administration for use in child and adolescent patients, however these agents are used off-label for the treatment of various psychiatric disorders. This study aims to describe the initiation and maintenance dosing strategies of LAIAs in child and adolescent psychiatry inpatients. Methods: This was a single-site retrospective chart review of patients less than 18 years of age initiated on an LAIA during an acute psychiatric hospitalization between October 1, 2015, and October 31, 2022. Patient demographics and hospital encounter information were collected and analyzed using descriptive statistics. Results: Of the 6402 unique pediatric patients discharged from the acute psychiatric hospital within the specified timeframe, 45 (0.7%) were newly initiated on an LAIA. The average age was 15.6 years (range 10-17), with a greater proportion of male (n = 26, 57.8%) and Black or African American (n = 27, 60%) patients. The LAIA agents prescribed included paliperidone palmitate (n = 21, 46.7%), aripiprazole monohydrate (n = 15, 33.3%), aripiprazole lauroxil (n = 7, 15.6%), haloperidol decanoate (n = 1, 2.2%), and risperidone microspheres (n = 1, 2.2%). Primary diagnosis via International Classification of Diseases-10 code at discharge included schizophrenia spectrum and other psychotic disorders (n = 19, 42.2%); bipolar disorder (n = 14, 31.1%); disruptive, impulse control, and conduct disorders (n = 6, 13.3%); autistic disorder (n = 5, 11.1%); and attention-deficit/hyperactivity disorder (n = 1, 2.2%). Seventeen patients (37.8%) received a loading dose regimen and/or a maintenance dose regimen that differed from adult package-insert dosing. The mean length of stay was 23.7 days, and 14 patients (31.1%) were readmitted to the psychiatric hospital within 6 months of discharge. The mean number of days to readmission was 71.9 days. Conclusions: This retrospective study is the first to focus on LAIA initiation and maintenance dosing strategies of multiple agents in both a child and adolescent patient population. Further research is required to evaluate the impact of LAIAs on clinical outcomes in this patient population.

Postoperative use of sleep aids and delirium in older adults after major surgery: A retrospective cohort study.

Sleep aids are commonly prescribed to treat sleep disturbance, a modifiable risk factor for postoperative delirium in older patients. The use of melatonin receptor agonists in the postoperative period has been increasing. The comparative safety of melatonin receptor agonists, zolpidem, and temazepam remains uncertain. This retrospective study included 22,083 patients ≥65 years old who initiated melatonin receptor agonists, zolpidem, or temazepam after major surgery in the Premier Healthcare Database 2009-2018. We performed propensity score-based overlap weighting and estimated the risk ratio (RR) and risk difference (RD) of postoperative delirium as the primary outcome and a composite of delirium or new antipsychotic initiation, pneumonia, and in-hospital mortality as secondary outcomes. The mean age of the study population was 78 (SD, 7) years and 50% were female. There was no significant difference in the risk of postoperative delirium among patients treated with melatonin receptor agonists (3.4%, reference group), zolpidem (2.9%; RR [95% CI], 0.9 [0.7-1.2]; RD [95% CI] per 100 persons, -0.3 [-1.1 to 0.6]), and temazepam (3.1%; 0.9 [0.7-1.1]; RD [95% CI] per 100 persons, -0.5 [-1.2 to 0.3]). The risks of delirium or new antipsychotic initiation, pneumonia, and in-hospital mortality were also similar among all groups. Melatonin receptor agonists were not associated with a lower risk of postoperative delirium and other adverse outcomes compared with zolpidem and temazepam in older adults after major surgery.

New initiation of opioids, benzodiazepines and antipsychotics following hospitalization for COVID-19.

Patients newly initiated on opioids (OP), benzodiazepines (BZD), and antipsychotics (AP) during hospitalization are often prescribed these on discharge. Implications of this practice on outcomes remains unexplored. To explore the prevalence and risk factors of new initiation of select OP, BZD and AP among patients requiring in-patient stays. Test the hypothesis that new prescriptions are associated with higher odds of readmission or death within 28 days of discharge. Single center retrospective cohort study. Patients admitted to a tertiary-level medical center with either a primary diagnosis of RT-PCR positive for COVID-19 or high index of clinical suspicion thereof. None. Exposure was the new initiation of select common OP, BZD, and AP which were continued on hospital discharge. Outcome was a composite of 28-day readmission or death following index admission. Multivariable logistic regression was used to assess patient mortality or readmission within 28 days of discharge associated with new prescriptions at discharge. One thousand three hundred and nineteen patients were included in the analysis. 11.3% (149/1319) were discharged with a new prescription of select OP, BZD, or AP either alone or in combination. OP (110/149) were most prescribed followed by BZD (41/149) and AP (22/149). After adjusting for unbalanced confounders, new prescriptions (adjusted odds ratio: 2.44, 95% confidence interval: 1.42-4.12; p = .001) were associated with readmission or death within 28 days of discharge. One in nine patients admitted with a diagnosis of COVID-19 or high clinical suspicion thereof were discharged with a new prescription of either OP, BZD or AP. New prescriptions were associated with higher odds of 28-day readmission or death. Strengthening medication reconciliation processes focused on these classes may reduce avoidable harm.

Evaluation of the Safer Use of Antipsychotics in Youth Study on Population Level Antipsychotic Initiation: An Interrupted Time Series Analysis.

Background: Antipsychotics carry a higher-risk profile than other psychotropic medications and may be prescribed for youth with conditions in which other first-line treatments are more appropriate. This study aimed to evaluate the population-level effect of the Safer Use of Antipsychotics in Youth (SUAY) trial, which aimed to reduce person-days of antipsychotic use among participants. Methods: We conducted an interrupted time series analysis using segmented regression to measure changes in prescribing trends of antipsychotic initiation rates pre-SUAY and post-SUAY trial at four U.S. health systems between 2013 and 2020. Results: In our overall model, adjusted for age and insurance type, antipsychotic initiation rates decreased by 0.73 (95% confidence interval [CI]: 0.30, 1.16, p = 0.002) prescriptions per 10,000 person-months before the SUAY trial. In the first quarter following the start of the trial, there was an immediate decrease in the rate of antipsychotic initiations of 6.57 (95% CI: 0.99, 12.15) prescriptions per 10,000 person-months. When comparing the posttrial period to the pretrial period, there was an increase of 1.09 (95% CI: 0.32, 1.85) prescriptions per 10,000 person-months, but the increasing rate in the posttrial period alone was not statistically significant (0.36 prescriptions per 10,000 person-months, 95% CI: -0.27, 0.99). Conclusion: The declining trend of antipsychotic initiation seen between 2013 and 2018 (pre-SUAY trial) may have naturally reached a level at which prescribing was clinically warranted and appropriate, resulting in a floor effect. The COVID-19 pandemic, which began in the final three quarters of the posttrial period, may also be related to increased antipsychotic medication initiation.

27 Racial-Ethnic Differences in Antipsychotic Initiation Among Youth with Diagnosed ADHD, Depression, or Conduct Disorder

OBJECTIVES/GOALS: This study examined racial-ethnic differences in antipsychotic initiation within psychiatric diagnostic groups. This is a follow-up to our prior work, which reported that, overall, youth from minority backgrounds had 30-65% lower odds of initiating antipsychotics compared to White youth. METHODS/STUDY POPULATION: This study used 2009-2021 data from Optum’s® Clinformatics® Data Mart, a database containing longitudinal patient information from nationwide commercial insurance claims. We created three separate samples of antipsychotic users and matched non-user controls between the ages of 6-17 years old. These groups contained individuals with clinically diagnosed ADHD, conduct disorder, and depressive disorder, respectively. We used conditional logistic regression to estimate the odds of antipsychotic initiation based on race-ethnicity within each diagnostic group. RESULTS/ANTICIPATED RESULTS: There were no racial-ethnic differences in the odds of antipsychotic initiation among youth diagnosed with ADHD. Among youth with depression diagnoses, Asian youth had 19% lower odds of initiating antipsychotics and Hispanic youth had 11% lower odds compared with White youth. Similar results were observed for conduct disorders, with Asian and Black youth having approximately 10% lower odds of initiating antipsychotic treatment and Hispanic youth having 18% lower odds relative to White youth. DISCUSSION/SIGNIFICANCE: Previously observed lower rates of antipsychotic initiation among racial-ethnic minority groups may be at least partially due to factors leading to disparities in diagnosis. Further research is needed to evaluate factors that may lead to differential antipsychotic use, as the disparities may occur upstream of receiving clinical diagnoses.

Prescription practices for antipsychotic medication in an acute inpatient ward: Risks / benefits discussions with patients and performance of baseline investigations as per NICE guidelines

IntroductionAntipsychotic medications are essential for managing psychiatric disorders, offering symptom relief and improved functioning. However, their use carries potential risks. Vigilant monitoring and patient engagement are crucial when initiating antipsychotics.ObjectivesTo explore whether comprehensive discussions with patients concerning the benefits and risks of antipsychotics are taking place, and whether baseline investigations are performed before initiation of antipsychotics as per NICE guidelines.MethodsThis retrospective study focused on admissions to a male acute ward between March 1 and May 31, 2023. Data from electronic patient records included demographics, Mental Health Act (MHA) status, psychiatric diagnoses, medical co-morbidities, documentation of medication benefits / side effects discussions with patients, medication information provision, as well as baseline investigations involving weight, height, waist/hip circumference, pulse, blood pressure, blood glucose, HbA1c, lipid profile, prolactin levels, movement disorder assessment, nutritional status, diet, physical activity, and ECG.ResultsAmong 23 admitted patients, 15 were newly initiated or reintroduced to antipsychotics, with 14(93.3%) admitted under the MHA. Primary diagnoses included Paranoid Schizophrenia (33.33%), Unspecified Non-Organic Psychosis (20%), Bipolar Affective Disorder (20%), and others. Medical comorbidities were observed in 10(66.7%), notably type 2 diabetes (40%). Among initiates, 6(40%) were new to treatment, while in 9(60%) it was re-initiated.Within the 15-patient group, discussions on treatment benefits engaged 11(73.3%), while 4(26.7%) lacked complete documentation. Only 6(40%) had discussions about side effects. Metabolic side effects were discussed with 3(20%), extrapyramidal effects with 2(13.33%), while 4(26.7%) had general side effect talks. Patient information leaflets were given to 5(33.3%) patients. Baseline measurements: 12(80%) had weight/height, 4(26.7%) waist/hip, and 14(93.3%) pulse/blood pressure assessed. Blood tests were declined by 4(26.7%). Baseline glucose, HbA1c, lipids, and prolactin were assessed in 8(53.3%), 10(66.7%), 9(60%), and 8(53.3%) patients respectively. Nutritional status was assessed in 13(86.7%), movement disorders in 1(6.7%), and physical activity in 1(6.7%). All 15(100%) patients were offered ECGs, although 5(33.3%) declined.ConclusionsAdherence to NICE guidelines for baseline investigations and risk/benefit discussions prior to antipsychotic initiation was low, apart from ECGs, weight/height, pulse/blood pressure, assessment of nutritional status, and discussions about antipsychotics’ benefits. Implementing effective monitoring and patient engagement to mitigate potential side effects, is crucial to facilitating the safe and efficient utilisation of antipsychotics.Disclosure of InterestNone Declared

Retrospective evaluation of sociodemographic and clinical characteristics of patients with schizophrenia receiving clozapine monotherapy and clozapine combined with different antipsychotics

IntroductionSchizophrenia is a chronic mental disorder and clozapine is an atypical antipsychotic that can be used in treatment-resistant schizophrenia patients. However, treatment-resistant schizophrenia may also include patients with an inadequate response to clozapine.ObjectivesIn our study, we retrospectively analysed the sociodemographic and clinical characteristics of patients receiving clozapine monotherapy and patients receiving clozapine in combination with different antipsychotics. In this way, we aimed to evaluate the factors that influence the response to clozapine.MethodsClozapine monotherapy and clozapine in combination with different antipsychotics were identified by retrospective chart review of patients followed up at the Schizophrenia and Other Psychotic Disorders Outpatient Clinic, Department of Psychiatry, Faculty of Medicine, Selçuk University. Sociodemographic and clinical characteristics were recorded and subjected to statistical analysis. The study was approved by the Ethics Committee of Selçuk University.Results Of the 143 patients whose data were analysed, 60 (42%) were female. The mean age of the patients was 40.2±12.0 years and the mean duration of training was 10.4±4.3 years. 62 patients (43.4%) used long-acting antipsychotics. 90 patients (62.9%) were using clozapine, 52 (36.4%) were using clozapine as monotherapy, 5 (3.5%) were using clozapine together with another oral antipsychotics drug, and 33 (23.1%) were using clozapine together with a long-acting antipsychotic. No statistically significant difference was found when comparing mean age, age at first antipsychotic initiation, age at clozapine initiation and mean clozapine dose between patients using clozapine monotherapy (n=52) and patients using different antipsychotics in combination with clozapine (n=38). When the two groups were compared, a significant difference was found in the mean number of antipsychotics used before starting clozapine and the mean number of hospitalisations, with a lower number in the monotherapy group (3.1±1.4 vs 4.1±2.0, p=0.01 and 2.8±2.2 vs 4.5±3.2, p=0.006, respectively).ConclusionsIt is important to assess the concept of treatment resistance appropriately in the treatment of schizophrenia patients. The results of our study suggest that starting clozapine treatment promptly in treatment-resistant patients may increase the likelihood that patients will benefit from clozapine and reduce the need for additional treatments. Although our data and criteria for evaluating response to treatment are limited, it is important to draw attention to the clinical results of proceeding in accordance with the guidelines in the treatment of schizophrenia. Evaluating the response to clozapine treatment needs studies with stronger data and larger sample sizes.Disclosure of InterestNone Declared

Evaluation of the Impact of the Addition of Atypical Antipsychotics to Continuous Infusion Propofol Therapy.

Purpose: The administration of sedatives to critically ill patients is a common practice in intensive care units (ICU) and has been associated with negative outcomes. To mitigate this, atypical antipsychotics are utilized as adjunctive therapy. This study aims to review and quantify overall effectiveness of the atypical antipsychotics quetiapine, risperidone, and olanzapine on reduction in the amount of continuous infusion propofol utilized in the ICU. Methods: This was an observational study that took place from February 27, 2021 to December 31, 2022. The primary outcome of this study was the percentage change in average propofol infusion rate (mcg/kg/min) from baseline to the greater than 24 to 48 hours period after atypical antipsychotic initiation. Secondary outcomes included ICU length of stay, duration of mechanical ventilation, QTc interval monitoring, and continuation of the antipsychotic without a valid indication. Descriptive statistics were utilized for the statistical analysis. Results: A total of 47 patients were included in the study. The average baseline propofol rate was 31 mcg/kg/min, which reduced 8.6% to 28.35 mcg/kg/min over the 0 to 24 hours period, was reduced by 19.4% compared to baseline to a rate of 25 mcg/kg/min during the greater than 24 to 48 hours period, and finally a percent reduction of 54.2% seen during the greater than 48 to 72 hours period to a rate of 14 mcg/kg/min. Conclusions: Patients who received an adjunctive antipsychotic saw resulting propofol rate reductions of 8.6% at 24 hours, 19.4% at 48 hours, and 54.2% at 72 hours. However, research on this topic should not end here, as further investigation with higher-level study design is needed to determine the true impact of these agents for this indication.

Antipsychotic-associated neuroleptic malignant syndrome (NMS) in schizophrenia patients: a narrative review

Neuroleptic malignant syndrome (NMS) is a neurological disorder with an high mortality rate among schizophrenia patients who receive antipsychotics as the primary long-term therapy. Appropriate selection of antipsychotics in NMS should be carefully considered to obtain maximal effectiveness with minimal side effects. An evaluation of the safety profile of the antipsychotics is important due to their different treatment patterns and rapid onset of symptoms. This review article aimed to compare the safety profile of antipsychotics in relation to NMS in schizophrenia patients. It was a narrative review using multiple search engines included PubMed, Google Scholar, and Springer to collect publications from 2007 to 2023. Of the total 14 articles reviewed, 7 articles explained the role of antipsychotics in NMS, 5 articles about the onset of NMS, and 7 articles about mortality rate. The incidence of NMS was less then 0.11%, typical antipsychotics were the most common cause of NMS, especially high-potency antipsychotics compared with atypical antipsychotics. Meanwhile, the onset of NMS consistently occured within 30 d of antipsychotic initiation with a symptom duration of 1 to 30 d, and the mortality rate was also higher for typical antipsychotics. In conclusion, the choice of antipsychotics must be carefully considered and its use must be monitored due to the rapid onset and high mortality. The use of antipsychotics is not free from the risk of NMS. The heterogeneous symptoms of NMS require earlier detection to reduce disease progression.

Phenobarbital Versus Benzodiazepines for the Treatment of Severe Alcohol Withdrawal.

Phenobarbital may offer advantages over benzodiazepines for severe alcohol withdrawal syndrome (SAWS), but its impact on clinical outcomes has not been fully elucidated. The purpose of this study was to determine the clinical impact of phenobarbital versus benzodiazepines for SAWS. This retrospective cohort study compared phenobarbital to benzodiazepines for the management of SAWS for patients admitted to progressive or intensive care units (ICUs) between July 2018 and July 2022. Patients included had a history of delirium tremens (DT) or seizures, Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar) >15, or Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score ≥4. The primary outcome was hospital length of stay (LOS). Secondary outcomes included progressive or ICU LOS, incidence of adjunctive pharmacotherapy, and incidence/duration of mechanical ventilation. The final analysis included 126 phenobarbital and 98 benzodiazepine encounters. Patients treated with phenobarbital had shorter median hospital LOS versus those treated with benzodiazepines (2.8 vs 4.7 days; P < 0.0001); a finding corroborated by multivariable analysis. The phenobarbital group also had shorter median progressive/ICU LOS (0.7 vs 1.3 days; P < 0.0001), and lower incidence of dexmedetomidine (P < 0.0001) and antipsychotic initiation (P < 0.0001). Fewer patients in the phenobarbital group compared to the benzodiazepine group received new mechanical ventilation (P = 0.045), but median duration was similar (1.2 vs 1.6 days; P = 1.00). Scheduled phenobarbital was associated with decreased hospital LOS compared to benzodiazepines for SAWS. This was the first study to compare outcomes of fixed-dose, nonoverlapping phenobarbital to benzodiazepines in patients with clearly defined SAWS and details a readily implementable protocol.

Antipsychotic initiation in mechanically ventilated patients in a medical intensive care unit

Objectives: Guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients (PADIS) in the intensive care unit (ICU) promote use of analgosedation to minimize pain, reduce anxiety, and facilitate care. They also suggest against routine use of antipsychotics (APs) for delirium. Our institution’s adaptation incorporates assessment-driven, protocol-based pain, and sedation management and suggests a short course of APs in patients with agitated delirium, defined as Confusion Assessment Method for the ICU (CAM-ICU) positive with Richmond Agitation Sedation Scale (RASS) ≥ +2. While the use of APs in the ICU is typically for delirium, a recent study assessed whether quetiapine reduced sedative requirements among non-delirious patients. The purpose of this study was to assess adherence to our institutional guideline for AP use and to describe sedative and opioid use in relation to AP initiation. Materials and Methods: This retrospective study included patients who were mechanically ventilated and received ≥ 3 new start AP doses. The primary outcome was adherence to our guideline for use of APs in agitated delirium. The secondary outcomes were CAM-ICU and RASS scores in relation to AP initiation and change in sedative and analgesic infusion rates following AP initiation. Results: Thirty-eight patients were included in the study. Five had APs initiated appropriately per our guideline. There was no clinically significant change in continuous infusion rates in the 24 h before and after AP initiation. Conclusion: Overall, AP use was liberal with patients being started on APs who did not have agitated delirium, thus indicating potential alternative indications for initiation. APs did not result in a clinically significant change in continuous infusion requirements in the 24 h following initiation.

Metformin co-commencement at time of antipsychotic initiation for attenuation of weight gain: a systematic review and meta-analysis.

Antipsychotic medications are associated with weight gain and metabolic derangement. However, comprehensive evidence for the efficacy of co-commenced pharmacological treatments to mitigate initial weight gain is limited. Metformin has been shown to be effective in reducing weight among people on antipsychotic medications who are already overweight, but the potential benefits of metformin co-commencement in mitigating antipsychotic-induced weight gain has not been systematically reviewed. We conducted a systematic review of PubMed, EMBASE, PsychInfo, CINAHL, the Cochrane database, and China National Knowledge Infrastructure from inception to 18 November 2023. We undertook a meta-analysis of concomitant commencement of metformin versus placebo for attenuation of weight gain and metabolic syndrome for people with schizophrenia commencing a new antipsychotic. Fourteen studies from Australia, United States, Venezuela, and China with 1126 participants were included. We found that metformin was superior to placebo in terms of attenuating weight gain (-3.12 kg, 95% CI -4.22 to -2.01 kg). Metformin also significantly attenuated derangement of fasting glucose levels, total cholesterol, and total triglyceride levels. Sensitivity analysis on study quality, duration, and antipsychotic agent did not impact the results. Meta-analysis was also conducted on adverse drug reactions (ADR) reported in each study which showed no significant difference in ADR incidence between metformin and placebo groups. Subgroup analysis on antipsychotic-naïve participants and participants switching to new antipsychotic did not impact the results. Metformin led to statistically significant and clinically meaningful attenuation of weight gain as well as attenuation of several other metabolic parameters when commenced concomitantly with antipsychotic medications. Co-commencement of metformin with antipsychotic medications, where tolerated, should be considered in the clinical setting with aim to improve long-term cardiometabolic outcomes for patients with long-term need of antipsychotic treatments.

The effect of early or late initiation of long-acting antipsychotics on the caregiver burden in schizophrenia.

The effective treatment in the early stages of schizophrenia is of critical importance to improve the prognosis. Schizophrenia affects patients' relatives too. The effects of early or late initiation of long-acting injectable antipsychotics (LAI-APs) on the patient have been shown, yet their effects on the caregiver are still unknown. We aimed to determine how the time of initiation of LAI-APs affects the caregiver burden by comparing the patients who were started on LAI-APs in the first 5 years of diagnosis and those who were started at a later period. Patients were classified as 'early-LAI' and 'late-LAI' according to the time of initiation of a LAI-AP. Their caregivers were also classified as the same way, as 'caregiver-early' and 'caregiver-late' and were compared in terms of caregiver burden. The quality of life, depression, anxiety, and caregiver burden scores of the caregiver-late group were significantly worse. The time of initiation of LAI-APs and the functioning levels of the patients were found to be determinant factors for the caregiver burden. This is the first study to investigate the effects of LAI-AP's initiation time on the caregivers to our knowledge. The use of LAI-APs in the early stages is associated with better outcomes for the caregiver.

APOEε4, in-hospital delirium and long-term cognitive impairment: A longitudinal memory clinic study

IntroductionDelirium is common among hospitalized elderly. Previous short-term studies reported inconsistent associations between APOEε4 allele, in-hospital delirium, and post-delirium cognitive impairment. We examined the association of APOEε4 allele with in-hospital delirium and long-term cognitive outcomes following delirium. MethodsThe electronic medical records were linked to the Korean National Health Insurance Service database of all citizens from January 2002 to July 2019. The study population consisted of 1057 memory clinic visitors with APOE genotype, longitudinal neuropsychological tests, and hospitalization records. Incident in-hospital delirium was defined as the initiation of antipsychotics during hospitalization after excluding prevalent users. Incidence analysis was conducted using Cox proportional hazards models, while longitudinal outcomes were analyzed using multivariable mixed models with an interrupted time series design. ResultsAt baseline, APOEε4 carriers (N = 298, 28.2%) performed poorly on cognitive tests compared to non-carriers (CDR-SB mean±SD: 3.3 ± 3.5 vs 2.8 ± 2.9, P = 0.016; MMSE 22.3 ± 5.8 vs 23.2 ± 5.2, P = 0.029). The carriers developed more in-hospital delirium than noncarriers after covariate adjustments (HR 1.96, 95%CI 1.30–2.96, P = 0.002). The APOEε4 allele also had a more detrimental impact on four out of the five cognitive and functional measurements after the delirium (beta estimates of post-delirium change by APOEε4 for CDR-SB = 3.20, P < 0.001; CDR = 0.60, P < 0.001; KIADL = 0.99, P < 0.001; SIADL = 14.07, P < 0.001). These findings remained robust even after adjusting for covariates. ConclusionsAPOEε4 carriers demonstrated robust associations with in-hospital delirium and exhibited more post-delirium cognitive and functional impairment compared to non-carriers. Individuals with APOEε4 allele may need more attention to prevent in-hospital delirium and post-delirium cognitive and functional deterioration.

Hospitalization and the Risk of Initiation of Antipsychotics in Persons With Parkinson's Disease.

The use of antipsychotics in persons with Parkinson's disease (PD) is common, although their use may aggravate the symptoms of PD. Clozapine and quetiapine are the only antipsychotics recommended in PD treatment guidelines. Information on factors associated with initiation of antipsychotics is needed. We investigated whether recent hospitalization is associated with initiation of antipsychotics in persons with PD, and whether discharge diagnoses differ between those who had antipsychotics initiated and those who did not. Nested case-control study in the nationwide register-based Finnish Study on Parkinson's disease (FINPARK). The FINPARK study includes 22,189 persons who received an incident, clinically verified PD diagnosed during 1996-2015 and were community-dwelling at the time of diagnosis. The cases were 5088 persons who had antipsychotics initiated after PD diagnosis, identified with 1-year washout. The controls were 5088 age-, sex-, and time from PD diagnosis-matched persons who did not use antipsychotics on the matching date (antipsychotic purchase date). Recent hospitalization was defined as discharge in the 2-week period preceding the matching date. Associations were investigated with conditional logistic regression. Quetiapine was the most commonly initiated antipsychotic (72.0% of cases), followed by risperidone (15.0%). Clozapine was initiated rarely (1.1%). Recent hospitalization associated strongly with antipsychotic initiation [61.2% of cases and 14.9% of controls, odds ratio (OR) 9.42, 95% CI 8.33-10.65], and longer hospitalizations were more common among cases. PD was the most common discharge diagnosis category (51.2% of hospitalized cases and 33.0% controls), followed by mental and behavioral disorders (9.3%) and dementia (9.0%) among cases. Antidementia and other psychotropic medication use were more common among cases. These results suggest that antipsychotics were initiated because of neuropsychiatric symptoms or aggravation of those symptoms. Antipsychotics should be prescribed after careful consideration to avoid adverse effects in persons with Parkinson's disease.

Association of Long-acting Injectable Antipsychotics with Inpatient Seclusion and Restraint Events at a Public Psychiatric Hospital

Objective: Seclusion and restraint (S/R) are emergency safety measures to manage aggressive behaviour and prevent physical harm to self and others during psychiatric hospitalisations. Antipsychotics have been reported to reduce the incidence of S/R events during psychiatric hospitalisation. This study explores factors associated with inpatient S/R events and investigates whether long-acting injectable (LAI) antipsychotic prescription is associated with a reduction of S/R events. Method: Data on the number of S/R events during hospital stay were collected from the medical records of 741 psychiatric inpatients admitted between 2012 and 2017, and categorised into groups of 0, 1–2 and recurrent (≥3) S/R. Multinomial logistic regression analysis was performed to find the association between S/R events and several demographic and clinical variables, including the time to initiation of LAI (TLAI). Results: TLAI was not significantly associated with S/R events. Antipsychotic medication prescription was associated with a decreased risk of recurrent S/R events (OR = 0.47; 95% Cl = 0.24–0.92), however, it was not significant for the group having 1–2 S/R events (OR = 0.74; 95% Cl = 0.37–1.49). Individuals with recurrent S/R events were more likely to have forensic admission, transfer from jail or supervised facility, higher psychiatric comorbidity, and higher inpatient medications and prescription changes. Conclusion: Early initiation of LAI antipsychotics was not associated with S/R events; however, routine oral antipsychotic medication prescription was associated with decreased risk of S/R events. Specific predictors of S/R episodes may be used in preventative efforts aimed at decreasing S/R events.