Antipsychotic Initiation Research Articles

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.

Acute psychosis as initial presentation for Neurofibromatosis Type 2 (P11-9.006)

<h3>Objective:</h3> To describe the clinical course of a pediatric patient presenting with acute auditory hallucinations with workup revealing a new diagnosis of NF2. <h3>Background:</h3> NF2 is an autosomal dominant neurocutaneous disorder characterized by vestibular schwannomas, meningiomas, neurofibromas, gliomas, cerebral calcifications, cataracts, and cognitive impairment. Acute onset psychosis is an uncommon sequela of NF2, and if present, is usually attributed to the known prior history of NF2. However, here we present a case of acute psychosis that precipitated the <i>initial</i> diagnosis of NF2. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 13-year-old Hispanic male with no known intracranial tumors or other neurocutaneous stigmata presented with acute-onset psychosis, agitation, delusions, and painless monocular vision loss. Upon further review, he was reported to have a remote history of morning headaches, right upper extremity weakness and paresthesias thought to be due to a trampoline accident, and multiple dermal lesions that were diagnosed as pilonidal cysts despite biopsy and sectioning. He presented with complaints of hearing a constant “airplane sound,” poor sleep, agitation, persecutory delusions and paranoia, pressured speech, and discontinuity of thought. On exam, he was agitated and not oriented to situation, responding rapidly to questions with the incorrect answer, hyperkinetic, and generally distressed and labile. MRI brain with and without contrast demonstrated bilateral enhancing vestibular schwannomas, a meningioma, and nerve sheath tumor, all radiographically diagnostic for NF2. Though he was initially treated empirically for encephalitis with steroids, he improved rapidly upon initiation of antipsychotics; all other workup for the psychosis was unremarkable and a pathogenic variant of NF2 was confirmed. <h3>Conclusions:</h3> It is important to look for stigmata of NF2 in patients with psychosis as bilateral vestibular schwannomas can cause auditory hallucinations secondary to continuous tinnitus. Early identification of NF2 will lead to targeted therapeutic/surgical intervention that may relieve cranial nerve compression and thus reduce the odds of developing psychosis. <b>Disclosure:</b> Dr. Domingue has nothing to disclose. Dr. Sandweiss has nothing to disclose. Dr. Salazar has nothing to disclose. Dr. Gill has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Elite Medical Experts. The institution of Dr. Gill has received research support from NIH-NINDS.

Changes in the Initiation of Antipsychotics and Trazodone Over Time: A Cohort Study of New Admissions to Nursing Homes in Ontario, Canada

ObjectivesTo investigate whether trazodone is being initiated in lieu of antipsychotics following antipsychotic reduction efforts, this study described changes in medication initiation over time. MethodsWe conducted a retrospective cohort study of new admissions to nursing homes in Ontario, Canada between April 2010 and December 2019 using health administrative data (N = 61,068). The initiation of antipsychotic and trazodone use was compared by year of admission using discrete time survival analysis and stratified by history of dementia. ResultsRelative to residents admitted in 2014, antipsychotic initiation significantly decreased in later years (e.g., 2017 admission year hazard odds ratio [HOR2017]=0.72 [95% confidence interval (95%CI)=0.62–0.82]) while trazodone initiation modestly increased (e.g., HOR2017=1.09 [95%CI=0.98–1.21]). The relative increase in trazodone initiation was larger among residents with dementia (e.g., HOR2017Dem =1.22 [95%CI=1.07–1.39]). ConclusionsDifferences in which medications were started following nursing home admission were observed and suggest trazodone may be initiated in lieu of antipsychotics.

Predicting antipsychotic-induced weight gain in first episode psychosis - a field-wide systematic review and meta-analysis of non-genetic prognostic factors.

Whether non-genetic prognostic factors significantly influence the variable prognosis of antipsychotic-induced weight gain (AIWG) has not yet been systematically explored. Searches for both randomized and non-randomized studies were undertaken using four electronic databases, two trial registers, and via supplemental searching methods. Unadjusted and adjusted estimates were extracted. Meta-analyses were undertaken using a random-effects generic inverse model. Risk of bias and quality assessments were undertaken using Quality in Prognosis Studies (QUIPS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Seventy-two prognostic factors were assessed across 27 studies involving 4426 participants. Only age, baseline body mass index (BMI), and sex were suitable for meta-analysis. Age (b=-0.044, 95%CI -0.157-0.069), sex (b=0.236, 95%CI -0.086-0.558), and baseline BMI (b=-0.013 95%CI -0.225-0.200) were associated with nonsignificant effects on AIWG prognosis. The highest quality GRADE rating was moderate in support of age, trend of early BMI increase, antipsychotic treatment response, unemployment, and antipsychotic plasma concentration. Trend of early BMI increase was identified as the most clinically significant prognostic factor influencing long-term AIWG prognosis. The strong prognostic information provided by BMI trend change within 12 weeks of antipsychotic initiation should be included within AIWG management guidance to highlight those at highest risk of worse long-term prognosis. Antipsychotic switching and resource-intensive lifestyle interventions should be targeted toward this cohort. Our results challenge previous research that several clinical variables significantly influence AIWG prognosis. We provide the first mapping and statistical synthesis of studies examining non-genetic prognostic factors of AIWG and highlight practice, policy, and research implications.

Mortality in Patients with Parkinson's Disease-Related Psychosis Treated with Pimavanserin Compared with Other Atypical Antipsychotics: A Cohort Study.

Pimavanserin is approved in the USA to treat hallucinations and delusions associated with Parkinson's disease psychosis (PDP). We evaluated mortality in patients with PDP after initiation of pimavanserin or comparator atypical antipsychotics, overall, over time, and across subgroups. A cohort of patients aged ≥65years in the USA with PDP newly initiating pimavanserin or a comparator atypical antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) was identified in 2016-2019 Medicare claims data. All-cause mortality in the propensity score-matched treatment groups was compared with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated with Cox-proportional hazards models. Cumulative incidence curves and time period-specific models evaluated risk over time. Subgroup and sensitivity analyses were performed, including a sub-cohort of long-term care (LTC) or skilled nursing facility (SNF) residents. We identified 2892 pimavanserin initiators and 19,083 comparator initiators (overall 47% female, mean age=80.9years, LTC/SNF residents=30%). Before matching, pimavanserin users had fewer severe comorbidities and more anti-Parkinson medication use than comparators. Matching resulted in 2891 patients in both groups, and all covariates were well balanced. In the matched cohort, the HR for mortality for pimavanserin versus comparator was 0.78 (95% CI 0.67-0.91), with the lowest time period-specific HRs in the first 180days. Hazard ratios were similar across sensitivity analyses and subgroups. In LTC/SNF residents, the HR was 0.78 (95% CI 0.60-1.01). The observed mortality rates were lower among patients treated with pimavanserin compared with those treated with other atypical antipsychotics. European Union Post-authorization Study (EU PAS) register number 46331.

Meta-analysis of peripheral insulin-like growth factor 1 levels in schizophrenia.

We aimed to investigate if there is a significant difference in peripheral insulin-like growth factor 1 (IGF-1) levels between schizophrenia patients and healthy controls and to determine whether a difference exists before and after initiation of antipsychotics. PubMed/MEDLINE, Scopus, and Web of Science were searched up to March 27, 2022. Original clinical studies of any type that reported peripheral blood, serum or plasma IGF-1 levels measured after fasting in schizophrenia patients and/or healthy control group were selected based on inclusion and exclusion criteria. Data were analyzed using Meta-Essentials: Workbooks for meta-analysis and pooled through random-effects meta-analyses. Twelve publications met eligibility criteria. Schizophrenia patients under antipsychotic treatment had significantly lower peripheral IGF-1 levels compared to healthy controls (n=632, Hedges' g -0.42, 95% CI from -0.79 to -0.04, p=.006, I2 =70.38%), while no significant difference was found between schizophrenia patients regardless of the antipsychotic treatment status and healthy controls, as well as between antipsychotic naïve or free schizophrenia patients and healthy controls, and before and after initiation of antipsychotic treatment. However, high heterogeneity was observed and its potential sources in some of the subgroup analyses included sample type and region. Schizophrenia patients under antipsychotic treatment seem to have lower peripheral IGF-1 levels compared to healthy controls. Additional studies with larger and more homogenous samples are needed to confirm these findings.

A Marked Low-Grade Inflammation and a Significant Deterioration in Metabolic Status in First-Episode Schizophrenia: A Five-Year Follow-Up Study.

The objective of this study was to evaluate how schizophrenia spectrum disorders and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum level of acylcarnitines (ACs), cytokines and metabolic biomarkers and to characterize the dynamics of inflammatory and metabolic changes in the early course of the disorder. A total of 112 adults participated in the study (54 patients with first-episode psychosis (FEP) and 58 control subjects). Biomolecule profiles were measured at the onset of first-episode psychosis and 0.6 years and 5.1 years after the initiation of APs. The results of the present study confirmed that specific metabolic–inflammatory imbalance characterizes AP-naïve patients. Short-term (0.6-years) AP treatment has a favourable effect on psychotic symptoms, as well as the recovery of metabolic flexibility and resolution of low-level inflammation. However, 5.1 years of AP treatment resulted in weight gain and increased serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon-γ, hexoses, acetylcarnitine, short-chain ACs (C3, C4) and long-chain ACs (C16:2, C18:1, C18:2). In conclusion, despite the improvement in psychotic symptoms, 5.1 years of AP treatment was accompanied by a pronounced metabolic–inflammatory imbalance, which was confirmed by the presence of enhanced pro-inflammatory activity and increased obesity with changes in the metabolism of carbohydrates, lipids, and their metabolites.

Pediatric Off-label Antipsychotic Use for Attention-Deficit/Hyperactivity Disorder

PurposeOff-label antipsychotic use for behavioral symptoms in pediatric attention-deficit/hyperactivity disorder (ADHD) poses safety concerns, and evidence to support such use is limited. This study aims to investigate the risk of off-label antipsychotic use associated with comorbid disruptive behavior disorder (DBD) among a cohort of youth with ADHD. MethodsA cohort study was conducted using IQVIA PharMetrics Plus for Academics data from 2007 to 2020. Youth 5 to 15 years of age at the index ADHD visit were included in the cohort. The index ADHD visit meets at least 1 of the following criteria: (1) 1 inpatient ADHD visit, (2) 2 outpatient ADHD visits within 90 days, or (3) an ADHD medication prescription fill within 30 days of an outpatient ADHD visit. We excluded youth who had a diagnosis of DBD or a US Food and Drug Administration (FDA)–approved indication for antipsychotics at baseline. Youth were followed up until antipsychotic initiation or were censored at a loss of coverage, receipt of an FDA-indicated diagnosis, or end of the study. A Cox proportional hazards regression model with DBD as a time-varying covariate estimated the hazard of antipsychotic use after the index ADHD visit. FindingsOf 41,098 youth with ADHD who met the study criteria, 4557 were diagnosed with DBD during follow-up. The incidence of antipsychotic initiation was 19.6 (95% CI, 18.7– 20.5) per 1000 person-years. After adjustment for baseline covariates, the hazard ratio of antipsychotic initiation associated with DBD was 4.64 (95% CI, 4.15–5.18). ImplicationsAntipsychotic use among youth with ADHD is more likely in the presence of DBD, suggesting that an off-label use is for behavior problems.

Improving Outcomes in Schizophrenia—A Case for Initiation of Long-Acting Antipsychotics in Early-Phase Illness

Improving Outcomes in Schizophrenia—A Case for Initiation of Long-Acting Antipsychotics in Early-Phase Illness

Health resource utilization and cost before versus after initiation of second-generation long-acting injectable antipsychotics among adults with schizophrenia in Alberta, Canada: a retrospective, observational single-arm study

BackgroundLong-acting injectable (LAI) antipsychotics, along with community treatment orders (CTOs), are used to improve treatment effectiveness through adherence among individuals with schizophrenia. Understanding real-world medication adherence, and healthcare resource utilization (HRU) and costs in individuals with schizophrenia overall and by CTO status before and after second generation antipsychotic (SGA)-LAI initiation may guide strategies to optimize treatment among those with schizophrenia.MethodsThis retrospective observational single-arm study utilized administrative health data from Alberta, Canada. Adults (≥ 18 years) with schizophrenia who initiated a SGA-LAI (no use in the previous 2-years) between April 1, 2014 and March 31, 2016, and had ≥ 1 additional dispensation of a SGA-LAI were included; index date was the date of SGA-LAI initiation. Medication possession ratio (MPR) was determined, and paired t-tests were used to examine mean differences in all-cause and mental health-related HRU and costs (Canadian dollars), comprised of hospitalizations, physician visits, emergency department visits, and total visits, over the 2-year post-index and 2-year pre-index periods. Analyses were stratified by presence or absence of an active CTO during the pre-index and/or post-index periods.ResultsAmong 1,211 adults with schizophrenia who initiated SGA-LAIs, 64% were males with a mean age of 38 (standard deviation [SD] 14) years. The mean overall antipsychotic MPR was 0.39 (95% confidence interval [CI] 0.36, 0.41) greater during the 2-year post-index period (0.84 [SD 0.26]) compared with the 2-year pre-index period (0.45 [SD 0.40]). All-cause and mental health-related HRU and costs were lower post-index versus pre-index (p < 0.001) for hospitalizations, physician visits, emergency department visits, and total visits; mean total all-cause HRU costs were $33,788 (95% CI -$38,993, -$28,583) lower post- versus pre-index ($40,343 [SD $68,887] versus $74,131 [SD $75,941]), and total mental health-related HRU costs were $34,198 (95%CI -$39,098, -$29,297) lower post- versus pre-index ($34,205 [SD $63,428] versus $68,403 [SD $72,088]) per-patient. Forty-three percent had ≥ 1 active CTO during the study period; HRU and costs varied according to CTO status.ConclusionsSGA-LAIs are associated with greater medication adherence, and lower HRU and costs however the latter vary according to CTO status.

Antipsychotic Use and Risk of Stroke Among Community-Dwelling People With Alzheimer's Disease.

Antipsychotic use for neuropsychiatric symptoms in Alzheimer's disease (AD) is common despite the increased risk of cardiovascular events and mortality. There is limited and inconsistent evidence on the possible risk of stroke. We assessed whether antipsychotic initiation increases the risk of stroke in people with a verified diagnosis of AD and whether there is a difference in stroke risk between the 2 most commonly used antipsychotics, risperidone and quetiapine. Register-based exposure-matched cohort study. The Medication Use and Alzheimer's Disease (MEDALZ) cohort included 70,718 community-dwelling people with AD in Finland during 2005-2011. People with previous strokes were excluded. For each incident antipsychotic user (n = 20,467), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with inverse probability of treatment-weighted (IPTW) Cox proportional hazards models. Compared with nonuse, antipsychotic use was associated with an increased risk of stroke within 60days of antipsychotic initiation [IPTW hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.32-2.28]. However, there was no significant overall association between antipsychotic use and the risk of stroke (IPTW HR 1.09, 95% CI 0.98-1.22). There was no difference in stroke risk between risperidone and quetiapine (IPTW HR 1.12, 95% CI 0.91-1.37). Stroke risk is increased shortly after antipsychotic initiation in people with AD, suggesting that even short-term use of antipsychotics should be avoided if possible. If antipsychotics are prescribed, effectiveness and safety should be assessed soon after initiation and treatment limited to the shortest possible duration.

Health resource utilization, costs, and community treatment order status before and after the initiation of second-generation long acting-injectable antipsychotics in patients with schizophrenia in Alberta, Canada

IntroductionLong-acting injectable (LAI) antipsychotics and community treatment orders (CTOs) are used in patients with schizophrenia to improve treatment effectiveness through adherence.ObjectivesUnderstanding healthcare resource utilization (HRU) and associated costs, and medication adherence in patients with schizophrenia overall and by CTO status before and after second generation antipsychotic (SGA) LAI initiation may guide strategies to optimize health.MethodsA retrospective observational single-arm study using administrative data from Alberta was performed. Adults with schizophrenia who initiated SGA-LAI (index date) were included. Medication possession ratio (MPR) was determined; paired t-tests were used to examine differences in HRU and costs ($CDN) between the 2-year pre-index period and 2-year post-index period. Stratified analysis by presence or absence of an active CTO during the pre-post periods was performed.ResultsAmong 1,211 patients who initiated SGA-LAIs, MPR was greater post-index (0.84) compared with pre-index (0.45; 95% confidence interval [CI] 0.36, 0.41). All-cause and mental health-related HRU and costs were lower post-index versus pre-index (p&lt;0.001); total all-cause HRU costs were $33,788 lower post- versus pre-index ($40,343 [standard deviation, SD $68,887] versus $74,131 [SD $75,941], 95% CI [-$38,993, -$28,583]), and total mental health-related HRU costs were $34,198 lower post- versus pre-index ($34,205 [SD $63,428] CDN versus $68,403 [SD $72,088] CDN, 95%CI [-$39,098, -$29,297]). Forty-three percent had ≥1 active CTO during the study period; HRU and costs varied according to CTO status.ConclusionsSGA-LAIs are associated with improved adherence, and lower HRU and costs however the latter vary according to CTO status.DisclosureThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this abstract: SD and MS have no competing interest to declare. LR, SK, KW, and KM are members of the Real-World Evidence

Antipsychotic prescribing practices and patient, family member and healthcare professional perceptions of antipsychotic prescribing in acute care settings: a scoping review protocol

IntroductionAntipsychotic medications are commonly prescribed off-label in acutely ill patients for non-psychiatric clinical indications such as delirium or insomnia. New prescription initiation of antipsychotics in acute care settings increases the...

Buckinghamshire Early Intervention Service’ (BEIS) Compliance With the National Institute for Health and Care Excellence (NICE) Antipsychotic Monitoring Guidelines: Practical Challenges, Including Those Posed by the Pandemic, in an Outpatient Setting

AimsAntipsychotic use is associated with cardiovascular and metabolic side-effects, which may contribute to increase mortality and morbidity in this patient group. This highlights the importance of physical health monitoring. We aimed to assess our compliance with the more stringent NICE guidelines, updated in September 2021.MethodsHalf of BEIS team's caseload was audited (n = 67) during October 2021 for compliance with NICE's monitoring guidelines for patients initiated on antipsychotic medication. These included initial and, if indicated, repeat monitoring of body mass index (BMI), pulse, blood pressure (BP), blood results, electrocardiogram, and adverse effects. Patients who were not on antipsychotics were excluded. 61% of patients were initiated on antipsychotics as inpatients, and 39% were outpatients. These patients have been started on antipsychotics within the last three years. Data were collected via electronic record systems. 80% compliance was set as the standard, in line with National Clinical Audit of Psychosis standards.ResultsIn the first three months of antipsychotic initiation (61% as inpatients, 39% in the community) six out of nine parameters met standards (ranging from 2% to 100%), with BMI measurement (weekly), pulse and BP measurements and one month repeat haemoglobin A1C (HbA1c) failing. When only accounting for patients who were started on antipsychotics in outpatient settings (BEIS or crisis team), compliance was only met on two parameters.Three months post initiation, when patients were mainly monitored in the community, only three of the nine parameters met compliance (lipids, HBA1c, and side-effects).ConclusionAdherence to the NICE standards for physical health monitoring in the community poses significant challenges. Possible barriers include reduced patient contact during the pandemic, lack of awareness of monitoring requirements, poor documentation (particularly of declined screening) and a lack of time and resources. There is also a possibility of unnecessarily stringent and impractical guidelines which are difficult to achieve in outpatient settings – such as weekly BMI. We plan to implement interventions including providing a checklist for medical and nursing staff and encouraging patients to monitor their own blood pressure and weight at home. We will reaudit the same parameters in 6 months’ time.

Incidence of hospital contacts with acute kidney injury after initiation of second-generation antipsychotics in older adults: a Danish population-based cohort study

PurposeTo investigate the association between acute kidney injury (AKI) and use of second-generation antipsychotics (SGA) in older adults.MethodsIn a population-based cohort study using Danish national registries, new users of SGAs (aged ≥ 65) were identified during 2005–2015. Each SGA user was matched to 10 population controls on age, sex, and the SGA initiation date. The outcome was incident AKI within 90 days after the index date. Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders.ResultsIn the study, 36,581 new SGA users and 365,810 controls were included. The 90-day incidence rate of AKI was 4.38 and 1.70 per 1000 person-years among SGA users and controls, respectively, corresponding to a crude HR of 2.57 (1.79–3.68). The fully adjusted HR (aHR) was 1.43 (0.89–2.27) for all SGAs. The risk differed among individual drugs with aHRs for olanzapine 3.50 (1.20–10.23), quetiapine 1.62 (0.81–3.26), and risperidone 0.68 (0.28–1.64). In sensitivity analyses, the aHR declined to 1.24 (0.95–1.61) at 1-year follow-up.ConclusionsOlanzapine use was associated with a significantly increased 90-day AKI risk. For quetiapine, the risk was elevated but not significant, and risperidone had no association. CIs were wide and confounder adjustment largely impacted the estimates. Main limitations included residual confounding and incomplete recording of AKI diagnoses.

Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, and Other Neurodevelopmental Outcomes Associated With Antipsychotic Drug Exposure During Pregnancy.

Between 0.3%-4.6% of women use antipsychotic (AP) drugs during pregnancy. Two large, retrospective, population-based cohort studies, conducted in Nordic countries and in the US, examined the risk of neurodevelopmental disorders (NDDs) following gestational exposure to APs. The Nordic study found that, in unadjusted analyses, exposure to APs during pregnancy was associated with increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring; that the risk all but disappeared after adjusting for covariates; and that the risk appeared to be related to maternal major mental illness rather than to gestational exposure to APs. The US study also found that, in unadjusted analyses, gestational exposure to APs was associated with an increased risk of almost all of the study-specified NDDs in offspring; however, after adjusting for covariates, the risks were no longer meaningfully increased and, importantly, were no longer statistically significant for ADHD and ASD. Thus, these 2 studies suggest that gestational exposure to APs is a marker of NDD risk in offspring rather than a potential cause. Whereas a small but significantly increased risk was identified for aripiprazole in the US study, the signal was inconsistent across analyses, and confounding due to maternal mental illness was not ruled out. Previous studies have suggested that the use of APs during pregnancy is not associated with an increased risk of major congenital malformations and other adverse gestational outcomes. Considering the potential harm and suffering associated with major mental illness and the very low risks associated with AP use during pregnancy, initiation or continuation of APs appears to carry a favorable risk-benefit ratio in pregnant women who need these drugs; however, decision-making should be shared between patients, their caregivers, and the treating team.

Healthcare resource utilization and costs before and after long-acting injectable antipsychotic initiation in commercially insured young adults with schizophrenia

BackgroundLong-acting injectable (LAI) antipsychotics use is associated with improved adherence which can reduce the rate of relapse, hospitalization, and associated costs in patients with schizophrenia. Young adults could be at higher risk of poor adherence, hence use of LAI in this population may offer a benefit but the evidence is limited. This study aimed to compare clinical and economic outcomes before and after the initiation of LAI antipsychotics in commercially insured young adults (18-35 years of age) with schizophrenia.MethodsA retrospective claims data study was conducted using the data from the IBM MarketScan® Commercial Claims and Encounters (CCAE) Database. Patients with a continuous enrollment of at least 1-year before and 1-year after the first observed schizophrenia diagnosis (index date) and with the use of ≥1 typical or atypical LAI antipsychotic during the post-index follow-up period were included. A pre-post analysis was conducted to compare relapse rates, healthcare resource utilization, and costs before (from index date to LAI initiation) and after LAI initiation (to end of follow up).ResultsA total of 2222 patients who initiated LAIs after an index schizophrenia diagnosis were identified. The per patient per month (PPPM) composite relapse event rate (0.109 pre-LAI to 0.073 post-LAI) and hospitalization rate (0.091 to 0.058), all-cause inpatient visits (0.231 to 0.119), and length of stay (2.694 to 1.092 days) significantly decreased from before LAI initiation to after LAI initiation with similar trends seen for mental health and schizophrenia-related measures (all significant; P < 0.0001). All-cause total costs ($4898 to $3078 PPPM) were also decreased after LAI initiation, with similar trends seen for mental health and schizophrenia-related costs (all significant; P < 0.0001). Although medication costs were higher post-LAI period ($311 to $542 PPPM), the cost increase was substantially offset by the decreased costs associated with total healthcare costs.ConclusionsTreatment with LAI antipsychotics was associated with a decrease in relapse event rate, healthcare resource utilization, and costs after LAI initiation compared to before LAI initiation in commercially insured young adults with schizophrenia. Treatment with LAIs in young adults with schizophrenia is potentially associated with significant cost savings to commercial payers.

Florida Medicaid Children's Receipt of First-Line Psychosocial Care Prior to Antipsychotic Initiation.

First-line, nonpharmacological therapy is recommended for many pediatric mental health (MH) conditions prior to initiating antipsychotic prescription therapies. Many children do not receive these recommended services, despite the known association between antipsychotic medications and metabolic dysfunction. The main objective of this study was to quantify the association among children's MH diagnosis categories, sociodemographic characteristics and receipt of first-line psychosocial care among children in Florida Medicaid METHODS: Florida Medicaid enrollment, healthcare and pharmacy claims were used for this multivariate analysis. Children were assigned to condition clusters wherein related diagnoses were grouped into clinically relevant categories. A total of 7704 children were included in the final analysis. Twenty-four percent of children in Florida Medicaid do not receive first-line, nonpharmacological psychosocial care. Age was significantly associated with not receiving psychosocial services, with older children less likely to receive. Non-Hispanic White children as well as those living in rural areas had lower odds of receiving behavioral intervention prior to initiating antipsychotics. Children with mood-disorders, behavior problems, anxiety and stress related disorders were more likely to receive first-line psychosocial care. This study provides an important understanding of the variability in receipt of first-line psychosocial care before antipsychotic medication initiation among children in Medicaid based on sociodemographic and MH health characteristics. These analyses can be used to develop quality improvement initiatives targeted toward children that are most vulnerable for not receiving recommended care.

Subthreshold Change in Glycated Hemoglobin and Body Mass Index After the Initiation of Second-Generation Antipsychotics Among Patients With Schizophrenia or Bipolar Disorder: A Nationwide Prospective Cohort Study in Japan.

Objective: The risk of diabetes development has been reported to differ among second-generation antipsychotics (SGAs). However, few studies have focused on the subthreshold change in glycated hemoglobin (HbA1c). Therefore, this study examined the subthreshold change in HbA1c and change in body mass index (BMI) 3 months after patients initiated one of 6 SGAs widely prescribed in Japan.Methods: This is a prospective cohort study of patients followed up based on the Japanese blood glucose monitoring guidelines for patients with schizophrenia. We collected eligible patients' demographic data, medication history, blood tests, and weight measurements both at baseline and 3 months after recruitment, between April 2013 and March 2015. In the 378 patients with schizophrenia, schizoaffective disorder, and bipolar disorder based on ICD-10, we compared the subthreshold change in HbA1c and the change in BMI 3 months after antipsychotic initiation by using multivariate regression analysis.Results: The subthreshold change in HbA1c 3 months after initiating blonanserin was significantly lower compared with olanzapine (B = -0.17, 95% CI = -0.31 to -0.04). In addition, the change in BMI 3 months after initiating blonanserin and aripiprazole was significantly lower compared with olanzapine (B = -0.93, 95% CI = -1.74 to -0.12; B = -0.71, 95% CI = -1.30 to -0.12, respectively).Conclusions: This is the first study to clarify the differences in the subthreshold change in HbA1c among SGAs. Our results suggest that blonanserin is likely to be a favorable treatment for patients with high risk of diabetes.Trial Registration: UMIN Clinical Trial Registry identifier: UMIN000009868.

Comparative effectiveness and safety of antipsychotic drugs in patients with schizophrenia initiating or reinitiating treatment: A Real-World Observational Study.

To compare the effectiveness and safety of various second-generation antipsychotics (SGAs), newer oral and long-acting injectable (LAI) SGAs, and first-generation antipsychotics (FGAs) treatments in patients with schizophrenia or schizoaffective disorder (SCZ). This retrospective cohort study included medical administrative information for patients with a diagnosis of SCZ living in Quebec (Canada), initiating or reinitiating at least one antipsychotic (AP) drug (with a clearance baseline period of 12months without any APs). Effectiveness was defined by a reduced risk of hospitalization for mental disorder and discontinuation, and safety by a reduced risk of all-cause death and hospitalization for non-mental disorder, 2years after AP initiation or reinitiation. Cox proportional hazard models were used to estimate the events associated with different antipsychotics compared with oral olanzapine. The study cohort included 19,615 patients initiating or reinitiating an antipsychotic drug between January 2006 and December 2015. Results showed better effectiveness of clozapine (adjusted HR 0.36, 95% CI 0.30-0.42, p<0.0001) and LAI SGAs (adjusted HR 0.56, 95% CI 0.51-0.61, p<0.0001) compared with oral olanzapine when adding discontinuation to hospitalizations for mental disorder as a composite measure of effectiveness, as opposed to oral FGAs (adjusted HR 1.36, 95% CI 1.27-1.46, p<0.0001) and LAI FGAs (adjusted HR 1.22, 95% CI 1.12-1.32, p<0.0001). Most APs were as safe as oral olanzapine. The effectiveness of LAI SGAs and clozapine appears to justify their use and are as safe as a recognized treatment (oral olanzapine) in Quebec (Canada).