Off-label Use Of Antipsychotics Research Articles

Outpatient Antipsychotic Use and Severe COVID-19: Avoiding the Impact of Age in a Real-World Data Study.

The association between use of antipsychotics and COVID-19 outcomes is inconsistent, which may be linked to use of these drugs in age-related diseases. Furthermore, there is little evidence regarding their effect in the nongeriatric population. We aim to assess the association between antipsychotic use and risk of disease progression and hospitalization due to COVID-19 among the general population, stratifying by age. We conducted a population-based, multiple case-control study to assess risk of hospitalization, with cases being patients with a PCR(+) test who required hospitalization and controls being individuals without a PCR(+) test; and risk of progression to hospitalization, with cases being the same as those used in the hospitalization substudy and controls being nonhospitalized PCR(+) patients. We calculated adjusted odds-ratios (aOR) and 95% confidence intervals (CI), both overall and stratified by age. Antipsychotic treatment in patients younger than 65 years was not associated with a higher risk of hospitalization due to COVID-19 (aOR 0.94 [95%CI = 0.69-1.27]) and disease progression among PCR(+) patients (aOR 0.96 [95%CI = 0.70-1.33]). For patients aged 65 years or older, however, there was a significant, increased risk of hospitalization (aOR 1.58 [95% CI = 1.38-1.80]) and disease progression (aOR 1.31 [95% CI = 1.12-1.55]). The results of our large-scale real-world data study suggest that antipsychotic use is not associated with a greater risk of hospitalization due to COVID-19 and progression to hospitalization among patients younger than 65 years. The effect found in the group aged 65 years or older might be associated with off-label use of antipsychotics.

HPR106 Identifying Value Drivers for a Novel Treatment Targeting Core Symptoms of Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a highly heterogenous neurodevelopmental condition that affects communication skills, social interaction, learning skills, and behavior. There are currently no pharmacological treatments indicated for the core symptoms of ASD. Treatment often relies on patients’ access to behavioral therapy and the management of associated symptoms through off-label use of antipsychotics, SSRI's, and other medicines, which often come with significant adverse events. This research explores payer and physician perceptions of the unmet need in ASD and what stakeholders view as the most important value drivers for a potential novel treatment targeting core symptoms of ASD.

Quetiapine for the Treatment of Pediatric Delirium.

Delirium is a common complication of critical illness, with a prevalence of 25% among pediatric intensive care unit (ICU) patients. Pharmacological treatment options for ICU delirium are limited to off-label use of antipsychotics, but their benefit remains uncertain. The purpose of this study was to evaluate quetiapine effectiveness for the treatment of delirium in critically ill pediatric patients and to describe the safety profile of quetiapine. A single-center, retrospective review of patients aged ≤ 18 years who screened positive for delirium via the Cornell Assessment of Pediatric Delirium (CAPD ≥ 9) and received ≥ 48 hours of quetiapine therapy was conducted. The relationship between quetiapine and deliriogenic medication doses was evaluated. This study included 37 patients who received quetiapine for the treatment of delirium. The change in sedation requirements before quetiapine initiation to 48 hours after the highest quetiapine dose demonstrated a downward trend; 68% of patients had a decrease in opioid requirements and 43% of patients had a decrease in benzodiazepine requirements. The median CAPD score at baseline was 17 and the median CAPD score at 48 hours after the highest dose was 16. Three patients experienced QTc prolongation (defined as a QTc ≥ 500), although none developed dysrhythmias. Quetiapine did not have a statistically significant impact on deliriogenic medication doses. There were minimal changes in QTc and dysrhythmias were not identified. Therefore, quetiapine can be safe to use in our pediatric patients but further studies are needed to find an effective dose.

Use of atypical antipsychotics in the treatment of schizophrenia in the Brazilian National Health System: a cohort study, 2008-2017.

to investigate sociodemographic and clinical characteristics of users of atypical antipsychotics receiving care via the Specialized Component of Pharmaceutical Assistance (Componente Especializado da Assistência Farmacêutica - CEAF), for the treatment of schizophrenia in Brazil, between 2008 and 2017. this was a retrospective cohort study using records of the authorizations for high complexity procedures retrieved from the Outpatient Information System of the Brazilian National Health System, from all Brazilian states. of the 759,654 users, 50.5% were female, from the Southeast region (60.2%), diagnosed with paranoid schizophrenia (77.6%); it could be seen a higher prevalence of the use of risperidone (63.3%) among children/adolescents; olanzapine (34.0%) in adults; and quetiapine (47.4%) in older adults; about 40% of children/adolescents were in off-label use of antipsychotics according to age; adherence to CEAF was high (82%), and abandonment within six months was 24%. the findings expand knowledge about the sociodemographic and clinical profile of users and highlight the practice of off-label use.

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.

Off-label use of drugs in pediatrics: a scoping review.

To explore the current state of research on off-label drug use in children and identify the existing research gaps in this topic. Six literature databases were searched to identify studies focusing exclusively on off-label drug use in children (aged < 18years) published in Chinese or English between 2016 and 2021. We also searched clinicaltrials.gov for pediatric clinical trials conducted in the same period and compared the numbers of studies on off-label use and clinical trials for the most commonly reported drugs and drug types. Our search revealed 568 studies on off-label drug use. Almost half of the studies (n = 240) were cross-sectional. A total of 212 specific drugs or drug types were addressed in 361 studies, the most frequent being antipsychotic agents (n = 12), dexmedetomidine (n = 10), and rituximab (n = 8). Antipsychotic agents were also the most common type of drug examined in clinical trials in children. We identified a total of 435 different types of off-label use, the top three being unapproved indication (n = 157), population (n = 96), or age (n = 36). Only about one-third of the studies reported collecting informed consent (n = 195) or having ethics committee approval (n = 166). Conclusions: Off-label use of antipsychotics in children is widely reported in the literature. We suggest pediatric researchers to consider the number of studies on off-label use and existing clinical trials on different drugs when selecting target drugs for new studies and systematic reviews. What is Known: • There exist a large number of studies on off-label drug use in children. What is New: • This is the first scoping review of studies on off-label drug use in children. • Off-label use of antipsychotic agents is widely reported.

Characteristics and predictors of off-label use of antipsychotics in general population sample.

ObjectiveIncreasing number of people have been prescribed antipsychotics (APs) off‐label in recent decades. This study aimed to identify the characteristics and predictors of receiving prescription of antipsychotics off‐label.MethodsThe study sample was part of the Northern Finland Birth Cohort 1966 (n = 7071). Data included questionnaires and national register data. Information on prescribed medications was extracted from the national register. The sample was divided into three groups: Persons who had been prescribed APs off‐label (n = 137), individuals with non‐psychotic mental disorders without APs off label (n = 1478) and individuals who had been diagnosed with psychosis or bipolar disorder and who had been prescribed APs (n = 151). We compared sociodemographic, lifestyle and clinical characteristics between the off‐label and the comparison groups using logistic regression.ResultsThe most common diagnoses in the off‐label group were depression (n = 96, 70.1%) and anxiety (n = 55, 40.1%). Compared with individuals with non‐psychotic mental disorders who were not prescribed APs off‐label, individuals with prescribed off‐label APs had a lower level of education, lower socioeconomic status, were less often married, had a higher level of somatic and psychiatric morbidity, were more often smokers and more often had a substance abuse disorder and heavy alcohol consumption. When comparing the off‐label group to individuals with psychosis or bipolar disorder who used APs, there were less differences, though individuals with psychosis or bipolar disorder had more markers of morbidity and a lower level of education.ConclusionIndividuals who had been prescribed APs off label had a higher level of mental and somatic morbidity and poorer socioeconomic status than individuals with non‐psychotic mental disorders who did not use APs.

Off-label prescribing of antipsychotics: prescribing practices and clinical experiences of Finnish physicians

IntroductionOff-label use of antipsychotics has increased in many countries. In adult populations antipsychotics off-label prescriptions varied from 40 to 75% of all AP users.ObjectivesTo examine the off-label prescribing practices and experiences of antipsychotic medication in Finland.MethodsAn electronic questionnaire on physicians’ prescription practices of antipsychotics, especially for off-label use, was sent in 2019 for physicians (n=1195) in different health care facilities including primary health care, occupational health care, in- and outpatient mental health services and services for substance abuse. The sample was selected by systematic and convenience sampling covering five university hospital areas in Finland.ResultsIn total, 216 physicians (18% of the target sample) participated in the study, and 94% had prescribed antipsychotics for off-label use. The most common off-label indications were insomnia and anxiety. The most common antipsychotic used was quetiapine. Off-label antipsychotics was not prescribed as a first-choice medication: 99% of the physicians reported that the patients with off-label use have previously had other medications for the corresponding symptoms. In all, 88% of clinicians monitored the patients’ clinical condition, whereas metabolic values were followed more rarely. About 68% of physicians reported more benefit than harm from the antipsychotics off-label use.ConclusionsAntipsychotics are often prescribed for off-label use, most commonly for insomnia and anxiety. Most of the physicians see more benefits than harms for the patient in off-label use. There is a need to analyse the long-term benefits and harms of off-label use of antipsychotics and create more detailed treatment algorithms and clinical recommendations for such use.DisclosureNo significant relationships.

Evaluation of Antipsychotic Reduction Efforts in Patients With Dementia in Veterans Health Administration Nursing Homes.

The Veterans Health Administration (VHA) and the Centers for Medicare and Medicaid Services (CMS) each created initiatives to reduce off-label use of antipsychotics in patients with dementia in nursing homes. Although CMS has reported antipsychotic reductions, the impact on prescribing of antipsychotic and other CNS-active medications in the VHA remains unclear. The authors evaluated national trends in antipsychotic and other CNS-active medication prescribing for nursing home patients with dementia in the VHA. The study sample was all veterans with dementia residing in VHA nursing homes for more than 30 days (N=35,742). Using an interrupted time-series design, the quarterly prevalences of antipsychotic, antidepressant, antiepileptic, anxiolytic, opioid, and memory medication prescribing were evaluated from FY2009 through FY2018. Antipsychotic prescribing in VHA nursing homes declined from FY2009 to FY2018 (from 33.7% to 27.5%), with similar declines in anxiolytic prescribing (from 33.5% to 27.1%). During this period, prescribing of antiepileptics, antidepressants, and opioids increased significantly (antiepileptics: from 26.8% to 43.3%; antidepressants: from 56.8% to 63.4%; opioids: from 32.6% to 41.2%). Gabapentin served as the main driver of antiepileptic increases (from 11.1% to 23.5%). Increases in antidepressant prescribing included sertraline, mirtazapine, and trazodone. From FY2009 to FY2018, the overall prescribing of non-antipsychotic psychotropic medications grew from 75.0% to 81.1%. Antipsychotic and anxiolytic prescribing for VHA nursing home residents with dementia declined, although overall prescribing of other psychotropic and opioid medications increased. Policies focused primarily on reducing antipsychotic use without considering use in the context of other medications may contribute to growth in alternative medication classes with even less evidence of benefit and similar risks.

Trends in antipsychotic use for youth with attention-deficit/hyperactivity disorder and disruptive behavior disorders.

To examine trends in off-label antipsychotic use for youth with attention-deficit/hyperactivity disorder with and without a comorbid disruptive behavior disorder. This cross-sectional study of annual trends from 2007 through 2015 used the IQVIA PharMetrics® Plus for Academics data. We identified 165 794 commercially-insured youth 3-18-year-old who had a diagnosis of attention-deficit/hyperactivity disorder and classified them into subgroups with and without disruptive behavior disorders comorbidities. Antipsychotic use, with or without a stimulant, was the primary dependent outcome. Logistic regression estimated the odds of antipsychotic use associated with comorbid attention-deficit/hyperactivity disorder and disruptive behavior disorders, adjusting for age, sex, study year, and other psychotropic use. Over 70% of the 165 794 youth with attention-deficit/hyperactivity disorder were 5-14-year-old and male, and 12% had disruptive behavior disorders. Antipsychotic prevalence, with or without a stimulant, was 4.4% in 2007 and 3.4% in 2015. Stimulants with antipsychotics increased significantly from 2007 to 2015 for females (19.5%-28.7%) and youth 15-18-year-old (25.9%-32.7%). Adjusting for age, sex, study year, and other psychotropic use, youth with a comorbid disruptive behavior had a 2.5 (95% CI: 2.3, 2.7) higher likelihood of receiving an antipsychotic than youth with attention-deficit/hyperactivity disorder and no comorbidities. Antipsychotic use was associated with comorbid disruptive behaviors in youth with attention-deficit/hyperactivity disorder. Off-label antipsychotic use has increased for females and older adolescents.

Antipsychotics, Antiepileptics, and Fabrication: Are We Making It or Faking It?

Antipsychotics, Antiepileptics, and Fabrication: Are We Making It or Faking It?

Benefits and risks of off label use of antipsychotics in insomnia and anxiety – APSY Oulu project

Background Use of antipsychotics (APs) has increased in Europe. Main reason for this is off label use, most commonly the use of quetiapine for insomnia and anxiety. However, there is lack of studies analysing benefits and harms of APs in these conditions. APs have shown efficacy in the treatment of anxiety, but long term follow-ups are rare. Only two trials on effects of quetiapine in primary insomnia exist. Even small doses of APs may cause side-effects, such as increased weight, metabolic changes, and daytime drowsiness, but studies on small dose of APs are very few. The aim of the APSY Oulu project (https://www.oulu.fi/ltk/apsyoulu) is to study the benefits and risks of APs in off label use. Methods APSY Oulu project includes clinical patient data, questionnaire on physicians on APs off label prescriptions and systematic literature reviews on the topic. Results In 2019–2020, we have collected pilot sample of 10 individuals starting quetiapine for insomnia, followed up for 12 months. They all had severe or very severe symptoms of insomnia, and used very small dose of quetiapine (mostly 12.5–25 mg). Four of them used quetiapine still at the 12 months follow-up, and their insomnia symptoms decreased during the follow-up. Side effects were common (e.g. increase heart rate, drowsiness). Based on questionnaire for Finnish physicians, APs off label prescriptions are mostly for insomnia and anxiety, most common drug being quetiapine. There is a need for guideline on monitoring the patients. Conclusions Further studies on APs off label use and its safety are needed.

Prescription Pattern and Off-Label Use of Antipsychotics in a Middle Eastern Population.

Background: Understanding the prescription pattern of medications in a population can help reveal the potential usage scenarios, including off-label prescriptions, and the need for precision medicine implementation. Therefore, the aim of this study was to assess the prescription pattern and off-label use of antipsychotics in the Qatari population. Methods: We performed a cross-sectional study of Qatari patients who received antipsychotic prescriptions from the major healthcare providers in the country during the 2-year period between June 2018 and May 2020. The number of patients, prescriptions dispensed, and clinical indications were collected and statistical analysis using chi-square test was conducted. Results: Among the 9,349 Qatari patients prescribed with antipsychotics during the study period, the majority were female (57%; p < 0.001) and were in the age categories 20–39 and 30–39 years (both 22%; p < 0.001). Among the 35,938 antipsychotic prescriptions dispensed, second-generation antipsychotics were the most highly prescribed (59%), specifically, quetiapine (16%) and olanzapine (12%), but the first-generation antipsychotic prochlorperazine (13%) was also highly prescribed. Most of the indications of antipsychotics (69%) were for off-label use such as for controlling chronic diseases, sleeping disorders, benign paroxysmal positional vertigo and irritable bowel syndrome. Conclusion: Non-mental health and off-label prescriptions of several antipsychotics were observed. Integration of this data with pharmacogenomic and clinical outcome data will help in determining the course of action for implementing personalized and precision medicine in the country and beyond.

Off-label antipsychotic use patterns among Texas Medicaid adults 2013-2016.

Aim: To describe trends in off-label antipsychotic use among Texas Medicaid adults and examine whether demographic and clinical characteristics were associated with off-label use. Methods: Three diagnostic groups (i.e. no diagnosis, on label and off-label) were created based on mental health disorder diagnoses and related antipsychotic prescriptions. Results: During 2013-2016, the prevalence of off-label antipsychotic use decreased from 22.5% to 17.4% and the proportions of no mental health diagnosis remained stable (7.3-9.4%). Patients aged ≥25years and second-generation antipsychotic users had significantly lower odds of receiving antipsychotics off-label or with no diagnosis. Conclusion: Compared with previous Medicaid database studies, the proportions of off-label antipsychotic use and antipsychotic use with no concurrent psychiatric diagnosis were notably lower.

Trends in off-label use of antipsychotic medications among Texas Medicaid children and adolescents from 2013 to 2016.

BACKGROUND: Antipsychotics are frequently prescribed for off-label indications in the pediatric population. However, little is known regarding this issue in Texas Medicaid. OBJECTIVES: To (1) describe off-label antipsychotic use among Texas Medicaid children and adolescents and (2) examine factors associated with off-label use. METHODS: Texas Medicaid prescription and medical claims from January 2013 to August 2016 were analyzed retrospectively among subjects aged 2-17 years with an antipsychotic prescription. Three diagnostic status groups (on-label, off-label, no diagnosis) were categorized based on FDA-approved indications. Descriptive and chi-square tests were conducted to determine if diagnostic status differed by age group (2-4, 5-9, 10-14, and 15-17 years), sex, and antipsychotic type. A logistic regression analysis was used to identify factors associated with off-label use. RESULTS: In this study, 43,792, 44,335, 37,221, and 24,879 (January-August) children with at least 1 antipsychotic prescription were identified from 2013 to 2016, respectively. The proportions with off-label use declined from 66.9% (2013) to 59.8% (2016). Among off-label users, more than one-half (51.3%-55.8%) had a diagnosis of attention-deficit/hyperactivity disorder. Less than 8% (6.0%-7.7%) of subjects had no mental health disorder diagnosis. Chisquare analyses (2015 data) revealed that the proportion of off-label and no diagnosis users combined were significantly (P < 0.01) higher among users aged 5-9 years (82.5%) than adolescents 10-14 years (61.9%) and 15-17 years (56.5%); males (67.7%) than females (65.3%); and first-generation antipsychotics (FGAs; 79.3%) than second-generation antipsychotics (66.7%) users. Logistic regression analyses revealed younger age and FGA users had higher odds of off-label/no diagnosis use. CONCLUSIONS: The proportion of off-label/no diagnosis antipsychotic use declined from 2013 to 2016. Younger children and those receiving FGAs were more likely to be off-label antipsychotic users, with attention-deficit/hyperactivity disorder being the most prevalent off-label diagnosis. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. This study was presented as an abstract at the American Academy of Child and Adolescent Psychiatry's 67th Annual Meeting (Virtual), October 2020.

Off-label use of antipsychotic medications in psychiatric inpatients in China: a national real-world survey

BackgroundThe off-label use of antipsychotic medications is common in many countries, and the extent of such use in psychiatric inpatients in China has not been sufficiently studied. The purpose of this study was to survey the incidence and examine the correlates of off-label antipsychotic use in a large, nationally–representative sample in China.MethodsThis study included discharged psychiatric patients between March 19 and 31, 2019 from 41 tertiary psychiatric hospitals across 29 provinces in China. Their socio-demographic and clinical data were collected and analyzed.ResultsAfter excluding patients with schizophrenia spectrum disorder or bipolar disorder, 981 patients were included in the analysis. Overall, antipsychotics were prescribed to 63.2% (95%CI 60.2–66.2%) of the sample. Antipsychotics were used in a wide spectrum of psychiatric disorders, with the rate being the highest among patients with dissociative (conversion) disorders (89.9, 95%CI 83.0–94.8%), organic mental disorders (81.7, 95%CI 73.1–88.7%), dementia (79.0,95%CI 67.8–87.9%), obsessive-compulsive disorder (77.8, 95%CI 55.7–92.5%), mental disorders due to psychoactive substances (75.3,95%CI 64.7–84.2%), behavioural and emotional disorders with onset usually occurring in childhood and adolescence (71.4, 95%CI 45.5–90.1%), somatoform disorders (63.2, 95%CI 40.8%–82..2%), major depression disorder (53.7,95%CI 48.8–58.6%), anxiety disorder (38.8,95%CI 30.5–47.7%), and insomnia (25.0, 95%CI 8.5–28.9%). The top three most commonly used antipsychotics were olanzapine (29.1%), quetiapine (20.3%) and risperidone (6.8%), and their corresponding average doses were 9.04 ± 5.80 mg/day, 185.13 ± 174.72 mg/day, and 2.98 ± 1.71 mg/day, respectively. A binary logistic regression showed that younger age, having the Employee Health Insurance or Residents Health Insurance, having psychotic symptoms and requiring restraint during hospitalization were significantly associated with off-label use of antipsychotics.ConclusionOff-label use of antipsychotics is very common in psychiatric inpatients in China, mainly with moderate-dose use of single agents. However, the efficacy and safety of this practice is uncertain for many diagnoses and for the elderly. Clinicians should be cautious about this practice while waiting for more research data.

Off-label antipsychotics prescription to adolescents with acute psychotic episodes does not cause adverse drug reactions

Antipsychotics are often used to treat children and adolescents. Because of their age, there are a lot of off-label prescribed antipsychotics in that population. However, the off-label use of medications is considered to be potentially unsafe.Objective: to evaluate whether the off-label prescription of antipsychotics outside of the approved age group increased the risk of adverse drug reactions in adolescents experiencing an acute psychotic episode.Patients and methods. We analyzed 450 charts of adolescents hospitalized due to an acute psychotic episode (only completed cases). In addition, we evaluated adverse drug reactions adjusted by off-label antipsychotics prescription outside the approved age group using the Global Trigger Tool (GTT). We also registered prescriptions with duplicates drug classes and potentially dangerous drug interactions.Results and discussion. Off-label antipsychotics prescription outside the approved age group was less frequently associated with adverse drug reactions (3.2% vs. 10.5%; p=0.013). The logistic regression analysis did not show any significant associations between the off-label antipsychotic use and increased risk of adverse drug reactions (Odds ratio=0.994 (95% confidence interval 0.572-1.726), p=0.982). Although, patients with off-label use of antipsychotics were more likely to have potentially dangerous drug interactions (35.2% vs. 16.15%; p=0.0001) and prescriptions with duplicates drug classes (39.6% vs. 15.43%; p=0.0001).Conclusion. Off-label antipsychotic prescription outside the approved age group in adolescents with acute psychotic episode does not increase the risk of adverse drug reactions. However, an increase in potentially dangerous drug interactions and prescriptions with duplicates drug classes frequency could be considered red flags. Therefore, we have concluded that the concerns about off-label antipsychotics prescription outside of approved age groups in adolescents with acute psychotic episodes were overrated.

An audit into the monitoring of off-label antipsychotics in primary care

AimsTo ascertain whether patients prescribed second generation antipsychotics for off-label indications are being monitored and screened adequately for physical health side-effects.BackgroundThe prevalence of off-label antipsychotic use has increased significantly over recent decades. Common off-licence uses include dementia, post-traumatic stress disorder, adjunctive treatment for unipolar depression and personality disorders. Recent studies have demonstrated that up to 65% of antipsychotic prescriptions are now off-label. Since the metabolic side-effects of second-generation antipsychotics are well-established, guidelines have emphasised the need for active, routine physical health screening of all individuals taking these drugs. However, there have been few studies or reviews which have specifically investigated screening rates of individuals receiving antipsychotic medications for off-licence indications.MethodAn audit of patients taking second-generation antipsychotics for off-label indications, under the caseload of Neighbourhoods 1, 3 and 4 of Lewisham Assessment &amp; Liaison team, was conducted. After isolating individual patients fulfilling inclusion criteria, patient investigation documents were requested from relevant GP practices. 40 patients were isolated in total, and data were successfully collected in 60% (n = 24). Data were collected via a proforma. This consisted of patient information, indications for antipsychotic use, and each variable to be monitored. The audit standard used was the recommendations of the 12th Maudsley guidelines. Data were then entered into SPSS and analysed.ResultThe most common reasons for off-label antipsychotic prescribing were Emotionally Unstable Personality disorder (42%, n = 10) and depression (29%, n = 7). Findings demonstrated that 54% (n = 13) of patients audited had ‘basic’ blood screening (FBC, U&amp;E, LFTs), however glucose (38%, n = 9), Prolactin (13%, n = 3), and Creatine Kinase (0%, n = 0), and monitoring was less frequent. 0% (n = 0) were completely monitored as per audit standard.ConclusionPrimary care monitoring of off-label antipsychotics is unsatisfactory, with no patients having a complete set of investigations. Reasons for this are unclear at this stage, however based on initial discussion with GP surgeries, may be due to lack of education regarding screening investigations, patients lost between primary and secondary care services, and a lack of clarity regarding responsibility and designated roles. This audit will be expanded to also include patients from Neighbourhood 2 of the Lewisham Assessment &amp; Liaison team. A more detailed investigation will be conducted into the barriers to physical health screening, such that a targeted intervention can be implanted.

Head-to-Head Comparison of Sedation and Somnolence Among 37 Antipsychotics in Schizophrenia, Bipolar Disorder, Major Depression, Autism Spectrum Disorders, Delirium, and Repurposed in COVID-19, Infectious Diseases, and Oncology From the FAERS, 2004-2020.

Objective: Antipsychotic compounds are known to induce sedation somnolence and have expanded clinical indications beyond schizophrenia to regulatory approval in bipolar disorder, treatment-resistant depression, and is being repurposed in infectious diseases and oncology. However, the medical sciences literature lacks a comprehensive association between sedation and somnolence among a wide-range of antipsychotic compounds. The objective of this study is to assess the disproportionality of sedation and somnolence among thirty-seven typical and atypical antipsychotics. Materials and Methods: Patient adverse drug reactions (ADR) cases were obtained from the United States Food and Drug Administration Adverse Events Reporting System (FAERS) between January 01, 2004 and September 30, 2020 for a wide-array of clinical indications and off-label use of antipsychotics. An assessment of disproportionality were based on cases of sedation and somnolence and calculated using the case/non-case methodology. Statistical analysis resulting in the reporting odds-ratio (ROR) with corresponding 95% confidence intervals (95% CI) were conducted using the R statistical programming language. Results: Throughout the reporting period, there were a total of 9,373,236 cases with 99,251 specific ADRs reporting sedation and somnolence. Zuclopenthixol (n = 224) ROR = 13.3 (95% CI, 11.6–15.3) was most strongly associated of sedation and somnolence and haloperidol decanoate long-acting injection (LAI) was not statistically associated sedation and somnolence. Further, among atypical antipsychotic compounds, tiapride and asenapine were the top two compounds most strongly associated with sedation and somnolence. Comprehensively, the typical antipsychotics ROR = 5.05 (95%CI, 4.97–5.12) had a stronger association with sedation and somnolence when compared to atypical antipsychotics ROR = 4.65 (95%CI, 4.47–4.84). Conclusion: We conducted a head-to-head comparison of thirty-seven antipsychotics and ranked the compounds based on the association of sedation and somnolence from ADR data collected throughout 16 years from the FAERS. The results are informative and with recent interests in repurposing phenothiazine antipsychotics in infectious disease and oncology provides an informative assessment of the compounds during repurposing and in psychopharmacology.

Use of antipsychotics in Denmark 1997-2018: a nation-wide drug utilisation study with focus on off-label use and associated diagnoses.

Antipsychotics are primarily labelled for the treatment of severe mental illness and have documented clinical utility in certain neurological disorders or palliative care. However, off-label use of antipsychotics is common and increasing, and prior studies on antipsychotic utilisation have not specifically assessed users in neurology, palliative care or general practice. We aimed to explore diagnoses associated with antipsychotic use, treatment patterns and characteristics of users without diagnoses relevant to antipsychotic treatment. Population-based study identifiying all users of antipsychotics in Denmark (pop 5.7 mio.) 1997-2018 in the Danish National Prescription Register (DNPR). Possible indications for antipsychotic therapy were evaluated using in- and outpatient contacts from the DNPR. Users were divided hierarchically into six groups: severe mental disorders (schizophrenia, bipolar-spectrum disorders), chronic mental disorders (dementias, mental retardation, autism), other mental disorders (depression-spectrum, anxiety and personality disorders, etc.), selected neurological diseases, cancer and antipsychotic users without any of these diagnoses. This last group was characterised regarding demographics, antipsychotic use, health care utilisation and likely antipsychotic treatment initiator in 2018. Altogether, 630 307 antipsychotic users were identified, of whom 127 649 had filled prescriptions during 2018. Users without diagnoses relevant to antipsychotic treatment comprised of the largest group (37%), followed by schizophrenia and bipolar-spectrum disorders (34%), other mental disorders (15%), dementia, autism and mental retardation (11%), cancer (2.2%) and neurological diagnoses (2.0%). Of 37 478 incident users in 2018, 39% had no diagnosis relevant to antipsychotic treatment, 7.9% had major depression, 7.7% neurotic/stress-related disorders and 7.5% dementia. Quetiapine was most commonly used, both overall (51%) and among users without diagnoses relevant to antipsychotic treatment (58%). Of 14 474 incident users in 2018 without diagnoses relevant to antipsychotic treatment, treatment was most likely initiated by a general practitioner (65%), with only 17% seeing a psychiatrist during the following year. As many as 18% of patients with adjustment disorders and 14% of those without relevant diagnoses for antipsychotic use, remained on antipsychotic treatment 5 years after their first prescription. Over one-third of antipsychotic users in Denmark did not have psychiatric, neurological or cancer diagnoses as possible indications for antipsychotic therapy. Many antipsychotics are initiated or prescribed in general practice, and a concerningly large subgroup without documented diagnoses relevant for antipsychotics continued to receive them. Rational prescribing, adequate side effect monitoring and further research into reasons for the observed antipsychotic use patterns and their risk-benefit ratio are needed.