Trends in antipsychotic treatment of children and adolescents in Israel from post-mental health reform to post-COVID19 pandemic (2015-2023)

Trends in antipsychotic treatment of children and adolescents in Israel from post-mental health reform to post-COVID19 pandemic (2015-2023) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Trends in antipsychotic treatment of children and adolescents in Israel from post-mental health reform to post-COVID19 pandemic (2015-2023) Rachel Nega, Ron Walfisch, Michal Taler, Martin Efron, Nurit El Bar, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5337808/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Apr, 2025 Read the published version in European Child & Adolescent Psychiatry → Version 1 posted 11 You are reading this latest preprint version Abstract This study investigates the patterns of antipsychotic drug dispensations among children and adolescents from 2015 to 2023, with a focus on the impact of introducing national health reform (2015) and the COVID-19 pandemic. Data from Maccabi Healthcare Services, encompassing 1,105,439 individuals aged 6 to 18 years was analyzed using a retrospective cohort study. We investigated the incidence rates of antipsychotic prescriptions by age, sex, socioeconomic status, and geographical region. During the study period, there was a 15% overall increase in antipsychotics prescriptions. Higher rates of prescription were noted among males aged 6-11 and females aged 14-18. Significant increases in prescriptions were observed following the mental health reform and the COVID-19 pandemic. Low socioeconomic status and peripheral regions exhibited higher and increasing prescription rates. Seasonal patterns revealed peaks in the fourth quarter of each year. The study highlights an overall increase in antipsychotic prescriptions, influenced by policy changes and the pandemic. Inequality in prescription rates by socioeconomic status and geographical location underscore the need for targeted mental health interventions. The findings also indicate the enduring effects of the COVID-19 pandemic on youth mental health and the utilization of antipsychotic medications. Antipsychotics COVID-19 children adolescents prescription trends socioeconomic status Figures Figure 1 Figure 2 Introduction Antipsychotics are prescribed to youths for a range of psychiatric disorders including Schizophrenia, Bipolar Affective Disorder, Attention-Deficit/Hyperactivity Disorder (ADHD), Anxiety Disorders, Depression, Conduct Disorder, Disruptive Behavior Disorder and Autism Spectrum Disorder, [ 1 ]. Previous studies worldwide have raised concerns about the increasing prescription of antipsychotics to children and adolescents from the early 1990s to the present time [ 2 – 5 ]. There is a worldwide rise in antipsychotics’ prescriptions ranging from 29–114% between the 1990s and the 2010s, and continuing with more moderate increases or slight decrease in the 2020s [ 6 – 10 ]. There have been reports of a rise in mental health morbidity and use of medications in youth following the COVID-19 pandemic [ 11 ]. In a recent observational cohort study aiming to quantify the effect of the COVID-19 pandemic on adolescent mental health, our group found 28% increase in antipsychotic use during the COVID-19 pandemic (2021) compared to the pre-COVID period (2017) [ 11 ]. In the current study we aimed at extending our previous study to an elongated time period, from 2015 to 2023. Additionally, our previous study focused only on adolescents and in the present study we also included children from the age of 6. In 2015, as part of ongoing efforts to improve mental health services in Israel, the Ministry of Health introduced a comprehensive mental health care reform. The reform transferred the responsibility for delivering mental health services from the Ministry of Health to the Health Funds, thereby integrating mental and physical health care under one single provider [ 12 ]. The aims of this reform were to enhance the quality, availability, and simplicity of access to mental health services through the establishment of multiple clinics, extension of clinic operating hours, expansion of treatment choices, and reduction of waiting periods. In addition, the reform aimed to diminish the social stigma associated with mental health problems by incorporating mental health treatments into regular professional clinics [ 12 ]. The aim of the present study was to enhance our understanding of antipsychotic medication treatment trends in Israel across a broad age range, including both children and adolescents over an extended timeframe - within the eight years following the initiation of the Israeli mental health reform. Our specific aims were: 1. To investigate the antipsychotic medication treatment trends in Israel from July 1, 2015 (the time period since the initiation of the Israeli mental health reform) to June 30, 2023 (more than two years following the beginning of the COVID-19 pandemic). We hypothesized that there would be a gradual increase in antipsychotic prescriptions during the initial period, in response to the inclusion of psychiatric services in the health services basket. Additionally, we hypothesized that there would be another increase in prescribing antipsychotic medications immediately following the onset of the COVID-19 pandemic that will be maintained thereafter. 2. To examine the effect of sex, age, residential area and socioeconomic status (SES) on the trends of antipsychotic prescriptions during the study period. We hypothesized that factors related to inequality, such as low SES or residing in a peripheral area, would result in higher rates of antipsychotics treatment [ 11 , 13 ]. Conversely, we anticipated that lower accessibility to mental health services would lead to a decrease in antipsychotics’ prescription rates. 3. To explore change patterns in antipsychotic prescriptions during the year cycle. Based on previous studies, we predicted an increase in antipsychotics prescriptions during the fourth quartile (October to December) of each year, related to behavioral issues emerging with the return to school routine after the summer break and the Jewish holidays [ 14 , 15 ] Methods Study Design We conducted a retrospective cohort study examining antipsychotic medications’ dispensations records for children and adolescents aged 6-18 years between July 1, 2015, and June 30, 2023. Data in this study originated from Maccabi Healthcare Services (MHS), the second largest of four nationwide health funds that act both as the insurer and provider of universal healthcare services, which serves 25% of the Israeli population. The data from MHS includes only dispensations of psychiatric medications within the Health Maintenance Organization (HMO) or pharmacies under agreement with the HMO . Antipsychotic medications were identified by Anatomical Therapeutic Chemical code N05A. Approval for this study was granted by ' Maccabi ' Health Services institutional review board (MHS-0098-23), and informed consent was waived since this is a retrospective study that does not involve any intervention or require informed consent. The data was obtained in a de-identified manner and securely stored in accordance with the guidelines. Demographics We examined trends in antipsychotic medications dispensations stratified by age subgroups (6-7, 8-9, 10-11, 12-13, 14-15, 16-17), sex assigned at birth (male, female), region within Israel, and SES measured on a scale from 1 to 10 and categorized into low (1-3), medium (4-7), and high (8-10). SES was determined by the participants' geo-statistical area of residence using Points Location Services Ltd (POINTS). The POINTS scale is routinely used by the Israeli Ministry of Health and all 4 HMOs [11]. Individuals with unlisted SES or District were excluded from the SES or District sub analysis (2.49% and 1.14%, respectively) but were included in all other analyses. Sex and age were listed for all members. Statistical Analysis First time medication dispensation was identified for all MHS members between 6 and 18 (exclusive) years of age (referred to as the “Study population”) per year, at the end of the year, and per quartile, at the end of each quartile. Incidence rates per 10,000 members were deduced on a yearly and quartile basis, by dividing the number of first-time dispensations by the population size at the end of each such period. This was done for the entire cohort, and for sub-cohorts stratified by sex, age, SES and geographic location. Comparison of incidence rates between two time periods, such as consecutive years or quartiles, was done by computing incidence rate ratios (IRRs), and the associated 95% confidence intervals (CIs) and p-values. P-values <0.05 were considered statistically significant. To ensure that covariate distribution among the different study populations was similar throughout the observation period, standardized mean differences (SMD) among the study years were assessed, with a value smaller than 0.1 indicating that that is indeed the case. Trends in incidence rate were assessed using the Mann-Kendall [16, 17] test using the pymannkendal python package [18]. A nonparametric model was used, rather than a linear one, because an initial examination of the data suggested that the annual incidence did not follow a linear model. Analysis of dispensation patterns for different drug types was done by considering the study period as a whole, and stratifying first-time dispensations by age, sex, and drug type. Statistical analyses were conducted using Excel, SPSS 29.0 and Python 3.11.5. Results The study cohort included 1,105,439 children and adolescents, MHS members, aged 6-18 years; 1,668 members with antipsychotic dispensation records before the age of 6 were excluded because typically, children under the age of 6 are referred to a Child Development unit, where child neurologists, specializing in developmental delay provide care. From the age of 6 onwards, psychiatric care is generally provided by child and adolescent psychiatrists . Overall, incidence of antipsychotic dispensations during the study period was 18,911. Mean yearly numbers by demographics are presented in Table 1. Throughout the study period males constituted 51.23% of the population, age distribution was roughly uniform, and cohorts included about 13.35% low-SES members and 50.01% medium SES members. Most patients were geographically located at the center of Israel (Center, Sharon and Jerusalem-Shfela districts), with roughly 15% in each of the peripheral regions (North and South). The SES distribution is illustrated in figure A in the supplementary material. Table 1 Mean yearly demographic distribution and characteristics of the study population between 2015 and 2023 Variable Mean N (%) Mean Incidence (%) Mean incidence per 10,000 Standard mean deviation (SMD) Total 490,625 2,364 48.18 Sex Males 251,365 51.23 1477 62.48 58.76 0.002 Females 239,260 48.77 887 37.52 37.07 0.001 Age group 6 - 7 84,820 17.29 401 16.96 47.42 0.007 8 – 9 83,647 17.05 416 17.60 49.83 0.007 10 - 11 82,366 16.79 356 15.06 43.18 0.004 12 - 13 81,497 16.61 354 14.97 43.32 0.002 14 - 15 79,904 16.29 400 16.92 49.66 0.001 16 - 17 78,390 15.98 445 18.82 56.31 0.004 Socioeconomic status Low (0-3) 65,482 13.35 702 29.71 107.21 0.011 Med (4-7) 245,342 50.01 835 35.31 34.03 0.012 High (8-10) 179,801 36.65 768 32.49 42.71 0.022 District South 75,143 15.32 327 13.81 43.52 0.018 North 80,758 16.46 401 16.97 49.65 0.029 Sharon 107,638 21.94 322 13.64 29.92 0.008 Jerusalem and Shfela 122,380 24.94 738 18.54 35.79 0.018 Center 104,706 21.43 848 35.89 80.99 0.006 Figure 1 depicts the yearly incidence rate throughout the study period. Incidence rate of antipsychotics prescriptions rose from 44.09 prescriptions per 10,000 members at the onset of the study period in 2015-2016, to 50.62 during the 2022-2023 year at its end. However, overall, there is no clearly increasing trend (Mann-Kendel tau = 0.43, p = 0.17). Indeed, analysis of the incidence risk ratio between consecutive years suggested that for the most part, it was not significantly different from 1; There was a significant increase right after the reform (2016-2017 vs. 2016-2017; IRR 1.10 95% CI 1.04-1.16), and following the pandemic (2021-2022 vs 2020-2021; IRR 1.13 95% CI 1.08-1.19), yet there was also a significant decrease in the first year of the pandemic relative to the previous one (2019-2020 vs 2018-2019; IRR 0.92 95% CI 0.86-0.98). Stratifying this analysis by sex, age group, SES and region generally yielded similar results. Among females, among the two upper SES groups and among the northern region sub-cohort – there was a higher incidence rate at the end of the study period than at its onset, but not a statistically significant increasing trend. Conversely, trend analysis of the low SES cohort and the southern region suggested a statistically significant increase in both (tau = 0.64, p = 0.03 in both cases). Among males and among the central regions cohort, the incidence rate tended to remain the same throughout the study period. These trends are depicted in Supplementary Figures B-E. Examination of annual incidence patterns during each year (Figure 2) suggested a sharp increase in incidence during Q4 (Oct-Dec), which was evident in six of the eight years of observation, with significant IRR relative to Q3 in 4 of them, most notably in 2021 (IRR 1.44 relative to Q3, 95% CI 1.29-1.61). Conversely, a decrease was observed during Q2 in all years except 2021, and these decreases were statistically significant (relative to Q1) in four cases. Finally, we examined the study period as a whole, stratifying new dispensations by age, sex and drug type. As seen in Supplement Figure F, among males, incidence rate seems to decrease with age, from 70.59 among children 6-9, to 52.98 among teenagers. Conversely, among females, incidence is higher at older ages, increasing from 25.53 at ages 6-9 to 45.46 at ages 14-17. The most frequently prescribed medication was Risperidone (52%) followed by Aripiprazole (31.4%) and Quetiapine (7.9%). Among males, incidence of Risperidone prescriptions decreased with age (from 49.10 to 27.38), while among females it was similar level at all ages. Among both sexes, Quetiapine is prescribed mainly to teenagers, with increasing incidence from ages 12-13 to 16-17 (from 2.16 to 6.90 in males and from 4.90 to 13.59 in females). Discussion This study examined trends in antipsychotic treatment initiation among children and adolescents in Israel from 2015 to 2023, revealing a 15% increase in incidence rates along the study period. This rise was primarily driven by increases in males aged 6–11 and females aged 14–18. A significant rise in prescriptions occurred in the first year following the implementation of the mental health reform (2016–2017) and again in the year following the COVID-19 pandemic (2021–2022) an increase that persisted to the end of the study period- until the end of 2023. Additionally, antipsychotic prescriptions significantly increased in peripheral areas, especially among lower SES populations, while remaining stable in central regions. Finally, we observed seasonal patterns, with a consistent rise in antipsychotics prescription in the fourth quarter of each year. Trends in antipsychotic treatment initiation among children and adolescents in Israel from 2015 to 2023 reveal a 15% increase in incidence rates over the study period. Although this overall rise was not statistically significant across the full eight years, there were two time points with significant increases- following the implementation of mental health reform in Israel and following the COVID-19 pandemic. The initial sharp 10% increase in antipsychotics prescription following the implementation of the mental health reform can be attributed to improved access for new patients who previously faced geographic or financial barriers to care. The COVID-19 pandemic had a notable impact on antipsychotic prescription trends. Our findings support earlier studies that reported an initial decrease in mental health treatment during the first phase of the pandemic, followed by a sharp rise in psychiatric service utilization as restrictions eased and schools reopened [ 19 , 20 ]. This study extends findings by our group and others [ 21 , 22 ] demonstrating that the rise in antipsychotic prescriptions persisted throughout 2023, suggesting a continuous negative impact of the pandemic on pediatric mental health. Our results of an overall higher prescription rate among males compared to females with specific increases in males aged 6–11 and females aged 14–18, align with global trends indicating that males are prescribed antipsychotics more frequently than females [ 23 – 26 ]. The higher prescription rates in males aged 6–11 may be attributed particularly to treatments of impulsive or aggressive outbursts in children with ADHD and oppositional behaviors [ 23 , 26 – 28 ] which usually picks during elementary school age years in males [ 29 ]. Conversely, the increase in antipsychotic use among adolescent females aged 14–15 can be linked to increase in the prevalence of mood and behavioral dysregulation, and self-injuries, among females during adolescence [ 30 , 31 ]. We found that there was a more robust increase in antipsychotics prescriptions in the peripheral areas of Israel and in the lower SES group, a trend observed in previous studies as well [ 32 , 33 ]. This trend probably stems from the improved access to psychiatric services following Israel’s mental health reform, which targeted underserved populations by expanding services in peripheral areas and for disadvantaged populations. Additionally, the higher poverty indices reported for peripheral areas [ 34 ] and low SES populations may contribute to limited access to psychosocial interventions, inadequate social services, and lack of support in the educational services for students with support needs. Furthermore, the peripheral and low SES population also exhibited greater increase in antipsychotics prescriptions during the COVID-19 pandemic, in line with other publication of increased vulnerability of low SES populations to coping with the COVID-19 related stress [ 35 ]. The above factors may have contributed to more severe psychiatric presentations in these populations, necessitating more use of antipsychotics and also highlight the impact of expanded mental health services on prescription trends. The observed peak in prescriptions during the fourth quarter (October-December) of each year aligns with previous research showing that the return to school after the summer break is a period of increased demands for functioning and hence heightened stress [ 36 ], which is associated with exacerbation of psychiatric symptoms in children [ 14 , 15 ]. Our study has several strengths, including a large sample size and extended observation period, which allowed us to capture long-term trends across different demographic groups. Furthermore, our use of nonparametric trend analysis, as opposed to linear modelling, provided a more accurate depiction of fluctuations in prescription rates over time. By stratifying our analyses by sex, age, SES, and geographic region, we were able to identify patterns that offer valuable insights into the factors influencing antipsychotic use in this population. However, there are also several limitations to this study. First, because the data were drawn from Maccabi Healthcare Services, our findings may not be fully generalizable to the entire Israeli population, particularly individuals insured by other health maintenance organizations. Additionally, the study relied on prescription records, which only capture cases where antipsychotics were both prescribed and dispensed, potentially underestimating the true scope of medication use. Moreover, the lack of detailed clinical data regarding the indications for antipsychotic prescriptions limits our ability to recognize the specific conditions for which these medications were prescribed. In conclusion, this study highlights the growing prevalence of antipsychotic treatment initiation among children and adolescents in Israel, demonstrating a notable 15% increase in incidence rates over the period from 2015 to 2023. These findings are crucial for informing healthcare policies, as they reveal specific demographic patterns and the impact of the mental health reform in Israel and the COVID-19 pandemic, on treatment trends. Future research should incorporate longitudinal designs with clinical assessments to better understand the underlying factors driving antipsychotic prescriptions in children and adolescents. Declarations Conflict of interest The authors declare no conflict of interest to be present in this study. Ethics approval Approval for this study was granted by' Maccabi' Health Services institutional review board (MHS-0098-23). Informed consent Not applicable. Fundings This work was supported by grant from Kirsh Foundation. Author Contribution R.N. led the conceptualization, methodology, validation, formal analysis, and investigation, managed resources, and contributed to both the original draft and review, editing, and visualization. R.W. contributed resources, drafted the original manuscript, participated in review and editing, and handled data visualization. M.T. contributed to conceptualization, methodology, resources, and assisted in writing the original draft and review. R.P.G., L.L.S., M.E. (investigation, methodology, review, and editing), N.E.B., and G.B. contributed to conceptualization, validation, formal analysis, investigation, resources, and manuscript review and editing. Y.B. provided conceptualization, methodology, validation, formal analysis, investigation, resources, and contributed to drafting, review, editing, and visualization, as well as project supervision. D.G. oversaw project administration, provided supervision, and contributed to visualization, review, editing, resources, validation, methodology, and conceptualization.all authors approved the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Acknowledgement None Data availability statement The data that support the findings of this study are available from the corresponding author upon request. References Penfold RB, Stewart C, Hunkeler EM, et al (2013) Use of Antipsychotic Medications in Pediatric Populations: What do the Data Say? Curr Psychiatry Rep 15:426. https://doi.org/10.1007/s11920-013-0426-8 Crystal S, Olfson M, Huang C, et al (2009) Broadened Use Of Atypical Antipsychotics: Safety, Effectiveness, And Policy Challenges. Health Aff 28:w770–w781. https://doi.org/10.1377/hlthaff.28.5.w770 dosReis S, Yoon Y, Rubin DM, et al (2011) Antipsychotic Treatment Among Youth in Foster Care. Pediatrics 128:e1459–e1466. https://doi.org/10.1542/peds.2010-2970 Olfson M, Crystal S, Huang C, Gerhard T (2010) Trends in Antipsychotic Drug Use by Very Young, Privately Insured Children. J Am Acad Child Adolesc Psychiatry 49:13–23. https://doi.org/10.1097/00004583-201001000-00005 Olfson M, Blanco C, Liu S-M, et al (2012) National Trends in the Office-Based Treatment of Children, Adolescents, and Adults With Antipsychotics. Arch Gen Psychiatry 69:1247. https://doi.org/10.1001/archgenpsychiatry.2012.647 Rani F, Murray ML, Byrne PJ, Wong ICK (2008) Epidemiologic Features of Antipsychotic Prescribing to Children and Adolescents in Primary Care in the United Kingdom. Pediatrics 121:1002–1009. https://doi.org/10.1542/peds.2007-2008 Radojčić MR, Pierce M, Hope H, et al (2023) Trends in antipsychotic prescribing to children and adolescents in England: cohort study using 2000–19 primary care data. Lancet Psychiatry 10:119–128. https://doi.org/10.1016/S2215-0366(22)00404-7 Kalverdijk LJ, Bachmann CJ, Aagaard L, et al (2017) A multi-national comparison of antipsychotic drug use in children and adolescents, 2005–2012. Child Adolesc Psychiatry Ment Health 11:55. https://doi.org/10.1186/s13034-017-0192-1 Pringsheim T, Stewart DG, Chan P, et al (2019) The Pharmacoepidemiology of Psychotropic Medication Use in Canadian Children from 2012 to 2016. J Child Adolesc Psychopharmacol 29:740–745. https://doi.org/10.1089/cap.2019.0018 Pringsheim T, Lam D, Patten SB (2011) The Pharmacoepidemiology of Antipsychotic Medications for Canadian Children and Adolescents: 2005–2009. J Child Adolesc Psychopharmacol 21:537–543. https://doi.org/10.1089/cap.2010.0145 Bilu Y, Flaks-Manov N, Bivas-Benita M, et al (2023) Data-Driven Assessment of Adolescents’ Mental Health During the COVID-19 Pandemic. J Am Acad Child Adolesc Psychiatry 62:920–937. https://doi.org/10.1016/j.jaac.2022.12.026 The Mental Health Reform Ministry of Health. https://www.gov.il/en/pages/mental-health-reform. Accessed 24 Jul 2024 Bonnot O, Dufresne M, Herrera P, et al (2017) Influence of socioeconomic status on antipsychotic prescriptions among youth in France. BMC Psychiatry 17:82. https://doi.org/10.1186/s12888-017-1232-3 Radhakrishnan L, Carey K, Pell D, et al (2023) Seasonal Trends in Emergency Department Visits for Mental and Behavioral Health Conditions Among Children and Adolescents Aged 5–17 Years — United States, January 2018–June 2023. MMWR Morb Mortal Wkly Rep 72:1032–1040. https://doi.org/10.15585/mmwr.mm7238a3 Plemmons G, Hall M, Doupnik S, et al (2018) Hospitalization for Suicide Ideation or Attempt: 2008–2015. Pediatrics 141:. https://doi.org/10.1542/peds.2017-2426 Mann HB (1945) Nonparametric Tests Against Trend. Econometrica 13:245. https://doi.org/10.2307/1907187 Moran PAP, Kendall MG (1973) Rank Correlation Methods. Int Stat Rev 41:399. https://doi.org/10.2307/1402637 Hussain Md, Mahmud I (2019) pyMannKendall: a python package for non parametric Mann Kendall family of trend tests. J Open Source Softw 4:1556. https://doi.org/10.21105/joss.01556 Samji H, Wu J, Ladak A, et al (2022) Review: Mental health impacts of the COVID‐19 pandemic on children and youth – a systematic review. Child Adolesc Ment Health 27:173–189. https://doi.org/10.1111/camh.12501 Panchal U, Salazar de Pablo G, Franco M, et al (2023) The impact of COVID-19 lockdown on child and adolescent mental health: systematic review. Eur Child Adolesc Psychiatry 32:1151–1177. https://doi.org/10.1007/s00787-021-01856-w Costales B, Slama NE, Penfold RB, et al (2024) On- and Off-Label Atypical Antipsychotic Prescription Trends Across a Nine-Year Period Among Adolescents Pre- to Post-COVID-19. Acad Pediatr 24:995–1000. https://doi.org/10.1016/j.acap.2024.03.003 Valtuille Z, Acquaviva E, Trebossen V, et al (2024) Psychotropic Medication Prescribing for Children and Adolescents After the Onset of the COVID-19 Pandemic. JAMA Netw Open 7:e247965. https://doi.org/10.1001/jamanetworkopen.2024.7965 Olfson M, King M, Schoenbaum M (2015) Treatment of Young People With Antipsychotic Medications in the United States. JAMA Psychiatry 72:867. https://doi.org/10.1001/jamapsychiatry.2015.0500 Gangapersad RN, Zhou G, Garcia-Gomez P, et al (2024) Comparison of antipsychotic drug use in children and adolescents in the Netherlands before and during the COVID-19 pandemic. Eur Child Adolesc Psychiatry 33:2695–2703. https://doi.org/10.1007/s00787-023-02340-3 Kalverdijk LJ, Tobi H, van den Berg PB, et al (2008) Use of Antipsychotic Drugs Among Dutch Youths Between 1997 and 2005. Psychiatric Services 59:554–560. https://doi.org/10.1176/ps.2008.59.5.554 Harrison JN, Cluxton-Keller F, Gross D (2012) Antipsychotic Medication Prescribing Trends in Children and Adolescents. Journal of Pediatric Health Care 26:139–145. https://doi.org/10.1016/j.pedhc.2011.10.009 Rettew DC, Greenblatt J, Kamon J, et al (2015) Antipsychotic Medication Prescribing in Children Enrolled in Medicaid. Pediatrics 135:658–665. https://doi.org/10.1542/peds.2014-2260 Pathak P, West D, Martin BC, et al (2010) Evidence-Based Use of Second-Generation Antipsychotics in a State Medicaid Pediatric Population, 2001–2005. Psychiatric Services 61:123–129. https://doi.org/10.1176/ps.2010.61.2.123 Girard L-C, Tremblay RE, Nagin D, Côté SM (2019) Development of Aggression Subtypes from Childhood to Adolescence: a Group-Based Multi-Trajectory Modelling Perspective. J Abnorm Child Psychol 47:825–838. https://doi.org/10.1007/s10802-018-0488-5 Madge N, Hewitt A, Hawton K, et al (2008) Deliberate self‐harm within an international community sample of young people: comparative findings from the Child & Adolescent Self‐harm in Europe (CASE) Study. Journal of Child Psychology and Psychiatry 49:667–677. https://doi.org/10.1111/j.1469-7610.2008.01879.x American Psychiatric Association DSMTF, & APADS (2013) Diagnostic and statistical manual of mental disorders: DSM-5 (Vol. 5, No. 5) Verdoux H, Pambrun E, Cortaredona S, et al (2015) Antipsychotic prescribing in youths: a French community-based study from 2006 to 2013. Eur Child Adolesc Psychiatry 24:1181–1191. https://doi.org/10.1007/s00787-014-0668-y Bonnot O, Dufresne M, Herrera P, et al (2017) Influence of socioeconomic status on antipsychotic prescriptions among youth in France. BMC Psychiatry 17:82. https://doi.org/10.1186/s12888-017-1232-3 Israel National Insurance National Insurance’s publication: 2021 Poverty and Social Gaps Report in Israel. https://www.btl.gov.il/english%20homepage/publications/poverty_report/pages/default.aspx. Accessed 29 Jul 2024 Jeriček Klanšček H, Furman L (2023) Socioeconomic Deprivation and Inequalities in Mental Well-Being during the COVID-19 Pandemic among Adolescents. Int J Environ Res Public Health 20:6233. https://doi.org/10.3390/ijerph20136233 Hertz-Palmor N, Gothelf D (2024) Unexpected mental health improvement in children and adolescents during COVID-19-who benefits from staying at home? Eur Child Adolesc Psychiatry 33:1235–1237. https://doi.org/10.1007/s00787-024-02432-8 Additional Declarations No competing interests reported. Supplementary Files Supplementaryinformation.docx Cite Share Download PDF Status: Published Journal Publication published 04 Apr, 2025 Read the published version in European Child & Adolescent Psychiatry → Version 1 posted Editorial decision: Revision requested 13 Dec, 2024 Reviews received at journal 09 Dec, 2024 Reviews received at journal 04 Dec, 2024 Reviews received at journal 28 Nov, 2024 Reviewers agreed at journal 11 Nov, 2024 Reviewers agreed at journal 10 Nov, 2024 Reviewers agreed at journal 07 Nov, 2024 Reviewers invited by journal 06 Nov, 2024 Editor assigned by journal 29 Oct, 2024 Submission checks completed at journal 29 Oct, 2024 First submitted to journal 26 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5337808","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":375484345,"identity":"002642cf-507b-4d58-adfb-835b7fe81a27","order_by":0,"name":"Rachel Nega","email":"","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Rachel","middleName":"","lastName":"Nega","suffix":""},{"id":375484346,"identity":"dce668d3-20e5-418d-8841-d0be1938927b","order_by":1,"name":"Ron Walfisch","email":"","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ron","middleName":"","lastName":"Walfisch","suffix":""},{"id":375484349,"identity":"4c6663db-4721-4e7d-86f6-efb6056027d6","order_by":2,"name":"Michal Taler","email":"","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Michal","middleName":"","lastName":"Taler","suffix":""},{"id":375484350,"identity":"44b14a9d-2416-4de5-9dda-a3e7a3de42f2","order_by":3,"name":"Martin Efron","email":"","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"","lastName":"Efron","suffix":""},{"id":375484351,"identity":"9b8f3248-37bc-413a-833f-1fc957299285","order_by":4,"name":"Nurit El Bar","email":"","orcid":"","institution":"Maccabi Health Care Services","correspondingAuthor":false,"prefix":"","firstName":"Nurit","middleName":"El","lastName":"Bar","suffix":""},{"id":375484352,"identity":"866d339b-3edb-4d4b-9b54-7219cdb5a8b1","order_by":5,"name":"Revital Perlov Gavze","email":"","orcid":"","institution":"Maccabi Health Care Services","correspondingAuthor":false,"prefix":"","firstName":"Revital","middleName":"Perlov","lastName":"Gavze","suffix":""},{"id":375484353,"identity":"3fbb4f53-3964-4f55-aab1-f4c1ee188035","order_by":6,"name":"Liat Lev-Shalem","email":"","orcid":"","institution":"Maccabi Health Care Services","correspondingAuthor":false,"prefix":"","firstName":"Liat","middleName":"","lastName":"Lev-Shalem","suffix":""},{"id":375484354,"identity":"bacac875-2ae8-4915-aca2-576c10d4c094","order_by":7,"name":"Gilad Bodenheimer","email":"","orcid":"","institution":"Maccabi Health Care Services","correspondingAuthor":false,"prefix":"","firstName":"Gilad","middleName":"","lastName":"Bodenheimer","suffix":""},{"id":375484355,"identity":"ad4f12f7-fe4b-44cd-ba7d-aa7da890f8e9","order_by":8,"name":"Yonatan Bilu","email":"","orcid":"","institution":"KI Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Yonatan","middleName":"","lastName":"Bilu","suffix":""},{"id":375484357,"identity":"6d4a3cbb-b5d2-4951-8c1c-db71bd6ec828","order_by":9,"name":"Doron Gothelf","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIie2PsWrDMBCGrxjs5aCrQsF+hV8InA4JHfsaDh66OBDIkrGdsohkdd/CeYIKDO2SB+jYUsjUQVAoGTxUhHZIwcqaQR/coDt9/HdEgcB5EhPN0vRfE9ceI3IKlOLfr3+KOKlM9LFC/Up2u35+s8DdU7KVH0xdBhO9W5r1K3LbJrIGpporJWuCbEyshG8xWZfxFaObaqpyYQkXjaHce8tB6dxifPk53BeEm8Yk314lE04hoGBR5eRSJo1hfwq4zQcakPp1Nx/UUOVjy3NR+FKWDzuxXyBL1uXmixfpePWy3FjbjfpTzPHTVeSq6BVcyr1nGAgEAoEDP6snRT9aW8jrAAAAAElFTkSuQmCC","orcid":"","institution":"Sheba Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Doron","middleName":"","lastName":"Gothelf","suffix":""}],"badges":[],"createdAt":"2024-10-26 13:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5337808/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5337808/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00787-025-02691-z","type":"published","date":"2025-04-04T15:57:31+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":69437418,"identity":"af3cdf2a-0d78-4c0a-be04-a52f59f506dd","added_by":"auto","created_at":"2024-11-20 10:47:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":43016,"visible":true,"origin":"","legend":"\u003cp\u003eYearly incidence rate of antipsychotic medication dispensation: a. entire population; b. females by age group; c. males by age group\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5337808/v1/4aa2233d4e2375977d18ce3a.png"},{"id":69437416,"identity":"c0537b8c-940b-47b8-a74f-03dff2be91c6","added_by":"auto","created_at":"2024-11-20 10:47:58","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":78007,"visible":true,"origin":"","legend":"\u003cp\u003eQuartile incidence rates of antipsychotic medication dispensation at each year\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5337808/v1/b43ac50cce1f6fb2276af9fe.png"},{"id":80082292,"identity":"ad72cce7-de8c-4d80-acae-86716f2fedff","added_by":"auto","created_at":"2025-04-07 16:08:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":711797,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5337808/v1/ac1a20d1-1cb1-492c-b75c-eae1f4f0ca4d.pdf"},{"id":69437419,"identity":"e8addff3-98bd-49a9-892b-e80d5cb4467f","added_by":"auto","created_at":"2024-11-20 10:47:58","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":520944,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryinformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-5337808/v1/5c331b528cfb2e1f738ba116.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Trends in antipsychotic treatment of children and adolescents in Israel from post-mental health reform to post-COVID19 pandemic (2015-2023)","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAntipsychotics are prescribed to youths for a range of psychiatric disorders including Schizophrenia, Bipolar Affective Disorder, Attention-Deficit/Hyperactivity Disorder (ADHD), Anxiety Disorders, Depression, Conduct Disorder, Disruptive Behavior Disorder and Autism Spectrum Disorder, [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Previous studies worldwide have raised concerns about the increasing prescription of antipsychotics to children and adolescents from the early 1990s to the present time [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. There is a worldwide rise in antipsychotics\u0026rsquo; prescriptions ranging from 29\u0026ndash;114% between the 1990s and the 2010s, and continuing with more moderate increases or slight decrease in the 2020s [\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere have been reports of a rise in mental health morbidity and use of medications in youth following the COVID-19 pandemic [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In a recent observational cohort study aiming to quantify the effect of the COVID-19 pandemic on adolescent mental health, our group found 28% increase in antipsychotic use during the COVID-19 pandemic (2021) compared to the pre-COVID period (2017) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In the current study we aimed at extending our previous study to an elongated time period, from 2015 to 2023. Additionally, our previous study focused only on adolescents and in the present study we also included children from the age of 6.\u003c/p\u003e \u003cp\u003eIn 2015, as part of ongoing efforts to improve mental health services in Israel, the Ministry of Health introduced a comprehensive mental health care reform. The reform transferred the responsibility for delivering mental health services from the Ministry of Health to the Health Funds, thereby integrating mental and physical health care under one single provider [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The aims of this reform were to enhance the quality, availability, and simplicity of access to mental health services through the establishment of multiple clinics, extension of clinic operating hours, expansion of treatment choices, and reduction of waiting periods. In addition, the reform aimed to diminish the social stigma associated with mental health problems by incorporating mental health treatments into regular professional clinics [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aim of the present study was to enhance our understanding of antipsychotic medication treatment trends in Israel across a broad age range, including both children and adolescents over an extended timeframe - within the eight years following the initiation of the Israeli mental health reform. Our specific aims were: 1. To investigate the antipsychotic medication treatment trends in Israel from July 1, 2015 (the time period since the initiation of the Israeli mental health reform) to June 30, 2023 (more than two years following the beginning of the COVID-19 pandemic). We hypothesized that there would be a gradual increase in antipsychotic prescriptions during the initial period, in response to the inclusion of psychiatric services in the health services basket. Additionally, we hypothesized that there would be another increase in prescribing antipsychotic medications immediately following the onset of the COVID-19 pandemic that will be maintained thereafter. 2. To examine the effect of sex, age, residential area and socioeconomic status (SES) on the trends of antipsychotic prescriptions during the study period. We hypothesized that factors related to inequality, such as low SES or residing in a peripheral area, would result in higher rates of antipsychotics treatment [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Conversely, we anticipated that lower accessibility to mental health services would lead to a decrease in antipsychotics\u0026rsquo; prescription rates. 3. To explore change patterns in antipsychotic prescriptions during the year cycle. Based on previous studies, we predicted an increase in antipsychotics prescriptions during the fourth quartile (October to December) of each year, related to behavioral issues emerging with the return to school routine after the summer break and the Jewish holidays [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a retrospective cohort study examining antipsychotic medications\u0026rsquo; dispensations records for children and adolescents aged 6-18 years between July 1, 2015, and June 30, 2023. Data in this study originated from Maccabi Healthcare Services (MHS), the second largest of four nationwide health funds that act both as the insurer and provider of universal healthcare services, which serves 25% of the Israeli population. The\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003edata from MHS includes\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eonly dispensations of psychiatric medications within the Health Maintenance Organization (HMO) or pharmacies under agreement with the HMO\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e Antipsychotic medications were identified by Anatomical Therapeutic Chemical code N05A.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eApproval for this study was granted by\u003cspan dir=\"RTL\"\u003e\u0026apos;\u0026nbsp;\u003c/span\u003eMaccabi\u003cspan dir=\"RTL\"\u003e\u0026apos;\u003c/span\u003e Health\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eServices institutional review board\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e(MHS-0098-23), and\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003einformed\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003econsent\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003ewas waived since this is a retrospective study that does not involve any intervention or require informed consent. The data was obtained in a de-identified manner and securely stored in accordance with the guidelines.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDemographics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe examined trends in antipsychotic medications dispensations stratified by age subgroups (6-7, 8-9, 10-11, 12-13, 14-15, 16-17), sex assigned at birth (male, female),\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eregion within Israel, and SES measured on a scale from 1 to 10 and categorized into low (1-3), medium (4-7), and high (8-10). SES was determined by the participants\u0026apos; geo-statistical area of residence using Points Location Services Ltd (POINTS). The POINTS scale is routinely used by the Israeli Ministry of Health and all 4 HMOs [11]. Individuals with unlisted SES or District were excluded from the SES or District sub analysis (2.49% and 1.14%, respectively) but were included in all other analyses. Sex and age were listed for all members.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFirst time medication dispensation was identified for all MHS members between 6 and 18 (exclusive) years of age (referred to as the \u0026ldquo;Study population\u0026rdquo;) per year, at the end of the year, and per quartile, at the end of each quartile. Incidence rates per 10,000 members were deduced on a yearly and quartile basis, by dividing the number of first-time dispensations by the population size at the end of each such period. This was done for the entire cohort, and for sub-cohorts stratified by sex, age, SES and geographic location.\u003c/p\u003e\n\u003cp\u003eComparison of incidence rates between two time periods, such as consecutive years or quartiles, was done by computing incidence rate ratios (IRRs), and the associated 95% confidence intervals (CIs) and p-values. P-values \u0026lt;0.05 were considered statistically significant. To ensure that covariate distribution among the different study populations was similar throughout the observation period, standardized mean differences (SMD) among the study years were assessed, with a value smaller than 0.1 indicating that that is indeed the case.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTrends in incidence rate were assessed using the Mann-Kendall [16, 17] test using the pymannkendal python package [18]. A nonparametric model was used, rather than a linear one, because an initial examination of the data suggested that the annual incidence did not follow a linear model.\u003c/p\u003e\n\u003cp\u003eAnalysis of dispensation patterns for different drug types was done by considering the study period as a whole, and stratifying first-time dispensations by age, sex, and drug type.\u003c/p\u003e\n\u003cp\u003eStatistical analyses were conducted using Excel, SPSS 29.0 and Python 3.11.5.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study cohort included 1,105,439 children and adolescents, MHS members,\u0026nbsp;aged 6-18 years; 1,668 members with antipsychotic dispensation records before the age of 6 were excluded because typically, children under the age of 6 are referred to a Child Development unit, where child neurologists, specializing in developmental delay provide care. From the age of 6 onwards, psychiatric care is generally provided by child and adolescent psychiatrists\u003cspan dir=\"RTL\"\u003e.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eOverall, incidence of antipsychotic dispensations during the study period was 18,911. \u0026nbsp;Mean yearly numbers by demographics are presented in Table 1. Throughout the study period males constituted 51.23% of the population, age distribution was roughly uniform, and cohorts included about 13.35% low-SES members and 50.01% medium SES members. Most patients were geographically located at the center of Israel (Center, Sharon and Jerusalem-Shfela districts), with roughly 15% in each of the peripheral regions (North and South). The SES distribution is illustrated in figure A in the supplementary material.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u0026nbsp; Mean yearly demographic distribution and characteristics of the study population between 2015 and 2023\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"654\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean N\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Incidence\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean incidence per 10,000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStandard mean deviation (SMD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e490,625\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e2,364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e48.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Males\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e251,365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e51.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e1477\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e62.48\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e58.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Females\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e239,260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e48.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e887\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e37.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e37.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;6 - 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e84,820\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e17.29\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e401\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e16.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e47.42\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;8 \u0026ndash; 9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e83,647\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e17.05\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e416\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e17.60\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e49.83\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;10 - 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e82,366\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e16.79\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e15.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e43.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;12 - 13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e81,497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e16.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e14.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e43.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;14 - 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e79,904\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e16.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e16.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e49.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;16 - 17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e78,390\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e15.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e445\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e18.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e56.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSocioeconomic status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Low (0-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e65,482\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e13.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e702\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e29.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e107.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Med (4-7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e245,342\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e50.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e835\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e35.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e34.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;High (8-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e179,801\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e36.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e768\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e32.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e42.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDistrict\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;South\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e75,143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e15.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e13.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e43.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;North\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e80,758\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e16.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e401\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e16.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e49.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.029\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Sharon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e107,638\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e21.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e13.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e29.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003eJerusalem and Shfela\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e122,380\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e24.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e738\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e18.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e35.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.7706%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Center\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6208%;\"\u003e\n \u003cp\u003e104,706\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14.9847%;\"\u003e\n \u003cp\u003e21.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12.3853%;\"\u003e\n \u003cp\u003e848\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8.7156%;\"\u003e\n \u003cp\u003e35.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e80.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 13.7615%;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eFigure 1 depicts the yearly incidence rate throughout the study period. Incidence rate of antipsychotics prescriptions rose from 44.09 prescriptions per 10,000 members at the onset of the study period in 2015-2016, to 50.62 during the 2022-2023 year at its end. However, overall, there is no clearly increasing trend (Mann-Kendel tau = 0.43, p = 0.17). Indeed, analysis of the incidence risk ratio between consecutive years suggested that for the most part, it was not significantly different from 1; There was a significant increase right after the reform (2016-2017 vs. 2016-2017; IRR 1.10 95% CI 1.04-1.16), and following the pandemic (2021-2022 vs 2020-2021; IRR 1.13 95% CI 1.08-1.19), yet there was also a significant decrease in the first year of the pandemic relative to the previous one (2019-2020 vs 2018-2019; IRR 0.92 95% CI 0.86-0.98).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStratifying this analysis by sex, age group, SES and region generally yielded similar results. Among females, among the two upper SES groups and among the northern region sub-cohort \u0026ndash; there was a higher incidence rate at the end of the study period than at its onset, but not a statistically significant increasing trend. Conversely, trend analysis of the low SES cohort and the southern region suggested a statistically significant increase in both (tau = 0.64, p = 0.03 in both cases). Among males and among the central regions cohort, the incidence rate tended to remain the same throughout the study period. These trends are depicted in Supplementary Figures B-E. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eExamination of annual incidence patterns during each year (Figure 2) suggested a sharp increase in incidence during Q4 (Oct-Dec), which was evident in six of the eight years of observation, with significant IRR relative to Q3 in 4 of them, most notably in 2021 (IRR 1.44 relative to Q3, 95% CI 1.29-1.61). Conversely, a decrease was observed during Q2 in all years except 2021, and these decreases were statistically significant (relative to Q1) in four cases.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFinally, we examined the study period as a whole, stratifying new dispensations by age, sex and drug type. As seen in Supplement Figure F, among males, incidence rate seems to decrease with age, from 70.59 among children 6-9, to 52.98 among teenagers.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConversely, among females, incidence is higher at older ages, increasing from 25.53 at ages 6-9 to 45.46 at ages 14-17.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe most frequently prescribed medication was Risperidone (52%) followed by Aripiprazole (31.4%) and Quetiapine (7.9%). Among males, incidence of Risperidone prescriptions decreased with age (from 49.10 to 27.38), while among females it was similar level at all ages. Among both sexes, Quetiapine is prescribed mainly to teenagers, with increasing incidence from ages 12-13 to 16-17 (from 2.16 to 6.90 in males and from 4.90 to 13.59 in females).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study examined trends in antipsychotic treatment initiation among children and adolescents in Israel from 2015 to 2023, revealing a 15% increase in incidence rates along the study period. This rise was primarily driven by increases in males aged 6\u0026ndash;11 and females aged 14\u0026ndash;18. A significant rise in prescriptions occurred in the first year following the implementation of the mental health reform (2016\u0026ndash;2017) and again in the year following the COVID-19 pandemic (2021\u0026ndash;2022) an increase that persisted to the end of the study period- until the end of 2023. Additionally, antipsychotic prescriptions significantly increased in peripheral areas, especially among lower SES populations, while remaining stable in central regions. Finally, we observed seasonal patterns, with a consistent rise in antipsychotics prescription in the fourth quarter of each year.\u003c/p\u003e \u003cp\u003eTrends in antipsychotic treatment initiation among children and adolescents in Israel from 2015 to 2023 reveal a 15% increase in incidence rates over the study period. Although this overall rise was not statistically significant across the full eight years, there were two time points with significant increases- following the implementation of mental health reform in Israel and following the COVID-19 pandemic. The initial sharp 10% increase in antipsychotics prescription following the implementation of the mental health reform can be attributed to improved access for new patients who previously faced geographic or financial barriers to care.\u003c/p\u003e \u003cp\u003eThe COVID-19 pandemic had a notable impact on antipsychotic prescription trends. Our findings support earlier studies that reported an initial decrease in mental health treatment during the first phase of the pandemic, followed by a sharp rise in psychiatric service utilization as restrictions eased and schools reopened [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This study extends findings by our group and others [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] demonstrating that the rise in antipsychotic prescriptions persisted throughout 2023, suggesting a continuous negative impact of the pandemic on pediatric mental health.\u003c/p\u003e \u003cp\u003eOur results of an overall higher prescription rate among males compared to females with specific increases in males aged 6\u0026ndash;11 and females aged 14\u0026ndash;18, align with global trends indicating that males are prescribed antipsychotics more frequently than females [\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The higher prescription rates in males aged 6\u0026ndash;11 may be attributed particularly to treatments of impulsive or aggressive outbursts in children with ADHD and oppositional behaviors [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] which usually picks during elementary school age years in males [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Conversely, the increase in antipsychotic use among adolescent females aged 14\u0026ndash;15 can be linked to increase in the prevalence of mood and behavioral dysregulation, and self-injuries, among females during adolescence [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe found that there was a more robust increase in antipsychotics prescriptions in the peripheral areas of Israel and in the lower SES group, a trend observed in previous studies as well [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. This trend probably stems from the improved access to psychiatric services following Israel\u0026rsquo;s mental health reform, which targeted underserved populations by expanding services in peripheral areas and for disadvantaged populations. Additionally, the higher poverty indices reported for peripheral areas [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] and low SES populations may contribute to limited access to psychosocial interventions, inadequate social services, and lack of support in the educational services for students with support needs. Furthermore, the peripheral and low SES population also exhibited greater increase in antipsychotics prescriptions during the COVID-19 pandemic, in line with other publication of increased vulnerability of low SES populations to coping with the COVID-19 related stress [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. The above factors may have contributed to more severe psychiatric presentations in these populations, necessitating more use of antipsychotics and also highlight the impact of expanded mental health services on prescription trends.\u003c/p\u003e \u003cp\u003eThe observed peak in prescriptions during the fourth quarter (October-December) of each year aligns with previous research showing that the return to school after the summer break is a period of increased demands for functioning and hence heightened stress [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], which is associated with exacerbation of psychiatric symptoms in children [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study has several strengths, including a large sample size and extended observation period, which allowed us to capture long-term trends across different demographic groups. Furthermore, our use of nonparametric trend analysis, as opposed to linear modelling, provided a more accurate depiction of fluctuations in prescription rates over time. By stratifying our analyses by sex, age, SES, and geographic region, we were able to identify patterns that offer valuable insights into the factors influencing antipsychotic use in this population.\u003c/p\u003e \u003cp\u003eHowever, there are also several limitations to this study. First, because the data were drawn from Maccabi Healthcare Services, our findings may not be fully generalizable to the entire Israeli population, particularly individuals insured by other health maintenance organizations. Additionally, the study relied on prescription records, which only capture cases where antipsychotics were both prescribed and dispensed, potentially underestimating the true scope of medication use. Moreover, the lack of detailed clinical data regarding the indications for antipsychotic prescriptions limits our ability to recognize the specific conditions for which these medications were prescribed.\u003c/p\u003e \u003cp\u003eIn conclusion, this study highlights the growing prevalence of antipsychotic treatment initiation among children and adolescents in Israel, demonstrating a notable 15% increase in incidence rates over the period from 2015 to 2023. These findings are crucial for informing healthcare policies, as they reveal specific demographic patterns and the impact of the mental health reform in Israel and the COVID-19 pandemic, on treatment trends. Future research should incorporate longitudinal designs with clinical assessments to better understand the underlying factors driving antipsychotic prescriptions in children and adolescents.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of interest\u003c/h2\u003e\n\u003cp\u003eThe authors declare no conflict of interest to be present in this study.\u003c/p\u003e\n\u003ch2\u003eEthics approval\u003c/h2\u003e\n\u003cp\u003eApproval for this study was granted by\u0026apos; Maccabi\u0026apos; Health Services institutional review board (MHS-0098-23).\u003c/p\u003e\n\u003ch2\u003eInformed consent\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eFundings\u003c/h2\u003e\n\u003cp\u003eThis work was supported by grant from Kirsh Foundation.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eR.N. led the conceptualization, methodology, validation, formal analysis, and investigation, managed resources, and contributed to both the original draft and review, editing, and visualization. R.W. contributed resources, drafted the original manuscript, participated in review and editing, and handled data visualization. M.T. contributed to conceptualization, methodology, resources, and assisted in writing the original draft and review. R.P.G., L.L.S., M.E. (investigation, methodology, review, and editing), N.E.B., and G.B. contributed to conceptualization, validation, formal analysis, investigation, resources, and manuscript review and editing. Y.B. provided conceptualization, methodology, validation, formal analysis, investigation, resources, and contributed to drafting, review, editing, and visualization, as well as project supervision. D.G. oversaw project administration, provided supervision, and contributed to visualization, review, editing, resources, validation, methodology, and conceptualization.all authors approved the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003ch2\u003eData availability statement\u003c/h2\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePenfold RB, Stewart C, Hunkeler EM, et al (2013) Use of Antipsychotic Medications in Pediatric Populations: What do the Data Say? Curr Psychiatry Rep 15:426. https://doi.org/10.1007/s11920-013-0426-8 \u003c/li\u003e\n\u003cli\u003eCrystal S, Olfson M, Huang C, et al (2009) Broadened Use Of Atypical Antipsychotics: Safety, Effectiveness, And Policy Challenges. Health Aff 28:w770\u0026ndash;w781. https://doi.org/10.1377/hlthaff.28.5.w770 \u003c/li\u003e\n\u003cli\u003edosReis S, Yoon Y, Rubin DM, et al (2011) Antipsychotic Treatment Among Youth in Foster Care. Pediatrics 128:e1459\u0026ndash;e1466. https://doi.org/10.1542/peds.2010-2970 \u003c/li\u003e\n\u003cli\u003eOlfson M, Crystal S, Huang C, Gerhard T (2010) Trends in Antipsychotic Drug Use by Very Young, Privately Insured Children. J Am Acad Child Adolesc Psychiatry 49:13\u0026ndash;23. https://doi.org/10.1097/00004583-201001000-00005 \u003c/li\u003e\n\u003cli\u003eOlfson M, Blanco C, Liu S-M, et al (2012) National Trends in the Office-Based Treatment of Children, Adolescents, and Adults With Antipsychotics. Arch Gen Psychiatry 69:1247. https://doi.org/10.1001/archgenpsychiatry.2012.647 \u003c/li\u003e\n\u003cli\u003eRani F, Murray ML, Byrne PJ, Wong ICK (2008) Epidemiologic Features of Antipsychotic Prescribing to Children and Adolescents in Primary Care in the United Kingdom. Pediatrics 121:1002\u0026ndash;1009. https://doi.org/10.1542/peds.2007-2008 \u003c/li\u003e\n\u003cli\u003eRadojčić MR, Pierce M, Hope H, et al (2023) Trends in antipsychotic prescribing to children and adolescents in England: cohort study using 2000\u0026ndash;19 primary care data. Lancet Psychiatry 10:119\u0026ndash;128. https://doi.org/10.1016/S2215-0366(22)00404-7 \u003c/li\u003e\n\u003cli\u003eKalverdijk LJ, Bachmann CJ, Aagaard L, et al (2017) A multi-national comparison of antipsychotic drug use in children and adolescents, 2005\u0026ndash;2012. Child Adolesc Psychiatry Ment Health 11:55. https://doi.org/10.1186/s13034-017-0192-1 \u003c/li\u003e\n\u003cli\u003ePringsheim T, Stewart DG, Chan P, et al (2019) The Pharmacoepidemiology of Psychotropic Medication Use in Canadian Children from 2012 to 2016. J Child Adolesc Psychopharmacol 29:740\u0026ndash;745. https://doi.org/10.1089/cap.2019.0018 \u003c/li\u003e\n\u003cli\u003ePringsheim T, Lam D, Patten SB (2011) The Pharmacoepidemiology of Antipsychotic Medications for Canadian Children and Adolescents: 2005\u0026ndash;2009. J Child Adolesc Psychopharmacol 21:537\u0026ndash;543. https://doi.org/10.1089/cap.2010.0145 \u003c/li\u003e\n\u003cli\u003eBilu Y, Flaks-Manov N, Bivas-Benita M, et al (2023) Data-Driven Assessment of Adolescents\u0026rsquo; Mental Health During the COVID-19 Pandemic. J Am Acad Child Adolesc Psychiatry 62:920\u0026ndash;937. https://doi.org/10.1016/j.jaac.2022.12.026 \u003c/li\u003e\n\u003cli\u003eThe Mental Health Reform Ministry of Health. https://www.gov.il/en/pages/mental-health-reform. Accessed 24 Jul 2024\u003c/li\u003e\n\u003cli\u003eBonnot O, Dufresne M, Herrera P, et al (2017) Influence of socioeconomic status on antipsychotic prescriptions among youth in France. BMC Psychiatry 17:82. https://doi.org/10.1186/s12888-017-1232-3 \u003c/li\u003e\n\u003cli\u003eRadhakrishnan L, Carey K, Pell D, et al (2023) Seasonal Trends in Emergency Department Visits for Mental and Behavioral Health Conditions Among Children and Adolescents Aged 5\u0026ndash;17 Years \u0026mdash; United States, January 2018\u0026ndash;June 2023. MMWR Morb Mortal Wkly Rep 72:1032\u0026ndash;1040. https://doi.org/10.15585/mmwr.mm7238a3 \u003c/li\u003e\n\u003cli\u003ePlemmons G, Hall M, Doupnik S, et al (2018) Hospitalization for Suicide Ideation or Attempt: 2008\u0026ndash;2015. Pediatrics 141:. https://doi.org/10.1542/peds.2017-2426 \u003c/li\u003e\n\u003cli\u003eMann HB (1945) Nonparametric Tests Against Trend. Econometrica 13:245. https://doi.org/10.2307/1907187 \u003c/li\u003e\n\u003cli\u003eMoran PAP, Kendall MG (1973) Rank Correlation Methods. Int Stat Rev 41:399. https://doi.org/10.2307/1402637 \u003c/li\u003e\n\u003cli\u003eHussain Md, Mahmud I (2019) pyMannKendall: a python package for non parametric Mann Kendall family of trend tests. J Open Source Softw 4:1556. https://doi.org/10.21105/joss.01556 \u003c/li\u003e\n\u003cli\u003eSamji H, Wu J, Ladak A, et al (2022) Review: Mental health impacts of the COVID‐19 pandemic on children and youth \u0026ndash; a systematic review. Child Adolesc Ment Health 27:173\u0026ndash;189. https://doi.org/10.1111/camh.12501 \u003c/li\u003e\n\u003cli\u003ePanchal U, Salazar de Pablo G, Franco M, et al (2023) The impact of COVID-19 lockdown on child and adolescent mental health: systematic review. Eur Child Adolesc Psychiatry 32:1151\u0026ndash;1177. https://doi.org/10.1007/s00787-021-01856-w \u003c/li\u003e\n\u003cli\u003eCostales B, Slama NE, Penfold RB, et al (2024) On- and Off-Label Atypical Antipsychotic Prescription Trends Across a Nine-Year Period Among Adolescents Pre- to Post-COVID-19. Acad Pediatr 24:995\u0026ndash;1000. https://doi.org/10.1016/j.acap.2024.03.003 \u003c/li\u003e\n\u003cli\u003eValtuille Z, Acquaviva E, Trebossen V, et al (2024) Psychotropic Medication Prescribing for Children and Adolescents After the Onset of the COVID-19 Pandemic. JAMA Netw Open 7:e247965. https://doi.org/10.1001/jamanetworkopen.2024.7965 \u003c/li\u003e\n\u003cli\u003eOlfson M, King M, Schoenbaum M (2015) Treatment of Young People With Antipsychotic Medications in the United States. JAMA Psychiatry 72:867. https://doi.org/10.1001/jamapsychiatry.2015.0500 \u003c/li\u003e\n\u003cli\u003eGangapersad RN, Zhou G, Garcia-Gomez P, et al (2024) Comparison of antipsychotic drug use in children and adolescents in the Netherlands before and during the COVID-19 pandemic. Eur Child Adolesc Psychiatry 33:2695\u0026ndash;2703. https://doi.org/10.1007/s00787-023-02340-3 \u003c/li\u003e\n\u003cli\u003eKalverdijk LJ, Tobi H, van den Berg PB, et al (2008) Use of Antipsychotic Drugs Among Dutch Youths Between 1997 and 2005. Psychiatric Services 59:554\u0026ndash;560. https://doi.org/10.1176/ps.2008.59.5.554 \u003c/li\u003e\n\u003cli\u003eHarrison JN, Cluxton-Keller F, Gross D (2012) Antipsychotic Medication Prescribing Trends in Children and Adolescents. Journal of Pediatric Health Care 26:139\u0026ndash;145. https://doi.org/10.1016/j.pedhc.2011.10.009 \u003c/li\u003e\n\u003cli\u003eRettew DC, Greenblatt J, Kamon J, et al (2015) Antipsychotic Medication Prescribing in Children Enrolled in Medicaid. Pediatrics 135:658\u0026ndash;665. https://doi.org/10.1542/peds.2014-2260 \u003c/li\u003e\n\u003cli\u003ePathak P, West D, Martin BC, et al (2010) Evidence-Based Use of Second-Generation Antipsychotics in a State Medicaid Pediatric Population, 2001\u0026ndash;2005. Psychiatric Services 61:123\u0026ndash;129. https://doi.org/10.1176/ps.2010.61.2.123 \u003c/li\u003e\n\u003cli\u003eGirard L-C, Tremblay RE, Nagin D, C\u0026ocirc;t\u0026eacute; SM (2019) Development of Aggression Subtypes from Childhood to Adolescence: a Group-Based Multi-Trajectory Modelling Perspective. J Abnorm Child Psychol 47:825\u0026ndash;838. https://doi.org/10.1007/s10802-018-0488-5 \u003c/li\u003e\n\u003cli\u003eMadge N, Hewitt A, Hawton K, et al (2008) Deliberate self‐harm within an international community sample of young people: comparative findings from the Child \u0026amp;amp; Adolescent Self‐harm in Europe (CASE) Study. Journal of Child Psychology and Psychiatry 49:667\u0026ndash;677. https://doi.org/10.1111/j.1469-7610.2008.01879.x \u003c/li\u003e\n\u003cli\u003eAmerican Psychiatric Association DSMTF, \u0026amp; APADS (2013) Diagnostic and statistical manual of mental disorders: DSM-5 (Vol. 5, No. 5)\u003c/li\u003e\n\u003cli\u003eVerdoux H, Pambrun E, Cortaredona S, et al (2015) Antipsychotic prescribing in youths: a French community-based study from 2006 to 2013. Eur Child Adolesc Psychiatry 24:1181\u0026ndash;1191. https://doi.org/10.1007/s00787-014-0668-y \u003c/li\u003e\n\u003cli\u003eBonnot O, Dufresne M, Herrera P, et al (2017) Influence of socioeconomic status on antipsychotic prescriptions among youth in France. BMC Psychiatry 17:82. https://doi.org/10.1186/s12888-017-1232-3 \u003c/li\u003e\n\u003cli\u003eIsrael National Insurance National Insurance\u0026rsquo;s publication: 2021 Poverty and Social Gaps Report in Israel. https://www.btl.gov.il/english%20homepage/publications/poverty_report/pages/default.aspx. Accessed 29 Jul 2024 \u003c/li\u003e\n\u003cli\u003eJeriček Klan\u0026scaron;ček H, Furman L (2023) Socioeconomic Deprivation and Inequalities in Mental Well-Being during the COVID-19 Pandemic among Adolescents. Int J Environ Res Public Health 20:6233. https://doi.org/10.3390/ijerph20136233 \u003c/li\u003e\n\u003cli\u003eHertz-Palmor N, Gothelf D (2024) Unexpected mental health improvement in children and adolescents during COVID-19-who benefits from staying at home? Eur Child Adolesc Psychiatry 33:1235\u0026ndash;1237. https://doi.org/10.1007/s00787-024-02432-8 \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-child-and-adolescent-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ecap","sideBox":"Learn more about [European Child \u0026 Adolescent Psychiatry](http://link.springer.com/journal/787)","snPcode":"787","submissionUrl":"https://submission.nature.com/new-submission/787/3","title":"European Child \u0026 Adolescent Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Antipsychotics, COVID-19, children, adolescents, prescription trends socioeconomic status","lastPublishedDoi":"10.21203/rs.3.rs-5337808/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5337808/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"This study investigates the patterns of antipsychotic drug dispensations among children and adolescents from 2015 to 2023, with a focus on the impact of introducing national health reform (2015) and the COVID-19 pandemic. Data from Maccabi Healthcare Services, encompassing 1,105,439 individuals aged 6 to 18 years was analyzed using a retrospective cohort study. We investigated the incidence rates of antipsychotic prescriptions by age, sex, socioeconomic status, and geographical region. During the study period, there was a 15% overall increase in antipsychotics prescriptions. Higher rates of prescription were noted among males aged 6-11 and females aged 14-18. Significant increases in prescriptions were observed following the mental health reform and the COVID-19 pandemic. Low socioeconomic status and peripheral regions exhibited higher and increasing prescription rates. Seasonal patterns revealed peaks in the fourth quarter of each year. The study highlights an overall increase in antipsychotic prescriptions, influenced by policy changes and the pandemic. Inequality in prescription rates by socioeconomic status and geographical location underscore the need for targeted mental health interventions. The findings also indicate the enduring effects of the COVID-19 pandemic on youth mental health and the utilization of antipsychotic medications.","manuscriptTitle":"Trends in antipsychotic treatment of children and adolescents in Israel from post-mental health reform to post-COVID19 pandemic (2015-2023)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-20 10:47:53","doi":"10.21203/rs.3.rs-5337808/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-13T18:15:29+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-09T17:07:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-04T14:03:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-28T13:45:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"261311747685839942317784981131811887258","date":"2024-11-11T11:19:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"311454736954391383181333575228897730836","date":"2024-11-11T03:23:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"129937894884567338180800942480862034061","date":"2024-11-07T09:50:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-06T13:52:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-29T13:12:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-29T13:10:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Child \u0026 Adolescent Psychiatry","date":"2024-10-26T13:47:16+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-child-and-adolescent-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ecap","sideBox":"Learn more about [European Child \u0026 Adolescent Psychiatry](http://link.springer.com/journal/787)","snPcode":"787","submissionUrl":"https://submission.nature.com/new-submission/787/3","title":"European Child \u0026 Adolescent Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b58b71a4-5766-4a03-bd3f-bb16687add91","owner":[],"postedDate":"November 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-04-07T16:05:50+00:00","versionOfRecord":{"articleIdentity":"rs-5337808","link":"https://doi.org/10.1007/s00787-025-02691-z","journal":{"identity":"european-child-and-adolescent-psychiatry","isVorOnly":false,"title":"European Child \u0026 Adolescent Psychiatry"},"publishedOn":"2025-04-04 15:57:31","publishedOnDateReadable":"April 4th, 2025"},"versionCreatedAt":"2024-11-20 10:47:53","video":"","vorDoi":"10.1007/s00787-025-02691-z","vorDoiUrl":"https://doi.org/10.1007/s00787-025-02691-z","workflowStages":[]},"version":"v1","identity":"rs-5337808","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5337808","identity":"rs-5337808","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}