Use Of Antipsychotics In Children Research Articles

Impact of the COVID-19 pandemic on antidepressant and antipsychotic use among children and adolescents: a population-based study.

The COVID-19 pandemic was associated with increases in the prevalence of depression, anxiety and behavioural problems among children and youth. Less well understood is the influence of the pandemic on antidepressant and antipsychotic use among children. This is important, as it is possible that antidepressants and antipsychotics were used as a "stop-gap" measure to treat mental health symptoms when in-person access to outpatient care and school-based supportive services was disrupted. Furthermore, antipsychotics and antidepressants have been associated with harm in children and youth. We examined trends in dispensing of these medications two years following the pandemic among children 18 years of age and under in Ontario, Canada. We conducted a population-based time-series study of antidepressant and antipsychotic medication dispensing to children and adolescents ≤18 years old between September 1, 2014, and March 31, 2022. We measured monthly population-adjusted rates of antidepressant and antipsychotics obtained from the IQVIA Geographic Prescription Monitor (GPM) database. We used structural break analyses to identify the pandemic month(s) when changes in the dispensing of antidepressants and antipsychotics occurred. We used interrupted time series models to quantify changes in dispensing following the structural break and compare observed and expected use of these drugs. Overall, we found higher-than-expected dispensing of antidepressants and antipsychotics in children and youth. Specifically, we observed an immediate step decrease in antidepressant dispensing associated with a structural break in April 2020 (-55.8 units per 1,000 individuals; 95% confidence intervals [CI] CI: -117.4 to 5.8), followed by an increased monthly trend in the rate of antidepressant dispensing of 13.0 units per 1,000 individuals (95% CI: 10.2-15.9). Antidepressant dispensing was consistently greater than predicted from September 2020 onward. Antipsychotic dispensing increased immediately following a June 2020 structural break (26.4 units per 1,000 individuals; 95% CI: 15.8-36.9) and did not change appreciably thereafter. Antipsychotic dispensing was higher than predicted at all time points from June 2020 onward. We found higher-than-expected dispensing of antidepressants and antipsychotics in children and youth. These increases were sustained through nearly two years of observation and are especially concerning in light of the potential for harm with the long-term use of antipsychotics in children. Further research is required to understand the clinical implications of these findings.

Cost of Implementing an Evidence-Based Intervention to Support Safer Use of Antipsychotics in Youth.

To estimate the cost of implementing a clinical program designed to support safer use of antipsychotics in children and adolescents (youth) age 3-17years at the time of initiating an antipsychotic medication. We calculate the costs of implementing a psychiatric consultation and navigation program for youth prescribed antipsychotic medications across 4 health systems, which included an electronic health record (EHR) decision support tool, consultation with a child and adolescent psychiatrist, and up to 6months of behavioral health care navigation, as well as telemental health for patients (n = 348). Cost data were collected for both start-up and ongoing intervention phases and are estimated over a 1-year period. Data sources included study records and time-in-motion reports, analyzed from a health system perspective. Costs included both labor and nonlabor costs (2019 US dollars). The average total start-up and ongoing costs per health system were $34,007 and $185,174, respectively. The average total cost per patient was $2,128. The highest average ongoing labor cost components were telemental health ($901 per patient), followed by child and adolescent psychiatrist consultation ($659), and the lowest cost component was primary care/behavioral health provider time to review/respond to the EHR decision support tool and case consultation ($24). For health systems considering programs to promote safer and targeted use of antipsychotics among youth, this study provides estimates of the full start-up and ongoing costs of an EHR decision support tool, psychiatric consultation service, and psychotherapeutic services for patients and families.Trial registration: Clinicaltrials.gov, NCT03448575.

Adherence to antipsychotic laboratory monitoring guidelines in children and youth: a population-based study.

In 2011, the Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) published guidelines for the metabolic monitoring of antipsychotic-treated children and youth. Population-based studies examining adherence to these guidelines are needed to ensure the safe use of antipsychotics in children and youth. We conducted a population-based study of all Ontario residents aged 0 to 24 who were newly dispensed an antipsychotic between April 1, 2018, and March 31, 2019. We estimated prevalence ratios (PRs) and 95% confidence intervals (CI) associating sociodemographic characteristics with the receipt of baseline and follow-up (3- and 6-month) laboratory testing using log-Poisson regression models. Overall, 6,505 of 27,718 (23.5%) children and youth newly dispensed an antipsychotic received at least one guideline-recommended baseline test. Monitoring was more prevalent among individuals aged 10 to 14 years (PR 1.20; 95% CI 1.04 to 1.38), 15 to 19 years (PR 1.60; 95% CI 1.41 to 1.82), and 20 to 24 years (PR 1.71; 95% CI 1.50 to 1.94) compared to children under the age of 10. Baseline monitoring was associated with mental health-related hospitalizations or emergency department visits in the year preceding therapy (PR 1.76; 95% CI 1.65 to 1.87), a prior diagnosis of schizophrenia (PR 1.20; 95% CI 1.14 to 1.26) or diabetes (PR 1.35; 95% CI 1.19 to 1.54), benzodiazepine use (PR 1.13; 95% CI 1.04 to 1.24), and receipt of a prescription from a child and adolescent psychiatrist or developmental pediatrician versus a family physician (PR 1.41; 95% CI 1.34 to 1.48). Conversely, monitoring was less frequent in individuals co-prescribed stimulants (PR 0.83; 95% CI 0.75 to 0.91). The prevalence of any 3- and 6-month follow-up monitoring among children and youth receiving continuous antipsychotic therapy at these time points was 13.0% (1,179 of 9,080) and 11.4% (597 of 5,261), respectively. Correlates of follow-up testing were similar to those of baseline monitoring. Most children initiating antipsychotic therapy do not receive guideline-recommended metabolic laboratory monitoring. Further research is needed to understand reasons for poor guideline adherence and the role of clinician training and collaborative service models in promoting best monitoring practices.

The effect of therapeutic drug monitoring of risperidone and aripiprazole on weight gain in children and adolescents: the SPACe 2: STAR (trial) protocol of an international multicentre randomised controlled trial

BackgroundAntipsychotic drugs are an important part of the treatment of irritability and aggression in children with an autism spectrum disorder (ASD). However, significant weight gain and metabolic disturbances are clinically relevant side effects of antipsychotic use in children. In the SPACe study, we showed positive correlations between both risperidone and aripiprazole plasma trough concentrations and weight gain over a 6-month period. The trial SPACe 2: STAR is designed as a follow-up study, in which we aim to research whether therapeutic drug monitoring in clinical practice can prevent severe weight gain, while retaining clinical effectiveness.MethodsSPACe 2: STAR is an international, multicentre, randomised controlled trial (RCT). One hundred forty children aged 6 to 18 who are about to start risperidone or aripiprazole treatment for ASD related behavioural problems will be randomised into one of two groups: a therapeutic drug monitoring (TDM) group, and a care as usual (CAU) group. Participants will be assessed at baseline and 4, 10, 24, and 52 weeks follow-up. In the TDM group, physicians will receive dosing advice based on plasma levels of risperidone and aripiprazole and its metabolites at 4 and 10 weeks. Plasma levels will be measured in dried blood spots (DBS). The primary outcome will be BMI z-score at 24 weeks after start of antipsychotic treatment. Among the secondary outcomes are effectiveness, metabolic laboratory measurements, levels of prolactin, leptin and ghrelin, extrapyramidal side effects, and quality of life.DiscussionThis will be the first RCT evaluating the effect of TDM of antipsychotic drugs in children and adolescents. Thus, findings from SPACe 2: STAR will be of great value in optimising treatment in this vulnerable population.Trial registrationClinicalTrials.gov Identifier: NCT05146245. EudraCT number: 2020–005450-18. Sponsor protocol name: SPACe2STAR. Registered 8 June 2021. Protocol Version 6, Protocol date: 18 august 2022.

Correlating Psychotropic Use to Major Depressive Disorder and ADHD Research Diagnoses: Trends in a Prospective Pediatric Cohort From Ages 3 to 21.

Objective: To examine the associations of psychotropic usage to clinical characteristics in a pediatric research cohort with research diagnoses and severity scores. Methods: The cohort (N = 348) was enriched for children with mood and externalizing symptoms. Prospective longitudinal data were collected from ages 3 to 21 (September 2003–December 2019). At up to 10 time points, data on psychotropic medication use were collected by caregiver- and self-report from the MacArthur Health and Behavior Questionnaire, Parent Version and as part of the diagnostic interview, and research diagnoses (DSM-IV and DSM-5) and disease severity scores were acquired using an age-appropriate standardized research interview (Preschool Age Psychiatric Assessment, Child and Adolescent Psychiatric Assessment, Kiddie-Schedule for Affective Disorders and Schizophrenia). Results: The percentage of children with attention-deficit/hyperactivity disorder (ADHD) taking ADHD medications was preschool, 20.7%; school-age, 65.4%; and adolescence/early adulthood, 84.0%. The percentage with major depressive disorder (MDD) who were taking antidepressants was preschool, 0%; school-age, 21.6%; and adolescence/early adulthood, 42.6%. Antipsychotic use in children with research diagnoses of ADHD or MDD peaked in school-age: ADHD, 30.8%, and MDD, 21.6%. Children who were taking an antipsychotic concurrently with an ADHD medication or antidepressant had more comorbid conditions and higher disease severity than those taking ADHD medications or antidepressants without concurrent antipsychotics. Black children with MDD used antidepressants significantly less than White children with MDD (Black = 12.1%, White = 31.9%, FDR P = .0495). Conclusions: Concordance between research diagnosis and psychotropic use increased with age. Antipsychotic use was quite high, though more frequent in children with higher disease severity. Both findings suggest that psychotropic use is less tied to discrete diagnoses at earlier ages and that antipsychotic medication use may be motivated by severity/impairment rather than diagnosis.

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

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

Association of Treatment With Antipsychotics, Antidepressants, or Both With Movement Disorders and Seizures Among Children and Adolescents With Depression in Korea

Little evidence exists on neurological adverse events (movement disorders and seizures) that occur during adjuvant use of antipsychotics with antidepressants, especially in children and adolescents. To assess the association between neurological adverse events (movement disorders, including parkinsonism, dystonia, extrapyramidal symptoms, chorea, and tic, and seizures) and the adjuvant use of antipsychotics in children and adolescents with depression. A retrospective cohort study using the Health Insurance Review and Assessment claims database in Korea between 2008 and 2018. The study population was children and adolescents aged 2 to 18 years with depression who began treatment with antidepressants between January 1, 2010, and December 31, 2018. Data were analyzed between December 9, 2020, and December 10, 2021. Time-varying exposure to antidepressants, antipsychotics, and concomitant use of antidepressants and antipsychotics. Concomitant use was further subdivided according to the antipsychotic treatment status (dose and agent). The extended Cox proportional hazards regression model, with adjustment for sex, age, health insurance type, psychiatric comorbidities, psychiatric hospitalization, and comedication with other psychotropic drugs, was used to estimate adjusted hazard ratios (aHRs) and 95% CIs for the associations of movement disorders and seizures with use of antidepressants and antipsychotics. A total of 9890 patients were included in the study: 9541 (mean [SD] age, 14.8 [2.8] years; 4956 [51.9%] female) and 7731 (mean [SD] age, 14.9 [2.7] years; 4150 [53.7%] female) met the inclusion criteria for movement disorders and seizures, respectively. For movement disorders, associations were found between concomitant use (aHR, 3.68; 95% CI, 3.06-4.44) and antipsychotic-only use (aHR, 3.84; 95% CI, 3.03-4.87) compared with antidepressant-only use, but their CIs overlapped. The associations with seizure were similar (concomitant use: aHR, 2.06; 95% CI, 1.66-2.55; antipsychotic-only use: aHR, 2.05; 95% CI, 1.53-2.75). With concomitant use, the aHRs gradually increased with increasing doses of antipsychotics. Haloperidol had the highest aHR, 7.15 (95% CI, 3.89-10.00) for movement disorders. The highest aHR for seizure was observed with quetiapine (aHR, 2.36; 95% CI, 1.55-3.59), followed by aripiprazole (aHR, 2.05; 95% CI, 1.52-2.77). In this cohort study, adjunctive antipsychotics with antidepressants were associated with movement disorders and seizures compared with antidepressant monotherapy in children and adolescents with depression. These results suggest that careful consideration of the risk-benefit profile of the antipsychotic use as adjuvant therapy in this population is needed.

Polypharmacy in children and adolescents initiating antipsychotic drug in 2008–2016: a nationwide register study

Objective The use of antipsychotics in children and adolescents has increased rapidly. Little is known about psychotropic polypharmacy in children and adolescent initiating an antipsychotic drug. Thus, we investigated the frequency and predictors of polypharmacy during the first year of antipsychotic use in Finnish children and adolescents. Methods Between 2008 and 2016, 14 848 individuals aged 1–17 years initiating risperidone, quetiapine, aripiprazole, or olanzapine treatment were identified from Finnish Prescription Registry. Data on psychotropic drug prescriptions prior to and during antipsychotic treatment were collected. Associations between predictors and polypharmacy were analyzed with regression models. Results During the study period polypharmacy occurred in 44.9% of the new antipsychotic users, being more frequent in girls (55.5%) than in boys (44.5%, p < 0.001). The two most frequent concomitant psychotropic drug classes were antidepressants (66.2%) and psychostimulants/atomoxetine (30.8%). Adolescents aged 13–15 and 16–17 years, and girls showed an increased risk of polypharmacy during antipsychotic treatment (OR 2.37 [95% CI 1.91–2.92], OR 2.39 [95% CI 1.92–2.98], and OR 1.64 [95% CI 1.51–1.78], respectively). The use of psychostimulants/atomoxetine or antidepressants prior to initiation of antipsychotic treatment was strongly associated with polypharmacy during antipsychotic treatment (OR 8.39 [95% CI 7.49–9.41], OR 3.02 [95% CI 2.75–3.31]). Conclusions Polypharmacy was common in children and adolescents initiating antipsychotic treatment. Prior use of psychostimulants/atomoxetine and antidepressants increased the risk of polypharmacy. The use of antipsychotics was mainly off-label, thus, the risks of concomitant use of antipsychotics with other psychotropic drugs should be carefully weighed.

Using the microbiome in clinical practice.

Using the microbiome in clinical practice.

Antipsychotic long-term treatment in children and young people: a systematic review and meta-analysis of efficacy and tolerability across mental health and neurodevelopmental conditions.

Antipsychotic medications are used in a wide range of mental health and neurodevelopmental conditions in children and adolescents. Their efficacy and tolerability with long-term use have not been clearly established. We aimed to conduct a systematic review and meta-analysis to evaluate the long-term use of antipsychotics in children and adolescents. All relevant double-blind randomized control trials (RCTs), on any antipsychotic used for 12 weeks or longer in any mental health/neurodevelopmental condition in this age group, were included. We evaluated several efficacy and tolerability measures. Meta-analysis was performed for adverse events. Seven RCTs were identified (n = 939, age = 5-17 years), four on aripiprazole and three on risperidone. All studies reported symptomatic/functional improvements or more time before discontinuation with antipsychotics compared to placebo. Weight gain was identified as a significant side effect with antipsychotics. Serum prolactin was reduced with aripiprazole and increased with risperidone, and abdominal pain/discomfort, respiratory tract infections, were more common with Aripiprazole compared to placebo. Musculoskeletal pain may be more common with aripiprazole compared to placebo. Use of antipsychotics for 12 weeks or longer may be associated with symptomatic/functional improvements, but may be associated with additional side effects compared to short-term treatment. Further research in this population is needed.

Guideline Adherence of Monitoring Antipsychotic Use for Nonpsychotic Indications in Children and Adolescents: A Patient Record Review.

Antipsychotics are frequently prescribed to children and adolescents for nonpsychotic indications. Guidelines recommend regularly assessing treatment response and adverse effects and the ongoing need for their use. We aimed to assess adherence to recommendations of available guidelines regarding monitoring antipsychotic use and to test the influence of children's age, sex, intelligence quotient, and diagnosis on adherence. We reviewed 426 medical records from 26 centers within 3 large Dutch child and adolescent psychiatry organizations, excluding children with schizophrenia, psychosis, mania, or an intelligence quotient below 70. We investigated whether there was regular assessment of treatment response, adverse events (physical and laboratory), and at least annual discussion of the need of continued use. On average, treatment response was assessed in 69.3% of the recommended treatment periods, height in 25.6%, weight in 30.6%, blood pressure in 20.6%, evaluation of adverse events in 19.4%, and cardiometabolic measures in 13.7%; discontinuation and/or continued need was discussed at least annually in 36.2%. Extrapyramidal and prolactin-related adverse effects, waist circumference, glucose, and lipids were rarely investigated. Higher age was associated with lower rates of assessment of treatment response. Most antipsychotics were prescribed long-term. In those children with sufficient documentation of the course of treatment, 57.7% was still using an antipsychotic 3 years after initiation. Our findings indicate insufficient adherence to guideline recommendations for monitoring antipsychotic use in children and adolescents, as well as long duration of use in the majority of children. Especially, older children are at higher risk of receiving suboptimal care.

Metabolic events associated with the use of antipsychotics in children, adolescents and young adults: a multinational sequence symmetry study.

It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6-30years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00-1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88-1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04-1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85-1.12) and 1.24 (95% CI 0.97-1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns.

Second-Generation Antipsychotic Drugs for Children and Adolescents

The effectiveness and safety of antipsychotics have not been fully established in children and adolescents. Many antipsychotics approved for use in adults are prescribed off-label to children and adolescents. We investigated the effectiveness and tolerability of antipsychotics for children and adolescents with schizophrenia and bipolar disorder. A literature review of the empirical evidence regarding the use of antipsychotics, particularly second-generation antipsychotics, in children and adolescents showed that these drugs were safe and effective for this population. Antipsychotics were similarly effective for treatment of schizophrenia and bipolar disorder in children and adolescents. When prescribing antipsychotics to this population, clinicians should consider adverse events and the discontinuation rate in treated patients. However, the current evidence shows a lack of consensus regarding the use of antipsychotics in children and adolescents.

Prescribing antipsychotics in child and adolescent psychiatry: guideline adherence

Antipsychotics are often prescribed to children and adolescents, mostly off-label. We aimed to assess adherence to recommendations of guidelines for antipsychotic prescription. We reviewed 436 medical records from 155 clinicians from 26 clinics within three Dutch child and adolescent psychiatry organizations (n = 398 outpatient, n = 38 inpatient care). We assessed target symptoms, diagnostic process, prior and concomitant treatment, and consideration of contra-indications. Multiple logistic regression assessed the role of age, sex, and psychiatric diagnosis on adherence to three main recommendations: to (1) prescribe antipsychotics only after other treatments proved insufficient, (2) always combine antipsychotics with psychosocial interventions, and (3) not prescribe multiple antipsychotics simultaneously. Most patients received off-label antipsychotics. Main target symptoms were inattention/hyperactivity (25%), aggression (24%), and other disruptive behaviors (41%). Most patients underwent diagnostic evaluation before the first prescription; however, screening of contra-indications was low (0.2–19%). About 84% had previously received psychosocial treatment and 48% other psychoactive medication, but 9% had not received any treatment. Notably, only 37% continuously received concomitant psychosocial treatment. Simultaneous use of multiple antipsychotics occurred in 3.2%. Younger children were at higher risk of non-adherence to guideline recommendations regarding prior and concomitant treatment, children with autism spectrum disorder or attention-deficit/hyperactivity disorder more likely not to receive concomitant psychosocial treatment. Sex did not significantly affect adherence. Our findings implicate insufficient adherence to important recommendations regarding antipsychotic use in children and adolescents. Especially younger children are at higher risk of receiving suboptimal care. There is an urgency to consistently offer psychosocial interventions during antipsychotic treatment.

'Use of antipsychotics in children and adolescents: a picture from the ARITMO population-based European cohort study'.

Prevalence of the use of antipsychotics (APs) in the paediatric population is globally increasing. The aim of this study was to describe multinational trends and patterns in AP use in children and adolescents in Europe. This was a dynamic retrospective cohort study comprising all children and adolescents (⩽18 years of age). Data were extracted from five population-based electronic healthcare databases in Europe (Denmark, Germany, Italy, the Netherlands and United Kingdom) from 2000 to 2010. Yearly prevalence and incidence of AP use was expressed per 1000 person-years (PYs). Prevalence increased from 1.44 to 3.41/1000 PYs (2008) in Denmark and from 2.07 to 4.35/1000 PYs in the NL (2009), moderately increased from 2.8 to 3.24/1000 in UK (2009) and from 1.53 to 1.74/1000 PYs in Germany (2008) and remained low from 0.61 to 0.34/1000 PYs in Italy (2010). Similarly, incidence rates increased from 0.69 to 1.52/1000 PYs in Denmark and from 0.86 to 1.49/1000 PYs in the NL, stabilised from 2.29 to 2.37/1000 PYs in the UK and from 0.79 to 0.80/1000 PYs in Germany and remained low from 0.32 to 0.2/1000 PYs in Italy. AP use was highest in 15-18 year olds and in boys compared to girls. Yet, the use observed in the 5-9 year olds was found to be comparatively high in the NL. Prescriptions of second generation APs, especially risperidone, were privileged but the first generation APs were still prescribed in the youngest. A steady increase in AP use in children and adolescents was observed essentially in the NL and Denmark. The use in Germany and Italy was lowest among countries. The use of APs under 9 years of age underlines their off-label use and should be carefully monitored as the risk/benefit ratio of these medications remains unclear in young children. AP use was altogether lower in Europe as compared to that reported in North America.

73.2 EFFECTS OF REGULATION ON PRESCRIPTION OF ANTIPSYCHOTIC USE IN FOSTER CHILDREN

Few studies have examined the prevalence of antipsychotic use in children and adolescents in late adolescence. In this presentation, we will discuss the effects of state regulations on the prescription of antipsychotic medication, particularly, in foster children.

The Pharmacoepidemiology of Psychotropic Medication Use in Canadian Children from 2012 to 2016.

Objective: The goal of this study was to characterize the frequency and trends of psychotropic drug prescribing in Canadian children from 2010 to 2016 and to compare these results with a previous study conducted between 2005 and 2009. Methods: Using a national physician panel survey database from IQVIA Canada, aggregated frequencies of written prescriptions and therapeutic indications for antipsychotics, attention-deficit/hyperactivity disorder (ADHD) medications (psychostimulants and nonstimulants), and antidepressants were analyzed in children. Changes in frequency of written prescriptions and therapeutic indications are presented using descriptive statistics. Results: Written prescriptions for antipsychotics decreased by 10% from 2010 to 2016, in contrast to a 114% increase in written prescriptions for antipsychotics observed between 2005 and 2009. Written prescriptions for psychostimulants and antidepressants rose by 35% and 27%, respectively, between 2012 and 2016, comparable with previous results. The most common reasons for recommending an antipsychotic were ADHD and conduct disorder, although there appears to be a downward trend for ADHD compared with other conditions. In contrast, the share of written prescriptions for antipsychotics for autism increased 34% over the study period. Within the second-generation antipsychotics, written prescriptions for aripiprazole increased. An increase in the use of guanfacine extended release for ADHD was also observed. Conclusion: Several factors may be involved in stabilization and small decrease in antipsychotic use in recent years, including physician and patient awareness of adverse effects related to antipsychotic use, knowledge implementation strategies advocating short-term and judicious use of antipsychotics in children, and the approval of guanfacine extended release for use in Canada for ADHD in 2013.

High Doses of Off-Label Antipsychotics Linked to Increased Death Risk in Youth

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessHigh Doses of Off-Label Antipsychotics Linked to Increased Death Risk in YouthTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:31 Jan 2019https://doi.org/10.1176/appi.pn.2019.2a15AbstractYouth prescribed high doses of antipsychotics off label were found to be at an 80 percent increased risk of death, including more than a fourfold increased risk of death from cardiovascular or metabolic causes.Higher doses of antipsychotics raise the risk of death in youth aged 5 to 24 years who take the medications for conditions other than psychosis, when compared with those who take other psychiatric medications, according to a study in JAMA Psychiatry.Wayne Ray, Ph.D., says that most of the antipsychotics prescribed to children and young adults are for conditions for which other treatments are available.This underscores the need for vigilance in ensuring the most appropriate medications are prescribed for each condition, lead author Wayne Ray, Ph.D., a professor of health policy at Vanderbilt University in Nashville, Tenn., told Psychiatric News.“More than one million children and young adults receive antipsychotics, and most of them are for conditions for which other treatments are available. They are dangerous and carry cardiovascular, respiratory, and metabolic risks,” Ray said.In the study, Ray and his colleagues analyzed data from 247,858 patients who were enrolled in Tennessee’s Medicaid program between 1999 and 2014. Of those, 30,120 began taking high doses of antipsychotics (more than 50 mg chlorpromazine equivalents), 28,377 began taking low doses of antipsychotics (50 mg or less chlorpromazine equivalents), and 189,361 began taking other psychiatric medications including psychostimulants, antidepressants, and mood stabilizers (the control group).Among all participants, 70.6 percent had a diagnosis of behavioral symptoms such as attention-deficit/hyperactivity disorder (ADHD), conduct disorder, or impulsivity. Only 28.1 percent in the high-dose group had diagnoses for which there is an FDA-approved indication for taking antipsychotics, such as bipolar disorder or autism spectrum disorder.The researchers found that among patients without life-threatening somatic illness or psychosis who started antipsychotics, those in the high-dose group had an 80 percent increased risk of death, attributable to a 3.5-fold increase risk of unexpected deaths. After accounting for overdose, this increased risk for unexpected deaths persisted, with a 4.3-fold increased risk of death from cardiovascular or metabolic causes. Furthermore, when extrapolating the data out to death rates per 100,000 person-years, the researchers found a rate of 25.6 cardiovascular or metabolic deaths per 100,000 person-years in the high-dose group, compared with a rate of only 4.9 in the control group.“The bottom line is that the findings reinforce existing guidelines for care and cautious use of antipsychotics in younger populations,” said Ray. He noted the need to consider other treatments, provide pretreatment evaluations, identify patients with cardiac problems that might compound their risk, and ensure post-treatment monitoring for cardiac, respiratory, and metabolic effects.“These things are already in the recommendations, but we suspect that they are not followed in regular practice,” Ray said. “Most [high-dose antipsychotics] aren’t prescribed by psychiatrists, and they are primarily written for behavioral symptoms and mood disorders for which there are other medications and psychosocial interventions,” Ray added.Demands from parents and schools to quickly address certain disruptive behaviors may help drive off-label use of antipsychotics in children, says John Newcomer, M.D.John Newcomer, M.D., president and chief executive officer of South Florida Behavioral Network in Miami and an adjunct professor of psychiatry at Washington University School of Medicine in St. Louis, noted potential barriers to more appropriate prescribing of antipsychotics.“The logistics, needed training, and reimbursement structure for effective behavioral therapies that include CBT [cognitive-behavioral therapy] all present barriers to their increased use. This in combination with the perceived simplicity of antipsychotic prescription and perceived demands from parents and schools for a rapid fix for certain disruptive behaviors may be what contributes to higher off-label use of antipsychotics in children in the United States,” said Newcomer, who was not involved in the research.Ray agreed.“Reimbursement drives medication over other approaches. We need options other than just trying to use medications. These [nonpsychotic] conditions are more complex than that. There are bad-home situations, the need for parental training, and other kinds of issues,” said Ray. “There are nonpharmacologic interventions that can work. Psychiatrists have long been frustrated by a lack of resources for these, but it’s a matter of life or death.”This study was supported by the National Heart, Lung, and Blood Institute and the National Institute for Child Health and Human Development. ■“Association of Antipsychotic Treatment With Risk of Unexpected Death Among Children and Youths” can be accessed here. ISSUES NewArchived

Challenges of the use of antipsychotics in children and adolescents

The more frequent prescription of antipsychotics with high proportion of off label use, in particular for children and adolescents, is seen in many countries, including European Union, United States and Russian Federation. In accordance to current clinical guidelines, second-generation antipsychotics are preferred in clinical practice due to the higher tolerability compared to the first-generation antipsychotics. However, second-generation antipsychotics in children and adolescents, especially in continuous use, are associated with cardiac abnormalities and metabolic disorders, including hyperglycemia, and the risk of type 2 diabetes, weight gain and obesity, an increase in prolactin synthesis and hyperlipidemia. The adverse effects of antipsychotics in children and adolescents determine the need for more balanced approaches to their use, careful monitoring of the safety of treatment and the development of measures to prevent and correct side-effects of these drugs.

2.28 A Systematic Approach to Examining the Use of Long-Acting Injectable Antipsychotics in Children and Adolescents

2.28 A Systematic Approach to Examining the Use of Long-Acting Injectable Antipsychotics in Children and Adolescents