Antipsychotic Treatment In Children Research Articles

Incidence of Neuroleptic Malignant Syndrome During Antipsychotic Treatment in Children and Youth: A National Cohort Study.

Objective: The incidence of neuroleptic malignant syndrome (NMS), a rare, potentially fatal adverse effect of antipsychotics, among children and youth is unknown. This cohort study estimated NMS incidence in antipsychotic users age 5-24 years and described its variation according to patient and antipsychotic characteristics. Methods: We used national Medicaid data (2004-2013) to identify patients beginning antipsychotic treatment and calculated the incidence of NMS during antipsychotic current use. Adjusted hazard ratios (HRs) assessed the independent contribution of patient and antipsychotic characteristics to NMS risk. Results: The 1,032,084 patients had 131 NMS cases during 1,472,558 person-years of antipsychotic current use, or 8.9 per 100,000 person-years. The following five factors independently predicted increased incidence: age 18-24 years (HR [95% CI] = 2.45 [1.65-3.63]), schizophrenia spectrum and other psychotic disorders (HR = 5.86 [3.16-10.88]), neurodevelopmental disorders (HR = 7.11 [4.02-12.56]), antipsychotic dose >200mg chlorpromazine-equivalents (HR = 1.71 [1.15-2.54]), and first-generation antipsychotics (HR = 4.32 [2.74-6.82]). NMS incidence per 100,000 person-years increased from 1.8 (1.1-3.0) for those with none of these factors to 198.1 (132.8-295.6) for those with 4 or 5 factors. Findings were essentially unchanged in sensitivity analyses that restricted the study data to second-generation antipsychotics, children age 5-17 years, and the 5 most recent calendar years. Conclusion: In children and youth treated with antipsychotics, five factors independently identified patients with increased NMS incidence: age 18-24 years, schizophrenia spectrum and other psychotic disorders, neurodevelopmental disorders, first-generation drugs, and antipsychotic doses greater than 200 mg chlorpromazine-equivalents. Patients with 4 or 5 of these factors had more than 100 times the incidence of those with none. These findings could improve early identification of children and youth with elevated NMS risk, potentially leading to earlier detection and improved outcomes.

Weight Gain During Antipsychotic Treatment in Children, Adolescents, and Adults: A Disproportionality Analysis in the Global Pharmacovigilance Database, Vigibase®.

While antipsychotic-induced weight gain has been widely described in adults, it has yet to be better characterized in children and adolescents. The aim of this study was to assess antipsychotic-induced weight-gain reporting in children and adolescents as compared to adults, and according to the type of antipsychotic. The study is an observational, case-non-case study using individual case safety reports from the WHO global pharmacovigilance database VigiBase® from 1 January 2000 to 2 June 2021. Disproportionality in antipsychotic-related weight-gain reporting in children and adolescents compared to adults was evaluated based on reporting odds ratios (RORs) with corresponding 95% confidence intervals (CIs) through multivariate logistic regression modeling. Analysis was adjusted for sex, region of reporting, year of notification, reporter qualification, concomitant use of antidepressants, and use of more than one antipsychotic. Among 282,224 antipsychotic-related spontaneous reports included in this analysis, we identified 16,881 (6.0%) weight-gain cases. Disproportionality in weight-gain reporting was found in children (adjusted ROR (aROR) 3.6; 95% CI 3.3-3.8) and in adolescents (aROR 2.3; 95% CI 2.2-2.4) compared to adults. Use of risperidone was associated with the highest increase in weight-gain reporting in children (aROR 4.9; 95% CI 3.9-6.1) and adolescents (aROR 3.6; 95% CI 3.1-4.1). Compared to adults, weight-gain reporting with antipsychotics was disproportionally higher in the pediatric population, especially in children under 12 years of age. Considering the impact of weight gain on global morbidity and mortality, physicians should closely monitor weight gain in young patients, especially children on risperidone.

Antipsychotic treatment of children and adolescents is a double-edged sword

Antipsychotic treatment of children and adolescents is a double-edged sword

Increased Risk of Obesity and Metabolic Dysregulation Following 12 Months of Second-Generation Antipsychotic Treatment in Children: A Prospective Cohort Study.

To determine the risk of developing obesity and related metabolic complications in children following long-term treatment with risperidone or quetiapine. This was a 1-year naturalistic longitudinal study conducted between February 2009 and March 2012. A total of 130 children aged 2 to 18 years without prior exposure to second-generation antipsychotics (SGAs) were enrolled at initiation of treatment with either risperidone or quetiapine. Metabolic parameters were measured at baseline and months 6 and 12. Data of 37 participants (20 treated with risperidone and 17 treated with quetiapine) who completed 12-month monitoring were used in the analysis. After 1 year of SGA treatment, mean weight increased significantly by 10.8 kg (95% CI 7.9 kg to 13.7 kg) for risperidone and 9.7 kg (95% CI 6.5 kg to 12.8 kg) for quetiapine. Body mass index z score also increased significantly in both groups (P < 0.001). There was a high incidence of children becoming overweight or obese (6/15 [40.0%] for risperidone-treated and 7/14 [50.0%] for quetiapine-treated). The mean levels of fasting glucose (for risperidone-treated) and ratio of total cholesterol to high-density lipoprotein cholesterol (for quetiapine-treated) increased significantly by 0.23 mmol/L (95% CI 0.03 mmol/L to 0.42 mmol/L) and 0.48 mmol/L (95% CI 0.15 mmol/L to 0.80 mmol/L), respectively. Children treated with risperidone or quetiapine are at a significant risk for developing obesity, elevated waist circumference, and dyslipidemia during 12 months of treatment. These data emphasize the importance of regular monitoring for early identification and treatment of metabolic side effects.

16: Increased Risk of Metabolic Dysregulation Following 12 Months of Second-Generation Antipsychotic Treatment in Children: A Prospective Cohort Study

Over the last two decades, prescriptions of second-generation antipsychotics (SGAs) to children have increased significantly. During this time period, there has also been a growing body of literature demonstrating an increased risk of metabolic complications in children treated with SGAs. Prospective studies clearly suggest that SGAs confer increased risk for development of weight gain and dyslipidemia over the short term (<3 months). Although long-term SGA use in children is a common practice, investigation of metabolic complications over the long-term is limited to retrospective reports. Thus, we conducted a prospective longitudinal study to assess the impact of SGAs on metabolic complications during the first 12 months of treatment. To determine the risk of developing obesity and related metabolic complications in children following long-term treatment with risperidone or quetiapine. This was a one-year naturalistic longitudinal study conducted between February 2009 and March 2012. A total of 115 children aged two to 18 years without prior exposure to SGAs were enrolled at initiation of treatment with either risperidone or quetiapine. Metabolic parameters were measured at baseline and months 6, and 12. Data of 37 participants (20 risperidone-treated and 17 quetiapine-treated) who completed 12 month monitoring were used in the analysis. After one year of SGA treatment, mean weight increased significantly by 10.8 kg (95% CI 6.6, 10.5 kg) for risperidone and 9.7 kg (95% CI 6.5, 12.8 kg) for quetiapine. BMI z-score also increased significantly in both groups (P<0.001). There was a high incidence of children becoming overweight or obese [6/15 (40.0%) for risperidone-treated and 7/14 (50.0%) for quetiapine-treated]. The mean levels of fasting glucose (for risperidone-treated) and ratio of total cholesterol to HDL cholesterol (for quetiapine-treated) increased significantly by 0.23 mmol/L (95% CI 0.03, 0.42 mmol/L) and 0.48 mmol/L (95% CI 0.15, 0.80 mmol/L), respectively. Children treated with risperidone or quetiapine are at a significant risk for developing obesity, elevated waist circumference and dyslipidemia over 12 months of treatment. These data emphasize the importance of regular monitoring for early identification and treatment of metabolic side-effects.

Twenty-Four Months of Antipsychotic Treatment in Children and Adolescents With First Psychotic Episode

The Child and Adolescent First-Episode Psychosis Study is a longitudinal study of early-onset first psychotic episodes. This report describes the naturalistic psychopharmacological treatment administered during a 24-month follow-up period, as well as discontinuation rates, reasons for discontinuation, and adverse effects. The sample comprised 110 patients, aged 9 to 17 years, with a first psychotic episode. Pharmacological treatment, changes, reasons for discontinuation, and the UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale were registered at 6, 12, and 24 months of follow-up. Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, were the most commonly used. The discontinuation rate was 44.5% at 6 months, 59.1% at 12 months, and 70.9% at 24 months. Discontinuation rates or reasons for discontinuation (adverse reaction, insufficient response, and other) did not differ significantly between antipsychotics. At 6 months, significant differences were found in body mass index increase and body mass index z score increase, which were higher with olanzapine, and in neurological effects, which were higher with risperidone; at 12 and 24 months, these differences were no longer significant. High maintenance rates were found in the clozapine group, although they had higher scores on the autonomic subscale of the UKU. A long follow-up period reveals high discontinuation rates similar to those observed in adults, particularly during the first year. No differences were found between antipsychotics. Differences in adverse effects were found at 6 months but not subsequently after changes in treatment. Clozapine had a high maintenance rate, and its tolerability was comparable to that of other antipsychotics.

Type 2 Diabetes in Children and Adolescents.

Anticipatory guidance regarding healthy eating and active lifestyle is recommended to prevent obesity. Regular targeted screening for type 2 diabetes is recommended in children at risk. Children with type 2 diabetes should receive care in consultation with an interdisciplinary pediatric diabetes healthcare team. Early screening, intervention and optimization of glycemic control are essential, as the onset of type 2 diabetes during childhood is associated with severe and early onset of microvascular complications.

Epidemiologic and Clinical Perspectives on Antipsychotic Treatment of Children and Adolescents

AbbreviationsADHD attention-deficit hyperactivity disorderCD conduct disorderDBD disruptive behaviour disorderODD oppositional defiant disorderSGA second-generation antipsychoticDuring the past several years, an increasing number of children and adolescents have been treated with antipsychotics. A substantial proportion of these young people are diagnosed with ADHD, CD, or ODD.' Safety concerns, especially weight gain, have focused attention on the risk-benefit trade-offs of evolving antipsychotic prescribing standards and practices2 and have increased interest in evaluating the efficacy of antipsychotics for DBDs.In this issue of The Canadian Journal of Psychiatry, Dr Scott ? Patten and colleagues3 provide a timely review of trends in antipsychotic use among young people and Dr Tamara Pringsheim and Dr Daniel Gorman4 assess clinical trials of SGAs for DBDs. Taken together, these 2 articles inform critical ongoing clinical, policy, and academic discussions over the appropriate role of SGAs in child and adolescent mental health care.We learn from Dr Patten and colleagues3 that antipsychotic use in young people has increased in Canada, the United States, the United Kingdom, Italy, and the Netherlands, with considerably lower absolute use rates in Europe than in North America. Adults in Europe and North America are also increasingly receiving antipsychotics.5 In youth, uniformly higher rates of antipsychotic treatment among males than females, with peak use in late childhood and early adolescence, are consistent with the clinical epidemiology of the disruptive behavioural disorders.6 Although more detailed practice-based research is necessary to determine the most common target symptoms of child and adolescent antipsychotic treatment, the diagnostic patterns suggest that controlling problematic aggressive behaviours is a common clinical objective.Large cross-national differences in antipsychotics are unlikely to be explained in full by variations in the underlying prevalence of child and adolescent disorders in clinical care. Instead, Canadian and US physicians appear to be more receptive than their European colleagues to prescribing antipsychotics to young people. Greater SGAuse in the United States than in Germany or the Netherlands has also been described in the treatment of child-onset bipolar disorder.7 To help ensure that North American physicians strike an appropriate balance, now may be a good time to reassess the efficacy of nonpharmacological interventions for aggressive behaviours in youth, such as parent management training, cognitive problem solving skills training, multisystemic therapy,8 and other interventions that incorporate cognitive-behavioural therapy strategies.9Antipsychotics have traditionally been the province of psychiatric practice. Dr Patten and colleagues3 make the point that primary care physicians play a significant role in antipsychotic treatment of children and adolescents. While psychiatrists account for most (62%) antipsychotic prescriptions for Canadian youth, family physicians (17%) and general practitioners (17%) also make nontrivial contributions.10 Early adopters of medical interventions are often specialists rather than primary care For stimulants - the most well-established psychotropic treatment of youth, Canadian psychiatrists account for only 17% of prescriptions.10 Over time, it will be important to track the diffusion of antipsychotic treatment of children and adolescents from psychiatrists to primary care physicians. If pediatricians and family practitioners assume a more prominent role in prescribing antipsychotics to children and adolescents, increased consultations with psychiatrists will need to ensure appropriate patient selection and medication dosing.The review by Dr Pringsheim and Dr Gorman4 establishes that substantial progress has been made in defining the efficacy of risperidone in children with aggressive behaviour, especially in the context of CD or ODD. …

Antipsychotic Medication in Children and Adolescents: A Descriptive Review of the Effects on Prolactin Level and Associated Side Effects

This review reports the incidence of hyperprolactinemia, its relationship with genotype, and prolactin-related side effects in children and adolescents treated with antipsychotics. Data on prolactin levels were available for haloperidol, pimozide, risperidone, olanzapine, clozapine, ziprasidone, and quetiapine. Twenty-nine studies were selected after a literature search in the English Medline/Embase/Psychinfo/EBM databases (1965 to August, 2008). All antipsychotics, except clozapine, ziprasidone, and quetiapine, increase the mean prolactin level from baseline values of 8.0 ng/mL to 25-28 ng/mL after 4 weeks of treatment (reference range 0-15 ng/mL). The most and best data are available for risperidone. Five risperidone studies (n = 577) show an increase of prolactin level from 7.8 ng/mL to 17.7 ng/mL after 1 year of treatment, and two risperidone studies (n = 60) show an increase from 7.4 ng/mL to 24.9 ng/mL after 2 years of treatment. Aggregated over all antipsychotics, prolactin-related side effects, such as gynecomastia, galactorrhea, irregular menses, and sexual dysfunction, were reported by 4.8% of the children and adolescents. No data are available on bone mineral density in relation to antipsychotic-induced hyperprolactinemia in children and adolescents. Prolactin levels may be influenced by the genetic differences that influence prolactin metabolism and D2 dopamine receptor density. Persistent elevation of prolactin for periods up to 2 years has been documented in maintenance treatment with risperidone. Very limited long-term data of pimozide, olanzapine, and quetiapine prohibit drawing conclusions for these antipsychotics. Systematic long-term observational studies, including specific questionnaires as well as physical examination, are needed to investigate prolactin-related side effects of antipsychotic treatment in children and adolescents.

Hyperprolactinemia-Related Adverse Events Associated with Antipsychotic Treatment in Children and Adolescents

Purpose To characterize factors related to the development of hyperprolactinemia and the ensuing reproductive/sexual adverse events in children and adolescents treated with antipsychotic and other psychotropic agents, and the additional risk posed for those with comorbid obesity, metabolic, or endocrine disorders. Methods A retrospective cohort design evaluating medical and pharmacy claims from South Carolina's Medicaid program was used to compare incidence rates for sexual/reproductive adverse events in 4140 children and adolescents who were newly prescribed one of six atypical or two conventional antipsychotic medications, and a random sample of 4500 children not treated with psychotropic medications, January 1998 to December 2005. Logistic and Cox Proportional Hazards regression and Kaplan-Meier survival analysis were performed. Results The treated cohort was not significantly more likely to evince hyperprolactinemia-related disorders than the control sample, but females and adolescents 13 and older were. Incident reproductive/sexual conditions were more likely for females (odds ratio [OR] = 9.52; confidence interval [CI] = 7.63–11.90), adolescents (OR = 3.91; CI = 3.25–4.70), those also taking selective serotonin reuptake inhibitors (SSRIs) (OR = 2.04; CI = 1.56–2.37) or valproic acid derivatives (OR = 1.29; CI = 1.03–1.64), and those with comorbid obesity/weight gain (OR = 1.92; CI = 1.56–2.37), metabolic (OR = 1.41; CI = 1.12–1.78), or endocrine disorders (OR = 2.76; CI = 1.98–3.84). Conclusion In this treated cohort, female adolescents exposed to SSRIs or valproic acid derivatives and those with comorbid obesity, metabolic, or endocrine disorders while taking antipsychotics were at higher risk of developing hyperprolactinemia and ensuing sexual/reproductive adverse events.

Metabolic and Cardiovascular Adverse Events Associated With Antipsychotic Treatment in Children and Adolescents

To identify factors associated with incident cardiovascular events and metabolic disturbance in children and adolescents treated with antipsychotics. A retrospective cohort design evaluating Medicaid medical and pharmacy claims. South Carolina's Medicaid program covering outpatient and inpatient medical services and medication prescriptions from January 1, 1996, through December 31, 2005. A treatment cohort of 4140 children and adolescents prescribed 1 of 5 atypical or 2 conventional antipsychotics, and a random sample of 4500 children not treated with psychotropic medications. Main Exposure Antipsychotics. Incidence/prevalence rates for obesity, type 2 diabetes mellitus, dyslipidemia, cardiovascular events, cerebrovascular events, hypertension, and orthostatic hypotension. Compared with the control sample, the treated cohort had a higher prevalence of obesity (odds ratio [OR], 2.13), type 2 diabetes mellitus (OR, 3.23), cardiovascular conditions (OR, 2.70), and orthostatic hypotension (OR, 1.64). In the treated cohort, patients exposed to multiple antipsychotics were at significantly higher risk for incident obesity/weight gain (OR, 2.28), type 2 diabetes mellitus (OR, 2.36), and dyslipidemia (OR, 5.26). Incident cardiovascular events were more likely with the use of conventional (OR, 4.34) or multiple (OR, 1.57) antipsychotics and mood stabilizers (OR, 1.31). Incident orthostatic hypotension was more prevalent in those coprescribed selective serotonin reuptake inhibitors (OR, 1.77) and mood stabilizers (OR, 1.35). Antipsychotics are associated with several metabolic and cardiovascular-related adverse events in pediatric populations, especially when multiple antipsychotics or classes of psychotropic medications are coprescribed, controlling for individual risk factors.

Neurological Adverse Events Associated with Antipsychotic Treatment in Children and Adolescents

A retrospective cohort design using medical and pharmacy claims from one state's Medicaid program compared incidence rates for neurological adverse events associated with antipsychotic use in 4140 youths prescribed antipsychotic medications and an untreated sample of 4500 youths, January 1998 to December 2005. The treated cohort evinced a higher prevalence of involuntary movements, sedation, and seizures. The odds of incident involuntary movements were significantly higher for those taking aripiprazole, risperidone, haloperidol, and multiple antipsychotics. The odds of incident seizures were greater for those taking risperidone, multiple antipsychotics, and serotonin-specific reuptake inhibitors. The odds of incident sedation were greater for those taking ziprasidone, risperidone, quetiapine, multiple antipsychotics, and serotonin-specific reuptake inhibitors. Exposure to risperidone, multiple antipsychotics, and serotonin-specific reuptake inhibitors consistently confers a higher risk of developing a range of neurological adverse events in young patients, especially those with preexisting central nervous system, mental retardation, or cardiovascular disorders.

QTc Changes after 6 Months of Second-Generation Antipsychotic Treatment in Children and Adolescents

QTc Changes after 6 Months of Second-Generation Antipsychotic Treatment in Children and Adolescents

Reproductive Adverse Events Associated with Antipsychotic Treatment in Children and Adolescents

Background: Limited data is available on the association of adverse reproductive events with mood stabilizing treatment in children and adolescents. We aim to identify the incidence of adverse reproductive events in young patients using mood stabilizing drugs. Risk factors for the development of these adverse events will be identified. Time elapsed from treatment initiation to the development of adverse events will be investigated.

Care needed in antipsychotic treatment of children with autism

Care needed in antipsychotic treatment of children with autism

Atypical Antipsychotic Treatment of Children and Adolescents and Treatment-Emergent Diabetes

Atypical Antipsychotic Treatment of Children and Adolescents and Treatment-Emergent Diabetes