Journal of Child and Adolescent Psychopharmacology

Pediatric psychotropic polypharmacy (PPP) is the prescription of more than one medication targeting psychiatric disorders among people younger than 18 years. Recent data suggested that PPP rates may be plateauing. Few studies have evaluated this question in large, nationally recruited samples.

The National Health and Nutrition Examination Survey was used to examine the correlates and prevalence of PPP across assessment cycles. Independent assessments were obtained biannually between 2013 and 2018.

Eleven thousand four hundred thirty-nine participants (4–17 years; M_age  = 8.69 years; standard deviation = 5.16) were included in analyses. The Anatomic Therapeutic Chemical coding scheme was employed to classify medications, and participants were characterized as taking psychotropic medication if the medication was associated with a psychiatric diagnosis code. Participants self-reported past month medication use. Logistic regressions were used to examine correlates of pediatric psychotropic monotherapy compared with psychotropic polypharmacy.

Across assessments, 1.2% of respondents reported using two or more psychotropic medications. This estimate is lower than has been observed in specialized samples, but higher than other work using national samples. There was a small, significant difference in PPP across assessment cycles, such that rates of PPP were higher at the latter assessments. Correlates of PPP accorded with prior work, including male gender, increasing age, and markers of low socioeconomic status. The most robust predictor was having seen a mental health professional in the past year.

This study documents that ∼1% of U.S. participants from a nationally recruited sample endorsed PPP. Findings are situated in the broader literature and the need for additional, prospective data to better characterize those trends in the United States and around the world.

Many kids take more than one medication for psychological problems. We analyzed data from ∼11,000 children and adolescents from across the United States, evaluated between 2013 and 2018. The number of kids taking multiple medications for psychological problems was different (higher) when measured later in time. Being a boy, being older, living in poverty, and having seen a mental health professional in the past year were associated with taking multiple medications for psychological problems.

These findings suggest rates of pediatric psychotropic polypharmacy (PPP) remain high in the United States, and correlate with male gender, poverty, and having recently seen a mental health professional. Relative to White children and adolescents, Black participants were less likely and Hispanic participants more likely to endorse PPP. Policy considerations include fully educating families and practitioners about the benefits as well as potential downsides of PPP and additional intervention options for mental health problems.

To assess characteristics and correlates of metabolic syndrome (MetS) in adolescents with major depressive disorder (MDD) or bipolar disorder-depressive episode (BP-d).

Case–control study, using national inpatient sample data, including adolescents (age, 12–18 years) with a primary diagnosis of MDD or BP-d. Using propensity score matching (based on age, sex, and race/ethnicity), we extracted cases with MetS (≥3 of the following conditions: obesity, diabetes, hypercholesterolemia, and hypertension) and controls without MetS. We used a multivariable logistic regression model calculating adjusted odds ratios (aORs) for potential correlates of MetS, focusing on primary mood disorders and psychiatric comorbidities.

In 607 age-/sex-/race/ethnicity-matched adolescents (MDD = 83.5%, BP-d = 16.5%), comparing those with (N = 332) versus without MetS (N = 275), MetS was most prevalent in later-age adolescents (mean age 16.3 years), females (58.1%), Whites (40.3%), and Blacks (31.5%). MetS was characterized by obesity (84.9% vs. 3.6%), hypertension (81% vs. 1.8%), diabetes (72.8% vs. 9.1%), and hypercholesterolemia (67.2% vs. 3.6%) (all p < 0.001). MetS was associated with a primary diagnosis of BP-d versus MDD (aOR 2.42, 95% confidence interval [CI] 1.47–3.97) and comorbid disruptive behavior disorders (DBD) (aOR 4.45, 95% CI 1.55–12.78), while comorbid substance use disorder reduced MetS risk (aOR 0.31, 95% CI 0.19–0.50).

In adolescents with MDD or BP-d, MetS was associated with a primary BP-d diagnosis, and comorbid DBD. MetS-related parameters should be screened for early in adolescents with depression-spectrum disorders aiming to prevent the development or effects of MetS.

Cariprazine is a dopamine D₃-preferring D₃/D₂ and serotonin 5-HT_1A receptor partial agonist approved to treat adults with schizophrenia and manic/mixed or depressive episodes associated with bipolar I disorder. This sequential-cohort, dose-escalation study was the first to evaluate the pharmacokinetic, safety, and tolerability profile of cariprazine and its two major active metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR), in pediatric patients with schizophrenia or bipolar I disorder.

This phase I open-label study enrolled patients with schizophrenia (13–17 years of age) or bipolar I disorder (10–17 years of age). Patients met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for schizophrenia or bipolar I disorder and had Positive and Negative Syndrome Scale (PANSS) total scores ≥70 or Young Mania Rating Scale (YMRS) total scores ≥20. Patients were assigned to one of four treatment groups to receive 6 weeks of cariprazine treatment through slow titration to 1.5, 3, or 4.5 mg/d or fast titration to 4.5 mg/d. Pharmacokinetics, adverse events (AEs), and various safety parameters were analyzed. Efficacy was evaluated as an exploratory outcome.

A total of 50 participants were enrolled. Based on mean trough levels, steady state appeared to be reached within 1–2 weeks for cariprazine and DCAR and within 4–5 weeks for DDCAR. Systemic exposure of cariprazine, DCAR, and DDCAR generally increased approximately in proportion to the increases in dose from 1.5 to 4.5 mg/d. The most frequent treatment-related, treatment-emergent AEs included sedation, parkinsonism, tremor, dystonia, and blurred vision. Improvements from baseline on the PANSS and YMRS were observed throughout treatment.

In this first investigation of cariprazine in a pediatric population with schizophrenia or bipolar disorder, pharmacokinetic parameters were consistent with those observed in adults. Cariprazine appeared to be safe and tolerable in children and adolescents.

This study describes for the first time the characteristics by sex of patients with Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), including clinical phenotype, treatment, and psychosocial aspects of disease.

This cross-sectional study included 205 consecutive community patients evaluated between January 1, 2012 and March 30, 2019 and compared 87 females with 118 males. Our primary hypothesis was that males would display more aggression, as measured by the Modified Overt Aggression Scale (MOAS) and would be treated with immunotherapy earlier than females. The MOAS began to be administered 5 years into the study period, and 57 of the 205 families completed the MOAS for this study.

Our analysis revealed that males had a higher median MOAS score in the first year of clinic when compared with females (median 11, interquartile range [IQR] [4–24] vs. median 3, IQR [1–9]; p = 0.03) and a higher median subscore for physical aggression (median 4, IQR [0–12] vs. median 0, IQR [0–8]; p = 0.05). The median time from PANS symptom onset to first administration of immunotherapy, which did not include nonsteroidal anti-inflammatory drugs or short bursts of oral steroids, was 6.9 years for females and 3.7 years for males (p = 0.20). The two groups did not differ significantly in age of PANS onset, time from onset to clinic entry, other psychiatric symptom measures, or laboratory markers of inflammation.

Among patients with PANS, males exhibit more aggressive behavior when compared with females, which may advance the decision to treat with immunotherapy. Scores that capture a more global level of functioning show that despite there being a higher level of aggression in males, female patients with PANS have similar levels of overall impairment.

To describe the longer-term effectiveness, safety, and tolerability of open-label ziprasidone in children and adolescents with bipolar I disorder (BD-I).

A subset of 23 participants aged 10–17 years, who were previously treated in a multi-site, 4-week randomized controlled trial received open-label ziprasidone (20–80 mg twice a day) for up to 26 weeks.

The most common adverse events (AEs) were fatigue (30%), somnolence (17%), and nausea (13%). Effects on weight, body mass index, and metabolic parameters (glucose, cholesterol, and triglycerides) were minimal. No participant had a Fridericia-corrected QT interval ≥ 460 msec or a change from baseline of ≥60 msec, and there were no cardiac-related AEs. Both the participants who continued ziprasidone and those who initiated ziprasidone in the open-label extension showed improvements in their symptoms of mania.

The overall findings of the study are consistent with the accumulating knowledge on the safety profile of ziprasidone in the acute and long-term treatment of children and adolescents with BD-I, in the midst of a manic episode. ClinicalTrial.gov ID: NCT03768726.