Journal of child and adolescent psychopharmacology最新文献

Objective: Major depressive disorder (MDD) presents a significant psychosocial burden, and there is an unmet need for additional treatment options in pediatric patients. Here, we report the results of two phase 3 multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group studies evaluating the efficacy and safety of levomilnacipran extended release in children and adolescents with MDD. Methods: In the first study, LVM-MD-11, patients aged 12-17 years received daily doses of levomilnacipran 40 mg (n = 134), levomilnacipran 80 mg (n = 138), fluoxetine 20 mg (n = 134), or placebo (n = 141). In the second study, LVM-MD-14, patients aged 7-17 years received levomilnacipran 40 to 80 mg (n = 166), fluoxetine 20 mg (n = 166), or placebo (n = 160) daily. Primary and secondary efficacy endpoints were changes in Children's Depression Rating Scale-Revised (CDRS-R) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively. Results: In LVM-MD-11, there were no significant differences in change in CDRS-R total score between patients treated daily with placebo (least squares mean [LSM] change in CDRS-R total score -22.9) versus levomilnacipran 40 mg (-23.3; p = 0.8035) or 80 mg (-22.6; p = 0.8681). Similarly, in LVM-MD-14, there were no significant differences in LSM change in CDRS-R total score with placebo (-21.3) versus levomilnacipran 40 to 80 mg daily (-23.0; p = 0.2215). There were also no significant differences between the fluoxetine and placebo groups in either study for changes in CDRS-R total score. Changes in CGI-S score were not significant between placebo and levomilnacipran 40 to 80 mg daily or between placebo and fluoxetine. Levomilnacipran was generally well tolerated. Conclusions: The high placebo response in this study prevented the detection of an effect of levomilnacipran in children and adolescents. Clinical Trial Registration numbers: NCT02431806 and NCT03569475.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition with severe and life-long consequences. Adolescents and young adults represent a particularly vulnerable subgroup because of the unique demands of their developmental stage. Despite the well-known efficacy of medication treatment for ADHD, there remains a notable concern regarding poor medication adherence in this population. Objectives: This systematic literature review aimed to synthesize the existing empirical evidence on the outcomes and consequences of medication nonadherence among adolescents and young adults with ADHD. Methods: An extensive database search was conducted on September 26, 2022, with no time limits applied. The databases included Scopus, PubMed, CINAHL, Cochrane, and PsycINFO. Results: Six studies met the inclusion criteria. Each study revealed that medication nonadherence was associated with a range of adverse outcomes, including decreased academic performance, heightened familial, and psychological stress, and an increased likelihood of substance use, pregnancy, obesity, and injury. Conversely, adherence led to improvements in at least one ADHD-related outcome. Conclusions: Research exploring the consequences of suboptimal medication adherence in adolescents and young adults with ADHD is currently limited, and effective strategies to address this issue remain scarce. A thorough understanding of such consequences is critical for developing interventions aimed at improving medication adherence and mitigating the risk of adverse outcomes, especially considering the susceptibility of this population.

Background: Coronavirus disease 2019 (COVID-19) caused a global pandemic that dramatically altered infection control procedures in long-term care facilities. Mental health decline among residents of geriatric facilities during the pandemic has been described (Ferro Uriguen et al., 2022). Our study aims to evaluate psychological effects of the pandemic on residents of a pediatric long-term care facility, a population comprised of medically complex children. To characterize this, we compared patterns of psychotropic medication use during the COVID-19 pandemic to those of the prepandemic period among residents of a 76-bed pediatric long-term care facility. Methods: We conducted a retrospective study of psychotropic medication use from January 2019 to August 2022 using de-identified monthly facility medication refill data. Linear multivariable regression models were used to estimate the level and trends in the monthly rates of medication refills per 10,000 bed days among resident children before and after the pandemic onset. Six classes of psychotropic medications were analyzed including antipsychotics, antidepressants and anxiety medications, trazodone, clonidine, mood stabilizers, and gabapentin. Results: The pandemic onset was associated with a significant increase in the monthly prescribing rates of antidepressant and anxiety medications (20.83; 95% CI, 3.96-37.71; p = 0.017), mood stabilizers (10.44; 95% CI, 5.79-15.09; p < 0.001), and trazodone (-27.66; 95% CI, -40.44 to 14.88; p < 0.001) above those expected by prepandemic trends. The trend in trazodone use changed significantly during the pandemic from decreasing prepandemic to increasing (2.21; 95% CI, 1.28-3.14; p < 0.001). Antidepressant, anxiety medication, and gabapentin use increased throughout the study. Antidepressant and anxiety medication use surged early in the pandemic, but then continued growth at their prior rates of use. Discussion: Increased use of antidepressant and anxiety medications and trazodone suggests a possible impact of the COVID-19 pandemic on rates of anxiety, depression, sleep disturbance, and agitation among children with severe intellectual and developmental disabilities living in long-term care.

Objectives: This review aims to present recent innovations and advancements in attention-deficit/hyperactivity disorder (ADHD) care, encompassing international consensus statement, new medication formulations, digital therapeutics, and neurostimulation devices. Methods: A comprehensive literature search of relevant articles published in the past five years was conducted, emphasizing the evidence base, efficacy, safety, and practical implications of these advancements. Results: The World Federation of ADHD Consensus Statement offers an updated diagnostic and treatment framework rooted in global scientific evidence. There are several newer ADHD medication formulations, including a nonstimulant (Viloxazine extended release) and the first transdermal amphetamine patch approved to treat ADHD. These options offer some unique benefits to personalize treatment based on symptom profile, lifestyle, preferences, and response. Digital tools offer additional means to restructure environments for individuals with ADHD, reducing impairment and reliance on others. In addition, digital therapeutics enhance access, affordability, personalization, and feasibility of ADHD care, complementing or augmenting existing interventions. Trigeminal nerve stimulation emerges as a well-tolerated nonpharmacological, device-based treatment for pediatric ADHD, with initial trials indicating effect sizes comparable to nonstimulant medications. Conclusions: These innovations in ADHD care represent clinically significant new treatment options and opportunities for personalized care. Health care professionals should integrate these developments into clinical practice, mindful of individual patient and family needs and preferences. Future research should assess long-term outcomes, cost-effectiveness, and acceptability of these innovations.

Background: As many as 60% of pediatric patients taking second-generation antipsychotics (SGA) experience weight gain (antipsychotic-induced weight gain). However, the subgroup that experienced substantial weight increase was poorly understood. This study aimed to identify the development and predictors of clinically significant weight gain (CSWG) among pediatric SGA recipients. Methods: A retrospective analysis of the 2016 to 2021 IQVIA Ambulatory EMR-US database was conducted. The study cohort comprised SGA-naive patients ages 5 to 19, continuously prescribed SGA for ≥90 days. CSWG was defined as a weight gain in BMI z-score >0.5. The development of CSWG was described using the group-based trajectory model approach, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the CSWG trajectories. Results: Of the 16,262 SGA recipients who met the inclusion criteria, 4 distinctive CSWG trajectories were identified: (1) Rapid (14.6%), (2) Gradual (12.6%), (3) Transit (7%), and (4) no CSWG (65.8%). Factors associated with a higher likelihood of having rapid or gradual CSWG versus nonsignificant weight gain were being younger (OR [95% CI] = 12-17 vs. 5-11, Rapid, 0.727 [0.655-0.806]; Gradual, 0.776 [0.668-0.903]), male (Rapid, 1.131 [1.021-1.253]), non-Hispanic White (Black vs. White: Rapid, 0.833 [0.709-0.98]), with lower baseline BMI z-score (Rapid, 0.376 [0.361-0.392]; Gradual, 0.449 [0.424-0.476]), and receiving olanzapine as the initial SGA (Rapid, 1.38 [1.093-1.74]). The Area under the Receiver operating characteristic (ROC) Curve for the comparison of rapid and gradual CSWG with no CSWG trajectory were 0.83 and 0.80, respectively. Conclusions: SGA recipients experienced four distinctive CSWG trajectories (Rapid, Gradual, Transient, and No CSWG). The risk of CSWG could be predicted using patient characteristics at the SGA initiation. This insight highlights the importance of personalized monitoring and timely intervention strategies for at-risk individuals who experienced persistent CSWG in real practice.

Objective: Little U.S. pharmacoepidemiologic study is based on treatment during continuous enrollment for periods more than a year. This study aims to show pediatric patterns of stimulant use (alone or with other psychotropic classes) from Medicaid administrative claims data for stimulant patterns of 3- to 8-year continuous enrollees. Methods: A retrospective cohort study was derived from Medicaid enrollment, pharmacy, and diagnosis claims data (2007-2014) in a mid-Atlantic state. Youth aged 2-17 years with 3-8 years of continuous enrollment treated with stimulants were compared with a date-matched comparison group treated without stimulants. Major outcomes include prevalence and duration of stimulant use and patterns of stimulant polypharmacy across relatively long enrollments (3-8 years). Results: Among 264,518 unique 2- to 17-year olds with 3-8 years of continuous enrollment, 16.5% had stimulant prescription dispensings, doubling the annual national prevalence of 8.1%. Subgroup analysis showed that the highest prevalence of stimulant use was for 6- to 11-year olds (20.4%), foster care eligible youth (42.3%), and those with 7-8 years of continuous enrollment (20.1%). Externalizing psychiatric disorders were far more common in those treated with stimulants than in those treated without stimulants. The duration of stimulant exposure overall was a median of 487 days, half that of foster care stimulant users. Stimulant polypharmacy with two or more psychotropic classes concomitantly characterized 29.8% of stimulant users. Among those with three or four or more class polypharmacy, 85% and 88%, respectively, had concomitant stimulant and antipsychotic use. The adjusted odds ratio (AOR) of three or more class polypharmacy significantly increased in 12- to 17-year-old age group (AOR = 1.8), foster care eligibility (AOR = 4.5), and among those with the longest enrollment (AOR = 1.7). Conclusions and Relevance: Stimulant prevalence in Medicaid-insured youth with continuous enrollment of 3-8 years was twice as common as in annual data sets. Future research should investigate three to five interclass stimulant polypharmacy effectiveness in reliably diagnosed community populations.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by sudden onset of obsessive-compulsive disorder and/or eating restriction with associated neuropsychiatric symptoms from at least two of seven categories. The PANS 31-Item Symptom Rating Scale (PANS Rating Scale) was developed to identify and measure the severity of PANS symptoms. The objective of this study was to define the psychometric properties of the PANS Rating Scale. Methods: Children with PANS (N = 135) and their parents participated. Parents completed the PANS Rating Scale and other scales on Research Electronic Data Capture. The PANS Rating Scale includes 31 items that are rated on a Likert scale from 0 = none to 4 = extreme. Pearson's correlations were run between the PANS Total score and scores on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS), Modified Overt Aggression Scale (MOAS), Columbia Impairment Scale (CIS), PANS Global Impairment Score (GIS), and Children's Global Assessment Scale (CGAS). Results: Convergent validity was supported by significant correlations between the PANS Total and scores on the CY-BOCS, YGTSS, MOAS, CIS, GIS, and CGAS. The largest correlations were with measures of functional impairment: PANS Total and CIS (r = 0.81) and PANS Total and GIS (r = 0.74). Cronbach's alpha was 0.89 which demonstrates strong internal consistency of the 31 items. PANS Total score was significantly higher in children in a flare of their neuropsychiatric symptoms compared to children who were not in a flare. Conclusions: This study provides preliminary support for the PANS Rating Scale as a valid research instrument with good internal consistency. The PANS Rating Scale appears to be a useful measure for assessing children with PANS.