Journal of child and adolescent psychopharmacology最新文献

Introduction: Neuroinflammatory processes have been extensively implicated in the underlying neurobiology of numerous neuropsychiatric disorders. Elevated C-reactive protein (CRP), an indicator of nonspecific inflammation commonly utilized in clinical practice, has been associated with depression in adults. In adolescents, our group previously found CRP to be associated with altered neural reward function but not with mood and anxiety symptoms assessed cross-sectionally. We hypothesized that the distinct CRP findings in adolescent versus adult depression may be due to chronicity, with neuroinflammatory effects on psychiatric disorders gradually accumulating over time. Here, we conducted a longitudinal study to evaluate if CRP levels predicted future onset or progression of depression in adolescents. Methods: Participants were 53 adolescents (age = 14.74 ± 1.92 years, 35 female), 40 with psychiatric symptoms and 13 healthy controls. At baseline, participants completed semistructured diagnostic evaluations; dimensional assessments for anxiety, depression, anhedonia, and suicidality severity; and bloodwork to quantify CRP levels. Clinical assessments were repeated at longitudinal follow-up after ∼1.5 years. Spearman's correlation between CRP levels and follow-up symptom severity were controlled for body mass index, age, sex, and follow-up interval and considered significant at the two-tailed, Bonferroni-adjusted p < 0.05 level. Results: After correction for multiple comparisons, no relationships were identified between baseline CRP levels and follow-up symptom severity. Conclusion: CRP levels were not significantly associated with future psychiatric symptoms in adolescents in this preliminary analysis. This may suggest that CRP is not a useful biomarker for adolescent depression and anxiety. However, future longitudinal studies with larger sample sizes and incorporating additional indicators of neuroinflammation are needed.

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.

Background: Understanding how development influences medication and placebo responses in anxiety disorders could inform treatment decisions, including age-specific first- versus second-line psychopharmacological interventions. Objective: To meta-analytically compare the trajectory of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo response in youth and adults with anxiety disorders. Methods: Weekly symptom severity data were extracted from prospective, randomized, parallel-group, placebo-controlled trials of SSRIs and SNRIs in children, adolescents, and adults with anxiety disorders (generalized, separation, and social anxiety disorders as well as panic disorder). Treatment response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in symptom severity was evaluated as a function of time, and post hoc analyses were conducted to determine the sensitivity of these results across sample heterogeneity and alternative functional forms. Results: Data were included from 11 trials of youth (SSRI, κ = 7; SNRI, κ = 4) and 71 studies of adults (SSRI, κ = 46; SNRI, κ = 25). In total, 1067 youth participated in SSRI trials and 1024 in SNRI trials. In total, 10,826 adults participated in SSRI trials (placebo, n = 5367; SSRI n = 5,459) and 6232 in SNRI trials (placebo, n = 3,128; SNRI n = 3,094). A logarithmic model best described the response. Placebo response was similar in youth and adults (mean difference = -1.98 ± 6.21, 95% credible interval [CrI]: -10.2 to 14.2, p = 0.750), and statistically significant improvement from baseline emerged by week 2 in both adults (mean difference: -18.34 + 1.017, 95% CrI: -20.3 to 16.3, p < 0.001) and youth (mean difference: -23.74 + 3.736, 95% CrI: -31.1 to -16.4, p < 0.001). SSRIs produced similar improvements for youth and adults (p = 0.129), but SNRIs produced slower improvement in youth than adults (p = 0.018). Conclusions: Antidepressant-related improvement occurs early in youth and adults with anxiety disorders. SSRI response is similar in adults and youth; however, SNRIs produce greater responses in adults than youth, potentially representing a developmental effect.

Objective: Youth with bipolar spectrum disorders (BSD) are frequently prescribed second-generation antipsychotics (SGAs). Nonadherence to treatment often results in increased mood symptoms and diminished quality of life. We examined SGA adherence rates and adherence barriers among youth who have overweight/obesity and are diagnosed with BSD enrolled in a multisite pragmatic clinical trial. Methods: SGA adherence and adherence barriers at baseline via patient- and caregiver report was assessed. Adherence was defined as taking ≥70% of prescribed SGA doses in the past week. The weighted Kappa statistic was used to measure child-caregiver agreement about adherence rates, barriers, and caregiver assistance. Regression analyses were used to examine associations of caregiver assistance, age, sex, race, insurance status, dosing frequency, and number of concomitant medications with adherence. Barriers to adherence were analyzed separately for youth and their caregivers, using logistic regression to assess associations between informant-reported barriers and informant-reported adherence. Results: Participants included 1485 patients and/or caregivers. At baseline, 88.6% of patients self-reported as adherent; 92.0% of caregivers reported their child was adherent. Concordance between patients and caregivers was moderate (k = 0.42). Approximately, 50% of the sample reported no adherence barriers. Frequently endorsed barriers included forgetting, side effects, being embarrassed to take medications, and preferring to do something else. Concordance between informants regarding adherence barriers was weak (k = 0.05-0.36). Patients and caregivers who did not endorse adherence barriers reported higher adherence than those who endorsed barriers. Male sex and having once daily dosing of medications were associated with lower adherence. Discussion: One-week patient- and caregiver-reported adherence was high in this sample. Half of the sample reported adherence barriers. Most commonly endorsed barriers were forgetting, side effects, being embarrassed, and preferring to do something else. Caregivers and patients have unique perspectives regarding adherence barriers. Understanding and addressing treatment barriers in clinical practice may facilitate adherence.

Background: Antipsychotics carry a higher-risk profile than other psychotropic medications and may be prescribed for youth with conditions in which other first-line treatments are more appropriate. This study aimed to evaluate the population-level effect of the Safer Use of Antipsychotics in Youth (SUAY) trial, which aimed to reduce person-days of antipsychotic use among participants. Methods: We conducted an interrupted time series analysis using segmented regression to measure changes in prescribing trends of antipsychotic initiation rates pre-SUAY and post-SUAY trial at four U.S. health systems between 2013 and 2020. Results: In our overall model, adjusted for age and insurance type, antipsychotic initiation rates decreased by 0.73 (95% confidence interval [CI]: 0.30, 1.16, p = 0.002) prescriptions per 10,000 person-months before the SUAY trial. In the first quarter following the start of the trial, there was an immediate decrease in the rate of antipsychotic initiations of 6.57 (95% CI: 0.99, 12.15) prescriptions per 10,000 person-months. When comparing the posttrial period to the pretrial period, there was an increase of 1.09 (95% CI: 0.32, 1.85) prescriptions per 10,000 person-months, but the increasing rate in the posttrial period alone was not statistically significant (0.36 prescriptions per 10,000 person-months, 95% CI: -0.27, 0.99). Conclusion: The declining trend of antipsychotic initiation seen between 2013 and 2018 (pre-SUAY trial) may have naturally reached a level at which prescribing was clinically warranted and appropriate, resulting in a floor effect. The COVID-19 pandemic, which began in the final three quarters of the posttrial period, may also be related to increased antipsychotic medication initiation.

Aim: To establish significant risk factors for the development of adverse drug effects (ADEs) in children and adolescents with an acute psychotic episode taking antipsychotics. Materials and Methods: The research team randomly selected 15 patient records each month for 3 years (2016-2018). Overall, 450 patient records were included (223 boys and 227 girls, mean age was 14.52 ± 2.21 years). Adverse effects were identified using the standard algorithm of the Global Trigger Tool method. A "trigger" is an indication that an adverse reaction is likely to occur, e.g., an antihistamine prescription on a prescribing list. When a trigger was detected, the case history was studied in further detail to confirm the occurrence of ADEs. We divided patients into two groups: the "children" group (under 12 years old) and the "adolescents" group (13 years and older). Data were analyzed using the statistical package IBM SPSS Statistics 23.0. Results: Of the 450 patient records, 402 (89.3%) had at least one trigger detected. In total, 126 case histories contained evidence of ADE (28%). The total number of ADEs per 1000 patient days was 5.39 and the number of ADEs per 100 admissions was 32.0. Among adolescents, two or more triggers per patient were significantly more frequently identified (61.3% vs. 44.6%; p = 0.001). ADEs were rare in "Children" compared with "Adolescents" (13.8% vs. 30.4%; p = 0.006). The logistic regression analysis confirmed high predictive role of "Adolescence" (odds ratio [OR] = 2.58; 95% confidence interval [CI] 1.22-5.4; p = 0.013), "Polypharmacy" (OR = 1.96; 95% CI 1.23-3.1; p = 0.004), and "First-life hospitalization" (OR = 2.17; 95% CI 1.34-3.48; p = 0.001) for ADE fact in patient records. Conclusion: We found that significant risk factors for ADEs to antipsychotics in patients with acute psychotic episode were adolescence (13 years and older), polypharmacy, and first-life hospitalization. The fact that children (i.e., younger than 13 years of age) are less likely to experience ADEs was not associated with high-risk drugs or higher doses in our study.

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.

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.