A Systematic Review of Pharmacologic Treatments for School Refusal Behavior.

OBJECTIVE: School refusal is an important pediatric problem with significant negative short- and long-term outcomes. Specific psychosocial treatments appear effective in reducing school refusal, but many children do not respond to these treatments. Although systematic reviews have examined the efficacy of psychological interventions for school refusal, no systematic reviews on pharmacological interventions exist. METHODS: We conducted a comprehensive literature search of MEDLINE, PsycINFO, Scopus, and Embase for randomized controlled trials (RCTs) or quasi-experimental pharmacologic trials in children and adolescents with school refusal reported in English or Spanish until July 1, 2017. Two authors screened study titles and abstracts for eligibility. Data regarding the population, intervention, comparison, and outcomes for each trial were extracted and reported. Effect sizes for school attendance are presented. RESULTS: The search identified 6 articles, including 7 trials (6 RCTs and 1 open label) and 306 youths. Pharmacologic treatments investigated for school refusal included antidepressants (imipramine, clomipramine, and fluoxetine) and benzodiazepines (alprazolam). All pharmacotherapies studied had pretreatment to posttreatment improvements on school refusal, depression, and anxiety symptoms. However, included trials were severely underpowered and did not demonstrate significant improvement compared to placebo. CONCLUSIONS: Data regarding pharmacological treatments for school refusal are sparse. Most trials in this area were conducted before development of newer antidepressants, were underpowered, and have significant methodological limitations that are characteristic of the time in which they were conducted. This systematic review highlights the need for more trials with newer pharmacologic agents, larger sample sizes, and improved systematic assessments of school refusal and comorbidities. School refusal represents an important functional outcome for many children, especially those with anxiety and depression. Future pharmacologic studies of anxiety and depression in children may benefit from incorporating specific school refusal measures as secondary outcomes.

Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial.

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-h post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time × Treatment: F9,115=2.6, p=0.01) but not the VAS-Anxiety (Time × Treatment: F10,141=0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first 2 weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety.

Predictors of Long-Term Risky Driving Behavior in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: This study examines predictors of later risky driving behavior in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Stepwise logistic regression and receiver operating characteristic (ROC) analysis were used to explore baseline predictors of risky driving behavior for adolescents who completed the 8-year follow-up assessment in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (MTA). RESULTS: Stepwise logistic regression analysis explained 19% of the total variance in risky driving behavior. Increased likelihood of risky driving behavior was associated with parental history of conduct disorder, low parental monitoring and supervision, and increased age. ROC analysis identified discriminative predictors for adolescents older and younger than 16 years of age at follow-up. The most discriminative predictors of later risky driving behavior were parental stress at baseline (for children 16 years or older) and increased child-rated parental protectiveness (for children less than 16 years old). CONCLUSION: Risky driving behavior was significantly predicted by baseline characteristics for the MTA cohort. Aspects of parenting behavior (or the child's perception of them), including parental stress levels, parental protectiveness, and parental levels of monitoring and supervision, were most informative in predicting these outcomes. Our results suggest that interventions to reduce high-risk behaviors in these high-risk children with ADHD might involve targeted parenting interventions.

Predictors of Long-Term School-Based Behavioral Outcomes in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To explore predictors of 8-year school-based behavioral outcomes in attention-deficit/hyperactivity disorder (ADHD). METHODS: We examined potential baseline predictors of school-based behavioral outcomes in children who completed the 8-year follow-up in the multimodal treatment study of children with ADHD. Stepwise logistic regression and receiver operating characteristic (ROC) analysis identified baseline predictors that were associated with a higher risk of truancy, school discipline, and in-school fights. RESULTS: Stepwise regression analysis explained between 8.1% (in-school fights) and 12.0% (school discipline) of the total variance in school-based behavioral outcomes. Logistic regression identified several baseline characteristics that were associated with school-based behavioral difficulties 8 years later, including being male (associated with truancy and school discipline), African American (school discipline, in-school fights), increased conduct disorder (CD) symptoms (truancy), decreased affection from parents (school discipline), ADHD severity (in-school fights), and study site (truancy and school discipline). ROC analyses identified the most discriminative predictors of truancy, school discipline, and in-school fights, which were Aggression and Conduct Problem Scale Total score, family income, and race, respectively. CONCLUSIONS: A modest, but nontrivial portion of school-based behavioral outcomes, was predicted by baseline childhood characteristics. Exploratory analyses identified modifiable (lack of paternal involvement, lower parental knowledge of behavioral principles, and parental use of physical punishment), somewhat modifiable (income and having comorbid CD), and nonmodifiable (African American and male) factors that were associated with school-based behavioral difficulties. Future research should confirm that the associations between earlier specific parenting behaviors and poor subsequent school-based behavioral outcomes are, indeed, causally related and independent cooccurring childhood psychopathology. Future research might target increasing paternal involvement and parental knowledge of behavioral principles and reducing use of physical punishment to improve school-based behavioral outcomes in children with ADHD.