Journal of Child and Adolescent Psychopharmacology

Randomized controlled trials (RCTs) are the gold standard for evaluating medication efficacy. The absence of a universal definition of treatment response, based on the degree of symptom improvement measured by standardized rating scales in the field of attention-deficit/hyperactivity disorder (ADHD), makes it difficult to compare treatment outcomes across RCTs. Here, we aimed to assess to what extent and how “treatment response” is defined across RCTs of ADHD medications.

We identified eligible RCTs via the MED-ADHD database (https://med-adhd.org/), which compiles RCTs evaluating the efficacy and safety of pharmacological treatments for children, adolescents, and adults with ADHD, based on a comprehensive search in multiple electronic databases, including PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Registry of Controlled Trials, and EMBASE, up to 17 January 2025, alongside additional unpublished information gathered from manufacturers/study authors.

Out of 167 RCTs in MED-ADHD, 88 defined treatment response based on reductions in ADHD core symptom severity using rating scale scores. The most frequently used threshold was a ≥30% reduction in attention-deficit/hyperactivity disorder (ADHD-RS) scores, with other RCTs using ≥25%, ≥40%, or ≥50%. In addition, RCTs applied similar cutoff values to alternative scales, including Conner’s Adult ADHD Rating Scale, SNAP-IV, Adult ADHD Investigator Rating Scale, and Wender-Reimherr Adult Attention Deficit Disorder Scale. However, 79 studies did not specify any response threshold.

Our review underscores and quantitatively defines the inconsistency in the definition of treatment response across ADHD medication trials, highlighting the urgent need for the field to reach a consensus on the use of a standardized definition of “treatment response” for each rating scale, based on the percentage reduction in ADHD core symptom severity.

To describe the Sertraline Pediatric Registry for the Evaluation of Safety (SPRITES) safety results, including adverse events (AEs) (serious and nonserious, including suicide-related events) following long-term treatment with sertraline in children and adolescents aged 6–16 years.

SPRITES was a multicenter, prospective, observational study designed to compare cognitive, emotional, and physical development in pediatric patients exposed to sertraline or psychotherapy alone in routine care for up to 3 years. Safety outcomes included AEs collected on the Pediatric Adverse Event Rating Scale and suicidal ideation/behavior (SIB), as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS). AEs (unadjusted and adjusted for exposure) and C-SSRS data were summarized descriptively, and a marginal structural model (MSM) was applied to the C-SSRS results.

Between April 2012 and September 2020, 941 patients participated in SPRITES. At baseline, per treating physician discretion, 695 patients were administered sertraline, 243 patients were administered psychotherapy alone, and 3 patients were administered an antidepressant other than sertraline. At postbaseline timepoints, patients receiving sertraline reported higher overall rates of AEs relative to the other antidepressants and nonpharmacologic treatment groups. The most common AEs in the sertraline group were related to psychiatric and gastrointestinal disorders. In all exposure groups, the incidence of AEs and SIB decreased across study timepoints. MSM analyses did not demonstrate an effect of sertraline treatment on new onset or worsening SIB.

The safety profile of sertraline in a long-term, real-world setting is similar to that of prior pediatric sertraline studies. A greater proportion of AEs and SIB events reported in the sertraline group compared with the nonpharmacologic therapy group is not unexpected given the safety profile of sertraline and observation of baseline differences in psychiatric disease severity between exposure groups. With prolonged sertraline treatment, incidence rates of AEs and SIB events decreased, and worsening of SIB was not observed.

The purpose of this article was to review the safety, tolerability, and effectiveness of clozapine in youth and young adults with autism spectrum disorder (ASD) and/or intellectual disability.

An IRB-approved retrospective chart review of youth and young adults with autism and/or intellectual disability who were prescribed clozapine between January 2012 and June 2020 was completed. Information was collected from 1 year before through 1 year after clozapine initiation related to medications prescribed, hospitalizations, emergency department (ED) visits, and Clinical Global Impressions-Severity and Clinical Global Impressions-Improvement (CGI-I) ratings. Adverse effects and reasons for stopping clozapine were documented.

Fifty-eight patients were included in analysis. Forty patients remained on clozapine through June 2020 and 18 did not. Most patients were prescribed clozapine for treatment of irritability. Reasons for stopping clozapine included side effects, continued behavior concerns, difficulty with blood draws, and improvement in symptoms. For those who remained on clozapine for the duration of the review period, the number of hospitalizations and ED presentations for psychiatric concerns or medical concerns potentially related to clozapine significantly decreased in the year following clozapine initiation compared with the year prior (2.13 vs. 3.48, p = 0.010). There was a significant reduction in CGI-I scores from 3.96 to 2.53 (p < 0.001) from clozapine initiation to 1 year later. There was a nonsignificant trend toward reduction in use of multiple antipsychotics simultaneously from time of clozapine initiation to 1 year later in those who remained on clozapine (38.5% vs. 25%, p = 0.232).

Use of clozapine for treatment-refractory irritability in youth and young adults with ASD and/or intellectual disability is generally well-tolerated. Observed benefits included a decrease in number of hospitalizations and ED visits and a decrease in CGI-I score in the year after clozapine initiation.

Self-report questionnaires are common for measuring posttraumatic stress disorder (PTSD). The experience of life threat—Criterion A—serves a gatekeeper function for diagnosing PTSD, and evidence suggests false positives are common on questionnaires. It remains unknown how common they are and whether extra instructions can reduce them.

The present study assessed 42 youths, 10–17 years of age, from a clinic setting. Youths and parents completed regular PTSD questionnaires and then enhanced versions with more detailed instructions and examples of Criterion A and non-Criterion A events. Parents completed a semistructured interview as the verification of true versus false positives.

In the full sample, parents endorsed 41 and children endorsed 45 false positive events. The mean was significantly greater than zero for both parents and children. Parents endorsed 59 and children endorsed 138 false positive symptoms. When false positive events were endorsed, this was significantly associated with more false positive symptoms for both parents and children. An enhanced questionnaire failed to reduce false positive events for the full sample.

The common occurrence of false positives suggests caution is warranted when interpreting estimates from questionnaire-based research about the prevalence of PTSD. While this attempt to eliminate false positives was not fully successful, there may be other useful enhancements to consider in future research.

SPTAN1 variants are thought to affect the scaffolding that protects the axonal segment of neurons as well as neuronal synapses. The SPTAN1 gene is located in the 9q34.11 genomic region and encodes the cytoskeletal protein alpha II spectrin. Epilepsy, encephalopathy, and motor neuropathy are most commonly associated with SPTAN1 variants.

An informed consent and questionnaire were developed in order to gather information from caregivers regarding their family members’ SPTAN1 variant. Survey results are summarized descriptively, in order of frequency.

The results of a questionnaire filled out by the caregivers of loved ones who have a SPTAN1 mutation are summarized for 25 individuals, 14 males and 11 females, who have the SPTAN1 mutation.

The results of this survey mirror those reported by other authors and include epilepsy, intellectual and motor delays, encephalopathy, and motor neuropathy. Additional effects of the SPTAN1 mutation reported here include absent or difficult speech, happy personality, decline in cognitive and motor skills with age, vision and hearing abnormalities, organ and skeletal effects, autoimmune diseases, and weakened immune systems.

Many individuals with autism spectrum disorder (ASD) experience gastrointestinal (GI) symptoms, which can impact social interactions, exacerbate social communication deficits, and decrease the quality of life. GI symptoms have been shown to be correlated with the autonomic nervous system and endocrine response to stress in some people with ASD. Furthermore, propranolol, a central and peripheral beta-adrenergic antagonist that inhibits the stress response, has been shown to provide GI relief for some individuals with ASD, but not others. This pilot study examined whether baseline (i.e., resting) heart rate variability (HRV), a biomarker that is sensitive to the stress response, predicted the response to propranolol in decreasing GI symptoms.

In this pilot study, a sample of 37 individuals with ASD participated in a 12-week open-label trial of propranolol. The Gastrointestinal Severity Index and HRV were collected at baseline (i.e., prior to taking propranolol) and again at the end of the 12-week trial period.

Higher HRV was associated with the greatest reduction in GI symptoms, with a strong effect size, but only for adolescents and young adults (15–24 years old). Baseline HRV and GI change scores were not significantly correlated for younger children (7–14 years old).

The results from this open-label pilot trial suggest that autistic adolescents and young adults with higher baseline HRV, indicating greater parasympathetic tone, may respond better to propranolol and show the greatest reduction in GI symptoms. The data from this pilot should be interpreted with caution until larger, randomized, double-blinded, placebo-controlled trials of propranolol for GI symptoms in ASD are completed.