Journal of Child and Adolescent Psychopharmacology

Non-stimulant guanfacine is a common second-line medication for attention-deficit hyperactivity disorder (ADHD). Numerous randomized controlled trials (RCTs) have explored the efficacy of guanfacine in ADHD treatment. This meta-analysis combined data from selected RCTs to analyze the efficacy and safety of guanfacine in treating ADHD.

RCTs were identified from published sources through searches in PubMed, Cochrane Library, Web of Science, and Embase (up to February 2022), defining the Clinical Global Impression of Improvement (CGI-I) treatment response score of ≤2 as the primary outcome. Subgroup analysis was performed with a bound treatment duration of 10 weeks. Safety was defined by treatment-emergent adverse events (TEAEs).

Twelve out of 332 studies with 2653 participants were included. All studies compared guanfacine with placebos. Guanfacine was significantly more effective in treating ADHD (Risk Ratio [RR] 1.78, 95% CI: 1.59–2.01). In the <10 weeks subgroup, the efficacy in the guanfacine group compared with the placebo group was 58.5% versus 29.4%, respectively (RR 1.97, 95% CI: 1.71–2.26). In the >10 weeks subgroup, the efficacy in the guanfacine group compared with the placebo group was 63.6% versus 39.7%, respectively (RR 1.57, 95% CI: 1.37–1.79). Both subgroups lacked heterogeneity (I ² = 0), and a funnel plot showed a low publication bias risk. Around 80% of participants in the guanfacine group experienced at least one TEAE, compared with 66.5% in the placebo group (RR 1.23, 95% CI: 1.14–1.32), with low heterogeneity (I ² = 46, p = 0.05). The most common TEAEs in the guanfacine group were somnolence (38.6%), headaches (20.5%), and fatigue (15.2%).

Guanfacine is safe and effective for treating ADHD, with no serious adverse events. Guanfacine should be considered as an effective treatment option where effectiveness or tolerability of the central nervous system stimulant is of concern. There is stronger evidence of efficacy for children; more clinical studies are needed for adults.

Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is approved for the treatment of patients aged ≥6 years with attention-deficit/hyperactivity disorder (ADHD). A pivotal double-blind (DB) study of children aged 6–12 years with ADHD demonstrated efficacy for ADHD with good tolerability. In this study, we assessed the safety and tolerability of daily oral SDX/d-MPH for up to 1 year in children with ADHD.

This was a dose-optimized, open-label safety study with SDX/d-MPH in children aged 6–12 years with ADHD that included subjects who successfully completed the DB study (rollover) and new subjects. The study consisted of a 30-day screening phase, a dose optimization phase for new subjects only, a 360-day treatment phase, and follow-up. Adverse events (AEs) were assessed from the first day of SDX/d-MPH administration to the end of the study. During the treatment phase, ADHD Rating Scale-5 (ADHD-RS-5) and Clinical Global Impressions–Severity (CGI-S) scale assessments were used to evaluate ADHD severity.

Of the 282 subjects enrolled (70 rollover; 212 new), 28 discontinued treatment in the dose optimization phase and 254 entered the treatment phase. By study completion, 127 had discontinued and 155 had completed the study. The treatment-phase safety population included all enrolled subjects who received ≥1 dose of study drug and had ≥1 postdose safety assessment. Of 238 subjects assessed in the treatment-phase safety population, 143 (60.1%) had ≥1 treatment-emergent adverse events (TEAEs), and 36 (15.1%), 95 (39.9%), and 12 (5.0%) had mild, moderate, or severe TEAEs, respectively. The most common TEAEs were decreased appetite (18.5%), upper respiratory tract infection (9.7%), nasopharyngitis (8.0%), decreased weight (7.6%), and irritability (6.7%). There were no clinically meaningful trends in electrocardiograms, cardiac events, or blood pressure events, and none led to discontinuation. Two subjects had eight serious AEs that were unrelated to treatment. There were overall reductions in ADHD symptoms and severity as assessed by ADHD-RS-5 and CGI-S during the treatment phase.

In this 1-year study, SDX/d-MPH was found to be safe and well tolerated and comparable with other methylphenidate products, with no unexpected safety findings. SDX/d-MPH also showed sustained efficacy during the 1-year treatment period. ClinicalTrials.gov identifier: NCT03460652.

Psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), may serve as a risk factor for child abuse.

This study aimed to evaluate the association between children and adolescents with ADHD diagnosis and the risk of child abuse. The effectiveness of a pharmacological intervention on reducing the risk of child abuse was also assessed. A nationwide, population-based, retrospective with a matched-cohort study design was used. Data were from the National Health Insurance Research Database of Taiwan over a 15-year period (2000–2015).

Increased risk of child abuse in the ADHD group was noticed and the adjusted hazard ratio (HR) was 1.797 (95% confidence interval [CI] = 1.245–2.388, p < 0.001). The Kaplan–Meier analysis showed a significantly higher cumulative incidence in the ADHD group over the 15-year period (Log-rank test p < 0.001). ADHD patients with other psychiatric comorbidities had a higher risk of child abuse. Pharmacological treatment of either methylphenidate or atomoxetine was associated with a reduced risk of child abuse. The total adjusted HR was 1.466 (95% CI = 1.077–1.883, p < 0.001) in medicine group compared with the controls.

ADHD was associated with a subsequent risk of child abuse in Taiwan. Pharmacological treatment could reduce the risk of child abuse in ADHD patients.

We aimed to examine the antipsychotics used by patients hospitalized in the child and youth inpatient service providing tertiary care to investigate whether there is a difference between admission and discharge, polypharmacy, which antipsychotics are used, and which psychotropics are used concomitant with antipsychotics.

Research data were collected retrospectively from all children and adolescents hospitalized in a child and adolescent psychiatry inpatient service in a university hospital in a 4-year period (2015–2019). The sociodemographic and clinical characteristics of the patients, the antipsychotics they used at admission and discharge, the other psychotropics concomitantly used with antipsychotics, and the side effects associated with antipsychotics during hospitalization were collected from the files of the 363 patients.

Patients on antipsychotics increased 12.1% from hospitalization to discharge. Antipsychotic polypharmacy increased from 16.2% at admission to 30.7% at discharge. Logistic regression analysis was performed to investigate the factors affecting antipsychotic and antipsychotic polypharmacy. Self-harm, aggression/violence, and extended hospitalization were factors associated with increased antipsychotic use. Psychotic symptoms, psychotic disorder, and extended hospitalization were factors associated with an increase in antipsychotic polypharmacy.

Understanding the factors that may cause antipsychotic use and polypharmacy in inpatient services in children and adolescents may prevent unnecessary drug use and long-term side effects that may occur due to these drugs.