Common pitfalls, and how to avoid them, in child and adolescent psychopharmacology: Part I.

As Faculty of the British Association for Psychopharmacology course on child and adolescent psychopharmacology, we present here what we deem are the most common pitfalls, and how to avoid them, in child and adolescent psychopharmacology. In this paper, we specifically addressed common pitfalls in the pharmacological treatment of attention-deficit/hyperactivity disorder, anxiety, bipolar disorder, depression, obsessive-compulsive disorder and related disorders, and tic disorder. Pitfalls in the treatment of other disorders are addressed in a separate paper (part II).

Common pitfalls, and how to avoid them, in child and adolescent psychopharmacology: Part II.

As Faculty of the British Association for Psychopharmacology course on child and adolescent psychopharmacology, we present here what we deem are the most common pitfalls, and how to avoid them, in child and adolescent psychopharmacology. In this paper, we specifically addressed common pitfalls in the pharmacological treatment of autism and intellectual disability, eating disorders, neuropsychiatric correlates of epilepsy, and psychosis. Pitfalls in relation to the treatment of other disorders are addressed in a separate paper (Part I).

Attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD; also known as hyperkinetic disorder) is a common neurodevelopmental condition that affects children and adults worldwide. ADHD has a predominantly genetic aetiology that involves common and rare genetic variants. Some environmental correlates of the disorder have been discovered but causation has been difficult to establish. The heterogeneity of the condition is evident in the diverse presentation of symptoms and levels of impairment, the numerous co-occurring mental and physical conditions, the various domains of neurocognitive impairment, and extensive minor structural and functional brain differences. The diagnosis of ADHD is reliable and valid when evaluated with standard diagnostic criteria. Curative treatments for ADHD do not exist but evidence-based treatments substantially reduce symptoms and/or functional impairment. Medications are effective for core symptoms and are usually well tolerated. Some non-pharmacological treatments are valuable, especially for improving adaptive functioning. Clinical and neurobiological research is ongoing and could lead to the creation of personalized diagnostic and therapeutic approaches for this disorder.

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents: Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project.

OBJECTIVE: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age. METHOD: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age. RESULTS: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable. CONCLUSION: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.

Methylphenidate and Sleep Difficulties in Children and Adolescents With ADHD: Results From the 2-Year Naturalistic Pharmacovigilance ADDUCE Study.

OBJECTIVE: Short-term RCTs have demonstrated that MPH-treatment significantly reduces ADHD-symptoms, but is also associated with adverse events, including sleep problems. However, data on long-term effects of MPH on sleep remain limited. METHODS: We performed a 2-year naturalistic prospective pharmacovigilance multicentre study. Participants were recruited into three groups: ADHD patients intending to start MPH-treatment (MPH-group), those not intending to use ADHD-medication (no-MPH-group), and a non-ADHD control-group. Sleep problems were assessed with the Children's-Sleep-Habits-Questionnaire (CSHQ). RESULTS: 1,410 participants were enrolled. Baseline mean CSHQ-total-sleep-scores could be considered clinically significant for the MPH-group and the no-MPH-group, but not for controls. The only group to show a significant increase in any aspect of sleep from baseline to 24-months was the control-group. Comparing the MPH- to the no-MPH-group no differences in total-sleep-score changes were found. CONCLUSION: Our findings support that sleep-problems are common in ADHD, but don't suggest significant negative long-term effects of MPH on sleep.

Enhancing emotion regulation with an in situ socially assistive robot among LGBTQ+ youth with self-harm ideation: protocol for a randomised controlled trial.

INTRODUCTION: Purrble, a socially assistive robot, was codesigned with children to support in situ emotion regulation. Preliminary evidence has found that LGBTQ+ youth are receptive to Purrble and find it to be an acceptable intervention to assist with emotion dysregulation and their experiences of self-harm. The present study is designed to evaluate the impact of access to Purrble among LGBTQ+ youth who have self-harmful thoughts, when compared with waitlist controls. METHODS AND ANALYSIS: The study is a single-blind, randomised control trial comparing access to the Purrble robot with waitlist control. A total of 168 LGBTQ+ youth aged 16-25 years with current self-harmful ideation will be recruited, all based within the UK. The primary outcome is emotion dysregulation (Difficulties with Emotion Regulation Scale-8) measured weekly across a 13-week period, including three pre-deployment timepoints. Secondary outcomes include self-harm (Self-Harm Questionnaire), anxiety (Generalised Anxiety Disorder-7) and depression (Patient Health Questionnaire-9). We will conduct analyses using linear mixed models to assess primary and secondary hypotheses. Intervention participants will have unlimited access to Purrble over the deployment period, which can be used as much or as little as they like. After all assessments, control participants will receive their Purrble, with all participants keeping the robot after the end of the study. After the study has ended, a subset of participants will be invited to participate in semistructured interviews to explore engagement and appropriation of Purrble, considering the young people's own views of Purrble as an intervention device. ETHICS AND DISSEMINATION: Ethical approval was received from King's College London (RESCM-22/23-34570). Findings will be disseminated in peer review open access journals and at academic conferences. TRIAL REGISTRATION NUMBER: NCT06025942.

Seasonal trends in antidepressant prescribing, depression, anxiety and self-harm in adolescents and young adults: an open cohort study using English primary care data.

BACKGROUND: There is an increasing demand for mental health services for young people, which may vary across the year. OBJECTIVE: To determine whether there are seasonal patterns in primary care antidepressant prescribing and mental health issues in adolescents and young adults. METHODS: This cohort study used anonymised electronic health records from general practices in England contributing to QResearch. It included 5 081 263 males and females aged 14-18 (adolescents), 19-23 and 24-28 years between 2006 and 2019. The incidence rates per 1000 person-years and the incidence rate ratios (IRRs) were calculated for the first records of a selective serotonin reuptake inhibitor (SSRI) prescription, depression, anxiety and self-harm. The IRRs were adjusted for year, region, deprivation, ethnic group and number of working days. FINDINGS: There was an increase in SSRI prescribing, depression and anxiety incidence in male and female adolescents in the autumn months (September-November) that was not seen in older age groups. The IRRs for SSRI prescribing for adolescents peaked in November (females: 1.75, 95% CI 1.67 to 1.83, p<0.001; males: 1.72, 95% CI 1.61 to 1.84, p<0.001, vs in January) and for depression (females: 1.29, 95% CI 1.25 to 1.33, p<0.001; males: 1.29, 95% CI 1.23 to 1.35, p<0.001). Anxiety peaked in November for females aged 14-18 years (1.17, 95% CI 1.13 to 1.22, p<0.001) and in September for males (1.19, 95% CI 1.12 to 1.27, p<0.001). CONCLUSIONS: There were higher rates of antidepressant prescribing and consultations for depression and anxiety at the start of the school year among adolescents. CLINICAL IMPLICATIONS: Support around mental health issues from general practitioners and others should be focused during autumn.

Investigating the Feasibility, Acceptability, and Appropriation of a Socially Assistive Robot Among Minority Youth at Risk of Self-Harm: Results of 2 Mixed Methods Pilot Studies.

BACKGROUND: Minority youth are at an increased risk of experiencing self-harmful thoughts and behaviors. However, there is limited evidence of successful interventions to support young people in the moment of their distress. Digital interventions are considered a potential solution for providing in-the-moment support for those at risk of adverse mental health and self-harm. OBJECTIVE: These pilot studies aim to investigate the feasibility and acceptability of a new in situ intervention tool, Purrble, among two broad groups of minority youth: (1) lesbian, gay, bisexual, transgender, queer, and similar minority (LGBTQ+) youth and (2) racial and ethnic minority youth. Purrble was designed to support in-situ emotion regulation (ER) support when individuals are facing emotionally challenging situations. METHODS: This study consisted of 2 mixed methods pilot studies that followed the same mixed methods design, including 3 weeks of daily and weekly surveys and optional follow-up interviews. Inclusion criteria were (1) aged between 16 and 25 years, (2) part of a minority group, (3) had experiences of self-harmful thoughts or behaviors or elevated symptoms of depression or anxiety, and (4) living in the United Kingdom at the time of the study. The primary outcomes were (1) the feasibility of Purrble as an intervention among pilot samples (analyzed by consent rate, retention rate, adherence to surveys, and engagement with the device) and (2) the acceptability and appropriation of Purrble across pilot studies as a tool to support ER in situ (thematically analyzed qualitative open-ended questions and interview data). The secondary outcomes were descriptive pilot data concerning the mental health outcomes in each sample. RESULTS: In total, 21 LGBTQ+ young people participated in pilot study 1, with 86% (n=18) completing the baseline and 3 weeks of daily surveys. These young people maintained engagement with Purrble across deployment, across which period there was a decrease in self-harmful thoughts and anxiety symptoms. A total of 19 ethnic and racial minority youths participated in pilot study 2, and 84% (n=16) completed the study. Although pilot study 2 participants also maintained engagement with Purrble across deployment, this was to a lesser degree than participants of pilot study 1, and perceived mental health outcomes did not indicate potential change associated with the device. The thematic analysis indicated three superordinate themes: (1) stopping the self-harm cycle, (2) adopting ER strategies, and (3) stages of change. CONCLUSIONS: These were the first pilot studies of a novel intervention that aimed to provide in situ ER support for young people at risk of self-harm. Both quantitative and qualitative findings indicate that young people found Purrble to be a feasible and acceptable intervention, as they effectively incorporated the device into their ER practices. These engagements with Purrble were described as interrupting the cycle of self-harmful ideation and behavior.

Online remote behavioural intervention for tics in 9- to 17-year-olds: the ORBIT RCT with embedded process and economic evaluation.

Background: Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online. Objective: To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders. Design: Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation. Setting: Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals. Participants: Children aged 9-17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months. Interventions: Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control). Outcome: Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation. Results: Two hundred and twenty-four participants were randomised to the intervention (n = 112) or control (n = 112) group. Participants were mostly male (n = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was -2.29 points (95% confidence interval -3.86 to -0.71) in favour of therapy (effect size -0.31, 95% confidence interval -0.52 to -0.10). This effect was sustained throughout to the final follow-up at 18 months (-2.01 points, 95% confidence interval -3.86 to -0.15; effect size -0.27, 95% confidence interval -0.52 to -0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval -£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confidence interval -0.004 to 0.083) per participant. The mean incremental cost per quality-adjusted life-year gained was £16,708. The intervention was acceptable and delivered with high fidelity. Parental engagement predicted child engagement and more positive clinical outcomes. Harms: Two serious, unrelated adverse events occurred in the control group. Limitations: We cannot separate the effects of digital online delivery and the therapy itself. The sample was predominately white and British, limiting generalisability. The design did not compare to face-to-face services. Conclusion: Online, therapist-supported behavioural therapy for young people with tic disorders is clinically and cost-effective in reducing tics, with durable benefits extending up to 18 months. Future work: Future work should compare online to face-to-face therapy and explore how to embed the intervention in clinical practice. Trial registration: This trial is registered as ISRCTN70758207; ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information.

It can be difficult for children and young people with tics to access therapy. This is because there are not enough trained tic therapists. Online remote behavioural intervention for tics was a clinical trial to see whether an online platform that delivered two different types of interventions could help tics. One intervention focused on techniques to control tics; this type of therapy is called exposure and response prevention. The other intervention was psychoeducation, where participants learned about the nature of tics but not how to control them. The online remote behavioural intervention for tics interventions also involved help from a therapist and support from a parent. Participants were aged 9­17 years with Tourette syndrome/chronic tic disorder and were recruited from 16 clinics, two study sites (Nottingham and London) or via online self-referral. All individuals who were eligible for the online remote behavioural intervention for tics trial were randomised in a 50/50 split by researchers who were unaware of which treatment was being given. Participants received either 10 weeks of online exposure and response prevention or 10 weeks of online psychoeducation. A total of 224 children and young people participated: 112 allocated to exposure and response prevention and 112 to psychoeducation. Tics decreased more in the exposure and response prevention group (16% reduction) than in the psychoeducation group (6% reduction) 3 months after treatment. This difference is considered a clinically important difference in tic reduction. The treatment continued to have a positive effect on tic symptoms at 6, 12 and 18 months, showing that the effects are durable. This was achieved with minimal therapist involvement. The cost of online exposure and response prevention to treat young people with tics within this study was less when compared to the cost of face-to-face therapy. The results show that exposure and response prevention is an effective behavioural therapy for tics in this specific patient group. Delivering exposure and response prevention online with minimal therapist contact can be a successful and cost-effective treatment to improve access to behavioural therapy.

Practitioner Review: Clinical utility of the QbTest for the assessment and diagnosis of attention-deficit/hyperactivity disorder - a systematic review and meta-analysis.

BACKGROUND: Several computerised cognitive tests (e.g. continuous performance test) have been developed to support the clinical assessment of attention-deficit/hyperactivity disorder (ADHD). Here, we appraised the evidence-base underpinning the use of one of these tests - the QbTest - in clinical practice, by conducting a systematic review and meta-analysis investigating its accuracy and clinical utility. METHODS: Based on a preregistered protocol (CRD42022377671), we searched PubMed, Medline, Ovid Embase, APA PsycINFO and Web of Science on 15th August 2022, with no language/type of document restrictions. We included studies reporting accuracy measures (e.g. sensitivity, specificity, or Area under the Receiver Operating Characteristics Curve, AUC) for QbTest in discriminating between people with and without DSM/ICD ADHD diagnosis. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). A generic inverse variance meta-analysis was conducted on AUC scores. Pooled sensitivity and specificity were calculated using a random-effects bivariate model in R. RESULTS: We included 15 studies (2,058 participants; 48.6% with ADHD). QbTest Total scores showed acceptable, rather than good, sensitivity (0.78 [95% confidence interval: 0.69; 0.85]) and specificity (0.70 [0.57; 0.81]), while subscales showed low-to-moderate sensitivity (ranging from 0.48 [0.35; 0.61] to 0.65 [0.52; 0.75]) and moderate-to-good specificity (from 0.65 [0.48; 0.78] to 0.83 [0.60; 0.94]). Pooled AUC scores suggested moderate-to-acceptable discriminative ability (Q-Total: 0.72 [0.57; 0.87]; Q-Activity: 0.67 [0.58; 0.77); Q-Inattention: 0.66 [0.59; 0.72]; Q-Impulsivity: 0.59 [0.53; 0.64]). CONCLUSIONS: When used on their own, QbTest scores available to clinicians are not sufficiently accurate in discriminating between ADHD and non-ADHD clinical cases. Therefore, the QbTest should not be used as stand-alone screening or diagnostic tool, or as a triage system for accepting individuals on the waiting-list for clinical services. However, when used as an adjunct to support a full clinical assessment, QbTest can produce efficiencies in the assessment pathway and reduce the time to diagnosis.

Relationship between autonomic arousal and attention orienting in children and adolescents with ADHD, autism and co-occurring ADHD and autism.

INTRODUCTION: Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) may be characterized by different profiles of visual attention orienting. However, there are also many inconsistent findings emerging from the literature, probably due to the fact that the potential effect of autonomic arousal (which has been proposed to be dysregulated in these conditions) on oculomotor performance has not been investigated before. Moreover, it is not known how visual attention orienting is affected by the co-occurrence of ADHD and autism in people with a double diagnosis. METHODS: 99 children/adolescents with or without ADHD and/or autism (age 10.79 ± 2.05 years, 65% boys) completed an adapted version of the gap-overlap task (with baseline and overlap trials only). The social salience and modality of stimuli were manipulated between trials. Eye movements and pupil size were recorded. We compared saccadic reaction times (SRTs) between diagnostic groups and investigated if a trial-by-trial association existed between pre-saccadic pupil size and SRTs. RESULTS: Faster orienting (shorter SRT) was found for baseline compared to overlap trials, faces compared to non-face stimuli and-more evidently in children without ADHD and/or autism-for multi-modal compared to uni-modal stimuli. We also found a linear negative association between pre-saccadic pupil size and SRTs, in autistic participants (without ADHD), and a quadratic association in children with ADHD (without autism), for which SRTs were slower when intra-individual pre-saccadic pupil size was smallest or largest. CONCLUSION: Our findings are in line with previous literature and indicate a possible effect of dysregulated autonomic arousal on oculomotor mechanisms in autism and ADHD, which should be further investigated in future research studies with larger samples, to reliably investigate possible differences between children with single and dual diagnoses.

Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study.

OBJECTIVE: We assessed the feasibility and validity of remote researcher-led administration and self-administration of modified versions of two cognitive tasks sensitive to ADHD, a four-choice reaction time task (Fast task) and a combined Continuous Performance Test/Go No-Go task (CPT/GNG), through a new remote measurement technology system. METHOD: We compared the cognitive performance measures (mean and variability of reaction times (MRT, RTV), omission errors (OE) and commission errors (CE)) at a remote baseline researcher-led administration and three remote self-administration sessions between participants with and without ADHD (n = 40). RESULTS: The most consistent group differences were found for RTV, MRT and CE at the baseline researcher-led administration and the first self-administration, with 8 of the 10 comparisons statistically significant and all comparisons indicating medium to large effect sizes. CONCLUSION: Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.

Barriers to and Facilitators of Using Remote Measurement Technology in the Long-Term Monitoring of Individuals With ADHD: Interview Study.

BACKGROUND: Remote measurement technology (RMT) has the potential to address current research and clinical challenges of attention-deficit/hyperactivity disorder (ADHD) symptoms and its co-occurring mental health problems. Despite research using RMT already being successfully applied to other populations, adherence and attrition are potential obstacles when applying RMT to a disorder such as ADHD. Hypothetical views and attitudes toward using RMT in a population with ADHD have previously been explored; however, to our knowledge, there is no previous research that has used qualitative methods to understand the barriers to and facilitators of using RMT in individuals with ADHD following participation in a remote monitoring period. OBJECTIVE: We aimed to evaluate the barriers to and facilitators of using RMT in individuals with ADHD compared with a group of people who did not have a diagnosis of ADHD. We also aimed to explore participants' views on using RMT for 1 or 2 years in future studies. METHODS: In total, 20 individuals with ADHD and 20 individuals without ADHD were followed up for 10 weeks using RMT that involved active (questionnaires and cognitive tasks) and passive (smartphone sensors and wearable devices) monitoring; 10 adolescents and adults with ADHD and 12 individuals in a comparison group completed semistructured qualitative interviews at the end of the study period. The interviews focused on potential barriers to and facilitators of using RMT in adults with ADHD. A framework methodology was used to explore the data qualitatively. RESULTS: Barriers to and facilitators of using RMT were categorized as health-related, user-related, and technology-related factors across both participant groups. When comparing themes that emerged across the participant groups, both individuals with and without ADHD experienced similar barriers and facilitators in using RMT. The participants agreed that RMT can provide useful objective data. However, slight differences between the participant groups were identified as barriers to RMT across all major themes. Individuals with ADHD described the impact that their ADHD symptoms had on participating (health-related theme), commented on the perceived cost of completing the cognitive tasks (user-related theme), and described more technical challenges (technology-related theme) than individuals without ADHD. Hypothetical views on future studies using RMT in individuals with ADHD for 1 or 2 years were positive. CONCLUSIONS: Individuals with ADHD agreed that RMT, which uses repeated measurements with ongoing active and passive monitoring, can provide useful objective data. Although themes overlapped with previous research on barriers to and facilitators of engagement with RMT (eg, depression and epilepsy) and with a comparison group, there are unique considerations for people with ADHD, for example, understanding the impact that ADHD symptoms may have on engaging with RMT. Researchers need to continue working with people with ADHD to develop future RMT studies for longer periods.

Long-term safety of methylphenidate in children and adolescents with ADHD: 2-year outcomes of the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study.

BACKGROUND: Methylphenidate is the most frequently prescribed medication for the treatment of ADHD in children and adolescents in many countries. Although many randomised controlled trials support short-term efficacy, tolerability, and safety, data on long-term safety and tolerability are scarce. The aim of this study was to investigate the safety of methylphenidate over a 2-year period in relation to growth and development, psychiatric health, neurological health, and cardiovascular function in children and adolescents. METHODS: We conducted a naturalistic, longitudinal, controlled study as part of the ADDUCE research programme in 27 European child and adolescent mental health centres in the UK, Germany, Switzerland, Italy, and Hungary. Participants aged 6-17 years were recruited into three cohorts: medication-naive ADHD patients who intended to start methylphenidate treatment (methylphenidate group), medication-naive ADHD patients who did not intend to start any ADHD medication (no-methylphenidate group), and a control group without ADHD. Children with ADHD diagnosed by a qualified clinician according to the DSM-IV criteria and, in the control group, children who scored less than 1·5 on average on the Swanson, Nolan, and Pelham IV rating scale for ADHD items, and whose hyperactivity score on the parent-rated Strengths and Difficulties Questionnaire was within the normal range (<6) were eligible for inclusion. Participants were excluded if they had previously taken any ADHD medications but remained eligible if they had previously taken or were currently taking other psychotropic drugs. The primary outcome was height velocity (height velocity SD score; estimated from at least two consecutive height measurements, and normalised with reference to the mean and SD of a population of the same age and sex). FINDINGS: Between Feb 01, 2012, and Jan 31, 2016, 1410 participants were enrolled (756 in methylphenidate group, 391 in no-methylphenidate group, and 263 in control group). 1070 (76·3%) participants were male, 332 (23·7%) were female, and for eight gender was unknown. The average age for the cohort was 9·28 years (SD 2·78; IQR 7-11). 1312 (93·0%) of 1410 participants were White. The methylphenidate and no-methylphenidate groups differed in ADHD symptom severity and other characteristics. After controlling for the effects of these variables using propensity scores, there was little evidence of an effect on growth (24 months height velocity SD score difference -0·07 (95% CI -0·18 to 0·04; p=0·20) or increased risk of psychiatric or neurological adverse events in the methylphenidate group compared with the no-methylphenidate group. Pulse rate and systolic and diastolic blood pressure were higher in the methylphenidate group compared with the no-methylphenidate group after 24 months of treatment. No serious adverse events were reported during the study. INTERPRETATION: Our results suggest that long-term treatment with methylphenidate for 2 years is safe. There was no evidence to support the hypothesis that methylphenidate treatment leads to reductions in growth. Methylphenidate-related pulse and blood pressure changes, although relatively small, require regular monitoring. FUNDING: EU Seventh Framework Programme.

Impact of the COVID-19 pandemic on incidence of tics in children and young people: a population-based cohort study.

Background: Since the onset of the coronavirus (COVID-19) pandemic, clinicians have reported an increase in presentations of sudden and new onset tics particularly affecting teenage girls. This population-based study aimed to describe and compare the incidence of tics in children and young people in primary care before and during the COVID-19 pandemic in England. Methods: We used information from the UK Clinical Practice Research Datalink (CPRD) Aurum dataset and included males and females aged 4-11 years and 12-18 years between Jan 1, 2015, and Dec 31, 2021. We grouped the pre-pandemic period (2015-2019) and presented the pandemic years (2020, 2021) separately. We described the characteristics of children and young people with a first record of a motor or vocal tic in each time period. Incidence rates of tics by age-sex groups in 2015-2019, 2020, and 2021 were calculated. Negative binomial regression models were used to calculate incidence rate ratios. Findings: We included 3,867,709 males and females aged 4-18 years. Over 14,734,062 person-years of follow-up, 11,245 people had a first tic record during the whole study period. The characteristics of people with tics differed over time, with the proportion of females aged 12-18 years and the proportion with mental health conditions including anxiety increasing during the pandemic. Tic incidence rates per 10,000 person-years were highest for 4-11-year-old males in all three time periods (13.4 [95% confidence interval 13.0-13.8] in 2015-2019; 13.2 [12.3-14.1] in 2020; 15.1 [14.1-16.1] in 2021) but increased markedly during the pandemic in 12-18-year-old females, from 2.5 (2.3-2.7) in 2015-2019, to 10.3 (9.5-11.3) in 2020 and 13.1 (12.1-14.1) in 2021. There were smaller increases in incidence rates in 12-18-year-old males (4.6 [4.4-4.9] in 2015-2019; 4.7 [4.1-5.3] in 2020; 6.2 [5.5-6.9] in 2021) and 4-11-year-old females (4.9 [4.7-5.2] in 2015-2019; 5.7 [5.1-6.4] in 2020; 7.6 [6.9-8.3] in 2021). Incidence rate ratios comparing 2020 and 2021 with 2015-2019 were highest in the 12-18-year-old female subgroup (4.2 [3.6-4.8] in 2020; 5.3 [4.7-6.0] in 2021). Interpretation: The incidence of tics in children and young people increased across all age and sex groups during the COVID-19 pandemic, with a differentially large effect in teenage girls (a greater than four-fold increase). Furthermore, in those with tic symptoms, proportions with mental health disorders including anxiety increased during the pandemic. Further research is required on the social and contextual factors underpinning this rise in onset of tics in teenage girls. Funding: National Institute for Health Research Nottingham Biomedical Research Centre.

Identifying and Categorizing Adverse Events in Trials of Digital Mental Health Interventions: Narrative Scoping Review of Trials in the International Standard Randomized Controlled Trial Number Registry.

BACKGROUND: To contextualize the benefits of an intervention, it is important that adverse events (AEs) are reported. This is potentially difficult in trials of digital mental health interventions, where delivery may be remote and the mechanisms of actions less understood. OBJECTIVE: We aimed to explore the reporting of AEs in randomized controlled trials of digital mental health interventions. METHODS: The International Standard Randomized Controlled Trial Number database was searched for trials registered before May 2022. Using advanced search filters, we identified 2546 trials in the category of mental and behavioral disorders. These trials were independently reviewed by 2 researchers against the eligibility criteria. Trials were included where digital mental health interventions for participants with a mental health disorder were evaluated through a completed randomized controlled trial (protocol and primary results publication published). Published protocols and primary results publications were then retrieved. Data were extracted independently by 3 researchers, with discussion to reach consensus when required. RESULTS: Twenty-three trials met the eligibility criteria, of which 16 (69%) included a statement on AEs within a publication, but only 6 (26%) reported AEs within their primary results publication. Seriousness was referred to by 6 trials, relatedness by 4, and expectedness by 2. More interventions delivered with human support (9/11, 82%) than those with only remote or no support (6/12, 50%) included a statement on AEs, but they did not report more AEs. Several reasons for participant dropout were identified by trials that did not report AEs, of which some were identifiable or related to AEs, including serious AEs. CONCLUSIONS: There is significant variation in the reporting of AEs in trials of digital mental health interventions. This variation may reflect limited reporting processes and difficulty recognizing AEs related to digital mental health interventions. There is a need to develop guidelines specifically for these trials to improve future reporting.

Long-term clinical and cost-effectiveness of a therapist-supported online remote behavioural intervention for tics in children and adolescents: extended 12- and 18-month follow-up of a single-blind randomised controlled trial.

BACKGROUND: Little is known about the long-term effectiveness of behavioural therapy for tics. We aimed to assess the long-term clinical and cost-effectiveness of online therapist-supported exposure and response prevention (ERP) therapy for tics 12 and 18 months after treatment initiation. METHODS: ORBIT (online remote behavioural intervention for tics) was a two-arm (1:1 ratio), superiority, single-blind, multicentre randomised controlled trial comparing online ERP for tics with online psychoeducation. The trial was conducted across two Child and Adolescent Mental Health Services in England. Participants were recruited from these two sites, across other clinics in England, or by self-referral. This study was a naturalistic follow-up of participants at 12- and 18-month postrandomisation. Participants were permitted to use alternative treatments recommended by their clinician. The key outcome was the Yale Global Tic Severity Scale Total Tic Severity Score (YGTSS-TTSS). A full economic evaluation was conducted. Registrations are ISRCTN (ISRCTN70758207); ClinicalTrials.gov (NCT03483493). RESULTS: Two hundred and twenty-four participants were enrolled: 112 to ERP and 112 to psychoeducation. The sample was predominately male (177; 79%) and of white ethnicity (195; 87%). The ERP intervention reduced baseline YGTSS-TTSS by 2.64 points (95% CI: -4.48 to -0.79) with an effect size of -0.36 (95% CI: -0.61 to -0.11) after 12 months and by 2.01 points (95% CI: -3.86 to -0.15) with an effect size of -0.27 (95% CI -0.52 to -0.02) after 18 months, compared with psychoeducation. Very few participants (<10%) started new tic treatment during follow-up. The cost difference in ERP compared with psychoeducation was £304.94 (-139.41 to 749.29). At 18 months, the cost per QALY gained was £16,708 for ERP compared with psychoeducation. CONCLUSIONS: Remotely delivered online ERP is a clinical and cost-effective intervention with durable benefits extending for up to 18 months. This represents an efficient public mental health approach to increase access to behavioural therapy and improve outcomes for tics.