Medication adherence and persistence in children and adolescents with attention deficit hyperactivity disorder (ADHD): a systematic review and qualitative update.

Low medication-adherence and persistence may reduce the effectiveness of ADHD-medication. This preregistered systematic review (PROSPERO CRD42020218654) on medication-adherence and persistence in children and adolescents with ADHD focuses on clinically relevant questions and extends previous reviews by including additional studies. We included a total of n = 66 studies. There was a lack of consistency in the measurement of adherence/persistence between studies. Pooling the medication possession ratios (MPR) and using the most common adherence definition (MPR ≥ 80%) indicated that only 22.9% of participants had good adherence at 12-month follow-up. Treatment persistence on medication measured by treatment duration during a 12-month follow-up averaged 170 days (5.6 months). Our findings indicate that medication-adherence and persistence among youth with ADHD are generally poor and have not changed in recent years. Clinicians need to be aware that various factors may contribute to poor adherence/persistence and that long-acting stimulants and psychoeducational programs may help to improve adherence/persistence. However, the evidence to whether better adherence/persistence contributes to better long-term outcomes is limited and requires further research.

Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors.

BACKGROUND: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities. METHODS: The large sample of children and adolescents aged 8-18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla. RESULTS: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for. CONCLUSIONS: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.

Beyond "Psychotropic": Repurposing Psychiatric Drugs for COVID-19, Alzheimer's Disease, and Cancer.

Importance: "Psychotropic" drugs have widespread reach and impact throughout the brain and body. Thus, many of these drugs could be repurposed for non-psychiatric indications of high public health impact.Observations: The selective serotonin reuptake inhibitor (SSRI) fluvoxamine was shown efficacious as a COVID-19 treatment based on randomized controlled trials (RCTs), and a benefit of other antidepressants has been posited based on observational and preclinical studies. In this review, we illuminate features of SSRIs and other psychiatric drugs that make them candidates to repurpose for non-psychiatric indications. We summarize research that led to fluvoxamine's use in COVID-19 and provide guidance on how to use it safely. We summarize studies suggestive of benefit of other antidepressants versus COVID-19 and long COVID. We also describe putative mechanisms of psychiatric drugs in treating long COVID, Alzheimer's disease, cancer, and other conditions.Conclusion and Relevance: There is a potentially great clinical and public health impact of psychotropic drug repurposing. Challenges exist to such repurposing efforts, but solutions exist for researchers, regulators, and funders that overcome these challenges.

The importance of clinicians' and parents' awareness of suicidal behaviour in adolescents reaching the upper age limit of their mental health services in Europe.

BACKGROUND: To study clinicians' and parents' awareness of suicidal behaviour in adolescents reaching the upper age limit of their Child and Adolescent Mental Health Service (CAMHS) and its association with mental health indicators, transition recommendations and mental health service (MHS) use. METHODS: 763 CAMHS users from eight European countries were assessed using multi-informant and standardised assessment tools at baseline and nine months follow-up. Separate ANCOVA's and pairwise comparisons were conducted to assess whether clinicians' and parents' awareness of young people's suicidal behaviour were associated with mental health indicators, clinician's recommendations to continue treatment and MHS use at nine months follow-up. RESULTS: 53.5 % of clinicians and 56.9 % of parents were unaware of young people's self-reported suicidal behaviour at baseline. Compared to those whose clinicians/parents were aware, unawareness was associated with a 72-80 % lower proportion of being recommended to continue treatment. Self-reported mental health problems at baseline were comparable for young people whose clinicians and parents were aware and unaware of suicidal behaviour. Clinicians' and parents' unawareness were not associated with MHS use at follow-up. LIMITATIONS: Aspects of suicidal behaviour, such as suicide ideation, -plans and -attempts, could not be distinguished. Few young people transitioned to Adult Mental Health Services (AMHS), therefore power to study factors associated with AMHS use was limited. CONCLUSION: Clinicians and parents are often unaware of suicidal behaviour, which decreases the likelihood of a recommendation to continue treatment, but does not seem to affect young people's MHS use or their mental health problems.

Leaving child and adolescent mental health services in the MILESTONE cohort: a longitudinal cohort study on young people's mental health indicators, care pathways, and outcomes in Europe.

BACKGROUND: The configuration of having separate mental health services by age, namely child and adolescent mental health services (CAMHS) and adult mental health services (AMHS), might be a barrier to continuity of care that adversely affects young people's mental health. However, no studies have investigated whether discontinuity of care in the transition period affects mental health. We aimed to discern the type of care young people receive after reaching the upper age limit of their CAMHS and examine differences in outcomes at 24-month follow-up between young people receiving different types of care. METHODS: To assess mental health in young people from 39 CAMHS in eight European countries (Belgium, Croatia, France, Germany, Italy, Ireland, the Netherlands, and the UK), we did a longitudinal cohort study. Eligible young people were CAMHS users up to 1 year younger than the upper age limit of their CAMHS or up to 3 months older, if they were still in CAMHS. Information on mental health service use, mental health problems (ie, using the Health of the Nation Outcome Scale for Children and Adolescents, Youth Self-Report and Adult Self-Report, DSM-5, and ICD-10), and sociodemographic characteristics were collected using self-reported, parent-reported, and clinician-reported interviews and questionnaires. Mixed models were applied to assess relationships between baseline characteristics, mental health service use, and outcomes. FINDINGS: The MILESTONE cohort included 763 young people. The participants were 60·0% female (n=458) and 40·0% male (n=305), 90·3% White (n=578), and had a mean age of 17·5 years (range 15·2-19·6 years). Over the 24-month follow-up period, 48 young people (6·3%) actively withdrew from the study. For young people, the higher their scores on the Health of the Nation Outcome Scale for Children and Adolescents (p=0·0009) and Youth Self-Report and Adult Self-Report (p=0·046), and who had a clinical classification of severe mental illness (p=0·0033), had suicidal thoughts or behaviours or self-harm (p=0·034), used psychotropic medication (p=0·0014), and had a self-reported or parent-reported need for continued treatment (p<0·0001) at baseline, were more likely to transition to AMHS or stay in CAMHS than to have care end. Overall, over the 24-month follow-up period, the mental health of young people improved, but 24·4% of young people reported an increase in problems calculated using the reliable change index, of whom 5·3% had a clinically relevant increase in problems. At 24-month follow-up, no differences in change in mental health problems since baseline were found between young people who used different types of care (CAMHS, AMHS, or no care). INTERPRETATION: Although approximately half of young people reaching the upper age limit of their CAMHS stop using mental health services, this was not associated with a deterioration in their mental health. Young people with the most severe mental health problems are more likely to receive continued care. If replicated, our findings suggest investments in improving transitional care for all CAMHS users might not be cost-effective in times of rising health-care costs, but might be better targeted at a subgroup of young people with increasing mental health problems who do not receive continued treatment. FUNDING: European Commission's 7th Framework Programme.

Lifestyle intervention in obese pregnancy and cardiac remodelling in 3-year olds: children of the UPBEAT RCT.

BACKGROUND/OBJECTIVES: Obesity in pregnancy has been associated with increased childhood cardiometabolic risk and reduced life expectancy. The UK UPBEAT multicentre randomised control trial was a lifestyle intervention of diet and physical activity in pregnant women with obesity. We hypothesised that the 3-year-old children of women with obesity would have heightened cardiovascular risk compared to children of normal BMI women, and that the UPBEAT intervention would mitigate this risk. SUBJECTS/METHODS: Children were recruited from one UPBEAT trial centre. Cardiovascular measures included blood pressure, echocardiographic assessment of cardiac function and dimensions, carotid intima-media thickness and heart rate variability (HRV) by electrocardiogram. RESULTS: Compared to offspring of normal BMI women (n = 51), children of women with obesity from the trial standard care arm (n = 39) had evidence of cardiac remodelling including increased interventricular septum (IVS; mean difference 0.04 cm; 95% CI: 0.018 to 0.067), posterior wall (PW; 0.03 cm; 0.006 to 0.062) and relative wall thicknesses (RWT; 0.03 cm; 0.01 to 0.05) following adjustment. Randomisation of women with obesity to the intervention arm (n = 31) prevented this cardiac remodelling (intervention effect; mean difference IVS -0.03 cm (-0.05 to -0.008); PW -0.03 cm (-0.05 to -0.01); RWT -0.02 cm (-0.04 to -0.005)). Children of women with obesity (standard care arm) compared to women of normal BMI also had elevated minimum heart rate (7 bpm; 1.41 to 13.34) evidence of early diastolic dysfunction (e prime) and increased sympathetic nerve activity index by HRV analysis. CONCLUSIONS: Maternal obesity was associated with left ventricular concentric remodelling in 3-year-old offspring. Absence of remodelling following the maternal intervention infers in utero origins of cardiac remodelling. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The UPBEAT trial is registered with Current Controlled Trials, ISRCTN89971375.

The effects of callous-unemotional traits and aggression subtypes on amygdala activity in response to negative faces.

BACKGROUND: Brain imaging studies have shown altered amygdala activity during emotion processing in children and adolescents with oppositional defiant disorder (ODD) and conduct disorder (CD) compared to typically developing children and adolescents (TD). Here we aimed to assess whether aggression-related subtypes (reactive and proactive aggression) and callous-unemotional (CU) traits predicted variation in amygdala activity and skin conductance (SC) response during emotion processing. METHODS: We included 177 participants (n = 108 cases with disruptive behaviour and/or ODD/CD and n = 69 TD), aged 8-18 years, across nine sites in Europe, as part of the EU Aggressotype and MATRICS projects. All participants performed an emotional face-matching functional magnetic resonance imaging task. RESULTS: Differences between cases and TD in affective processing, as well as specificity of activation patterns for aggression subtypes and CU traits, were assessed. Simultaneous SC recordings were acquired in a subsample (n = 63). Cases compared to TDs showed higher amygdala activity in response to negative faces (fearful and angry) v. shapes. Subtyping cases according to aggression-related subtypes did not significantly influence on amygdala activity; while stratification based on CU traits was more sensitive and revealed decreased amygdala activity in the high CU group. SC responses were significantly lower in cases and negatively correlated with CU traits, reactive and proactive aggression. CONCLUSIONS: Our results showed differences in amygdala activity and SC responses to emotional faces between cases with ODD/CD and TD, while CU traits moderate both central (amygdala) and peripheral (SC) responses. Our insights regarding subtypes and trait-specific aggression could be used for improved diagnostics and personalized treatment.

Cohort profile: demographic and clinical characteristics of the MILESTONE longitudinal cohort of young people approaching the upper age limit of their child mental health care service in Europe.

PURPOSE: The presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports. PARTICIPANTS: Seven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at. FINDINGS TO DATE: This cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be 'markedly ill', 'severely ill' or 'among the most extremely ill' by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year. FUTURE PLANS: Analysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared. TRIAL REGISTRATION NUMBER: NCT03013595.

Aggression subtypes relate to distinct resting state functional connectivity in children and adolescents with disruptive behavior.

There is increasing evidence for altered brain resting state functional connectivity in adolescents with disruptive behavior. While a considerable body of behavioral research points to differences between reactive and proactive aggression, it remains unknown whether these two subtypes have dissociable effects on connectivity. Additionally, callous-unemotional traits are important specifiers in subtyping aggressive behavior along the affective dimension. Accordingly, we examined associations between two aggression subtypes along with callous-unemotional traits using a seed-to-voxel approach. Six functionally relevant seeds were selected to probe the salience and the default mode network, based on their presumed role in aggression. The resting state sequence was acquired from 207 children and adolescents of both sexes [mean age (standard deviation) = 13.30 (2.60); range = 8.02-18.35] as part of a Europe-based multi-center study. One hundred eighteen individuals exhibiting disruptive behavior (conduct disorder/oppositional defiant disorder) with varying comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms were studied, together with 89 healthy controls. Proactive aggression was associated with increased left amygdala-precuneus coupling, while reactive aggression related to hyper-connectivities of the posterior cingulate cortex (PCC) to the parahippocampus, the left amygdala to the precuneus and to hypo-connectivity between the right anterior insula and the nucleus caudate. Callous-unemotional traits were linked to distinct hyper-connectivities to frontal, parietal, and cingulate areas. Additionally, compared to controls, cases demonstrated reduced connectivity of the PCC and left anterior insula to left frontal areas, the latter only when controlling for ADHD scores. Taken together, this study revealed aggression-subtype-specific patterns involving areas associated with emotion, empathy, morality, and cognitive control.

Specific cortical and subcortical alterations for reactive and proactive aggression in children and adolescents with disruptive behavior.

Maladaptive aggression, as present in conduct disorder (CD) and, to a lesser extent, oppositional defiant disorder (ODD), has been associated with structural alterations in various brain regions, such as ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, insula and ventral striatum. Although aggression can be subdivided into reactive and proactive subtypes, no neuroimaging studies have yet investigated if any structural brain alterations are associated with either of the subtypes specifically. Here we investigated associations between aggression subtypes, CU traits and ADHD symptoms in predefined regions of interest. T1-weighted magnetic resonance images were acquired from 158 children and adolescents with disruptive behavior (ODD/CD) and 96 controls in a multi-center study (aged 8-18). Aggression subtypes were assessed by questionnaires filled in by participants and their parents. Cortical volume and subcortical volumes and shape were determined using Freesurfer and the FMRIB integrated registration and segmentation tool. Associations between volumes and continuous measures of aggression were established using multilevel linear mixed effects models. Proactive aggression was negatively associated with amygdala volume (b = -10.7, p = 0.02), while reactive aggression was negatively associated with insula volume (b = -21.7, p = 0.01). No associations were found with CU traits or ADHD symptomatology. Classical group comparison showed that children and adolescents with disruptive behavior had smaller volumes than controls in (bilateral) vmPFC (p = 0.003) with modest effect size and a reduced shape in the anterior part of the left ventral striatum (p = 0.005). Our study showed negative associations between reactive aggression and volumes in a region involved in threat responsivity and between proactive aggression and a region linked to empathy. This provides evidence for aggression subtype-specific alterations in brain structure which may provide useful insights for clinical practice.

Continuity of Care and Mental Health Service Use Among Medicaid-enrolled Youths.

BACKGROUND: Recent reports of increased national estimates of pediatric psychiatric emergency department (ED) visits and psychiatric hospitalizations emphasize the need to research these utilization patterns. OBJECTIVES: To assess the patient-provider continuity of care (CoC) and compare the risk of psychiatric ED visits or hospitalization according to the CoC level. RESEARCH DESIGN: A cohort design was applied to Medicaid administrative claims data (2007-2014) for 3-16-year olds with a first psychiatric diagnosis between 2009 and 2013 (n=38,825). SUBJECTS: Continuously enrolled youths with (1) ≥1 outpatient psychiatric visits and (2) ≥4 pediatric outpatient visits in the prior 24 months. MEASURES: The authors assessed CoC in the 24 months before the first psychiatric outpatient visit and quantified CoC using the Alpha Index. The authors assessed patient-provider CoC before first psychiatric diagnosis and the odds of psychiatric ED visits or psychiatric hospitalizations in the year after diagnosis. RESULTS: Of the 38,825 youths, 88.9% received a first psychiatric diagnosis by age 14. The odds of ED visits were significantly higher among youths with low CoC [6.63%, adjusted odds ratio (AOR), 1.27; 95% confidence interval (CI), 1.13-1.41] or moderate CoC (5.76%; AOR, 1.14; 95% CI, 1.02-1.27) compared with those with high CoC (4.96%). Greater odds of psychiatric hospitalization related to low (7.53%; AOR, 1.17; 95% CI, 1.06-1.29) or moderate CoC (7.01%; AOR, 1.15; 95% CI, 1.03-1.27) compared with high CoC (6.06%). CONCLUSIONS: The odds of potentially disruptive clinical management and costly psychiatric ED visits or hospitalizations were lower for youths with high CoC. The findings support the need to research the impact of CoC on long-term pediatric mental health service use.

Distinct associations between fronto-striatal glutamate concentrations and callous-unemotional traits and proactive aggression in disruptive behavior.

Disruptive behavior is associated with societally and personally problematic levels of aggression and has been linked to abnormal structure and function of fronto-amygdala-striatal regions. Abnormal glutamatergic signalling within this network may play a role in aggression. However, disruptive behavior does not represent a homogeneous construct, but can be fractionated across several dimensions. Of particular interest, callous-unemotional (CU) traits have been shown to modulate the severity, neural and behavioural characterisation, and therapeutic outcomes of disruptive behaviour disorders (DBDs) and aggression. Further, individuals showing disruptive behavior differ to the extent that they engage in subtypes of aggression (i.e., proactive [PA] and reactive aggression [RA]) which may also represent distinct therapeutic targets. Here we investigated how glutamate signalling within the fronto-amygdala-striatal circuitry was altered along these dimensions in youths showing disruptive behavior (n = 140) and typically developing controls (TD, n = 93) within the age-range of 8-18 years. We used proton magnetic resonance spectroscopy (1H-MRS) in the anterior cingulate cortex (ACC), striatum, amygdala and insula and associated glutamate concentrations with continuous measures of aggression and CU-traits using linear mixed-effects models. We found evidence of a dissociation for the different measures and glutamate concentrations. CU traits were associated with increased ACC glutamate ('callousness': b = .19, t (108) = 2.63, p = .01, r = .25; 'uncaring': b = .18, t (108) = 2.59, p = .011, r = .24) while PA was associated with decreased striatal glutamate concentration (b = -.23, t (28) = -3.02, p = .005, r = .50). These findings suggest dissociable correlates of CU traits and PA in DBDs, and indicate that the ACC and striatal glutamate may represent novel pharmacological targets in treating these different aspects.

Patterns of Early Mental Health Diagnosis and Medication Treatment in a Medicaid-Insured Birth Cohort.

Importance: The increased use of psychiatric services in the US pediatric population raises concerns about the appropriate use of psychotropic medications for very young children. Objective: To assess the longitudinal patterns of psychotropic medication use in association with diagnosis and duration of use in a Medicaid-insured birth cohort. Design, Setting, and Participants: A cohort design was applied to computerized Medicaid administrative claims data for 35 244 children born in a mid-Atlantic state in 2007 and followed up for up to 96 months through December 31, 2014. Children were included in the birth cohort if they had an enrollment record at birth or within 3 months of birth and at least 6 months of continuous enrollment from birth. The cohort represents 92.2% of 38 225 Medicaid-insured newborns in 2007. Exposures: Mental health treatments from birth through age 7 years. Main Outcomes and Measures: Cumulative incidence of first psychiatric diagnosis and psychotropic medication use (monotherapy or concomitant use of psychotropic medications) from birth through age 7 years, total and by sex, and the cumulative incidence of the use of psychosocial services (age, 0-7 years) as well as the annual duration of medication use (ie, number of days of psychotropic medication use among children 3-7 years of age). Results: Of the 35 244 children in the cohort, 17 267 were girls and 17 977 were boys. By age 8 years, 4550 children in the birth cohort (19.7% [percentage adjusted for right censoring]) had received a psychiatric diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification codes 290-319); 2624 of these diagnoses (57.7%) were behavioral (codes 312, 313, or 314). Girls were more likely than boys to receive an incident psychiatric diagnosis of adjustment disorder (355 of 1598 [22.2%] vs 427 of 2952 [14.5%]; P < .001) or anxiety disorder (114 of 1598 [7.1%] vs 120 of 2952 [4.1%]; P < .001). By age 8 years, 2196 children in the cohort (10.2% [percentage adjusted for right censoring]) had received a psychotropic medication. Among medication users, 1763 of 2196 (80.5% [percentage adjusted for right censoring]) received monotherapy, 343 of 2196 (16.4% [percentage adjusted for right censoring]) received 2 medication classes concomitantly, and 90 of 2196 (4.3% [percentage adjusted for right censoring]) received 3 or more medication classes concomitantly for 60 days or more (range, 78-180 days). The annual median number of days of psychotropic medication use among medicated children increased with age, reaching 210 of 365 days for children 7 years of age. Among children 7 years of age, the median number of days of use of an antipsychotic (193 days [interquartile range, 60-266 days]), stimulant (183 days [interquartile range, 86-295 days]), or α-agonist (199 days [interquartile range, 85-305 days]) exceeded half of the year. Conclusions and Relevance: Medicaid-insured children received substantial mental health services and had prolonged exposure to psychotropic medications in the early years of life. These findings highlight the need for outcomes research in pediatric populations.

Propranolol for treating emotional, behavioural, autonomic dysregulation in children and adolescents with autism spectrum disorders.

OBJECTIVES: To date, there is no single medication prescribed to alleviate all the core symptoms of Autism Spectrum Disorder (ASD; National Institute of Health and Care Excellence, 2016). Both serotonin reuptake inhibitors and drugs for psychosis possess therapeutic drawbacks when managing anxiety and aggression in ASD. This review sought to appraise the use of propranolol as a pharmacological alternative when managing emotional, behavioural and autonomic dysregulation (EBAD) and other symptoms. MATERIALS AND METHODS: Sixteen reports examined the administration of propranolol in the context of ASD. RESULTS: Sixteen reports broadly covered cognitive domains, neural correlates, and behavioural domains. From the eight single-dose clinical trials, propranolol led to significant improvements in cognitive performance - verbal problem solving, social skills, mouth fixation, and conversation reciprocity; and changes in neural correlates - improvement in semantic networks and functional connectivity. The remaining eight case series and single case reports showed improvements in EBAD, anxiety, aggressive, self-injurious and hypersexual behaviours. Additionally, propranolol significantly improved similar behavioural domains (aggression and self-injury) for those with acquired brain injury. CONCLUSION: This review indicates that propranolol holds promise for EBAD and cognitive performance in ASD. Given the lack of good quality clinical trials, randomised controlled trials are warranted to explore the efficacy of propranolol in managing EBAD in ASD.

Pediatric Antipsychotic Use and Outcomes Monitoring.

Antipsychotic (ATP) prescription rates have increased in children and adolescents despite concern regarding the safety and effectiveness of ATP usage in community populations. Rising safety concerns and uncertainty regarding ATP effectiveness in children stress the need for improvement in routine clinical outcome monitoring and research. Due to the growing number of children exposed to atypical ATPs, studies assessing the risk/benefit ratio of administering ATPs in this age group-especially in off-label conditions-become of high importance. The Centre for Interventional Pediatric Psychopharmacology and Rare Diseases (CIPPRD) uses a suite of instruments to monitor outcomes using the web-based HealthTracker™, a health monitoring platform. The HealthTracker allows for capture of symptoms, side effects, quality of life, patient experience, and lifetime response to individualized treatments using a multi-informant multimodal methodology. It enables the tracking of ongoing medical treatments and assists in shared treatment decision-making, longitudinal patient centered outcome monitoring, and helps optimize care. An example of its use in the CIPPRD is provided to demonstrate how it can be used for ATP-related outcome monitoring in complex neurodisability within routine clinical practice.

Facilitating support groups for siblings of children with neurodevelopmental disorders using audio-conferencing: a longitudinal feasibility study.

BACKGROUND: Siblings of children with chronic illness and disabilities are at increased risk of negative psychological effects. Support groups enable them to access psycho-education and social support. Barriers to this can include the distance they have to travel to meet face-to-face. Audio-conferencing, whereby three or more people can connect by telephone in different locations, is an efficient means of groups meeting and warrants exploration in this healthcare context. This study explored the feasibility of audio-conferencing as a method of facilitating sibling support groups. METHODS: A longitudinal design was adopted. Participants were six siblings (aged eight to thirteen years) and parents of children with complex neurodevelopmental disorders attending the Centre for Interventional Paediatric Psychopharmacology (CIPP). Four of the eight one-hour weekly sessions were held face-to-face and the other four using audio-conferencing. Pre- and post-intervention questionnaires and interviews were completed and three to six month follow-up interviews were carried out. The sessions were audio-recorded, transcribed and thematic analysis was undertaken. RESULTS: Audio-conferencing as a form of telemedicine was acceptable to all six participants and was effective in facilitating sibling support groups. Audio-conferencing can overcome geographical barriers to children being able to receive group therapeutic healthcare interventions such as social support and psycho-education. Psychopathology ratings increased post-intervention in some participants. Siblings reported that communication between siblings and their family members increased and siblings' social network widened. CONCLUSIONS: Audio-conferencing is an acceptable, feasible and effective method of facilitating sibling support groups. Siblings' clear accounts of neuropsychiatric symptoms render them reliable informants. Systematic assessment of siblings' needs and strengthened links between Child and Adolescent Mental Health Services, school counsellors and young carers groups are warranted.

Paediatric European Risperidone Studies (PERS): context, rationale, objectives, strategy, and challenges.

In children and adolescents with conduct disorder (CD), pharmacotherapy is considered when non-pharmacological interventions do not improve symptoms and functional impairment. Risperidone, a second-generation antipsychotic is increasingly prescribed off-label in this indication, but its efficacy and tolerability is poorly studied in CD, especially in young people with normal intelligence. The Paediatric European Risperidone Studies (PERS) include a series of trials to assess short-term efficacy, tolerability and maintenance effects of risperidone in children and adolescents with CD and normal intelligence as well as long-term tolerability in a 2-year pharmacovigilance. In addition to its core studies, secondary PERS analyses will examine moderators of drug effects. As PERS is a large-scale academic project involving a collaborative network of expert centres from different countries, it is expected that results will lead to strengthen the evidence base for the use of risperidone in CD and improve standards of care. Challenging issues faced by the PERS consortium are described to facilitate future developments in paediatric neuropsychopharmacology.

Treatable metabolic psychoses that go undetected: what Niemann-Pick type C can teach us.

OBJECTIVE: The objective of this review is to raise awareness of the prevalence of inborn errors of metabolism, in particular NP-C, in psychiatric populations. METHODS: This review summarises research presented at a satellite symposium held on 28 August 2010 at the 23rd European College of Neuropsychopharmacology (ECNP) meeting. RESULTS AND CONCLUSION: Organic causes of psychoses may have an unrecognised yet notable prevalence, particularly in adolescent or adult patients. Several inherited metabolic disorders can present with psychiatric signs. In some disorders, such as Niemann-Pick type C (NP-C), the disease may remain unrecognised for many years due to a heterogeneous and subtle clinical presentation. In patients presenting with psychoses, subtle signs such as vertical supranuclear gaze palsy, ataxia and splenomegaly should raise the suspicion of NP-C. Miglustat is so far the only approved treatment for NP-C. Miglustat can stabilise neurological disease, particularly in adolescent or adult-onset patients who are detected as early as possible, before irreversible neurological damage occurs.