Faculty Bibliography

OBJECTIVE:Impulsive choices can lead to suboptimal decision making, a tendency which is especially marked in individuals with ADHD. We compared two different paradigms assessing impulsive choice: the simple choice paradigm (SCP) and the temporal discounting paradigm (TDP). METHOD/METHODS:Random effects meta-analyses on 37 group comparisons (22 SCP; 15 TDP) consisting of 3.763 participants (53% ADHD). RESULTS:Small-to-medium effect sizes emerged for both paradigms, confirming that participants with ADHD choose small immediate over large delayed rewards more frequently than controls. Moderation analyses show that offering real rewards in the SCP almost doubled the odds ratio for participants with ADHD. CONCLUSION/CONCLUSIONS:We suggest that a stronger than normal aversion toward delay interacts with a demotivating effect of hypothetical rewards, both factors promoting impulsive choice in participants with ADHD. Furthermore, we suggest the SCP as the paradigm of choice due to its larger ecological validity, contextual sensitivity, and reliability.

BACKGROUND:Sleep disturbances, in particular insomnia, represent a common problem in children with neurodevelopmental disabilities (NDDs). Currently, there are no approved medications for insomnia in children by the US Food and Drug Administration or European Medicines Agency and therefore they are prescribed off-label. We critically reviewed pediatric literature on drugs as well as nonpharmacological (behavioral) interventions used for sleep disturbances in children with NDDs. METHODS:, and Embase), and Web of Knowledge databases were searched through February 12, 2017, with no language restrictions. Two authors independently and blindly performed the screening. RESULTS:Good sleep practices and behavioral interventions, supported by moderate-to-low level evidence, are the first recommended treatments for pediatric insomnia but they are often challenging to implement. Antihistamine agents, such as hydroxyzine or diphenhydramine, are the most widely prescribed sedatives in the pediatric practice but evidence supporting their use is still limited. An increasing body of evidence supports melatonin as the safest choice for children with NDDs. Benzodiazepines are not recommended in children and should only be used for transient insomnia, especially if daytime anxiety is present. Only few studies have been carried out in children's and adolescents' zolpidem, zaleplon, and eszopiclone, with contrasting results. Limited evidence supports the use of alpha-agonists such as clonidine to improve sleep onset latency, especially in attention deficit/hyperactivity disorder subjects. Tricyclic antidepressants, used in adults with insomnia, are not recommended in children because of their safety profile. Trazodone and mirtazapine hold promise but require further studies. CONCLUSIONS:Here, we provided a tentative guide for the use of drugs for insomnia in children with NDDs. Well-controlled studies employing both objective polysomnography and subjective sleep measures are needed to determine the efficacy, effectiveness, and safety of the currently prescribed pediatric sleep medicines in children with NDDs.

Rigorously conducted meta-analyses provide evidence synthesis that has the potential to inform daily clinical decision making and development of clinical guidelines. In the past decade, there has been an increasing number of studies on pharmacologic and non-pharmacologic treatments for childhood and adolescent psychiatric disorders. Given this large body of research, busy clinicians might tend to rely on meta-analyses, rather than individual trials, to keep abreast of the evidence base supporting intervention strategies in child and adolescent psychiatry. Many meta-analyses focused on treatments for child and adolescent mental health problems have primarily addressed the question: Is treatment X more efficacious/effective (or safer) than the control condition? This is clearly an important starting point for clinicians when discussing with their patients and families the benefits and risks of treatment X, but clinicians need to know more. For instance, they might look for the evidence base to answer the following questions: Is treatment X the most efficacious and effective (or safest) option for my patient? When will treatment X likely start working? If the dose or intensity of the treatment does not seem to be effective, is it worthwhile to increase it? And if so, how?

BACKGROUND: Diffusion tensor imaging studies have shown atypical fractional anisotropy (FA) in individuals with attention-deficit/hyperactivity disorder (ADHD), albeit with conflicting results. We performed meta-analyses of whole-brain voxel-based analyses (WBVBA) and tract-based spatial statistics (TBSS) studies in ADHD, along with a qualitative review of TBSS studies addressing the issue of head motion, which may bias results. METHODS: We conducted a systematic literature search (last search on April 1st, 2016) to identify studies comparing FA values between individuals with ADHD and typically developing (TD) participants. Signed differential mapping was used to compute effect sizes and integrate WBVBA and TBSS studies, respectively. TBSS datasets reporting no between-group motion differences were identified. RESULTS: We identified 14 WBVBA (ADHDn = 314, TDn = 278) and 13 TBSS datasets (ADHDn = 557, TDn = 568). WBVBA meta-analysis showed both significantly lower and higher FA values in individuals with ADHD; TBSS meta-analysis showed significantly lower FA in ADHD compared with TD in four clusters: two in the corpus callosum (isthmus and posterior midbody), one in right inferior fronto-occipital fasciculus, and one in left inferior longitudinal fasciculus. However, four of six datasets confirming no group-differences in motion showed no significant between-group FA differences. CONCLUSIONS: A growing diffusion tensor imaging (DTI) literature (total N = 1,717) and a plethora of apparent findings suggest atypical interhemispheric connection in ADHD. However, FA results in ADHD should be considered with caution, since many studies did not examine potential group differences in head motion, and most of the studies reporting no difference in motion showed no significant results. Future studies should address head motion as a priority and assure that groups do not differ in head motion.

A systematic review with meta-analyses was performed to: 1) quantify the association between ADHD and risk of unintentional physical injuries in children/adolescents ("risk analysis"); 2) assess the effect of ADHD medications on this risk ("medication analysis"). We searched 114 databases through June 2017. For the risk analysis, studies reporting sex-controlled odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries were combined. Pooled ORs (28 studies, 4,055,620 individuals without and 350,938 with ADHD) and HRs (4 studies, 901,891 individuals without and 20,363 with ADHD) were 1.53 (95% CI=1.40,1.67) and 1.39 (95% CI=1.06,1.83), respectively. For the medication analysis, we meta-analysed studies that avoided the confounding-by-indication bias [four studies with a self-controlled methodology and another comparing risk over time and groups (a "difference in differences" methodology)]. The pooled effect size was 0.879 (95% CI=0.838,0.922) (13,254 individuals with ADHD). ADHD is significantly associated with an increased risk of unintentional injuries and ADHD medications have a protective effect, at least in the short term, as indicated by self-controlled studies.

Emotional dysregulation (ED) is a dysfunction in modifying an emotional state in an adaptive and goal oriented way, with excitability, ease anger, and mood lability. It is present in up to 70% of adults with ADHD, regardless of other comorbidities, and substantially worsens the psychosocial outcomes of the disorder. Besides fronto-parietal circuits mediating top-down control, brain regions involved in bottom-up processes (e.g., amygdala, orbitofrontal cortex, and ventral striatum) are implicated in ED. We performed a systematic review/meta-analysis of double-blind randomized controlled trials of ADHD medications to assess their effects on ED in adults with ADHD. We searched an extensive set of databases, international trials registries, and contacted study authors/drug companies for unpublished data. We retained 21 trials. We found small-to-moderate effects (methylphenidate: SMD=0.34, 95% CI=0.23-0.45; atomoxetine: SMD=0.24, 95% CI=0.15-0.34; lisdexamfetamine: SMD=0.50, 95% CI=0.21-0.8). We suggest that, whilst ADHD medications are effective on ADHD core symptoms, they may be less effective on bottom-up mechanisms underlying ED. Further research on novel pharmacological and non-pharmacological strategies for ED in adults with ADHD is warranted.