The world has experienced an unprecedented mental health crisis associated with the COVID‐19 pandemic (Liu et al., 2020). After more than two years navigating the associated uncertainty and distress, ...the impact on youth mental health continues to be a pressing concern. Those in the mental health field, as well as the children and families plagued by its impact, are inundated with seeing firsthand the impact on youth’s functioning. This includes increases in depression and suicide (Asarnow & Chung, 2021; Manzar et al., 2021), and having to navigate siloes in care and often even an inability when in crisis to access a continuum of services (Zhai, 2021). This has highlighted the significant issues with accessibility of mental health care and inequitable access to care for youth mental health both in the United States and globally. We continue to experience daily the impact of insufficient resources for youth behavioral health. For those in the field who prioritize the need for more robust intervention approaches, the child mental health crisis associated with the pandemic has highlighted the need for us to develop more novel and innovative interventions.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Many children with pervasive developmental disorders (PDD) exhibit behaviors and symptoms of attention-deficit/hyperactivity disorder (ADHD). We sought to determine the relative efficacy of ...medications for treating ADHD symptoms in children with PDD by identifying all double-blind, randomized, placebo-controlled trials examining the efficacy of medications for treating ADHD symptoms in children with PDD. We located seven trials involving 225 children. A random effects meta-analysis of four methylphenidate trials showed methylphenidate to be effective for treating ADHD symptoms in children with PDD (ES = .67). Several adverse events were greater for children were taking methylphenidate compared to placebo. An individual trial of clonidine and two trials of atomoxetine suggest these agents may also be effective in treating ADHD symptoms in children with PDD.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Several studies have examined levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. This meta-analysis was conducted to examine the association ...between obsessive-compulsive disorder (OCD) and plasma serum levels of proinflammatory cytokines. Twelve studies met inclusion criteria. The meta-analysis demonstrated a significant reduction in IL-1β levels in OCD. No significant difference in plasma levels of IL-6 or TNF-α was demonstrated. Stratified subgroup analysis revealed possible moderating effects of age and medication use on IL-6 levels. Studies including children on psychotropic medication had lower plasma IL-6 levels. Stratified subgroup analysis revealed a moderating effect of comorbid depression on TNF-α levels. Elevated TNF-α levels were reported in studies that included individuals with comorbid depression. Future studies examining immune function in OCD should adjust for potential confounding due to medication use and comorbid depression. Further studies assessing cerebrospinal fluid cytokine levels in OCD are also needed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
We aimed to examine the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) for anxiety disorders examining overall symptom ...improvement, likelihood of treatment response, time course of treatment response, individual pharmacological agent, diagnostic indication dose, and tolerability.
Methods
We searched PubMed and Cochrane Central Register of Controlled Trials. We included randomized placebo‐controlled clinical trials of SSRIs/SNRIs in adult patients with anxiety disorders that provided data at three or more time points. Extracted data included trial duration, weekly/biweekly anxiety scores for 12 weeks.
Results
Meta‐analysis included 57 trials (N = 16,056). A linear mixed model analysis based on weekly outcome data suggested that for SNRI a logarithmic model offered the best fit compared to placebo (indicating the greatest incremental improvement from baseline occurred early in treatment); whereas for SSRI a linear model provided the best fit (indicating a similar improvement over the duration of the acute treatment phase). There were no significant differences in efficacy between pharmacological agents within each class or when comparing SSRIs to SNRIs. The greatest treatment benefits were observed for social anxiety disorder for both medication classes. Higher doses of SSRIs, but not SNRIs, were associated with significantly greater symptom improvement and likelihood of treatment response. For both medical classes, higher doses were associated with an increased likelihood of dropout due to side effects.
Conclusions
SSRIs and SNRIs are effective in treating anxiety disorders. Higher doses of SSRIs within the therapeutic range are associated with greater treatment benefit, whereas higher doses of SNRIs are not.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Cognitive dysfunction in schizophrenia (SCZ) and Alzheimer's disease (AD) is a major driver of functional disability but is largely unresponsive to current therapeutics. Animal models of cognitive ...dysfunction relevant to both disorders suggest the α7 nicotinic acetylcholine receptor (nAChR) may be a promising drug development target, with multiple clinical trials subsequently testing this hypothesis in individuals with SCZ and AD. However, the translational value of rodent cognitive tasks for predicting the overall efficacy of this therapeutic target in clinical trials is unknown. To compare effect sizes between rodent and human studies, we searched PubMed and the Cochrane Library for all randomized, placebo-controlled trials of compounds with pharmacological activity at the α7 nAChR for treatment of cognitive dysfunction in SCZ and AD and identified 18 studies comprising 2670 subjects treated with eight different compounds acting as full or partial agonists. Cognitive outcomes were standardized, and random-effects meta-analyses revealed no statistically significant effects of α7 nAChR agonists on overall cognition or any of eight cognitive subdomains when all doses were included (Range of all cognitive outcomes: Cohen's d=−0.077 to 0.12, negative favoring drug). In contrast, analysis of 29 rodent studies testing the same α7 agonists revealed large effect sizes in multiple commonly used preclinical behavioral tests of cognition (Range: d=−1.18 to – 0.73). Our results suggest that targeting the α7 nAChR with agonists is not a robust treatment for cognitive dysfunction in SCZ or AD and necessitate a better understanding of the translational gap for therapeutics targeting the α7 nAChR.
•Novel drugs to improve cognition in schizophrenia and Alzheimer's disease are needed.•The α7 nicotinic receptor is a potential drug target to treat cognitive dysfunction.•Meta-analyses find large effect sizes of α7 agonists in rodent cognitive studies.•Meta-analyses find no or limited effects of α7 agonists on human subject cognition.•Significant translational barriers exist for α7 nicotinic receptor-targeting drugs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To examine the efficacy of pharmacological treatments for restricted and repetitive behaviors (RRB) in autism spectrum disorders (ASD).
We searched PubMed, Embase, and CENTRAL to identify all ...double-blind, randomized, placebo-controlled trials that examined the efficacy of pharmacological agents in the treatment of ASD and measured RRB as an outcome. Our primary outcome was the standardized mean difference in rating scales of RRB.
We identified 64 randomized, placebo-controlled trials involving 3,499 participants with ASD. Antipsychotics significantly improved RRB outcomes compared to placebo (standardized mean difference SMD = 0.28, 95% CIs = 0.08-0.49), z = 2.77, p = .01) demonstrating a small effect size. Larger significant positive effects on RRB in ASD were seen in individual studies with fluvoxamine, buspirone, bumetanide, divalproex, guanfacine, and folinic acid that have not been replicated. Other frequently studied pharmacological treatments in ASD including oxytocin, omega-3 fatty acids, selective serotonin reuptake inhibitors (SSRI), and methylphenidate did not demonstrate significant benefit in reducing RRB compared to placebo (oxytocin: SMD = 0.23, 95% CI = -0.01 to 0.47, z = 1.85, p = .06; omega-3 fatty acids: SMD = 0.19, 95% CI = -0.05 to 0.43, z = 1.54, p = .12; SSRI: SMD = 0.09, 95% CI = -0.21 to 0.39, z = 0.60, p = .56; methylphenidate: SMD = 0.18, 95% CI = -0.11 to 0.46, z = 1.23, p = .22).
The results of the present meta-analysis suggest that currently available pharmacological agents have at best only a modest benefit for the treatment of RRB in ASD, with the most evidence supporting antipsychotic medications. Additional randomized controlled trials with standardized study designs and consistent and specific assessment tools for RRB are needed to further understand how we can best help ameliorate these behaviors in individuals with ASD.
The initial results of the Multimodal Treatment of Attention Deficit Hyperactivity Disorder (MTA) trial had profound effects on the way that Attention-Deficit Hyperactivity Disorder (ADHD) is managed ...clinically. Children from the original MTA cohort as well as a control group have been followed longitudinally for well over a decade and are beginning to provide important data regarding the long-term clinical course, treatment and consequences of ADHD into adulthood. Two articles in this issue of JCPP highlight important contributions from the MTA cohort. Swanson et al. highlights the potential long-term effects of stimulants on height whereas Sibley et al. highlights the importance of using multiple informants in assessing adulthood ADHD symptoms similar to children and suggest that current DSM criteria for ADHD may be overly stringent.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Tourette syndrome (TS) is estimated to have a prevalence of 0.30–0.77% in school aged children. Longitudinal studies suggest that roughly half-to-two-thirds of children with TS experience a ...substantial improvement in tic symptoms during adolescence. By contrast, few studies have examined adulthood prevalence of TS. Accurate prevalence estimates across the lifespan are needed to support regulatory and public health decisions.
We searched PubMED and EMBASE for studies that examined the prevalence of TS in adults. We conducted a random-effects meta-analysis of logit event rates to estimate prevalence of TS across studies. Too few studies are available to conduct moderator analysis or examine publication bias. We also examined the risk ratio of TS prevalence in adults for males compared to females.
Three studies involving 2,356,485 participants were included. There were significant differences in TS adulthood prevalence estimates between studies ranging from 49 to 657 cases of TS per million adults. Overall prevalence of TS in adulthood was estimated to be 118 cases of TS per million adults (95%CI: 19–751 cases per million adults). There was a large amount of heterogeneity between studies (I2 = 99%) that was likely related to differences in their methods of identification of TS cases. By contrast, the male:female ratio of risk of adulthood TS was similar between studies with a Risk Ratio = 2.33 (95% CI: 1.72–3.16).
Estimates of adulthood prevalence of TS are sparse and likely highly affected by differences in method of case identification. Diagnosis and diagnostic estimates of TS could be aided by including a requirement for impairment as well as potential remission criteria similar to other psychiatric conditions.
•Overall prevalence of Tourette syndrome (TS) in adulthood was estimated to be 118 cases per million adults (95%CI: 19-751 cases per million adults).•There was large heterogeneity in prevalence estimates between studies, likely related to differences in methods of identification of TS cases.•Previous research suggests TS prevalence is much higher in school aged children (0.30-0.77%).•Diagnosis/diagnostic estimates of TS could be aided by including a requirement for impairment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this issue, Whittington et al. (2016) present a systematic review that reports the efficacy of three primary treatments for children with Tourette syndrome (TS) – (a) α2‐adrenergic receptor ...agonists; (b) antipsychotic medications; and (c) habit reversal training/comprehensive behavioral intervention. In this commentary, we highlight the large degree of heterogeneity observed in the meta‐analysis of trials involving alpha‐2 agonist medications and present possible explanations for the observed heterogeneity. Among these possible explanations is the possibility that presence of comorbid ADHD may moderate the efficacy of alpha‐2 agonists in the treatment of tic disorder with the medications being more effective in patients with both conditions. The commentary reviews the evidence supporting this possible moderating effect of ADHD and discusses the implications for such a relationship.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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