Faculty Bibliography
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Placebo and nocebo responses in randomised, controlled trials of medications for ADHD: a systematic review and meta-analysis
The nature and magnitude of placebo and nocebo responses to ADHD medications and the extent to which response to active medications and placebo are inter-correlated is unclear. To assess the magnitude of placebo and nocebo responses to ADHD and their association with active treatment response. We searched literature until June 26, 2019, for published/unpublished double-blind, randomised placebo-controlled trials (RCTs) of ADHD medication. Authors were contacted for additional data. We assessed placebo effects on efficacy and nocebo effects on tolerability using random effects meta-analysis. We assessed the association of study design and patient features with placebo/nocebo response. We analysed 128 RCTs (10,578 children/adolescents and 9175 adults) and found significant and heterogenous placebo effects for all efficacy outcomes, with no publication bias. The placebo effect was greatest for clinician compared with other raters. We found nocebo effects on tolerability outcomes. Efficacy outcomes from most raters showed significant positive correlations between the baseline to endpoint placebo effects and the baseline to endpoint drug effects. Placebo and nocebo effects did not differ among drugs. Baseline severity and type of rating scale influenced the findings. Shared non-specific factors influence response to both placebo and active medication. Although ADHD medications are superior to placebo, and placebo treatment in clinical practice is not feasible, clinicians should attempt to incorporate factors associated with placebo effects into clinical care. Future studies should explore how such effects influence response to medication treatment. Upon publication, data will be available in Mendeley Data: PROSPERO (CRD42019130292).
PMID: 33972692
ISSN: 1476-5578
CID: 4867262
Journal of the American Academy of Child and Adolescent Psychiatry. 2022:61(1):4-9.DOI: 10.1016/j.jaac.2021.11.003
Editors' Best of 2021 [Editorial]
There is, in the content of the Journal, an embarrassment of riches, and picking a "best" seems to demand a certain qualification: is the "best" the most interesting, most surprising, most educational, most important, most provocative, most enjoyable? How to choose? We are hardly unbiased and can admit to a special affection for the ones that we and the authors worked hardest on, hammering version after version into shape. Acknowledging these biases, here are the 2021 articles that we think deserve your attention or at least a second read.
PMID: 34949338
ISSN: 1527-5418
CID: 5470352
Current Pharmacological Treatments for ADHD
Attention-Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental condition associated with impaired function and increased risk of poor outcomes in children, young people and adults with the condition. Currently approved pharmacological treatments for ADHD include a range of stimulant (methylphenidate, amphetamine) and nonstimulant (atomoxetine, guanfacine, clonidine) medications. All have been shown to be effective in treating the symptoms of ADHD and improving other functional outcomes including quality of life, academic performance, rates of accidents and injuries, and do not appear to be associated with significant adverse outcomes or side effects. In this chapter, we review medications for ADHD by summarising the mechanisms of action of each of the two main classes of compounds (stimulants and nonstimulants), the formulations of the most commonly prescribed medications within each class, their efficacy in treating ADHD symptoms and other outcomes, and other factors that influence treatment decisions including side effects and tolerability, comorbidities and medical history. We conclude with a summary of the treatment decisions made by clinicians and suggest some next steps for research. Further research is needed to understand the mechanisms of action of these medications and how exactly they improve symptoms, and to examine their effects on commonly occurring comorbidities.
PMID: 35507282
ISSN: 1866-3370
CID: 5216182
Food Perceptions in Adults with and without ADHD
INTRODUCTION/BACKGROUND:Adults with attention-deficit/hyperactivity disorder (ADHD) have unhealthy eating habits, associated with overweight/obesity. We explored whether they present with different food-related benefit/risk perceptions, compared to those without ADHD. METHODS:One hundred five university students with (n = 36) and without (n = 69) ADHD, aged 22-30, participated in the study. They rated the level of frequency and likelihood of food consumption, as well as the perceived attractiveness, convenience, and risk of 32 healthy and unhealthy food items. RESULTS:The findings revealed significantly lower healthy/unhealthy food frequency consumption ratios for the ADHD group compared with the non-ADHD one but no differences in the ratios of estimated likelihood of food consumption and perceptions (attractiveness, convenience, and risk). CONCLUSION/CONCLUSIONS:The results of this study demonstrated a discrepancy between the eating behavior (more unhealthy eating patterns in adults with ADHD compared with controls) and their food-related perceptions (same perceptions regarding the benefit and risk of foods in both groups).
PMID: 35512646
ISSN: 1423-033x
CID: 5470392
Toward Precision Medicine in ADHD
Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.
PMCID:9299434
PMID: 35874653
ISSN: 1662-5153
CID: 5276162
Journal of the American Academy of Child and Adolescent Psychiatry. 2021:60(12):1448-1451.DOI: 10.1016/j.jaac.2021.10.002
Editors' Note: First Annual Report Regarding JAACAP's Antiracist Journey [Editorial]
Last year, we wrote to you of our dedication and vision for this journal "to be antiracist at every level," outlining the following 6 initiatives "to reshape the Journal to pursue this vision:" (1) Issuing a Call for Papers "on racism and its impacts on child development and children's mental health;" (2) updating our Guide for Authors "to emphasize that we will evaluate articles submitted to the Journal on whether their study designs and discussions consider and address human diversity in the context of their research questions and hypotheses; (3) assembling a special collection of "Journal articles on bias, bigotry, racism, and mental health disparities;" (4) accelerating "our efforts to make our editorial board inclusive and representative of our community of scientists and practitioners as well as the communities we all serve;" (5) engaging in "continuing education and dialogue as an Editorial Board that will include antiracism training;" and (6) critically examining "our editorial and peer review process to ensure it is antiracist.1 In this Editors' Note, we write to update you on our progress.
PMID: 34648925
ISSN: 1527-5418
CID: 5470342
The management of ADHD in children and adolescents: bringing evidence to the clinic: perspective from the European ADHD Guidelines Group (EAGG)
ADHD is the most common neurodevelopmental disorder presenting to child and adolescent mental health, paediatric, and primary care services. Timely and effective interventions to address core ADHD symptoms and co-occurring problems are a high priority for healthcare and society more widely. While much research has reported on the benefits and adverse effects of different interventions for ADHD, these individual research reports and the reviews, meta-analyses and guidelines summarizing their findings are sometimes inconsistent and difficult to interpret. We have summarized the current evidence and identified several methodological issues and gaps in the current evidence that we believe are important for clinicians to consider when evaluating the evidence and making treatment decisions. These include understanding potential impact of bias such as inadequate blinding and selection bias on study outcomes; the relative lack of high-quality data comparing different treatments and assessing long-term effectiveness, adverse effects and safety for both pharmacological and non-pharmacological treatments; and the problems associated with observational studies, including those based on large national registries and comparing treatments with each other. We highlight key similarities across current international clinical guidelines and discuss the reasons for divergence where these occur. We discuss the integration of these different perspective into a framework for person/family-centered evidence-based practice approach to care that aims to achieve optimal outcomes that prioritize individual strengths and impairments, as well as the personal treatment targets of children and their families. Finally, we consider how access to care for this common and impairing disorder can be improved in different healthcare systems.
PMCID:8532460
PMID: 34677682
ISSN: 1435-165x
CID: 5068192
Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis
There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63-2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06-1.56), guanfacine (OR = 1.43, 95% CI = 1.12-1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09-1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.
PMID: 34635194
ISSN: 1469-8978
CID: 5091852
Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A)
BACKGROUND:The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. METHODS:The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. RESULTS:Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries. LIMITATIONS/CONCLUSIONS:Cross-sectional and anonymous design. CONCLUSIONS:Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents' and families', mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.
PMCID:8486586
PMID: 34606810
ISSN: 1573-2517
CID: 5099492
A Practical, Evidence-informed Approach to Managing Stimulant-Refractory Attention Deficit Hyperactivity Disorder (ADHD)
Stimulants (methylphenidate or amphetamines) are the recommended first-line option for the pharmacological treatment of individuals with attention deficit hyperactivity disorder (ADHD). However, some patients with ADHD will not respond optimally to stimulants. Here, we discuss strategies to manage stimulant-refractory ADHD, based on the recommendations advanced in clinical guidelines, knowledge of expert practice in the field, and our own clinical recommendations, informed by a comprehensive literature search in PubMed, PsycInfo, EMBASE + EMBASE classic, OVID Medline, and Web of Science (up to 30 March 2021). We first highlight the importance of stimulant optimization as an effective strategy to increase response. We then discuss a series of factors that should be considered before using alternative pharmacological strategies for ADHD, including poor adherence, time action properties of stimulants (and wearing-off of effects), poor tolerability (that prevents the use of higher, more effective doses), excessive focus on or confounding from presence of comorbid non-ADHD symptoms, and tolerance. Finally, we consider the role of non-stimulants and combined pharmacological approaches. While the choice of medication for ADHD is still to a large extent based on a trial-and-error process, there are reasonably accepted data and guidelines to aid in clinical decision-making. It is hoped that advances in precision psychiatry in the years ahead will further guide prescribers to tailor medication choice to the specific characteristics of the patient.
PMID: 34403134
ISSN: 1179-1934
CID: 5091332
