Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): a meta-analysis of randomized controlled trials with blinded and objective outcomes

This meta-analysis investigated the effects of computerized cognitive training (CCT) on clinical, neuropsychological and academic outcomes in individuals with attention-deficit/hyperactivity disorder (ADHD). The authors searched PubMed, Ovid, and Web of Science until 19th January 2022 for parallel-arm randomized controlled trials (RCTs) using CCT in individuals with ADHD. Random-effects meta-analyses pooled standardized mean differences (SMD) between CCT and comparator arms. RCT quality was assessed with the Cochrane Risk of Bias 2.0 tool (PROSPERO: CRD42021229279). Thirty-six RCTs were meta-analysed, 17 of which evaluated working memory training (WMT). Analysis of outcomes measured immediately post-treatment and judged to be “probably blinded” (PBLIND; trial n = 14) showed no effect on ADHD total (SMD = 0.12, 95%CI[−0.01 to −0.25]) or hyperactivity/impulsivity symptoms (SMD = 0.12, 95%[−0.03 to−0.28]). These findings remained when analyses were restricted to trials (n: 5–13) with children/adolescents, low medication exposure, semi-active controls, or WMT or multiple process training. There was a small improvement in inattention symptoms (SMD = 0.17, 95%CI[0.02–0.31]), which remained when trials were restricted to semi-active controls (SMD = 0.20, 95%CI[0.04–0.37]), and doubled in size when assessed in the intervention delivery setting (n = 5, SMD = 0.40, 95%CI[0.09–0.71]), suggesting a setting-specific effect. CCT improved WM (verbal: n = 15, SMD = 0.38, 95%CI[0.24–0.53]; visual-spatial: n = 9, SMD = 0.49, 95%CI[0.31–0.67]), but not other neuropsychological (e.g., attention, inhibition) or academic outcomes (e.g., reading, arithmetic; analysed n: 5–15). Longer-term improvement (at ~6-months) in verbal WM, reading comprehension, and ratings of executive functions were observed but relevant trials were limited in number (n: 5–7). There was no evidence that multi-process training was superior to working memory training. In sum, CCT led to shorter-term improvements in WM, with some evidence that verbal WM effects persisted in the longer-term. Clinical effects were limited to small, setting specific, short-term effects on inattention symptoms

Comparative efficacy and tolerability of pharmacological interventions for attention-deficit/hyperactivity disorder in children, adolescents and adults: Protocol for a systematic review and network meta-analysis

Introduction Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles. Methods and analysis We will search a broad range of electronic databases, including PubMed, MEDLINE, EMBASE, PsycINFO, ERIC and Web of Science, with no date or language restrictions. We will also search for unpublished studies using international clinical trial registries and contacting relevant drug companies. We will identify and include available parallel-group, cross-over and cluster randomised trials that compare methylphenidate, dexmethylphenidate, amphetamine derivatives (including lisdexamfetamine), atomoxetine, clonidine, guanfacine, bupropion or modafinil (as oral therapy) either with each other or to placebo, in children, adolescents or adults with ADHD. Primary outcomes will be efficacy (indicated by reduction in severity of ADHD core symptoms measured on a standardised scale) and tolerability (the proportion of patients who left a study early due to side effects). Secondary outcomes will be global functioning, acceptability (proportion of patients who left the study early by any cause) and changes in blood pressure and body weight. NMA will be conducted in STATA within a frequentist framework. The quality of RCTs will be evaluated using the Cochrane risk of bias tool, and the quality of the evidence will be assessed using the GRADE approach. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. Ethics and dissemination No ethical issues are foreseen. Results from this study will be published in a peer-reviewed journal and possibly presented at relevant national and international conferences

The European ADHD Guidelines Group replies

Dr. Micoulaud-Franchi et al. raise concerns relating to our 2016 meta-analysis1 of neurofeedback as a treatment for attention-deficit/hyperactivity disorder (ADHD). It is encouraging that Dr. Micoulaud-Franchi et al. agree with us that there is “an urgent need to conduct future research that associates both high quality of [randomized controlled trial] RCT and high quality of [electroencephalography] EEG-neurofeedback sessions.” Consistent with this, we wrote, “Future efforts should focus on implementing standard neurofeedback protocols, ensuring learning, and optimizing clinically relevant transfer.”1(p444) This is in line with the significant advantage for neurofeedback demonstrated in our additional preliminary analysis of the few studies meeting such standards

Emerging challenges in pharmacotherapy research on attention-deficit hyperactivity disorder—outcome measures beyond symptom control and clinical trials

Although pharmacological therapies are recommended as a key component in the treatment of attention-deficit hyperactivity disorder, their use continues to prompt intense debate. Despite considerable research efforts, several gaps in the knowledge base and several questions over the quality of evidence exist. Particular issues surrounding pharmacological treatments include uncertainties about long-term effectiveness and safety, safety profiles in adults, and the comparative effectiveness of different medications. In this Review, we focus on four key methodological issues for future research: (1) the use of appropriate trial designs; the need for (2) outcome measures targeting effectiveness beyond symptom control and (3) safety outcome measures; and (4) the application of clinical and administrative research databases to assess real-world outcomes. Potential solutions include increased use of randomised placebo-controlled withdrawal trials and large pharmacoepidemiological studies that use electronic health-care records on the long-term effectiveness and safety of medications. Pragmatic head-to-head randomised trials would also provide direct evidence on comparative effectiveness and safety profiles.</p

Computerized cognitive training in attention-deficit/hyperactivity disorder (ADHD): A meta-analysis of randomized controlled trials with blinded and objective outcomes

This meta-analysis investigated the effects of computerized cognitive training (CCT) on clinical, neuropsychological and academic outcomes in individuals with attention-deficit/hyperactivity disorder (ADHD). The authors searched PubMed, Ovid, and Web of Science until 19th January 2022 for parallel-arm randomized controlled trials (RCTs) using CCT in individuals with ADHD. Random-effects meta-analyses pooled standardized mean differences (SMD) between CCT and comparator arms. RCT quality was assessed with the Cochrane Risk of Bias 2.0 tool (PROSPERO: CRD42021229279). Thirty-six RCTs were meta-analysed, 17 of which evaluated working memory training (WMT). Analysis of outcomes measured immediately post-treatment and judged to be “probably blinded” (PBLIND; trial n = 14) showed no effect on ADHD total (SMD = 0.12, 95%CI[−0.01 to −0.25]) or hyperactivity/impulsivity symptoms (SMD = 0.12, 95%[−0.03 to−0.28]). These findings remained when analyses were restricted to trials (n: 5–13) with children/adolescents, low medication exposure, semi-active controls, or WMT or multiple process training. There was a small improvement in inattention symptoms (SMD = 0.17, 95%CI[0.02–0.31]), which remained when trials were restricted to semi-active controls (SMD = 0.20, 95%CI[0.04–0.37]), and doubled in size when assessed in the intervention delivery setting (n = 5, SMD = 0.40, 95%CI[0.09–0.71]), suggesting a setting-specific effect. CCT improved WM (verbal: n = 15, SMD = 0.38, 95%CI[0.24–0.53]; visual-spatial: n = 9, SMD = 0.49, 95%CI[0.31–0.67]), but not other neuropsychological (e.g., attention, inhibition) or academic outcomes (e.g., reading, arithmetic; analysed n: 5–15). Longer-term improvement (at ~6-months) in verbal WM, reading comprehension, and ratings of executive functions were observed but relevant trials were limited in number (n: 5–7). There was no evidence that multi-process training was superior to working memory training. In sum, CCT led to shorter-term improvements in WM, with some evidence that verbal WM effects persisted in the longer-term. Clinical effects were limited to small, setting specific, short-term effects on inattention symptoms

Cognitive Training for Attention-Deficit/Hyperactivity Disorder:Meta-Analysis of Clinical and Neuropsychological Outcomes From Randomized Controlled Trials

Objective: the authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD.Method: the authors searched Pubmed, Ovid, Web of Science, ERIC, and CINAHAL databases through May 18, 2014. Data were aggregated using random-effects models. Studies were evaluated with the Cochrane risk of bias tool.Results: sixteen of 695 nonduplicate records were analyzed (759 children with ADHD). When all types of training were considered together, there were significant effects on total ADHD (standardized mean difference [SMD] = 0.37, 95% CI = 0.09–0.66) and inattentive symptoms (SMD = 0.47, 95% CI = 0.14–0.80) for reports by raters most proximal to the treatment setting (i.e., typically unblinded). These figures decreased substantially when the outcomes were provided by probably blinded raters (ADHD total: SMD = 0.20, 95% CI = 0.01–0.40; inattention: SMD = 0.32, 95% CI = ?0.01 to 0.66). Effects on hyperactivity/impulsivity symptoms were not significant. There were significant effects on laboratory tests of working memory (verbal: SMD = 0.52, 95% CI = 0.24–0.80; visual: SMD = 0.47, 95% CI = 0.23–0.70) and parent ratings of executive function (SMD = 0.35, 95% CI = 0.08–0.61). Effects on academic performance were not statistically significant. There were no effects of working memory training, specifically on ADHD symptoms. Interventions targeting multiple neuropsychological deficits had large effects on ADHD symptoms rated by most proximal assessors (SMD = 0.79, 95% CI = 0.46–1.12).Conclusion: despite improving working memory performance, cognitive training had limited effects on ADHD symptoms according to assessments based on blinded measures. Approaches targeting multiple neuropsychological processes may optimize the transfer of effects from cognitive deficits to clinical symptom

Cognitive training for attention-deficit/hyperactivity disorder: meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials

OBJECTIVE: The authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD. METHOD: The authors searched Pubmed, Ovid, Web of Science, ERIC, and CINAHAL databases through May 18, 2014. Data were aggregated using random-effects models. Studies were evaluated with the Cochrane risk of bias tool. RESULTS: Sixteen of 695 nonduplicate records were analyzed (759 children with ADHD). When all types of training were considered together, there were significant effects on total ADHD (standardized mean difference [SMD] = 0.37, 95% CI = 0.09-0.66) and inattentive symptoms (SMD = 0.47, 95% CI = 0.14-0.80) for reports by raters most proximal to the treatment setting (i.e., typically unblinded). These figures decreased substantially when the outcomes were provided by probably blinded raters (ADHD total: SMD = 0.20, 95% CI = 0.01-0.40; inattention: SMD = 0.32, 95% CI = -0.01 to 0.66). Effects on hyperactivity/impulsivity symptoms were not significant. There were significant effects on laboratory tests of working memory (verbal: SMD = 0.52, 95% CI = 0.24-0.80; visual: SMD = 0.47, 95% CI = 0.23-0.70) and parent ratings of executive function (SMD = 0.35, 95% CI = 0.08-0.61). Effects on academic performance were not statistically significant. There were no effects of working memory training, specifically on ADHD symptoms. Interventions targeting multiple neuropsychological deficits had large effects on ADHD symptoms rated by most proximal assessors (SMD = 0.79, 95% CI = 0.46-1.12). CONCLUSION: Despite improving working memory performance, cognitive training had limited effects on ADHD symptoms according to assessments based on blinded measures. Approaches targeting multiple neuropsychological processes may optimize the transfer of effects from cognitive deficits to clinical symptoms.status: publishe

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