Therapeutic effects of methylphenidate for attention-deficit/hyperactivity disorder in children with borderline intellectual functioning or intellectual disability: A systematic review and meta-analysis

Abstract

Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with intellectual disability in children, and may further compromise learning. Methylphenidate is a first-line treatment for ADHD, however no previous meta-analysis has evaluated its overall efficacy for ADHD in children with comorbid intellectual disability (ID) or borderline intellectual functioning. The PubMed/MEDLINE, Cochrane CENTRAL and ScienceDirect databases were systematically searched from inception through 2018/7/15 for clinical studies that investigated the effects of methylphenidate in children with ADHD and ID. A random-effects model meta-analysis was used for data synthesis. Eight studies (average Jadad score = 2.5) enrolling 242 participants receiving methylphenidate and 181 participants receiving placebo were included. The meta-analysis showed that methylphenidate led to a significant improvement in ADHD symptoms relative to placebo (Hedges’ g = 0.878, p < 0.001). Meta-regression analysis pointed to an association between the dose of methylphenidate and overall improvement in ADHD severity (slope = 1.334, p < 0.001). Finally, there was no significant difference in drop-out rate [odds ratio (OR) = 1.679, p = 0.260] or rate of treatment discontinuation due to adverse events (OR = 4.815, p = 0.053) between subjects receiving methylphenidate and those taking placebos. Our study suggests that methylphenidate retains its efficacy in children with ADHD and borderline intellectual functioning or ID.

Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review

“…We ultimately included 14 NMAs and 90 MAs, reporting on 15 disorders or groups of disorders. For ADHD, we included three NMAs 5,20,21 and 21 MAs 22‐42 ; for autism, one NMA 43 and 21 MAs 12,44‐63 (including one focusing on comorbid anxiety disorders and autism) 12 ; for depressive disorders, two NMA 7,10 and seven MAs 64‐70 ; for obsessive‐compulsive disorder, one NMA 71 and six MAs 72‐77 ; for anxiety disorders, two NMAs 11,78 and five MAs 12,79‐82 (plus two MAs specific on social anxiety disorder 83,84 ); for enuresis, one NMA 85 and six MAs 86‐91 , for disruptive behavior/dissocial/conduct disorders, five MAs 92‐96 (plus one focusing on youth with comorbid ADHD) 25 ; for eating disorders, one NMA 97 and four MAs 98‐101 ; for schizophrenia spectrum disorders, three NMAs 8,102,103 and two MAs 104,105 ; for bipolar disorder, four MAs 106‐109 ; for tic disorder, two MAs 110,111 ; for Tourette's disorder, two MAs 112,113 ; for encopresis, two MAs 114,115 ; for developmental coordination disorder, one MA 116 ; and for PTSD, one MA 117 .…”

Commentary: Identifying individualized predictions of response in ADHD pharmacotherapy – a commentary on Rodrigues et al. (2020)

“…The conundrum of whether to rely on the limited data from treatment studies involving subpopulations, or to generalize from the larger ADHD literature, also affects clinicians treating ADHD symptoms in multiple other subpopulations. Figure 1 illustrates a comparison of the efficacy data from different meta‐analyses of RCTs evaluating pharmacological treatments for ADHD in general versus ADHD in the context of other comorbid conditions such as tic disorders (Bloch, Panza, Landeros‐Weisenberger, & Leckman, 2009), intellectual disability (Sun et al, 2019) and autism (Rodrigues et al (2020). Similar to the recent meta‐analysis of treatments for ADHD in the context of autism, the data of treatments for ADHD in the context of tic disorders or intellectual disability are unclear when contrasted to the larger evidence base of ADHD in general.…”

“…The figure depicts the estimated standardized mean difference with 95% confidence intervals from the different meta‐analyses of randomized controlled trials evaluating treatments for ADHD in general and for ADHD in the context of other conditions, more specifically autism (Rodrigues et al (2020), intellectual disability (ID) (Sun et al, 2019) and tic disorders (TD) (Bloch et al, 2009). For alpha‐2 agonists, results from the meta‐analysis of ADHD in general were stratified by guanfacine (GUAN) and clonidine (CLON)…”

“…We should additionally be leveraging the future pivotal clinical trials of medications for ADHD to help answer questions about predictors and moderators of pharmacological treatment effects. Previous studies in the field have attempted to identify predictors based Figure 1 The figure depicts the estimated standardized mean difference with 95% confidence intervals from the different meta-analyses of randomized controlled trials evaluating treatments for ADHD in general and for ADHD in the context of other conditions, more specifically autism (Rodrigues et al (2020), intellectual disability (ID) (Sun et al, 2019) and tic disorders (TD) (Bloch et al, 2009). For alpha-2 agonists, results from the meta-analysis of ADHD in general were stratified by guanfacine (GUAN) and clonidine (CLON) on clinical experience and have investigated their effect in a stepwise manner.…”

“…The large number of pharmacological RCTs in ADHD continue to answer the same, largely settled underlying question that of whether psychostimulant medications (or variants of nonpsychostimulant ADHD medication) are effective in treating ADHD. We should Figure 1 The figure depicts the estimated standardized mean difference with 95% confidence intervals from the different meta-analyses of randomized controlled trials evaluating treatments for ADHD in general and for ADHD in the context of other conditions, more specifically autism (Rodrigues et al (2020), intellectual disability (ID) (Sun et al, 2019) and tic disorders (TD) (Bloch et al, 2009). For alpha-additionally be leveraging the future pivotal clinical trials of medications for ADHD to help answer questions about predictors and moderators of pharmacological treatment effects.…”