Risk of Bias and Quality of Evidence for Treatment of ADHD With Stimulant Medication

Abstract

Storebø et al. provide a concise summary of two Cochrane reviews about benefits and harms of treatment of attention-deficit/hyperactivity disorder (ADHD) with methylphenidate: (1) a review of 185 randomized controlled trials that estimated benefits (e.g., moderate-to-large reduction in teacher-rated ADHD symptoms) and (2) a review of 260 nonrandomized trials that estimated harms (e.g., infrequent serious but frequent nonserious adverse events). They also mention (without providing much detail) additional information from the structured Cochrane method about the risk for bias in the trials reviewed (assessed as being high) and quality of evidence of the outcomes considered (rated as being very low). This led to the conclusion that "the jury is still out on benefits and harms." A similar conclusion of the first review generated an extensive debate in the literature. Some details will be summarized and discussed herein to provide context in case the recent review and the summary by Storebø et al. revive the debate.

Methylphenidate for ADHD rejected from the WHO Essential Medicines List due to uncertainties in benefit-harm profile

“…9 Even though methylphenidate has been used for over 60 years for this indication, the evidence concerning the benefits and harms of this medication in children, adolescents, and adults with ADHD remains uncertain. [10][11][12][13][14][15][16] Several studies have shown a possible favorable effect on ADHD symptoms, but the true magnitude of this effect is unknown. [10][11][12][13][14][15][16] In spite of these findings, a network meta-analysis from 2018 concluded that there is sufficient evidence to support short-term use within 12 weeks of methylphenidate in both children and adults, and there so far there are no trials investigating the effects beyond the 12-week treatment period or close to that.…”

“…[10][11][12][13][14][15][16] Several studies have shown a possible favorable effect on ADHD symptoms, but the true magnitude of this effect is unknown. [10][11][12][13][14][15][16] In spite of these findings, a network meta-analysis from 2018 concluded that there is sufficient evidence to support short-term use within 12 weeks of methylphenidate in both children and adults, and there so far there are no trials investigating the effects beyond the 12-week treatment period or close to that. 17 Some methodological problems with the network meta-analysis should be mentioned.…”

“…We have in many articles argued that the evidence base for the use of methylphenidate for children and adolescents with ADHD is very weak. 12 Not everyone agrees with us on this, 16 but almost all researchers and clinicians agree that there is no evidence for neither the benefits or harms from randomised clinical trials with a duration exceeding 12 weeks. This is very problematic as ADHD is considered a chronic condition S41 and most patients are treated for years.…”

Does Methylphenidate Work in Children and Adolescents with Attention Deficit Hyperactivity Disorder?

“…Methylphenidate significantly increased adverse events considered non-serious and the risks of serious adverse events could not be assessed due to lack of data [7]. This review was heavily criticised in articles and editorials [8][9][10][11][12][13]. The criticism was focused on erratic inclusion of studies, risk of bias assessment, and assessment of the quality of included studies and meta-analyses as well as errors in the data.…”

Treating a Child With Mental Illness

“…challenge this notion, based on their ongoing work of Cochrane review, which critically examined existing evidence on the very issue of methylphenidate use in ADHD treatment. Their results provoked intense debate in the field, which is well described in the mini‐review by Swanson …”