Methylphenidate for ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable disorder presenting with persistent patterns of inattention, hyperactivity, and impulsivity that can continue across the life course and impact on functional outcomes such as peer and family relationships.1 2 Yet the many unknowns associated with the treatment of the disorder overshadow much of the clinical needs of those living with ADHD. Challenges include a lack of gold standard diagnostic measures, a blurred boundary between what is “normal” and “the condition,” and poor academic and clinical consensus as to the best treatment approaches and outcome measurements. We are left with large variations between studies in how symptom profiles are assessed, making it difficult to determine treatment effects in both the short term and the long term.3

In a linked paper, Storebø and colleagues (doi:10.1136/bmj.h5203) present a comprehensive and rigorous Cochrane systematic review and meta-analysis of the use of methylphenidate in young people with ADHD.4 Its findings are potentially important and at the same time confusing for clinicians and millions of affected families, thanks to the poor overall quality of the evidence on methylphenidate for young people with ADHD. Notably, they found “high quality data” gathered from just 183 participants in six trials, out of a potential 12 245 participants in the 185 trials included. The authors were unable to draw any firm conclusions about the risks and benefits associated with methylphenidate—not helped by a median duration of treatment of less than two months.

In placing this review in the context of the extensive body of literature available on ADHD, four areas are worth highlighting. First is the sorry state of research into one of the most common childhood neurodevelopmental disorders. Inadequate funding for mental health research that falls well below population morbidity, combined with practical, ethical, and cultural barriers to conducting research on children, limit the generalisability of findings from all existing studies.5 The lack of integration of research within the fabric of health service provision complicates this further.

Secondly, in complex conditions where study populations and research measures are so variable, a greater focus needs to be placed on methodological triangulation in research. We need to work more collaboratively, incorporating multiple research designs, including observational research and qualitative research reporting patients’ and carers’ own perspectives. The data from randomised controlled studies is, of course, important. However, given the barriers to conducting large trials in children, we must make full use of other sources of data, while not ignoring clinical consensus. Cochrane methodology is confined to trials. A further limitation is that any study that did not meet one domain of quality assessment was categorised as low quality. Study heterogeneity is arguably even more of a problem in systematic reviews of non-pharmacological interventions for ADHD, which nevertheless have been able to show an important role for psychoeducation, for example.6 7

Thirdly, more research is needed on the harms associated with drugs for treating ADHD. In this review, about one quarter of participants reported minor adverse events (mostly related to sleep or appetite), which is less than might be expected clinically. The new review underlines the difficulties in adequately powering trials for rare and serious adverse events. Again, observational designs using register data and prescription databases are important alternative approaches to gathering the required information.8

Finally, the woeful lack of understanding of what happens long term to children with ADHD is unfortunate considering the numbers affected. The clinical relevance of findings from short term studies is questionable, given that most international guidelines recommend methylphenidate2 and most clinicians evaluate the effect of drugs in ways that are different from those used in trials. Despite the authors’ conclusions, the short term beneficial effects of methylphenidate on ADHD symptoms are broadly accepted and reflected in the prevailing consensus among clinicians and in guidelines.9 10 For trial data to be clinically relevant, the long term trajectory of clinical decision making needs to be considered. Most clinicians will monitor early response to treatment by evaluating symptoms and side effects. However, the more functional assessment of treatment—evaluating whether drugs improve a child’s peer and family relationships and educational outcomes—takes longer, and is best assessed after six months. At this point, clinicians will be working outside the limited and short term evidence on drugs and non-pharmacological interventions.

Determining the clinically appropriate use of drugs is not a simple task in a condition such as ADHD, which lies at the intersection between cultural expectations of behaviour, parental concerns about using psychoactive substances, and children’s changing development. Identifying and dealing with the priority domains of functioning for each child must be at the forefront of our work. We need to find ways to deliver individually tailored interventions for ADHD that incorporate our growing understanding of the neurocognitive models of the condition, the potential neurotransmitter effects of methylphenidate, and findings from high quality observational evidence.

The slow progress of ADHD research and limited evidence base for treatments are in stark contrast with the hallmarks of the disorder itself, with its high prevalence and broad symptomology. This latest systematic review and meta-analysis is yet another reminder that we need a more meaningful research agenda—combining a variety of research methods with patient perspectives and a broader understanding of clinical outcomes—to test the long term consequences of treatments for ADHD. For now, the jury is still out.