November 25, 2015

expert reaction to Cochrane review of medication for ADHD

Publishing in The Cochrane Library a group of scientists have reviewed the evidence around the effects of a common drug which is used to treat ADHD in children and adolescents, reporting that methylphenidate is associated with some benefits but also an increased risk of “non-serious adverse effects”.

All our previous output on this subject can be seen here.

Dr Bernadka Dubicka, Vice-Chair of the Faculty of Child and Adolescent Psychiatry, Royal College of Psychiatrists, said:

“We welcome this detailed review and support the need for further large well-conducted trials, which examine longer term outcomes in young people. Most of these trials have been conducted in the US and a large government funded UK study would be welcome as these findings would be of direct relevance to young people treated for ADHD in the NHS. It is important to weigh up potential risks and benefits of treatment with families for each individual child; many young people will benefit from medication and the majority will not experience adverse effects. It is important that medication is offered as a potential treatment for young people with significant symptoms that adversely affect their lives, when other interventions have not been effective.

“This robust study looked at all RCTs and so we can trust the data it provides. As with all medications, prescribing should be cautious and risks/benefits should be carefully discussed. This study does provide some potential evidence of benefits and no evidence of serious harms, although the current evidence base is lacking in large high quality studies that we need to make fully informed decisions.”

Prof. Jonathan Green, Professor of Child and Adolescent Psychiatry, University of Manchester, said:

“It would be easy to draw the wrong overall conclusions from this Cochrane review.

“Despite the fact that generally speaking the studies find a positive effect of methylphenidate, the Cochrane reviewers define the trials as having a ‘high risk’ of bias – and this leads them to say that the evidence is weak.

“The basic issue that this review identifies is the poor design of studies to date in this field – specifically that the outcome measures, mainly parent and teacher report behaviour, may not have been made completely blind to whether the child was having the active medication or placebo. This leads to the Cochrane review of ‘high risk’ of bias.

“This problem is intrinsic to many psychological treatment studies since it is difficult to find ‘objective’ measures of the disorder in question outside parent and teacher report.  However until recently clinical scientists and trialists themselves in this field have been insufficiently focused on getting this aspect of trial design right (this has partly been a matter of culture within clinical trials in this field, partly that there are real challenges in finding appropriate objective measures).

“It would therefore be wrong to draw the conclusion from this review that methylphenidate is ineffective.  In fact clinical level evidence strongly supports the effectiveness of methylphenidate for many children with ADHD, and this is supported in the trial evidence (albeit with their design weaknesses as above).

“The evidence for the positive effect of methylphenidate on ADHD symptoms is for instance much stronger than for psychological treatment.

“My own view is that clinical scientists in this area should put more effort into finding valid objective measures of ADHD symptoms for use in trials, rather than concentrating on the use of so-called ‘nocebos’, as suggested in the report – a use that I think will be fraught with difficulty; partly because the incidence of unwanted-effects from methylphenidate is so variable and unpredictable.”

Prof. Guy Goodwin, President of European College of Neuropsychopharmacology and Professor of Psychiatry, University of Oxford, said:

“ADHD can be a severe disorder which blights child development and is associated with very sad outcomes like imprisonment. Recent review of the evidence by NICE concluded that medications were effective safe and cost effective. The present review looks at the same evidence and appears to discount the placebo-controlled trials as being of low quality because there may have been unblinding of active treatment by drug side effects. This interpretation seems to elevate a risk to a fact and, further, the authors recommend trials versus ’nocebo’ for which there exist no precedents. Moreover, effect sizes in these studies are much larger than studies of other drugs in which side effects are more obvious, suggesting a strong treatment effect is present.

“While average effects in trials offer limited evidence of real world efficacy, observational data in large populations have shown dramatic reductions in rates of offending associated with the treatment of ADHD.

“This review presents no new data and provides no reason to doubt that medication makes a major difference to the health of many young people with severe ADHD.”

Dr Daniel Hawcutt, member of the British Pharmacological Society and Senior Lecturer in Paediatric Pharmacology, University of Liverpool, said:

“This Cochrane review uses rigorous methodology, looking at lots of different groups (subgroup analyses), and includes 185 different studies. Methylphenidate produced some benefits in almost all of the studies, but with little difference between the effects seen for different doses.

“Overall these effects just about were large enough to be considered clinically relevant, but the medication also caused side effects (mainly reduced appetite and disturbed sleep) – so for an individual child the risk may outweigh the benefits or vice versa. As the reviewers concluded all studies were small and low quality, we cannot be sure of the overall size of the benefit.

“Carefully designed, large studies are needed to determine the size of both the beneficial and negative effects, so prescribers and parents can be confident using methylphenidate.

“Parents with questions or concerns should get in contact with their paediatrician, but there is no reason to immediately discontinue this medicine.”

‘Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)’ by Storebø et al. published in The Cochrane Library on Wednesday 25^th November. 

Declared interests

Prof Goodwin: “I have advised pharmaceutical companies on the development of medicines for psychiatry, but not ADHD specifically.”

Others: None declared