The academic battle over ADHD and its treatment has intensified with the retraction of a Cochrane review
The academic battle over ADHD and its treatment has intensified with the retraction, and scathing follow-up critique, of a Cochrane review that presented stimulants as both useful and safe for adults with the condition.
The initial review gave “misleading conclusions that gave a false sense of certainty of the benefits and the absence of harms” of methylphenidate (Ritalin, Concerta) treatment, according to the follow-up paper by Dr Kim Boesen and colleagues at the Nordic Cochrane Centre.
This retraction raised questions about the benefits of stimulant medication and underscored “a general inadequacy of clinical ADHD research”, at a time when methylphenidate use is sharply rising, the authors said.
Withdrawing a review is a highly unusual step for Cochrane, which is respected for its rigorous approach to evaluating the evidence.
The decision came after extensive criticisms of the methodology and conclusions in this instance.
Specifically, the original paper in favour of the drugs was flawed, with a reliance on cross-over designed trials which were small, of shorter duration and insufficiently blinded. They also excluded participants with psychiatric comorbidity, and there was an absence of useful, functional outcome measures.
Dr Boesen also criticised the conflicts of interest that existed among both the researchers and the reviewers. A 2008 investigation revealed some psychiatrists publishing these ADHD studies had received millions of dollars from the pharmaceutical industry without disclosure, and two of the three Cochrane reviewers on the original paper had financial conflicts of interest.
The Cochrane editorial group and editor-in-chief received substantial criticism of the review following its publication in 2014. Eventually, in mid-2016 the editorial group decided to withdraw the review.
The most recent paper by Dr Boesen and colleagues outlines the major problems with the original review.
Professor Jon Jureidini, an Adelaide psychiatrist and critic of overmedicating ADHD, applauded the Cochrane group for taking the “difficult and painful” step of retraction.
“One of the striking things about this review was how cavalier it was about assessing adverse events in relation to these drugs,” Dr Jureidini said.
“You only need to refer back to the Vioxx debacle to know that we have to be incredibly vigilant for adverse events in drugs that might seem to be highly unlikely to be dangerous.”
In particular, the original article said adverse effects from the drugs were “not of serious clinical significance”, despite failing to do a meta-analysis for pulse or blood pressure changes that could have indicated cardiovascular harms, and ignoring other research indicating possible links to psychosis, mania and aggression.
Dr Boesen said the original authors also failed to communicate the fundamental problems in the methodology of the research literature, and yet claimed to have “high” confidence in the evidence for most outcomes.
The effects and need to titrate stimulant drugs such as these, “virtually excludes the possibility that blinding was effective”, Dr Boesen said.
“Although you’d think that these scientific methodologies being used should be resistant to bias, of course they’re not.”
This paper illustrated the argument occurring within the medical community between those with “a vested interest and lots of associations with the pharmaceutical industry” and others who don’t have financial entanglements, Dr Jureidini said.
