Exciting findings on ADHD comorbidities shared on 3rd meeting of CoCA researchers in Dublin

A few weeks ago, researches from all over Europe (and some even from the USA) gathered in Dublin to discuss the progress of the CoCA project. This project, investigating the prevalence and causal factors of ADHD comorbidities, is now almost half way. Time for an update on what’s happening. 

CoCA Dublin
All attendees of CoCA’s 3rd general assembly meeting in Dublin

ADHD is a risk factor for developing other (psychiatric) disorders

One of CoCA’s aims is to estimate the prevalence of comorbid disorders that occur together with ADHD. By using very large data registries from Norway, Sweden, Denmark and Estonia we can estimate the risk of developing a psychiatric comorbidity when a person has ADHD. For instance, last month a paper was published based on data from Norway, stating that the prevalence of anxiety, depression, bipolar and personality disorders, schizophrenia and substance use disorders is 4 to 9 times higher in adults with ADHD compared to adults without ADHD [1]. Interesting differences between men and women were also observed in this study. Such that depression is much more prevalent in women with ADHD, compared to women without, while in men substance use disorders are more common together with ADHD.

ADHD does not only co-occur with other psychiatric disorders, but also with obesity. Earlier last year, we published a study based on the Swedish national registry, where it was observed that ADHD and being overweight or having obesity share familial risk factors [2]. In other words, when you have a sibling who is overweight or has obesity, you are more likely to have ADHD compared to similar people who do not have overweight siblings.

The data from these registries can not only be used to estimate prevalence, but also to predict the risk someone has to develop other disorders. Our partners in the USA are using advanced machine learning tools to predict within the ADHD population who will develop comorbid disorders. Using the Swedish registry data they have found that having an ADHD diagnosis combined with a high number of injuries before the age of 12 predicts a comorbid substance use disorder at a later age. High risk taking behavior could mediate this association, and may therefore be a trait to investigate further and monitor in young people with ADHD. These data are now being further investigated and have not yet been published.

Publications on other registries and data will come out soon, so keep your eye on this blog for more information on the co-occurrence of (psychiatric) disorders in persons with ADHD.

ADHD and (psychiatric) comorbidities share genetic variants

When you know that ADHD often co-occurs with other disorders, the next question is to understand how and why. Our geneticists are trying to map the genetic overlap between the different disorders and identify shared genetic risks. Much of the work is still ongoing, but you can expect some exciting findings to be published very soon. What I can already share is the recent publication on how polygenic risk scores of ADHD overlap with other disorders and traits [3]. Polygenic risk scores (PRS) were calculated based on 12 genetic loci that are associated with ADHD based on earlier studies. In other words, the more risk variants you have on these loci, the higher your risk is for ADHD. Using the UK Biobank data, the researchers found that ADHD PRS were associated with higher body mass index, neuroticism, anxiety, depression, alcohol and nicotine use, risk taking and lower general cognitive ability (verbal-numerical reasoning). This suggests that the genes that contribute to ADHD are also involved in other traits and disorders that are often observed in people with ADHD. More knowledge on these genetic factors is expected from the studies that are now being conducted.

Searching for new treatment possibilities for ADHD and comorbid disorders

At the moment, there are no good treatments for obesity and substance use disorders, and there is little progress in the development of medication for ADHD in combination with depression. Within the CoCA project we are therefore investigating new treatment possibilities. In Frankfurt, Barcelona and London the first people with ADHD have received bright light therapy and physical exercise training to reduce symptoms of depression (the PROUD study). In Nijmegen this study will soon start as well. Meanwhile in Rostock (Germany), the circadian rhythm of participants with ADHD and other disorders is being measured. And in Frankfurt researchers are investigating the effects of dopamine agonists and antagonists on the reward system in the brain.

CoCA researchers in Norway have been searching the literature for new druggable targets for ADHD and comorbid disorders. A publication on many promising druggable genes can be expected soon. The first group of targets will be tested in an animal models.

Collaborations with patient organisations

Two representatives of ADHD patient organisations also joined our meeting: Andrea Bilbow from ADHD Europe, who is a partner in the CoCA project, and Ken Kilbride from ADHD Ireland. It was good to have these experts with us, and discuss with them how we can best translate our research findings to the people who should benefit from these findings. In Ireland for instance, there is very little knowledge about adult ADHD amongst health care professionals. It is therefore essential that our knowledge is also transferred to them, so that they can provide better care.

With the help of Andrea and Ken, we came up with a lot of new ideas for ADHD Awareness Month. During the entire month of October we aim to generate more awareness about. We will specifically target schools, such as universities and German Berufschule to inform both pupils and teachers about how to recognise ADHD and comorbidities, in adolescence and adulthood.

What’s next?

With the project being almost half way, we feel that we’re progressing very well (and our external advisor Jim Swanson – who attend the meeting as well – agrees!). In the coming year, we expect many exciting publications to appear and we will organise several symposia on international scientific conferences to share with you what we’ve found. By collaborating with patient organisations across Europe we will also share our knowledge with patients, family members, health care professionals and teachers. You can follow all of our progress on this blog!

This blog was written by Jeanette Mostert. Jeanette is dissemination manager of the CoCA project.

Further reading

1: Solberg, Halmøy, Engeland, Igland, HAavik & Kungsøyr (2018) Gender differences in psychiatric comorbidity: a population‐based study of 40 000 adults with attention deficit hyperactivity disorder. Acat Psychiatria Scandinavia, 137 (3): 176 – 186. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838558/

2: Chen, Kuja-Halkola, Sjölander, Serlachius, Cortese, Farone, Almgvist & Larsson (2017) Shared familial risk factors between attention-deficit/hyperactivity disorder and overweight/obesity – a population-based familial coaggregation study in Sweden. Journal of child psychology and psychiatry, 58 (6): 711-718. https://www.ncbi.nlm.nih.gov/pubmed/28121008

3: Du Rietz, Coleman, Glanville, Wan Choi, O’Reilly & Kuntsi (2018) Association of Polygenic Risk for AttentionDeficit/Hyperactivity Disorder With Co-occurring Traits and Disorders. Biological Psychiary CNNI, in press. https://www.sciencedirect.com/science/article/pii/S2451902217302318?via%3Dihub

 

 

DOES ADHD MEDICATION CHANGE THE DEVELOPING BRAIN?

Treating children with ADHD medication is hotly debated. It’s shown to be effective in reducing ADHD symptoms, but what are the long-term effects on developing brains? We asked an expert.

How ADHD medication influences the brain in the short-term has been widely studied, but many children with ADHD take medication over several years. The effects of long-term ADHD medication treatment on the developing brain have been less researched. Lizanne Schweren conducted her PhD research on this very topic, with a focus on stimulants, the most commonly prescribed ADHD medication. We sat down with Lizanne and asked her a few questions:

Photo by en:User:Sponge

What are stimulants?

Stimulants are drugs that activate the body, including the brain. Stimulants are sometimes referred to as “uppers”, as their effects tend to be energizing and pleasant. The best-known prescribed stimulant to treat ADHD is methylphenidate. For 70-80% of children, as well as adults, methylphenidate reduces their ADHD symptoms and helps them concentrate.

What happens in the brain directly after taking stimulants?

Methylphenidate blocks the reuptake of dopamine within the synaptic cleft, the gap between pre- and postsynaptic cells. Dopamine transmits neural signals from one cell to the next, and does so until the presynaptic cell transports dopamine back for recycling. By blocking presynaptic reuptake, more dopamine is left in the synapse and more signal is transmitted.

Children with ADHD often take stimulants for several years. What effect does this have on their brains?

People with ADHD, their brains look subtly different from people without ADHD. Previous studies had suggested that after long-term stimulant treatment, these differences may become smaller or even disappear. However, in my own research we found subtle differences in brain structurebetween those with and those without ADHD, regardless of treatment history. This suggests that the treatment does not in fact change the way the brain develops structurally.

Photo by amenclinicsphoto ac 

As opposed to structural differences, we did find differences in brain activation patterns when comparing children who differed in the age of onset of ADHD as well as stimulant dosage. During an fMRI experiment, the group who began taking stimulants at a young age and at a higher dose, was more likely to show activation in brain regions important for cognitive control (dorsal anterior cingulate cortex, and supplementary motor area), compared to children who took stimulants at an older age and at a lower dose. All children were off their medication during the experiment. We think that people with ADHD, who often act impulsively, may benefit from activations in these brain regions.

What do these long-term effects of stimulants on the brain mean for children with ADHD? And for clinicians prescribing stimulants?

While neuroscientists were hoping for positive – normalizing – long-term effects of stimulant treatment on the brain, parents and clinicians have mostly been concerned about potential negative consequences. For them, the fact that we found no evidence of structural brain changes associated with stimulant treatment is probably a relief. Moreover, we showed that long-term stimulant treatment does not result in better clinical outcomes. Most often symptoms of ADHD decrease during adolescence, and these improvements happen whether the child took stimulants or not. For clinicians working with patients and their parents, it is important to communicate that stimulants may temporarily improve symptoms of ADHD but they do not alter outcomes in the long-term.

 

Lizanne’s research is based on data linked to the Donders Institute: the NeuroIMAGE sample.

We want to thank Lizanne for the interview with the Donders Wonders.

Her thesis can be found here.

 

Interview conducted by Corina Greven.

Blog written by Corina Greven.

Blog edited by: Marisha Manahova.

Featured image by Jonathan Rolande.

 

This blog was originally published on www.blog.donders.ru.nl. This is the official blog of the Donders Institute on brains and science.

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Mindfulness for children with ADHD – is that possible?!

International research shows that mindfulness can improve attention and self-control. This has already been shown for people without ADHD, and the initial results from research in children with ADHD are promising.

Many parents of children with attention-deficit hyperactivity disorder (ADHD) are looking for alternative treatments that do not involve ADHD medication. Mindfulness (paying attention without judgement) is becoming an increasingly popular training in Western societies, and is already successfully used in the treatment of depression and anxiety in adults. But may mindfulness also work as an intervention for ADHD? Especially in the case of children with ADHD who have difficulties with concentration, you may wonder whether they are able to pay enough attention for mindfulness training.

6035280806_b70fc7e2e0_bImage from: Sebastien Wiertz

What is mindfulness precisely?

Mindfulness involves paying attention in a particular way:

  • On purpose (meaning it involves effort)
  • To the present moment
  • Without judgement

With mindfulness you can learn to become aware of your body, emotions and thoughts. You learn to notice impulses, but to not immediately react to them.

An example: A boy sits in the classroom. His mind starts to wander away from the teacher towards his weekend activities which he is excited to share with his classmate. He deliberately notices feeling excited (awareness) and the urge to turn around to speak to his friend (impulse). He lets the sensation pass through him without judgement (non-judgement/ non-reactivity). He purposefully brings his attention back to the teacher.

Mindfulness for children with ADHD – is that possible?!

In many ways, mindfulness training seems an ideal intervention for ADHD. Children with ADHD have difficulties with paying attention, hyperactivity and regulating their impulses. In short, they experience problems around self-control. Research from non-ADHD populations shows that mindfulness training improves people’s self-control by increasing attention control, emotion regulation and self-awareness.

In addition, evidence suggests that mindfulness training alters the structure and function of brain areas involved in self-control, such as the anterior cingulate cortex, prefrontal cortex, posterior cingulate cortex, striatum, insula and amygdala. Several of the brain areas implicated in mindfulness overlap with those for ADHD. However, is mindfulness training feasible in children with ADHD?

 

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Image from: Todd Fahrner

The MindChamp project

A handful of Dutch studies have shown that mindfulness training clearly is feasible for children with ADHD. For this work, children with ADHD and their parents underwent the MYmind programme: 8 weekly mindfulness sessions of 1.5 hours. The training is adapted to the needs of families of ADHD, for example using shorter and more playful exercises. The studies showed that mindfulness training reduces ADHD symptoms, improves self-control and reduces parenting stress. However, the studies were small and used a less rigorous (non-randomised) design.

Research linked to the Donders Institute is taking this to the next level with the MindChamp project: Mindfulness for Children with ADHD and Mindful Parenting. This larger, randomised-controlled trial uses the MYmind mindfulness programme, and is based at Karakter Child and Adolescent Psychiatry, in collaboration with the Radboud Centre for Mindfulness and UvA Minds. Recruitment for the project is ongoing (children with ADHD aged 8-16 years), and the first results can be expected in 2018. The hope is that positive research results will allow more families with ADHD access to the intervention.

Links:

More information about MindChamp here

Questions about MindChamp? Email mindchamp@karakter.com

MindChamp is part of the MiND project. It is funded by a Marie Sklodowska-Curie grant and the Netherlands Foundation for Mental Health.

Blog written by Corina Greven.

Editor: Marisha Manahova.

Featured image by: papermoons

This blog was originally published on www.blog.donders.ru.nl. This is the official blog of the Donders Institute on brains and science.

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New England Journal of Medicine – Journal Watch Psychiatry Top Stories of 2016 – ADHD is a hot topic!

fireworkNow that the year is coming to an end, we are flooded with reviews of the year. For many reasons, 2016 wasn’t a particularly good year: especially some “democratic” decisions made this year cast some doubt on the so-called “swarm intelligence” which in 2016 apparently turned into “swarm dullness”. With alt-right, fake news and the post-factual world being an imminent threat to mental sanity, we can only hope for a better 2017. Anyway – that’s not the topic of this blog post. As many other journals did, the top journal of the Medical World, NEJM has nominated their top articles in each speciality (http://www.jwatch.org/na43004/2016/12/23/nejm-journal-watch-psychiatry-top-stories-2016).

Amazingly, amongst the Top 10 papers in psychiatry, three dealt with ADHD – and even better, two of them featured IMpACT / MiND / Aggressotype / CoCA researchers in the author list! The papers are in detail:

  • the finding that the use of stimulants is safe in bipolar disorder with comorbid ADHD (Viktorin et al.; http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2016.16040467 – also one of my favourite studies this year)(with H. Larsson, IMpACT / MiND / CoCA)
  • a meta-analysis showing that EEG-based neurofeedback does not have a significant beneficial effect in ADHD, and also suggesting that unblinding of the rater might have influenced positive reports (http://www.jaacap.com/article/S0890-8567(16)30095-8/abstract)(with Dani Brandeis, Aggressotype)
  • the equally sad as important report that young children (aged 5 to 11), who died by suicide, had more frequently symptoms of ADHD, rather than depressive features (almost 60% of 87 children). Also for this most devastating outcome, it is thus very important to adequately diagnose ADHD (http://pediatrics.aappublications.org/content/138/4/e20160436) especially considering that ADHD goes along with an increased risk for suicide life-long which can be lowered by MPH treatment.

In my opinion, the fact that the editors picked three ADHD-relevant papers for their top 10 list demonstrates that ADHD is a hot topic and that we provide cutting edge research in the field – and we will continue to do so in 2017! Watch out at this space for more news on ADHD / ASD, my personal top picks in 2016 and more exciting research in the coming year! Merry New Year and all the best for 2017 for all of you, may it bring peace, happiness and reason to this discomposed world.

Ghost busters: why even high ranking psychotherapy studies might be lousy

img_4358The last half year saw two high ranking psychotherapy studies in depression, published in the most prestigious journals of our profession. While in principle this is laudable, in these specific cases it is not doing any good as the studies fall short to prove what they are actually claiming and also, because they sack medical care for the sake of cost. Let’s have a closer look.

The first paper (https://www.ncbi.nlm.nih.gov/pubmed/27461440), on the “COBRA” study, was published in Lancet (!!!) and compared „behavioral activation” delivered by „junior mental health workers“ (i.e. relatively untrained and, first and foremost, receiving relatively small wages) is just as effective as routine CBT delivered by trained psychologist (which is the gold standard psychotherapy treatment in depression). So depression treatment can be quite unspecific and cheap! Yay!

Not.

The most important drawback is the that the primary endpoint was set at twelve months. As the average length of a depressive episode is six to eight month without treatment, this makes no sense at all. Imagine that a study on two treatments aimed at relieving common cold would set its primary endpoint at 4 weeks. Would you buy this? As neither a survival plot (Kaplan-Meier-Plot) nor any other time course are shown, being suspicious is appropriate.

A further, unfortunately quite common, drawback is the lack of a sham psychotherapy group (i.e., this study is not placebo controlled). Given the year-long course, it may quite well have shown that it is as effective as the two other groups.

This is made even worse by the fact that 80% of participants in both groups received anti-depressant drug treatment. Likely, a ceiling effect is effective, further obscuring any effect of whatever psychotherapy is done.

This is not a non-inferiority trial. This is a failed trail.

Another study published in JAMA Psychiatry (https://www.ncbi.nlm.nih.gov/pubmed/27487573) echoes the COBRA study, although changing the flavor. Here, psychodynamic (not behavioral activation) was compared against CBT in depression. I don’t want to nag about the underpowered sample for a non-inferiority trial (especially when looking at how many patients attended more than five sessions (116 in total). Again, we have an endpoint which is rather late (5 month) without any description of time courses, and again sham psychotherapy is lacking. Even worse, that average Hamilton score (HAM-D, likely HAM-D 17) was 21±6 points. This is quite low and barely reaches the border to moderate depression; the usual cut-off for study inclusion in pharma trials lies between 20 and 22. This means that many patients with mild depression were included, that usually are not the target population for depression studies. Any differences to placebo/sham are hard to demonstrate due to floor effects, especially when considering the low number of patients adhering to therapy and the measured effect size of 0.6 (Cohen’s d, corresponding to a medium effect size). Considering all this, watchful waiting, mere psychoeducation or having a beer every week or so would have had the same effect, namely, a reduction of five points on the HAM-D 17, as this is just the naturalistic course of mild to medium depression. An indicator of this are the significantly overlapping SD measurements pre- and post-treatment (wisely enough, the authors did not go for graphical display of their data). The most parsimonious interpretation of the data thus is that both treatments are equally ineffective!

You may ask about antidepressant use here as well. There is a simple answer: we don’t know. The numbers of patients on antidepressants are not given at all! That they were there, we know, as there is a small subclause: „We found no statistically significant interaction between the use of psychotropic medication and treatment group on the rate of change in the HAM-D”.

This is another failed trail. Although it was highly published…

Unsurprisingly, the rate of recidivism (which is a major effect of psychotherapy) is not given in any of the studies.

It is very surprising however that these studies were published so well, despite of these obvious flaws. I can only speculate on the reasons for this. Regarding the Lancet paper (COBRA), I assume that economic reasons play a major role. Cheap BA treatment by “juniors” (did not we just learn to abandon that word from our vocabulary?) is as effective as CBT by expensive, greedy psychologist. That makes treatment less expensive, which however is somewhat tainted by the fact that it is ineffective (notwithstanding the commonsense experience that unspecific BA especially in early stage depression by be quite helpful). Never mind. The psychodynamic study might have undergone a “wishful thinking” review process – so many people are out there who desperately wish that psychodynamic therapy works as well as CBT… so this one came in quite handy. However, no favor was done to the field, on contrary. We do not need so badly designed (or at least presented) studies; what we do need are psychotherapy trials adhering to the highest standards in analogy to drug trials: i.e. presenting time courses, studying severe cases, being well powered with low attrition rates, and – most important – including a sham (=placebo) condition.

Transitioning from child to adult: a new declaration demands continuing support for ADHD in Europe

growing_up_by_sillysirry-da7illn
image ‘growing up’ by sillysirry via Diviantart

ADHD Europe – the European patient organisation for people with ADHD – has launched a declaration on behalf of teenagers with ADHD. The declaration states that adult services in all European countries should offer suitable care for teenagers with ADHD who transition into adulthood, and to adults who are newly diagnosed. Andrea Bilbow is the president of the ADHD Europe organisation. I asked her about the importance of this declaration, and what she thinks that the consequences of the declaration will be.

Why was this declaration to urgently needed?

“Well it’s a bit of a long story that goes back 20 years. We started as organisations to raise awareness for ADHD in children, and to organise good services for these children. In most European countries there now are good services for children with ADHD.”

“However, these children are all becoming adults. For many young people across Europe as soon as they reach 18 years of age, they find that transition to adult services is very poor.  In many cases treatment is withdrawn altogether leaving them vulnerable and at risk.  And for those fortunate enough to receive the medication that they need for ADHD in adulthood, the medication is no longer reimbursed. This puts a huge burden on families who often have two or more children with ADHD and who do not have the resources to pay for the medication. Only in one or two countries in Europe are there official adult licences for the medication needed by adults with ADHD. Besides medication, young adults with ADHD do not have access to the services for ADHD in adult clinics, while they were receiving help in children’s services.”

Why is it so important that adults with ADHD receive suitable care?

“18 is a very vulnerable age. It’s the age when adolescents move up to Higher Education or start with their first jobs. Having ADHD, these young people are vulnerable to substance abuse, academic failure, job loss, becoming homeless or even crime. Furthermore, many of them will be starting to drive. Studies have shown that  a significant number of young people with untreated ADHD will be involved in car accidents.”

“For years the EU has been trying to address the problem of school dropout in Europe, without success. Having medication for ADHD continue to be reimbursable and proper services for young adults with ADHD available would go a long way to reduce the number of young people who abandon education. So it is very, very important that they receive proper treatment and support. It’s probably one of the most important things you can do for this age group.”

People can now sign the declaration to show their support. What do you think will happen next?

“Well first of all, it’s amazing to see how much support we are receiving. The Declaration has been launched for only a week and already we have more than 500 signatures. More importantly, these signatures come from all over the world. But it also shows that what this declaration states is very much needed. Clearly, 18+ people across Europe are really struggling.”

“First, we will let this run for a couple of months to see how many signatures we can receive. We encourage professionals to also show their support: professors, doctors, medics, researchers, teachers, police. Anybody who has any stake in improving the lives of people with mental health problems. Once we have gathered this support, we will encourage the member countries to take it to their MEPs and try to get the required number of MEPs to sign the declaration in order for it to be discussed in the European Parliament. That is our mission. We will try to find out why  in some countries they don’t want psychiatrists to diagnose and treat adults with ADHD. This is a human right that’s being breached.”

This October is ADHD awareness month. The perfect moment for the ADHD Europe patient organisation to bring out this Declaration and to raise awareness for this important issue. You can find, and sign, the Declaration at the website of ADHD Europe: http://www.adhdeurope.eu/adhd-europe/adhd-declaration-2016.html

The Declaration also shows the importance of research on ADHD. The CoCA project for example will investigate the societal costs of ADHD and comorbid disorders. Such data can assist in persuading governments about the importance of providing suitable care for those – children and adults- with ADHD.

This post was written by Jeanette Mostert. Jeanett is Dissemination Manager of the CoCA project.

Going bananas about methylphenidate studies!

Why did I chose to use the Minions as a feature image for this post, along with the catchy title? Simply to attract attention. Sheer clickbait. While this is perfectly acceptable for a blog post (well, almost…), it is not for scientific publications. This not only refers to the title of a paper, but also to the way it is disseminated; and in this respect, a series of manuscripts under the lead authorship from O. Storebo raised some brows with their bold claim that there is no evidence that methlyphenidate actually works. While most of us clinicians would readily agree that this medication requires experience, thorough assessment, responsibility, and that it is not rarely ill-prescribed (often however by doctors other than psychiatrists), most of us are sure that it is indeed an effective medication given that the ADHD diagnosis is valid. So are we all deluded?

Well… probably not. At least not when it comes to methylphenidate treatment.

The group around Storebo, who before worked in the ADHD research in one trial on social skills training (the SOSTRA study), conducted a Cochrane on the efficacy of methylphenidate in ADHD and found out that “methylphenidate may improve teacher-reported ADHD symptoms”, but “due to the very low quality of the evidence, the magnitude of the associated improvement is uncertain”. This led to some far-fetched conclusions and statements (see e.g. the conclusions section in the abstract here: http://www.ncbi.nlm.nih.gov/pubmed/26599576) and it was wide-spread communicated in the media that “methylphenidate is not effective”. A deleterious statement, which also outraged many patients and parents.

So far, so bad; Cochrane reviews are known for their methodological rigor, however there are many back doors so one should always look at them critically, as you can tweak your input. What was the fine-tuning done here?  To start with, the effect size estimate is based upon 19 (from 185 included) studies. 4 did investigate methylphenidate versus an active control, another study  was undertaken in children under 6 years (off-label). When these studies are excluded, which should have been done, effect sizes increase to a large effect of 0.89. On the other hand, 56 studies that employed a cross-over design were excluded for no clear and good reason.

 

This should be enough to cast doubt on the study. However, in addition, there was an unusually strict and almost arbitrary assessment of bias; this led the authors to rate ALL (!!!) 185 studies to be at high risk of bias – and hence categorizing all studies as “low quality”. However, the evidence to support this claim is little. Personally, I find it outragous (and as I did not take part in any of these studies, I am not biased…) especially as the most common source of potential bias were assumed “conflicts of interest”.  While I consider Disclosure of Interest as a very important thing, one cannot make a general accusation and suspect almost a whole speciality of being bribed. This is demagogue, not science. This categorization results in a striking devaluation of decades of evidence from RCTs and also contradicts e.g. a NICE review (http://www.ncbi.nlm.nih.gov/pubmed/16796929).

Finally, Storebo’s proposal to implement long-term nocebo-controlled studies – despite the strong actual evidence from several decades of RCTs on methylphenidate – implies to administer a substance with no known benefit, but significant side effects for a substantial time period to many patients including minors. In my opinion, this is deeply unethical and conflicts with §33 of the Declaration of Helsinki.

While the grounds for their bottomline claim may be slippery, the authors do a good job in selling it. They have published the original Cochrane review http://www.ncbi.nlm.nih.gov/pubmed/26599576, followed by a publication of the very same data in the prestigious BMJ http://www.ncbi.nlm.nih.gov/pubmed/26608309 and another publication of the same dataset in JAMA http://www.ncbi.nlm.nih.gov/pubmed/27163989. Bear with me, but haven’t I been told in grad school that one of the Ten Commandments in Science is “Thou shalt not publish the same data twice”?

Just by repeating their interpretation over and over in high impact journals, the notion that methylphenidate is not working will trickle in the general conscience while the empirical basis for this claim suggests otherwise. This will impose harm on our patients, and this is why we have to address and disprove these papers actively.