Ritalin may not help children with ADHD?

A few days ago, the media had a frenzy over a new study about the use of Ritalin (methylphenidate – a stimulant medication) for Attention Deficit Hyperactivity Disorder (ADHD) (http://goo.gl/Ht9GKF).

ADHD is always good for a headline grab because it is so polarizing. It’s like the new HIV – everyone’s got an opinion on ADHD, and most of them are facile or just plain ignorant. That doesn’t stop the armchair experts from sharing their opinions, and this new Cochrane review into the studies of Ritalin for ADHD just gives them another chance to vent their fatuous spleens.

Like a couple of the comments posted at the end of The Australian article. One suggested that ADHD was a disease invented so they could find another drug to treat it, and suggested that mobile phone games were the problem. Another thought he was rather humorous when he trotted out the tired old chestnut that it’s all the parents fault: “ADHD has been nicnamed {sic} ‘Absent Dad At Home’ syndrome!”  Sorry, but no one’s laughing. 

We need to take a step back from the uneducated and unwarranted opinion of the self-titled experts, and look at what the study actually said. To do that, lets have a look at what the study was, what it looked at, and what the results were. We’ll then compare the results with some of the other options available for treating ADHD, so we can make an informed decision about how to best manage ADHD.

First, what study are we talking about? The study in question is a Cochrane Review lead by Storebo, titled “Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)” [1]. (You can read the official press release here: http://www.cochrane.org/news/researchers-urge-caution-prescribing-commonly-used-drug-treat-adhd or the abstract here: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009885.pub2/abstract)

Cochrane reviews are scientific works that pool the best research on a particular topic and combine it into a mega-study, to get the best results available for a particular topic. First, all the papers written about the topic in question are found. The poorest quality studies are discarded, leaving studies that are suitable quality and are fairly uniform in how they did their research, so that the results from each study can be combined into one uniform result.

This process of meta-analysis increases the statistical power of the results enormously. The Cochrane Collaboration has been at the forefront of meta-analysis and has developed specific rules about the quality of evidence it accepts for its reviews, making a Cochrane review as trustworthy as medical research can be.

So what did the meta-analysis of methylphenidate for children with ADHD actually show? In short,

  • A strong improvement in the Teacher-Rated Symptoms score,
  • A strong improvement in the Teacher-Rated Behaviour score,
  • Small-to-moderate improvement in the ADHD rating scale,
  • Small increase in minor side effects such as poorer sleep and appetite, and
  • No increase in serious harm from methylphenidate.

So … that sounds pretty positive overall. Why the big hullabaloo? Why are these experts supposedly urging caution?

The concerns the researchers had was with the quality of the studies. Overall, the research that’s been done thus far has been deemed low quality by Cochrane’s standards. So they were cautious about suggesting that the results were reliable given the quality of the studies they had to work with. And that’s fair enough. Better quality studies are required to confirm the findings of the current Cochrane review, and this should be done as a matter of priority.

Unfortunately, the reviewer’s cautious approach to the research has been misinterpreted as a concern about the drug itself.

There are two important points here: 1. Accepting the limitations of the quality of the research it’s based on, the review still found a moderate effect of methylphenidate, and 2. Other “treatments” for ADHD have been proven in separate meta-analyses to be wholly ineffective.

There’s a little bit of statistical interpretation required here, but the Standardised Mean Difference (SMD, or sometimes called Cohens d) for the Teacher-Rated Symptoms score and Teacher-Rated Behaviour score was -0.77 and -0.87 respectively. The negative value here doesn’t mean that it’s bad; it’s just the arbitrary direction the reviewers chose to show improvement favouring Ritalin. Then there’s the SMD itself. The SMD takes into account the variability of the results overall, using a specific formula to take that into account.

The SMD used here doesn’t equate to the other value the reviewers used for the side effect statistics, which they expressed as a relative risk. So you can’t look at the numbers given and directly equate the power of the improvements with the chance of side effects of the medication.

However, it’s been said that an SMD of 0.2 is a small effect size, 0.5 is moderate, and 0.8 is large [2], so the effect of Ritalin given by the study was actually a strong effect. In comparison, the relative risk of minor adverse effects given by the review was 1.29, or a 29% increased risk, which is relatively small.

Then there’s the important consideration of the effects of other treatments for ADHD. The effect of Ritalin maybe backed by low quality evidence, but there’s no evidence of any effect for the other so-called ‘treatments’ for ADHD. As per the review by Sonuga-Barke (2013), there is a tiny amount of evidence for supplementation with omega-3 and 6 fatty acids, but none for:

  1. Elimination diets (including those for ‘antigenic’ foods, specific provoking foods, general elimination diets and ‘oligoantigenic’ diets)
  2. Food colouring (including certified food colours, Fein-gold diets and tartarazine)
  3. Cognitive training (including working memory specific, and attention specific training)
  4. Neurofeedback, and
  5. Behavioural intervention [3]

So no matter how inane or facile the arm-chair experts may be, there is no evidence that Ritalin for ADHD is harmful. There is a small risk of minor effects such as reduced appetite and sleep, but there is evidence (albeit low quality evidence) that it has a strong positive effect. In comparison, there’s no evidence of improvement from any other treatment that’s been adequately studied.

No drug is perfect, and that includes Ritalin. But it’s certainly not the devil in pill form either. It’s time to stop demonizing it, and ignorantly criticizing those children and their families who need it.

References

[1]       Storebo OJ, Ramstad E, Krogh HB, et al. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). The Cochrane database of systematic reviews 2015 Nov 25;11:CD009885.
[2]       Faraone SV. Interpreting estimates of treatment effects: implications for managed care. P & T : a peer-reviewed journal for formulary management 2008 Dec;33(12):700-11.
[3]       Sonuga-Barke EJ, Brandeis D, Cortese S, et al. Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments. The American journal of psychiatry 2013 Mar 1;170(3):275-89.

Dr Caroline Leaf – Serious questions, few answers (Part 2)

Yesterday I published the first part of an essay discussing the presentation of Dr Caroline Leaf, Audiologist, Communication Pathologist, and self-titled cognitive neuroscientist, at Kings Christian Church, Gold Coast.

Tonight I want to continue dissecting some of the more pertinent statements that she made, including her view of the mind-brain connection, a smattering of smaller issues, her over-reliance on case studies, and her opinion on the cause and treatment of ADHD.

Tomorrow I will publish the last, and most important part of my essay – That Dr Leaf believes that ‘toxic’ thoughts are sinful, and why this single statement unravels her most fundamental premise.

THE MIND IS IN CHARGE OF THE BRAIN

A large part of her sermon was based on her next premise, that the mind changes the brain, and not the other way around. That is half true. The mind influences the brain, and how we think will have effects on neural pathways within the brain. But for a cognitive neuroscientist to state that the brain does not influence the mind is somewhat concerning.

There are several reasons why her assertion is deeply flawed. For starters, where else does the mind or thought come from other than our neural networks? Thought is built on our neural connections. To say that the brain does not influence thought is like saying that the foundation of a building doesn’t influence the bricks.

There are clinical reasons as well. These come from a few areas – firstly the research that showed that newborn babies (who do not have thought like we have thoughts) are pre-wired for emotions which are refined as we learn. There is no time for neonates to have enough stimulation to form those emotions and reactions if it was from our mind.

Secondly, people with brain injuries or tumours can have personality or mood changes. The most famous was a man in the 1800’s called Phineas Gage, who on 13 September 1848 was packing explosives into rock with a tamping iron (a long, tapered, smooth crow-bar). History says that the explosives sent the tamping iron through his left face and skull, taking a fair chunk of his frontal lobe with it. Depending on who you believe, Gage’s personality changed after his physical recovery, reportedly from a moral, respectful man into a cursing, angry one (Kihlstrom 2010). Some reports of his story were that Gage made an almost full recovery, but assuming that some of the historical record is true, changes to his brain changed his mental function, ie: his thoughts.

Further, I have personally seen two patients with personality changes secondary to brain tumours. The first was a woman in her late 20’s who had six months of worsening anxiety, who did not seek help despite my referrals, until she had a seizure and the diagnosis was made. Then there was the sad case of a girl in her pre-teens who had only two weeks of rapidly escalating sullenness then aggression then violence. Her parents initially thought she was moody, and when they brought her into the Emergency Department they thought she was perhaps in the middle of a psychotic episode. It turned out that she had a very aggressive tumour near her frontal lobe.

It is clear from these cases, and from a basic understanding of the concept of thought, that changes to the brain result in changes to thoughts and the mind, and vice versa.

SOME MISCELLANEOUS ISSUES

If I had the time I would like to look at many others issues that she raised, but this isn’t a book. Suffice it to say that she claimed that stress prunes our “thought trees” although the evidence is only in animal models and only related to severe stress (Karatsoreos and McEwen 2011). She also stated that EVERY thought we EVER have is stored in ALL of our cells (so some random fibroblast in my big toe is somehow affected by my thought about tonights dinner), and that ALL our thoughts are stored in our gametes (our sperm and eggs) and are passed down to our 4th generation (but packed, like in a metaphysical zip-lock bag, and only opened if we choose to have the same thoughts.) And here I was thinking that nurture had something to do with learned behaviour.

ASD/ADHD – MORE OPINION THAN FACT?

She also claimed that 55-70% of ASD/ADHD cases are over-referred and the problem is in educational modeling. This one made me mad.

Not even professorial level researchers know exactly what’s going on in ASD/ADHD, so her statement is a brave one to make, especially without referencing her evidence.

She then espoused the party line of ADHD ignorance – that Ritalin is evil and all you need to do is stop their sugar intake and feed them organic foods and give them supplements. Ritalin isn’t perfect, to be sure, but it is the most effective treatment that’s currently available. If dietary measures and educational measures were effective, then ritalin wouldn’t be prescribed. I have never met a parent that has wanted their child on ritalin. Most of them have tried educational/psychological measures or dietary controls first. The reason why ritalin is prescribed is because dietary and psychological interventions on their own do not adequately control the symptoms, or fail altogether.

To confirm that I’m not just having a rant, there is published scientific literature to back me up. In their recently published meta-analysis, Nigg et al (2012) state, “An estimated 8% of children with ADHD may have symptoms related to synthetic food colors.” Eight percent. That’s all! That’s ninty-two percent of children with ADHD (real ADHD, not just rambunctious children with lots of energy) DID NOT have symptoms due to food colourings. Their conclusions: “A restriction diet benefits some children with ADHD. Effects of food colors were notable but susceptible to publication bias or were derived from small, nongeneralizable samples.” In terms of sugar, Kim and Chang (2011) note that, “children who consumed less sugar from fruit snacks or whose vitamin C intake was less than RI was at increased risks for ADHD (P < 0.05).” (emphasis added) The study was only of about 100 children, but the result was statistically significant. It wasn’t a chance effect.

The misinformation she stated as fact from the pulpit promotes scare-mongering and ignorance throughout the church, which has flow on effects. Church members with children with ADHD or ASD will avoid standard medical treatment on Dr Leaf’s advice. When her treatments fail in the majority of cases, those parents will either live with unnecessarily heightened stress because of their child’s poorly controlled condition, or the guilt of using ritalin, all the while believing that they are ruining their childs brain.

This also places the hosting church in a bind. Do they stand behind their guest speaker, or do they support the advice of the medical community? Is their duty of care to the reputation of the guest speaker or to the congregation under their protection? What would happen if Dr Leaf’s advice lead to the death or disability of a person in their congregation? Would they be libel?

CASE STUDIES – INSPIRATIONAL STORIES, BUT POOR SCIENTIFIC EVIDENCE

Dr Leaf also told a lot of stories of how everyone afflicted came to her and how she healed them all. If you took her at face value, she would have you believe that people with ASD, ADHD, anorexia, OCD, depression etc, just needed a glimpse of their self-worth and their inner gift and they would be cured. While her stories were inspirational, the world of scientific research demands more. If Dr Leaf’s insights are worth more than the hot air she produces when espousing them, then they should be put to the wider research community so they can pass through the fire of peer review. If peer review prove her insights to be valid, I would be happy to apply them and promote them.

Tomorrow, I will publish the last, and probably the most important part of my essay – that Dr Leaf believes that ‘toxic’ thoughts are sinful, and why this single statement unravels her most fundamental premise.

REFERENCES

Crum, A. J., P. Salovey and S. Achor (2013). “Rethinking stress: the role of mindsets in determining the stress response.” J Pers Soc Psychol 104(4): 716-733.

Karatsoreos, I. N. and B. S. McEwen (2011). “Psychobiological allostasis: resistance, resilience and vulnerability.” Trends Cogn Sci 15(12): 576-584.

Kihlstrom, J. F. (2010). “Social neuroscience: The footprints of Phineas Gage.” Social Cognition 28: 757-782.

Kim, Y. and H. Chang (2011). “Correlation between attention deficit hyperactivity disorder and sugar consumption, quality of diet, and dietary behavior in school children.” Nutr Res Pract 5(3): 236-245.

Leaf, C. (2009). Who Switched Off My Brain? Controlling toxic thoughts and emotions. Southlake, TX, USA, Inprov, Ltd.

Nigg, J. T., K. Lewis, T. Edinger and M. Falk (2012). “Meta-analysis of attention-deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms, restriction diet, and synthetic food color additives.” J Am Acad Child Adolesc Psychiatry 51(1): 86-97 e88.