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.

Advertisements

Dr Caroline Leaf and the Me-Too approach to mental health

Screen Shot 2015-11-13 at 3.44.33 pm

Since her recent less-than-successful attempt at portraying herself as a mental health expert, Dr Leaf has been laying low on social media, sticking to bland, innocuous quotes or passages of scripture.

Today, she thought it was safe enough to pop her head up from the trenches to fire off another opinionated volley on mental well-being, with a quote from one of her favourite authors, Peter Kinderman:

“It’s our framework of understanding the world, not our brains and not even the events that happen to us – not nature and not nurture – that determines our thoughts, emotions, behaviours and, therefore, our mental health.”

Dr Leaf is a communication pathologist and self-titled cognitive neuroscientist. Without any training or professional experience in mental illness, she has also taken it upon herself to act as an expert on mental health within the Christian church.

Unfortunately, posting quotes like today’s offering only further destroys her flagging credibility among those with professional psychiatric experience, and adds to the confusion of the rest of the Christian church when it comes to understanding mental illness.

There are two main problems with Dr Leaf’s meme: the quote itself and it’s source.

The quote itself is wafer-thin, unable to stand up to even the most basic interrogation. For example, we know through basic common sense that the brain changes how we think, our moods, our emotions and our behaviours. We change our mood, our emotions and our alertness every time we have a cup of coffee, or a glass of wine. Hallucinogenic medications like LSD definitely change our framework of understanding the world. Coffee, alcohol, and illicit substances like LSD all change the mood or experience of the person using them because they all temporarily alter the function of the users brain.

Though it’s not just external substances that change how we experience our external and internal worlds, but our own internal hormonal ecosystem changes our emotions, our moods, our thoughts and our behaviours. This isn’t so obvious for most men as our hormones are fairly constant, though testicular failure is known to result in reduced energy, vitality, or stamina; depressed mood or diminished sense of well-being; increased irritability; and difficulty concentrating and other cognitive problems. For the female gender, monthly hormonal changes can sometimes result in sudden, marked changes in emotions, moods, thoughts and behaviours.

There are a lot of other reasons why the brain controls the mind, and our mental health, which I’ve also discussed numerous times in other blogs (here, here and here)

If you aren’t satisfied with a common sense approach, then consider the scientific evidence that personality, the name that we give to our inbuilt ‘framework of understanding the world’ is largely genetic, and dependent on the function of various neurotransmitter systems [1-4].

So to suggest that the brain is not responsible for our moods, our emotions, our thoughts and our behaviours isn’t supported by the weight of scientific evidence.

The quote by Kinderman doesn’t stop there, but suggests that “not even the events that happen to us … determines our thoughts, emotions, behaviours”, something that also flies in the face of current scientific evidence. For example, the other forty percent of personality is determined by our environment (specifically the ‘non-shared’ environment, the environment outside of our parental influence) [5, 6]. And common psychiatric illnesses are associated with early childhood adversity, such as schizophrenia [7] and ADHD [8]. So again, the quote is unscientific.

Who then is this Kinderman guy, and why does he disagree with the scientific literature?

Peter Kinderman is a Professor of Psychology at University of Liverpool, and the President-elect of the British Psychological Society. He’s a highly outspoken critic of modern psychiatry and what he perceives to be the medicalisation of normal moods and emotions and overuse of medications to treat these non-existent diagnoses. Kinderman believes that it’s our learning history that shapes the paths that our lives take, and so if we simply understand our personal models of the world and how they were shaped by the events and experiences to which we’ve been exposed, we can simply think our way out of any disease process [9].

Kinderman has come out in favour of talking treatments for psychosis in schizophrenia instead of medication, when there’s no scientific proof of benefit for psychosocial therapies in schizophrenia [10, 11] (and here).

This, and his staunch opposition of the DSM5 as invalid, makes me concerned about his bias against modern psychiatry, despite it’s many advances, scientifically and clinically.

However, I’m surprised that Kinderman would make such a statement because it’s such an asinine argument, I find it hard to believe that it came from a professor of psychology. Kinderman would surely recognise the role of biology in our mental health and wellbeing, even if he doesn’t agree with how it’s managed. Perhaps there’s an alternative explanation. Perhaps Kinderman didn’t say what Dr Leaf has claimed?

The answer is, he does, and he doesn’t.

Dr Leaf has quoted Kinderman correctly. Today’s quote is taken directly out of Kindermans 2014 book, “The New Laws of Psychology” [9], on the penultimate page of his introduction. So he does say that our brains and our experiences aren’t relevant for our mental health. But then again, in a blog on the militant anti-psychiatry blog ‘Mad in America’, Kinderman wrote this:

“I’ve spent much of my professional life studying psychological aspects of mental health problems. Inevitably, this has also meant discussing the role of biology. I hope I’ve made some progress in understanding these issues, in working out how the two relate to each other, and the implications for services. That’s my academic day-job. But it’s not just academic for me. I’m probably not untypical of most people reading this; I can see clear examples of how my experiences may have affected my own mental health, but I can also see reasons to suspect biological, heritable, traits. As in all aspects of human behaviour, both nature and nurture are involved and they have been intimately entwined in a complex interactive dance throughout my childhood and adult life.” http://www.madinamerica.com/2015/03/brain-baked-beans/

So he seems confused, both recognising that biological traits influence psychiatric illness, then denying it.

Personally, I disagree with the quote from his book, although I’m just a suburban GP from Australia, so what would I know, right? Though I think the evidence I’ve cited is on my side, and Kinderman is not without his critics who are more than his academic equal.

It also concerns me because the logical conclusion of this line of thinking is that psychiatric illnesses have no biological basis, and therefore psychiatric medications have no place in treatment of them. But as I outlined previously, there is good evidence for the beneficial effects of medications for schizophrenia and ADHD amongst other mental health disorders.

Dr Leaf continues to ignore the scientific evidence for the biological basis for mental ill-health, medications for their treatment, and even the most basic of all that our mind is a product of our brain. Instead, she’s nailed her colours to her mast and aligned herself with outspoken authors on the fringe of modern neuroscience. Rather than addressing the science behind her opposition to modern psychiatry and neuroscience, she has resorted to hiding behind their quotes, a ‘me-too’ commentator, rather than an actual expert.

Of more importance is the confusion that this brings to the vulnerable Christians who follow her social media “fan sites”. The more Dr Leaf criticises psychiatric medications and condemns their prescription and usage, the more likely it is that someone will come to serious harm when they inappropriately cease their medications. And if Dr Leaf won’t come to her senses, our church leaders are going to have to take action, before it’s too late.

References

[1]        Vinkhuyzen AA, Pedersen NL, Yang J, et al. Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion. Translational psychiatry 2012;2:e102.
[2]        Chen C, Chen C, Moyzis R, et al. Contributions of dopamine-related genes and environmental factors to highly sensitive personality: a multi-step neuronal system-level approach. PloS one 2011;6(7):e21636.
[3]        Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. The American journal of psychiatry 2010 May;167(5):509-27.
[4]        Felten A, Montag C, Markett S, Walter NT, Reuter M. Genetically determined dopamine availability predicts disposition for depression. Brain and behavior 2011 Nov;1(2):109-18.
[5]        Krueger RF, South S, Johnson W, Iacono W. The heritability of personality is not always 50%: gene-environment interactions and correlations between personality and parenting. Journal of personality 2008 Dec;76(6):1485-522.
[6]        Johnson W, Turkheimer E, Gottesman, II, Bouchard TJ, Jr. Beyond Heritability: Twin Studies in Behavioral Research. Current directions in psychological science 2010 Aug 1;18(4):217-20.
[7]        Howes OD, Murray RM. Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet 2014 May 10;383(9929):1677-87.
[8]        Thapar A, Cooper M, Eyre O, Langley K. What have we learnt about the causes of ADHD? Journal of child psychology and psychiatry, and allied disciplines 2013 Jan;54(1):3-16.
[9]        Kinderman P. The New Laws of Psychology: Why Nature and Nurture Alone Can’t Explain Human Behaviour: Robinson, 2014.
[10]      Buckley LA, Maayan N, Soares-Weiser K, Adams CE. Supportive therapy for schizophrenia. The Cochrane database of systematic reviews 2015;4:CD004716.
[11]      Jones C, Hacker D, Cormac I, Meaden A, Irving CB. Cognitive behaviour therapy versus other psychosocial treatments for schizophrenia. The Cochrane database of systematic reviews 2012;4:CD008712.