Ritalin and ADHD: What is the story so far?
The use of Ritalin to treat ADHD has become a highly contentious issue over the past decade. Part of this contention stems from a marked growth in use, with a 156% increase in the number of Ritalin prescriptions dispensed in England over the last ten years. Another source of contention comes from fragmented information about what the precise effects of Ritalin are (and ADHD medications in general) and what governs whether it is prescribed. We can unpick at least some of this debate by asking two questions: what is the evidence for what Ritalin does, and the extent to which it can help children with ADHD? And why could the number of Ritalin prescriptions have steadily increased over the past decade?
Methylphenidate medication in ADHD: What does Ritalin do, and can it help children with ADHD?
ADHD is a developmental disorder which, despite having a single diagnostic label, presents substantial individual differences between children who are affected. ADHD is characterised by deficits of inattention, impulsiveness, and hyperactive behaviour. These difficulties are often understood to be tied to reduced functionality of the prefrontal cortex (PFC) in individuals with ADHD. The PFC is important for attentional control and executive functions – a broad term for cognitive functions governing organised and controlled behaviour – and this reduced PFC functionality is suggested to result in the core ADHD symptoms of attentional and behaviour control deficits. However, ADHD also frequently co-occurs with other developmental disorders, such as dyslexia and autism. This means that children who are diagnosed with ADHD will range from those severely affected by difficulties in concentrating and sitting still, to those who struggle to pay attention and have comorbid difficulties in areas such as reading and communication. From the outset it is therefore important to recognise that there is huge individual variation in the children (and adults) whom fall under the ADHD diagnostic umbrella.
Ritalin, also known as methylphenidate, is a stimulant medicine which is commonly used to treat ADHD symptoms of inattention and hyperactivity. To understand the effects of Ritalin on cognition, research studies compare performance on tasks when participants have taken Ritalin to when they have taken a placebo. A meta-analysis of these studies by Coghill et al. (2014)1 combined papers investigating the effects of Ritalin in children and adolescents with ADHD. They found that the medication improved short term memory accuracy, working memory capacity, response speeds, and response inhibition relative to a placebo. Because the meta-analysis combined results across at least ten published studies for each aspect of cognition, these results are more representative than findings from a single study. A similar review by Epstein et al. (2014)2 assessed the effects of Ritalin medication in adults with ADHD, and observed that it improved inattentiveness, hyperactivity and impulsive behaviour. These findings overall suggest that Ritalin has positive effects on cognition and controlled behaviours compared to a placebo, in both children and adults with ADHD.
A suggested neurophysiological mechanism for Ritalin’s effect on cognition and hyperactivity is via increased functionality of the prefrontal cortex (Spencer et al., 2015)3. Ritalin prevents the reuptake of the neurotransmitters dopamine and norepinephrine in the PFC. Because these neurotransmitters allow nerve cells to communicate, their increased levels in the PFC strengthen its signalling and therefore improve its functionality. This increased activity of the PFC is measured in studies using fMRI, and is suggested to be tied to Ritalin’s effects of improving PFC-dependent cognitive skills such as attentional control, working memory, impulse control, and organised behaviour (Berridge & Devilbiss, 2011)4.
Importantly, however, these effects do not mean that the Ritalin treats the causes of ADHD. A key piece of evidence comes from the finding that Ritalin has the same ‘cognition-enhancing’ effects on individuals without ADHD. A review by Linssen et al. (2014)5 found that when adults without ADHD were given Ritalin their performance improved on tests of working memory and processing speed, and to a lesser extent attention and vigilance. Whilst these data do not allow us to assess if the magnitude of these methylphenidate effects were statistically identical to those in individuals with ADHD, they are an important indicator that Ritalin can improve these cognitive markers irrespective of an ADHD diagnosis (as current American college trends may also attest). These findings suggest that whilst Ritalin can be beneficial, it does not operate on the root aetiology of ADHD.
But interestingly, despite the cognitive benefits measured in short-term studies, Ritalin does not seem to improve children’s academic achievement in the long term. A large-scale longitudinal study reported by Molina et al. (2009)6 assessed the long-term outcomes of 579 children with ADHD who were randomly allocated to one of four treatment groups: methylphenidate medication, behaviour therapy, combined medication and behaviour therapy, or community care. At the end of the fourteen-month treatment period, all groups had improved relative to their pre-treatment baseline on a range of outcomes including parent and teacher-rated ADHD symptoms, teacher-rated social skills, and reading and maths achievement. Interestingly, the greatest improvements were for the medication group and combined medication plus behaviour therapy group. At the first follow-up ten months after treatment, the initial advantage of the medication and combined groups was still present (although the magnitude of this effect was about half what it had been immediately after treatment).
However, when the children were followed up several years later, this added benefit of medication had levelled out. At the three-year follow-up the four treatment groups remained above their pre-treatment baseline, but there was no difference between the treatment options; that is, the relative advantage of the medication groups was no longer present. After eight years the groups continued to perform above a pre-treatment baseline, but there remained no differential treatment benefit of medication. These findings suggest that medication can have a benefit during a relatively short-term treatment period, but beyond this initial treatment there is no evidence for a lasting medication advantage for the majority of children.
It is particularly interesting that there was no evidence for medication specifically improving long-term academic attainment in light of its short-term improvement of attention, short-term memory, and working memory. Because we know these cognitive skills are significant predictors of educational outcomes, we might have expected their improvement with Ritalin to also boost educational outcomes. Of course, the reason for no longer-term effects of medication may simply be that it can improve cognitive control during treatment, but these effects of the drug do not continue to have additive benefits after treatment is discontinued. There is also relatively little existing research on the effects of taking Ritalin for a longer time period, which limits our understanding of its effects from longer-term use.
However, another interesting explanation for the lack of such an effect may come from the heterogeneity of children diagnosed with ADHD. In their report Molina et al. (2009) identified three subgroups of children in the three-year follow-up, each with different ADHD trajectories as a result of treatment. One group showed an increasing steady benefit of medication use over three years; a second group showed a very large initial benefit for medication use which then plateaued, and was maintained three years after treatment; and a final group returned to pre-treatment levels with no ongoing benefit of treatment. These different profiles of children continued to be associated with their performance on the outcome measures of cognitive, social, and academic attainment at the eight-year follow-up. Importantly, these findings suggest that children’s longer-term outcomes may be determined more by their individual profile of symptoms than the specific type of treatment they receive.
So overall, what do these data us about the decision to use Ritalin for individuals with ADHD? Whilst research studies conducted over the short-term indicate that Ritalin can improve aspects of controlled cognition such as working memory and attention relative to a placebo, there is no evidence that medication continues to have an added benefit to non-medication treatments (such as behavioural therapy) after about two years following the start of treatment. The varying effects of medication may come from the heterogeneity of children diagnosed with ADHD. For many children, comorbid difficulties with reading or communication, for example, could be a key limiter on their performance at school, which Ritalin may do little to redress. Although Ritalin can undoubtedly be beneficial for children who substantially suffer with attention or behavioural control difficulties, the fact it is not universally helpful is an indicator of how much children diagnosed with ADHD can differ in their profile of strengths and weaknesses. Importantly, the effects of medication may therefore depend more on the symptoms of an individual child than the presence of an ADHD diagnosis.
156 percent: What are the reasons behind growing Ritalin use?
A herein lies the controversy: despite the above findings, and an anecdotal lack of consensus about its effects, the number of Ritalin prescriptions dispensed in England increased by 156% between 2004 and 2014. These data, published by the Health and Social Care Information Centre in 2015 and shown on the figure below, show Ritalin prescriptions at 359,068 in 2004 and 922,206 in 20147. (Interestingly, whilst the HSCIC data show that prescriptions for Ritalin are of a larger quantity than the other ADHD medicines on the market, the average use of other ADHD medicines also increased by a modest 136%).
What reasons could there be behind a growing number of Ritalin prescriptions? One obvious reason is an increase in the number of children (and adults) diagnosed with ADHD. In the United States at least, this argument for a relationship between prescription rates and ADHD diagnoses seems to hold. The Centre for Disease Control and Prevention collected comprehensive data on the percent of 4-17 year-olds with parent-reported ADHD diagnoses in each state, and the percent of children taking ADHD medication in each state, in 2007 and 20118. These data mean we can look at whether there is a relationship between each state’s change in ADHD diagnoses in this period, and their simultaneous change in medication use. The figure below shows the relationship between the change in the percentage of children with ADHD diagnoses and percent of children taking ADHD stimulant medication in each state, and there is indeed a significant positive correlation between the two. This positive correlation means that states with a larger increase in ADHD diagnoses also had a larger increase in the number of children prescribed stimulant medication. Whilst we cannot infer causality from these data (that is, we cannot assume that more ADHD diagnoses cause more medication prescriptions) they do suggest that the growth in diagnoses and prescriptions are related.
The main question these data raise – apart from what is going on in Texas – is why ADHD diagnoses have increased. In a recent paper investigating reasons behind the global expansion of ADHD diagnoses and medication use, Conrad and Bergey (2014)9 suggested that increased promotion of ADHD drugs by the pharmaceutical industry, the increased adoption of DSM (the Diagnostic and Statistical Manual of Mental Disorders, an American publication) diagnostic criteria, and more accessible information about ADHD online could all contribute to its steady growth. ADHD information being more visible and accessible online can prompt more individuals to seek and thus obtain a diagnosis, and promotions by pharmaceutical companies can result in medication treatment being more frequently offered to individuals diagnosed with ADHD. Further, the diagnostic criteria used are particularly important: Conrad and Bergey suggested that a shift towards the DSM criteria in the 1990s contributed to increasing rates of ADHD, as the DSM uses a lower threshold for diagnosis and allows the co-occurrence of ADHD with other developmental disorders. Whilst these are broad brush strokes for reasons for which Ritalin use has grown, they nonetheless suggest possible mechanisms for the increase in prescriptions.
However, it is important for us to recognise that measuring the number of prescriptions dispensed may not be the best indicator of how many individuals are actually taking the medication. A good example of this comes from looking at the headline finding from a 2008 study which reported huge variation in the number of Ritalin prescriptions dispensed across England, with as much as a 23-fold difference between the lowest and highest-prescribing areas of the UK (Stoke-on-Trent and Wirral, respectively). However, the prescription rate for each region was measured by the number of prescriptions dispensed as a proportion of the population in that region. These figures meant that differences in prescribing practises across regional primary care trusts, such as the standard frequency of repeat prescriptions, could contribute to a lot of this variation. The overall population of a region also influenced its ‘rate’ of prescribing; this might explain why the relatively small Isle of Wight had the second-highest rate at 107 prescriptions per 1000 children. Although just one example, this points to the need to look at Ritalin use in terms of the number of individuals prescribed Ritalin and ask how this aligns with the number of individuals actually diagnosed with ADHD.
So the story about Ritalin seems to have two parts: first, it can have beneficial effects on cognition, but these benefits may critically depend on children’s individual profile of symptoms. Second, it is possible that Ritalin use has increased in line with growing ADHD diagnoses, but we need to carefully evaluate the evidence we have to assess this. Possible vehicles for growth include more individuals seeking a diagnosis due to the information now available about ADHD, promotion by pharmaceutical companies for the use of medication, and a shift in diagnostic criteria meaning a higher proportion of people are identified as having ADHD. In the UK, however, we know relatively little about how increasing Ritalin use relates to the number of individuals with ADHD taking medication, and the wider growth of ADHD as a disorder. This is the question we will turn to in our next post.
Coghill, D. R., Seth, S., Pedroso, S., Usala, T., Currie, J., & Gagliano, A. (2014). Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis. Biol Psychiatry, 76(8), 603-615. doi: 10.1016/j.biopsych.2013.10.005
Epstein, T., Patsopoulos, N. A., & Weiser, M. (2014). Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults. The Cochrane Review, (9). Retrieved from http://www.cochrane.org/CD005041/BEHAV_ritalin-for-adult-attention-deficit-hyperactivity-disorder-adhd
Spencer, R. C., Devilbiss, D. M., & Berridge, C. W. (2015). The cognition-enhancing effects of psychostimulants involve direct action in the prefrontal cortex. Biol Psychiatry, 77(11), 940-950. doi: 10.1016/j.biopsych.2014.09.013
Berridge, C. W., & Devilbiss, D. M. (2011). Psychostimulants as cognitive enhancers: the prefrontal cortex, catecholamines, and attention-deficit/hyperactivity disorder. Biol Psychiatry, 69(12), e101-111. doi: 10.1016/j.biopsych.2010.06.023
Linssen, A. M., Sambeth, A., Vuurman, E. F., & Riedel, W. J. (2014). Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies. International Journal of Neuropsychopharmacology, 17(6), 961-977. doi: 10.1017/S1461145713001594
Molina, B. S., Hinshaw, S. P., Swanson, J. M., Arnold, L. E., Vitiello, B., Jensen, P. S., . . . Group, M. T. A. C. (2009). The MTA at 8 years: prospective follow-up of children treated for combined-type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry, 48(5), 484-500. doi: 10.1097/CHI.0b013e31819c23d0
http://www.hscic.gov.uk/catalogue/PUB17644/pres-disp-com-eng-2004-14-rep.pdf, pp. 139-140. Data available in ‘Appendix 2 Tables’ Excel Spreadsheet here: http://www.hscic.gov.uk/catalogue/PUB17644
The researchers measured medication prevalence by the number of individual children who were prescribed ADHD medication, rather than the number of prescriptions being written.
Conrad, P., & Bergey, M. R. (2014). The impending globalization of ADHD: notes on the expansion and growth of a medicalized disorder. Soc Sci Med, 122, 31-43. doi: 10.1016/j.socscimed.2014.10.019