Polyunsaturated fatty acid supplementation for ADHD symptoms: response to commentary.

To the Editor: As aptly articulated by Busch1 in her commentary on a recent report in this journal by Sinn and Bryan on supplementation of polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) symptoms in children,2 it is valuable for clinical pediatricians to be cognizant of research with omega-3 (n-3) fatty acids and developmental problems in childhood. To this important end, a review was recently published by Richardson,3 which may be helpful. In addition, I would like to address some key issues raised and provide extra information. Busch is correct in highlighting inconsistencies in research with ADHD symptoms, and in attributing these to methodological issues. These issues are most notably small sample sizes, selection criteria, failure to exclude stimulant medication as a potentially confounding variable, and differences in the nature and dosages of the n-3 supplement used. Supplementation with a combination of long-chain n-3 PUFA docosahexaenoic acid (DHA) and its precursor eicosapentaenoic acid (EPA) has been most successful in alleviating symptoms as found in the two largest, independent randomized controlled trials in the United Kingdom4 and Australia.2 Note that neither of the latter studies had been published when Schachter et al considered all available evidence and concluded that “no definitive conclusions could be drawn about the use of omega-3 fatty acid supplementation as primary or supplementary treatment for ADHD. ”5 It is important to note also that a commonly cited, unsuccessful study used pure DHA,6 suggesting that EPA or a combination of EPA and DHA may be more efficacious. This study also included children using stimulant medication. Another potential shortcoming was the selection of children with “pure” ADHD symptoms. Developmental disorders including dyslexia, dyspraxia, the autistic spectrum disorders, and learning, mood and conduct disorders all show substantial overlap with ADHD.7 Given that co-morbidities in ADHD are more the rule rather than the exception, the validity and generalizability of a “pure” ADHD selection criterion is questionable. The results also raise the possibility, consistent with indications of lower n-3 PUFA levels in a range of developmental and psychiatric disorders,3 that children with comorbidities may be more likely to have an underlying problem with n-3 levels and/or metabolism and may therefore derive greater benefit from n-3 PUFA supplementation. This leads us to the pivotal issue of diagnosing ADHD. Many studies with n-3 PUFA and ADHD symptoms in childhood have not required a formal diagnosis of ADHD. It should be noted though that parent reports, as used by Sinn and Bryan2 to select children with symptoms 90th percentile on Conners’ ADHD Index,8 have a high degree of accuracy in identifying ADHD in their children.9 Therefore it may be more unjust to ignore than to consider this population of children as having probable ADHD (the study did of course include children with a formal diagnosis although numbers were not recorded). Nonetheless, the issue of diagnosis warrants further discussion. Although diagnostic criteria have been very carefully considered, debated, and constructed by researchers and diagnosticians using multiple sources, they are ultimately based on subjective and arbitrary criteria, and are subject to variability. Essentially, there is no test that definitively tells us whether someone has ADHD or not. However, as Busch pointed out, psychophysiological assessments like EEGs and MRIs are able to detect slower brain waves in children with ADHD symptoms, which is consistent with a biological disorder. Criticisms of a categorical DSM-IV diagnosis versus a dimensional approach to ADHD symptoms have been discussed elsewhere.10 Omega-3 PUFA research adds an interesting insight to this debate. Most notably, three studies have found improvements in symptoms with a combined EPA and DHA supplement.11,3,2 The first of these11 was a pilot study in children with a primary diagnosis of dyslexia. The study was underpowered to detect significant outcomes but reported medium treatment effects, notably on symptoms of inattention, impulsivity and hyperactivity. The second larger UK4 trial selected children for a primary diagnosis of dyspraxia and found significant improvements on the same primary ADHD symptoms. The Australian trial2 focussed on recruiting children in the upper, clinical range for ADHD on Conners’ Rating Scales and again found the same improvements. These studies all found medium effect sizes on core symptoms associated with ADHD regardless of diagnosis. This provides compelling support for the potential benefits of a symptomatic versus diagnostic approach to treatment and again suggests that we could be doing clinicians, children and parents a disservice to ignore this evidence in favour of an academic debate about diagnosis. Perhaps psychophysiological assessments before and after n-3 PUFA supplementation can help us understand this further and provide a means for identifying maladaptive brain wave patterns and likely responders. Returning to specific concerns raised by Busch,1 the “high attrition rate (approximately 35%)” (p. 142) in the study reported by Sinn and Bryan2 may reflect unreturned parent questionnaires, reducing available data at each assessment point as thus outlined: [out of 167 children], “132 children completed the first 15-week phase of the study, and a total of 109 completed the 30 weeks, although data were only available for 104 and 87 of these children, respectively, due to unreturned parent questionnaires” (p. 83). Therefore the attrition rate at each time point was closer to 20%, which is comparatively good for an intervention trial of this length. Pertaining to outcome measures, more research remains to be done using appropriately selected tests to investigate objective outcomes of n-3 PUFA supplementation for ADHD symptoms. However, subjective parent or teacherreported outcome measures in the UK3 and Australian2 trials were supplemented by objective cognitive assessCorrespondence