Anthony_Rostain_AIA_15_Bzb6ml.png.jpgProven ADHD Medications for Adults – OROS-methylphenidate

Many studies have documented that ADHD patients have difficulties with the type of complex brain processes neurologists call “Executive Functions” (EF). A 2011 study of ADHD in Adults for example found roughly 40% have executive function deficits (EFDs) (Biederman, et al. 2011). EFs help us organize our lives, manage time, remember complex material and complete complex sequences of behavior. A deficit in executive function is therefore one of the common symptoms of Adult ADHD.
A recent study on medication for ADHD in adults examines the effects of OROS-methylphenidate on executive function deficits (EFDs) (Tannetje I. et al.. “OROS-methylphenidate efficacy on specific executive functioning deficits in adults with ADHD: A randomized, placebo-controlled cross-over study.” European Neuropsychopharma-cology. Available online 17 January 2014, ISSN 0924-977X. http://dx.doi.org/10.1016/j.euroneuro.2014.01.007). The authors used a randomized, placebo-controlled cross-over design to examine the effects of a 72 mg dose of OROS-MPH on 22 subjects’ performance on two versions of the Continuous Performance Test (CPT), a measure of sustained attention and working memory.

Study subjects were stimulant medication-naive. 25% had no Continuous Performance Test (CPT) deficits, 50% had a few CPT deficits, and 25% had multiple deficits, which is consistent with the Biederman study previously noted. Compared with placebo, OROS-MPH improved performance only on reaction time variability (RTV), a measure of sustained attention. High RTV indicates a deficit in information processing and functional integration. Patients with higher EFDs and more severe ADHD symptoms had a better response to medication. Differences in commission errors and discriminative ability between placebo vs OROS-MPH individuals were not noted. In addition, there was a poor relationship between objective and subjective efficacy of the medication.

The findings of this well designed experimental study are interesting in several ways. First, even with a small sample, robust effects of OROS-MPH vs. placebo were seen on Response Time Variability (RTV). In individuals with ADHD, RTV has been shown to be highly responsive to stimulant medication (Kofler, et al, 2012). This study confirms this finding.
Second, this study validates the use of an objective neurocognitive test to measure the responsiveness of adults with ADHD to pharmacologic treatment. An objective test of medication response could help to allay public health concerns about ADHD treatment options and the safety and efficacy of stimulant medications for ADHD symptoms in adults.

Thirdly, the RTV finding is compelling. While there remains a great deal of controversy about the role of EFDs in the etiology of ADHD, it is reasonable to assert that RTV has a great deal of salience to the phenomenology of the disorder, especially in adults. Indeed, trouble maintaining sustained attention is the most common subjective complaint reported by adults with ADHD, and is arguably the most constant neurocognitive impairment seen in this population. Clearly it is not unique to ADHD, but it certainly comprises a core feature of the disorder, and has become a central construct in neuropsychological and neuroimaging research.

The authors are honest in their appraisal of the limitations of the study (most notably the small sample size and the heterogeneity of sample subjects’ performance on the CPT at baseline), and they are very reasonable in recommending that more research be undertaken to document the clinical relevance of using the CPT in patient care, as well as to extend our understanding of the underlying neuropsychology of ADHD.

 

References
Biederman J, Mick E, Fried R, Wilner N, Spencer TJ, Faraone SV (2011). “Are stimulants effective in the treatment of executive function deficits? Results from a randomized double blind study of OROS-methylphenidate in adults with ADHD.” Eur. Neuropsychopharmacol., 21: 508–515.
Kofler MJ, Rapport MD, Sarver DE, Raiker JS, Orban SA, Friedman LM, E.G. Kolomeyer EG (2013). “Reaction time variability in ADHD: a meta-analytic review of 319 studies.” Clin. Psychol. Rev., 33 795–811.
Tamm, L, Narad ME, Antonini TN, O’Brien KM, Hawk Jr. LW, J.N. Epstein JN (2012). “Reaction time variability in ADHD: a review.” Neurotherapeutics: J. Am. Soc. Exp. NeuroTherapeutics, 9: 500–508.

Anthony L. Rostain, MD MA

About Anthony L. Rostain, MD MA

Dr. Rostain is Director of Education, Department of Psychiatry, Professor of Psychiatry and Professor of Pediatrics at the Hospital of the University of Pennsylvania and the Children's Hospital of Philadelphia. He is immediate past President of APSARD, the American Professional Society of ADHD and Related Disorders, and is on the Advisory Board of ADHD in Adults.com.