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In the Hundred Acre Wood of ADHD

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In the Hundred Acre Wood of ADHD Guest Editorial Hunting for ‘Woozles’ in the Hundred Acre Wood of ADHD Myths abound in the imagina- Throughout my training from medi- tion of some clinicians, just as cal school, through fellowship, and during my tenure as a faculty member, Winnie-the-Pooh believed that I have found myself, at times, search- Woozles—imaginary, yet feared ing for Woozles and often have joined honey stealers—exist. Consider my colleagues on these hunts. Herein, I Jeffrey R. Strawn, MD the following excerpt from a classic would like to share with you 3 Woozles Child and Adolescent Psychiatry that have resulted in current false Section Editor children’s book. dogmas related to attention-deficit/ One fine winter’s day when Piglet was hyperactivity disorder (ADHD) and brushing away the snow in front of his stimulant psychopharmacology. house he happened to look up, and there was Winnie-the-Pooh. Pooh Stimulants worsen anxiety was walking round and round in a FDA-required labeling for stimulants circle, thinking of something else… includes strong language noting that So begins the 1926 Winnie-the-Pooh these drugs are “contraindicated in story.1 In this chapter, the well-meaning marked anxiety, tension, and agita- yellow bear, Winnie-the-Pooh, has found tion, since the drug may aggravate strange tracks in the snow, which he these symptoms.”3 However, data believes belong to a “Woozle.” Pooh fol- from randomized controlled trials and lows the tracks, not realizing that he’s meta-analyses consistently have failed walking in a circle. As such, he begins to demonstrate this effect. Moreover, to notice that the tracks have multiplied, sequenced treatment trials involving which he interprets as evidence of sev- adolescents with anxiety disorders and eral Woozles. co-occurring ADHD suggest that stim- This “Woozle Effect” has been well ulants actually could reduce anxiety described in research settings and is symptoms. believed to have resulted in conclusions A recent meta-analysis4 that evalu- that are not supported by or are inconsis- ated nearly 2 dozen studies involving tent with the original data, which are then approximately 3,000 pediatric patients propagated through successive citations, with ADHD reported that stimu- resulting in a scientific “urban legend.”2 lant treatment was associated with a decreased relative risk of anxiety (rela- To comment on this editorial Dr. Strawn is Associate Professor of Psychiatry, Child and or other topics of interest, Adolescent Psychiatry, University of Cincinnati College tive risk: 0.86). The study also observed of Medicine, Cincinnati, Ohio. visit www.facebook.com/ a dose-response relationship between CurrentPsychiatry, or go to Disclosure Dr. Strawn has received research support from the National stimulant dosage and anxiety (Figure, CurrentPsychiatry.com and click on Institutes of Health, the American Academy of Child and page 6).4 Although the authors note the “Send Letters” link. Adolescent Psychiatry, Eli Lilly, Edgemont, Forest Research Laboratories, Neuronetics, and Shire. that it is possible that some individu- Current Psychiatry 4 October 2016 als might experience increased anxiety analysis of 22 studies (involving nearly Editorial Staff with stimulants, many patients could 2,400 youths with ADHD) that sug- EDITOR Erica Vonderheid show improvement in anxiety symp- gested new-onset tics or worsening SENIOR EDITOR Patrice Kubik WEB ASSISTANTS toms when treated with stimulants, of tics to be present in 5.7% of patients Tyler Mundhenk, Kathryn Wighton and the authors also advise us, as cli- receiving stimulants and in 6.5% of Art & Production Staff nicians, to “consider re-challenging patients receiving placebo. In addition, CREATIVE DIRECTOR Mary Ellen Niatas children with ADHD who report … in this meta-analysis the class of stimu- ART DIRECTOR Pat Fopma DIRECTOR, JOURNAL MANUFACTURING anxiety with psychostimulants, as these lant, dosage, treatment duration, or Michael Wendt symptoms are much more likely to patient age did not seem to be associated PRODUCTION MANAGER Donna Pituras be coincidental rather than caused by with onset or worsening of tics.7 Publishing Staff psychostimulants.”4 PUBLISHER Sharon J. Spector DIGITAL ACCOUNT MANAGER More evidence of a lack of stimulant- Polypharmacy represents a Reinaldo Valdivia induced anxiety comes from a large therapeutic failure and is not MARKETPLACE ACCOUNT MANAGER Linda Wilson randomized controlled trial of pediatric evidence-based CONFERENCE MARKETING MANAGER patients (age 6 to 17) who met DSM-IV Although treatment guidelines gener- Kathy Wenzler criteria for ADHD and a co-occurring ally have discouraged combination ther- Editor-in-Chief Emeritus anxiety disorder who were treated with apy for treating ADHD, there are—on James Randolph Hillard, MD methylphenidate (open-label) and then the basis of efficacy—insufficient data Frontline Medical Communications CHAIRMAN Stephen Stoneburn randomized to fluvoxamine or placebo to support this prohibition. Moreover, EVP DIGITAL BUSINESS DEVELOPMENT/CFO for treatment of anxiety symptoms.5 over the last decade, several studies Douglas E. Grose Alan J. Imhoff However, in this trial >80% of the 32 have suggested benefits for combining PRESIDENT/CEO PRESIDENT, CUSTOM SOLUTIONS JoAnn Wahl medication-naïve youth improved after ADHD medications that have compli- VICE PRESIDENT, FINANCE Dennis Quirk stimulant treatment to the point that they mentary mechanisms. In this regard, VICE PRESIDENT, OPERATIONS Jim Chicca VICE PRESIDENT, AUDIENCE DEVELOPMENT no longer had anxiety symptoms severe 2 extended-release formulations of α2 Donna Sickles enough to be eligible for randomization agonists have received FDA approval VICE PRESIDENT, CUSTOM PROGRAMS Carol Nathan to adjunctive fluvoxamine or placebo. for as adjunctive treatments in pediatric VICE PRESIDENT, CUSTOM SOLUTIONS patients with ADHD (extended-release Wendy Raupers VICE PRESIDENT, eBUSINESS DEVELOPMENT Stimulants are contraindicated guanfacine and extended-release cloni- Lee Schweizer in patients with tic disorders dine). However, despite these FDA indi- VICE PRESIDENT, HUMAN RESOURCES The package inserts for most stimulant cations as adjunctive treatments, many & FACILITY OPERATIONS Carolyn Caccavelli VICE PRESIDENT, MARKETING & CUSTOMER medications warn clinicians that stimu- clinicians remain concerned about com- ADVOCACY Jim McDonough lants are “contraindicated in patients bination therapy. VICE PRESIDENT, SALES Mike Guire VICE PRESIDENT, SOCIETY PARTNERS with motor tics or with a family history Several months ago, a large, Mark Branca or diagnosis of Tourette’s syndrome.” 8-week, National Institutes of Health– CORPORATE DIRECTOR, RESEARCH & COMMUNICATIONS Lori Raskin This is particularly concerning, espe- sponsored trial shed more light on the EDITORIAL DIRECTOR Karen J. Clemments cially because of the medicolegal impli- use of α2 agonist + stimulant combina- Subscription Services: (800) 480-4851 cations of the term “contraindicated” tions. Patients age 7 to 17 (N = 179) In affiliation with Global Academy and given that as many as 1 in 5 pedi- were randomized to (1) guanfacine for Medical Education, LLC VICE PRESIDENT, MEDICAL EDUCATION atric patients with ADHD have a tic dis- + d-methylphenidate, (2) guanfacine & CONFERENCES Sylvia H. Reitman, MBA order.6 Therefore, labels that list motor monotherapy, or (3) d-methylphenidate VICE PRESIDENT, EVENTS David J. Small, MBA tics as a contraindication to stimulant monotherapy.8 In addition to clinical out- use potentially eliminate the choice of comes, the authors evaluated the effects stimulant pharmacotherapy—the most of the medication on background corti- 7 Century Drive, Suite 302 effective treatment for ADHD—for a cal activity. Of interest, monotherapies Parsippany, NJ 07054 Tel: (973) 206-3434 large number of patients. differed between one another and the Fax: (973) 206-9378 When hunting for the Woozle that combination treatment in their effects on www.frontlinemedcom.com linked stimulants and tics and led to cortical activity. Guanfacine decreased Published through an this language in the package insert, it alpha band power and methylphenidate educational partnership is worthwhile to review a recent meta- administration was associated with an with Saint Louis University Current Psychiatry Vol. 15, No. 10-A 5 Guest Editorial Figure Is stimulant use associated with anxiety symptoms? 3 2 1 0 Log risk ratio of anxiety -1 As we evaluate -2 evidence for our 0102030405060708090100 interventions, whether Methylphenidate equivalent daily dose (mg) psychopharmacologic A recent meta-regression of stimulant dosage and risk of anxiety symptoms reveals that higher doses were associated with a slight decrease in the risk of anxiety (vs placebo, or psychotherapeutic, z = −2.34, P < .02). we will do well to Source: Reprinted with permission from reference 4 relentlessly question the ‘evidence’ for our choices increase in frontal/central beta power, pharmacologic or psychotherapeutic, we while combination treatment damp- will do well to relentlessly question the ened theta band power and was associ- “evidence” for our choices and in doing ated with specific, focal increases in beta so strive to be like wise Christopher power.8 These results, although prelimi- Robin rather than Winnie-the-Pooh. nary, suggest not only that medication results in changes in cortical activity that References 1. Milne AA. Winnie-the-Pooh. London, United correlate with symptomatic improve- Kingdom: Methuen & Co. Ltd.; 1926. ment, but that combination
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