Objective: This study examines changes in severity of tics and ADHD during atomoxetine treatment in ADHD patients with Tourette syndrome (TS). Method: Subjects (7-17 years old) with ADHD (Diagnostic and Statistical Manual of Mental Disorders, DSM-IV) and TS were randomly assigned to double-blind treatment with placebo (n = 56) or atomoxetine (0.5-1.5 mg/kg/day, n = 61) for approximately 18 weeks. Results: Atomoxetine subjects showed significantly greater improvement on ADHD symptom measures. Treatment was also associated with significantly greater reduction of tic severity on two of three measures. Significant increases were seen in mean pulse rate and rates of treatment-emergent nausea, decreased appetite, and decreased body weight. No other clinically relevant treatment differences were observed in any other vital sign, adverse event, laboratory parameter, or electrocardiographic measure. Conclusion: Atomoxetine is efficacious for treatment of ADHD and its use appears well tolerated in ADHD patients with comorbid TS. (J. of Att. Dis. 2008; 11(4) 470-481)
Allen, A.J., Kurlan, R.M., Gilbert, D.L., Linder, S.L., Lewis, D.W., Winner, P.K., et al. (2005). Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders. Neurology, 65, 1941-1949.
2.
Bymaster, F.P., Katner, J., Nelson, D.L., Hemrick-Luecke, S.K., Threlkeld, P.G., Heiligenstein, J.H., et al. (2002). Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: A potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology,27, 699-711.
3.
Castellanos, F.X., Giedd, J.N., Elia, J., Marsh, W.L., Ritchie, G.F., Hamburger, S.D., et al. (1997). Controlled stimulant treatment of ADHD and comorbid Tourette's syndrome: Effects of stimulant and dose. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 589-596.
4.
Chappell, P.B., Riddle, M.A., Scahill, L., Lynch, K.A., Schultz, R., Arnsten, A., et al. (1995). Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: Preliminary clinical experience . Journal of the American Academy of Child and Adolescent Psychiatry, 34, 1140-1146.
5.
Cohen, D.J., Leckman, J.F., & Shaywitz, B.A. (1983). The Tourette's syndrome and other tics. In D. Shaffer, A. A. Erhardt, & L. Greenhill (Eds.), Diagnosis and treatment in pediatric psychiatry (pp. 3-28). New York: MacMillan Free Press.
6.
Comings, D.E. (2001). Clinical and molecular genetics of ADHD and Tourette syndrome. Two related polygenic disorders. Annals of the New York Academy of Sciences, 931, 50-83.
7.
Comings, D.E., & Comings, B.G. (1984). Tourette's syndrome and attention deficit disorder with hyperactivity: Are they genetically related?Journal of the American Academy of Child and Adolescent Psychiatry, 23, 138-146.
8.
Cummings, D.D., Singer, H.S., Krieger, M., Miller, T.L., & Mahone, E.M. (2002). Neuropsychiatric effects of guanfacine in children with mild Tourette syndrome: A pilot study. ClinicalNeuropharmacology , 25, 325-332.
9.
DuPaul, G.J., Power, T.J., Anastopoulos, A.D., & Reid, R. (1998). ADHD Rating Scale-IV: Checklists, norms, and clinical interpretations. New York: Guilford .
10.
Gadow, K.D., Sverd, J., Sprafkin, J., Nolan, E.E., & Grossman, S. (1999). Long-term methylphenidate therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder. Archives of General Psychiatry,56, 330-336.
11.
Gaffney, G.R., Perry, P.J., Lund, B.C., Bever-Stille, K.A., Arndt, S., & Kuperman, S. (2006). Risperidone versus clonidine in the treatment of children and adolescents with Tourette's syndrome. Journal of the American Academy of Child and Adolescent Psychiatry, 41, 330-336.
12.
Gilbert, D.L., Batterson, J.R., Sethuraman, G., & Sallee, F.R. (2004). Tic reduction with risperidone versus pimozide in a randomized, double-blind, crossover trial. Journal of the American Academy of Child and Adolescent Psychiatry, 43, 206-214.
13.
Golden, G.S. (1977). The effect of central nervous system stimulants on Tourette syndrome. Annals of Neurology, 2, 69-70.
14.
Guy, W. (1976). ECDEU assessment manual for psychopharmacology (Revised Publication No. ADM 76-338). Bethesda, MD: United States Department of Health, Education, and Welfare.
15.
Heil, S.H., Holmes, H.W., Bickel, W.K., Higgins, S.T., Badger, G.J., Laws, H.F., et al. (2002). Comparison of the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate in light drug users . Drug and Alcohol Dependence,67, 149-156.
16.
Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C., Moreci, P., et al. (1997). Schedule for affective disorders and schizophrenia for school-age children—present and lifetime version (K-SADS-PL): Initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 980-988.
17.
Kelsey, D.K., Sumner, C.R., Casat, C.D., Coury, D.L., Quintana, H., Saylor, K.E., et al. (2004). Once-daily atomoxetine treatment for children with attention-deficit/hyperactivity disorder, including an assessment of evening and morning behavior: A double-blind, placebo-controlled trial. Pediatrics, 114, e1-e8.
18.
Kratochvil, C.J., Heiligenstein, J.H., Dittmann, R., Spencer, T., Biederman, J., Wernicke, J.F., et al. (2002). Atomoxetine and methylphenidate treatment in children with ADHD: A prospective, randomized, open-label trial. Journal of the American Academy of Child and Adolescent Psychiatry, 41, 776-784.
19.
Law, S.F., & Schachar, R.J. (1999). Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder?Journal of the American Academy of Child and Adolescent Psychiatry, 38, 944-951.
20.
Leckman, J.F., Hardin, M.T., Riddle, M.A., Stevenson, J., Ort, S.I., & Cohen, D.J. (1991). Clonidine treatment of Gilles de la Tourette's syndrome. Archives of General Psychiatry,48, 324-328.
21.
Leckman, J.F., Riddle, M.A., Hardin, M.T., Ort, S.I., Swartz, K.L., Stevenson, J., et al. (1989). The Yale Global Tic Severity Scale: Initial testing of a clinician-rated scale of tic severity. Journal of the American Academy of Child and Adolescent Psychiatry, 28, 566-573.
22.
Ledbetter, M. (2005). Atomoxetine use associated with onset of a motor tic. Journal of Child and Adolescent Psychiatric Nursing, 15, 331-333.
23.
Lee, T.S.W., Lee, T.D., Lombroso, P.J., & King, R.A. (2004). Atomoxetine and tics in ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 43, 1068-1069.
24.
Lowe, T.L., Cohen, D.J., Detlor, J., Kremenitzer, M.W., & Shaywitz, B.A. (1982). Stimulant medications precipitate Tourette's syndrome. Journal of theAmerican Medical Association , 247, 1168-1169.
25.
Messiha, F.S., & Knopp, W. (1976). A study of endogenous dopamine metabolism in Gilles de la Tourette's disease. Diseases of the Nervous System, 37, 470-473.
26.
Meyerhoff, J.L., & Snyder, S.H. (1973). Gilles de la Tourette's disease and minimal brain dysfunction: Amphetamine isomers reveal catecholamine correlates in an affected patient. Psychopharmacologia, 29, 211-220.
27.
Michelson, D., Allen, A.J., Busner, J., Casat, C., Dunn, D., Kratochvil, C., et al. (2002). Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: A randomized, placebo-controlled study. American Journal of Psychiatry,159, 1896-1901.
28.
Michelson, D., Faries, D., Wernicke, J., Kelsey, D., Kendrick, K., Sallee, F.R., et al. (2001). Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: A randomized, placebo-controlled, dose-response study. Pediatrics, 108, e83.
29.
Physician's Desk Reference. (2005). Physician's desk reference. Montvale, NJ: Thomson Healthcare.
30.
Pollack, M.A., Cohen, N.L., & Friedhoff, A.J. (1977). Gilles de la Tourette's syndrome. Familial occurrence and precipitation by methylphenidate therapy. Archives ofNeurology, 34, 630-632.
31.
Poznanski, E.O., & Mokros, H.B. (1999). Children's Depression Rating Scale, Revised (CDRS-R) (2nd ed.). Los Angeles: Western Psychological Services.
32.
Riddle, M.A., Lynch, K.A., Scahill, L., deVries, A., Cohen, D.J., & Leckman, J.F. (1995). Methylphenidate discontinuation and reinitiation during long-term treatment of children with Tourette's disorder and attention-deficit hyperactivity disorder: A pilot study. Journal of Child and Adolescent Psychopharmacology, 5, 205-214.
33.
Sandyk, R., & Bamford, C.R. (1988). Beneficial effects of imipramine on Tourette's syndrome. International Journal of Neuroscience, 39, 27-29.
34.
Scahill, L., Chappell, P.B., Kim, Y.S., Schultz, R.T., Katsovich, L., Shepherd, E., et al. (2001). A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. American Journal of Psychiatry,158, 1067-1074.
35.
Scahill, L., Leckman, J.F., Schultz, R.T., Katsovich, L., & Peterson, B.S. (2003). A placebo-controlled trial of risperidone in Tourette syndrome. Neurology, 60, 1130-1135.
36.
Scahill, L., Riddle, M.A., McSwiggin-Hardin, M., Ort, S.I., King, R.A., Goodman, W.K., et al. (1997). Children's Yale-Brown Obsessive Compulsive Scale: Reliability and validity. Journal of the American Academy of Child and Adolescent Psychiatry,36, 844-852.
37.
Spencer, T., Biederman, J., Coffey, B., Geller, D., Crawford, M., Bearman, S.K., et al. (2002a). A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder. Archives of General Psychiatry,59, 649-656.
38.
Spencer, T., Biederman, J., Kerman, K., Steingard, R., & Wilens, T. (1993a). Desipramine treatment of children with attention-deficit hyperactivity disorder and tic disorder or Tourette's syndrome. Journal of the American Academy of Child and Adolescent Psychiatry, 32, 354-360.
39.
Spencer, T., Biederman, J., Wilens, T., Steingard, R., & Geist, D. (1993b). Nortriptyline treatment of children with attention-deficit hyperactivity disorder and tic disorder or Tourette's syndrome. Journal of the American Academy of Child and Adolescent Psychiatry, 32, 205-210.
40.
Spencer, T., Heiligenstein, J.H., Biederman, J., Faries, D.E., Kratochvil, C.J., Conners, C.K., et al. (2002b). Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder. Journal ofClinical Psychiatry, 63, 1140-1147.
41.
Starke, K., Endo, T., & Taube, H.D. (1975). Relative pre- and post-synaptic potencies of alpha-adrenoceptor agonists in the rabbit pulmonary artery. Naunyn Schmiedeberg'sArchives of Pharmacology, 291, 55-78.
42.
Sverd, J. (2000). Methylphenidate treatment for children with attention deficit hyperactivity disorder and tics: Inadvisable or indispensable. In L. L. Greenhill & B. B. Osman, (Eds.), Ritalin: Theory and practice, (2nd ed., pp. 301-320). Larchmont, NY: Mary Ann Liebert.
43.
Tourette's Syndrome Study Group. (2002). Treatment of ADHD in children with tics: A randomized controlled trial. Neurology, 58, 527-536.
