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Pharmacologic Treatment of Attention-Deficit/Hyperactivity Disorder: Efficacy, Safety and Mechanisms of Action

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Abstract

Studies examining the efficacy, safety and mechanisms of action of agents for the treatment of attention-deficit/hyperactivity disorder (ADHD) are reviewed, with an emphasis on newer agents such as the long acting stimulants and atomoxetine. Recent studies of medications are characterized by large, rigorously diagnosed samples of children, adolescents and adults with ADHD, use of standardized rating scales and extensive safety data. These studies confirm a robust treatment effect for the Food and Drug Administration approved agents ranging from 0.7 to 1.5. The most common short term side effects to the most commonly used agents include insomnia, loss of appetite, and headaches. Despite public controversy and labeling changes to warn of extremely rare cardiovascular and psychiatric side effects, the evidence does not support the hypothesis that medication for ADHD increases risk for sudden death, mania or psychosis. A wide variety of neuroimaging techniques including electrocephalogram (EEG) power, event related potentials (ERP), functional magnetic resonance imaging (fMRI), and positron emission tomography (PET) are beginning to examine the mechanisms of action of medications for ADHD, and implicating the catecholamines and prefrontal and anterior cingulate cortices as prime sites of actions for these agents.

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References

  • Abikoff, H., McGough, J., Vitiello, B., McCracken, J., Davies, M., Walkup, J., et al. (2005). Sequential pharmacotherapy for children with comorbid attention-deficit/hyperactivity and anxiety disorders. Journal of the American Academy of Child and Adolescent Psychiatry, 44, 418–427.

    Article  PubMed  Google Scholar 

  • Allen, A. J., Kurlan, R. M., Gilbert, D. L., Coffey, B. J., Linder, S. L., Lewis, D. W., et al. (2005). Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders. Neurology, 65, 1941–1949.

    Article  PubMed  CAS  Google Scholar 

  • Aman, M. G., Binder, C., & Turgay, A. (2004). Risperidone effects in the presence/absence of psychostimulant medicine in children with ADHD, other disruptive behavior disorders, and subaverage IQ. Journal of Child and Adolescent Psychopharmacology, 14, 243–254.

    Article  PubMed  Google Scholar 

  • Barkley, R. A. (1997). ADHD and the nature of self control. New York: Guildford Press.

    Google Scholar 

  • Barkley, R. A. (2006). Comorbid disorders, social and family adjustment, and subtyping. In R. A. Barkley (Ed.), Attention Deficit Hyperactivity Disorder (pp. 184–218). New York: Guilford Press.

    Google Scholar 

  • Barry, R. J., Clarke, A. R., & Johnstone, S. J. (2003). A review of electrophysiology in attention-deficit/hyperactivity disorder: I. Qualitative and quantitative electroencephalography. Clinical Neurophysiology, 114, 171–183.

    Article  PubMed  Google Scholar 

  • Barry, R. J., Johnstone, S. J., & Clarke, A. R. (2003). A review of electrophysiology in attention-deficit/hyperactivity disorder: II. Event-related potentials. Clinical Neurophysiology, 114, 184–198.

    Article  PubMed  Google Scholar 

  • Biederman, J., Lopez, F. A., Boellner, S. W., & Chandler, M. C. (2002). A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder. Pediatrics, 110, 258–266.

    Article  PubMed  Google Scholar 

  • Biederman, J., Mick, E., Surman, C., Doyle, R., Hammerness, P., Harpold, T., et al. (2006). A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder. Biological Psychiatry, 59, 829–835.

    Article  PubMed  CAS  Google Scholar 

  • Biederman, J., Spencer, T. J., Wilens, T. E., Weisler, R. H., Read, S. C., & Tulloch, S. J. (2005). Long-term safety and effectiveness of mixed amphetamine salts extended release in adults with ADHD. CNS Spectrum, 10, 16–25.

    Google Scholar 

  • Biederman, J., Wigal, S. B., Spencer, T. J., McGough, J. J., & Mays, D. A. (2006). A post hoc subgroup analysis of an 18-day randomized controlled trial comparing the tolerability and efficacy of mixed amphetamine salts extended release and atomoxetine in school-age girls with attention-deficit/hyperactivity disorder. Clinical Therapeutics, 28, 280–293.

    Article  PubMed  CAS  Google Scholar 

  • Bradley, C. (1937). The behavior of children receiving benzedrine. American Journal of Psychiatry, 94, 577–585.

    Google Scholar 

  • Broyd, S. J., Johnstone, S. J., Barry, R. J., Clarke, A. R., McCarthy, R., Selikowitz, M., et al. (2005). The effect of methylphenidate on response inhibition and the event-related potential of children with attention deficit/hyperactivity disorder. International Journal of Psychophysiology, 58, 47–58.

    Article  PubMed  Google Scholar 

  • Bush, G. (2005). Funcitional MRI: Recent advances in studying ADHD pathophysiology and treatment. Presented at the 52nd Annual Meeting of the American Academy of Child and Adolescent Psychiatry. Toronto, CA (Oct. 18–23).

  • Bush, G., Frazier, J. A., Rauch, S. L., Seidman, L. J., Whalen, P. J., Jenike, M. A., et al. (1999). Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop. Biological Psychiatry, 45, 1542–1552.

    Article  PubMed  CAS  Google Scholar 

  • Bush, G., Valera, E. M., & Seidman, L. J. (2005). Functional neuroimaging of attention-deficit/hyperactivity disorder: A review and suggested future directions. Biological Psychiatry, 57, 1273–1284.

    Article  PubMed  Google Scholar 

  • Castellanos, F. X. (2002). Proceed, with caution: SPECT cerebral blood flow studies of children and adolescents with attention deficit hyperactivity disorder. Journal of Nuclear Medicine, 43, 1630–1633.

    PubMed  Google Scholar 

  • Charach, A., Figueroa, M., Chen, S., Ickowicz, A., & Schachar, R. (2006). Stimulant treatment over 5 years: Effects on growth. Journal of the American Academy of Child and Adolescent Psychiatry, 45, 415–421.

    Article  PubMed  Google Scholar 

  • Clarke, A. R., Barry, R. J., Bond, D., McCarthy, R., & Selikowitz, M. (2002). Effects of stimulant medications on the EEG of children with attention-deficit/hyperactivity disorder. Psychopharmacology (Berl.), 164, 277–284.

    Article  CAS  Google Scholar 

  • Clarke, A. R., Barry, R. J., McCarthy, R., & Selikowitz, M. (2001). Electroencephalogram differences in two subtypes of attention-deficit/hyperactivity disorder. Psychophysiology, 38, 212–221.

    Article  PubMed  CAS  Google Scholar 

  • Clarke, A. R., Barry, R. J., McCarthy, R., & Selikowitz, M. (2002). EEG differences between good and poor responders to methylphenidate and dexamphetamine in children with attention-deficit/hyperactivity disorder. Clinical Neurophysiology, 113, 194–205.

    Article  PubMed  CAS  Google Scholar 

  • Conners, C. K., Casat, C. D., Gualtieri, C. T., Weller, E., Reader, M., Reiss, A., et al. (1996). Bupropion hydrochloride in attention deficit disorder with hyperactivity. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 1314–1321.

    Article  PubMed  CAS  Google Scholar 

  • Connor, D. F., Fletcher, K. E., & Swanson, J. M. (1999). A meta-analysis of clonidine for symptoms of attention-deficit hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 38, 1551–1559.

    Article  PubMed  CAS  Google Scholar 

  • Connor, D. F., Glatt, S. J., Lopez, I. D., Jackson, D., & Melloni, R. H., Jr. (2002). Psychopharmacology and aggression. I: A meta-analysis of stimulant effects on overt/covert aggression-related behaviors in ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 41, 253–261.

    Article  PubMed  Google Scholar 

  • Correll, C. U. & Carlson, H. E. (2006). Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents. Journal of the American Academy of Child and Adolescent Psychiatry, 45, 771–791.

    PubMed  Google Scholar 

  • Daly, J. M., & Wilens, T. (1998). The use of tricyclics antidepressants in children and adolescents. Pediatric Clinics of North America, 45, 1123–1135.

    Article  PubMed  CAS  Google Scholar 

  • Faraone, S. V., Biederman, J., Morley, C. P., & Spencer, T. J. (2006). The effect of stimulants on height and weight: a review of the literature (manuscript in preparation).

  • Feron, F. J., Hendriksen, J. G., van Kroonenburgh, M. J., Blom-Coenjaerts, C., Kessels, A. G., Jolles, J., et al. (2005). Dopamine transporter in attention-deficit hyperactivity disorder normalizes after cessation of methylphenidate. Pediatric Neurology, 33, 179–183.

    Article  PubMed  Google Scholar 

  • Findling, R. L., & Lopez, F. A. (2005). Efficacy of transdermal methylphenidate with reference to Concerta in ADHD. Presented at the 25th Annual Meeting of the American Academy of Child and Adolescent Psychiatry, Toronto, CA, (Oct 18–23).

  • Findling, R. L., Biederman, J., Wilens, T. E., Spencer, T. J., McGough, J. J., Lopez, F. A., et al. (2005). Short- and long-term cardiovascular effects of mixed amphetamine salts extended release in children. The Journal of Pediatrics, 147, 348–354.

    Article  PubMed  CAS  Google Scholar 

  • Food and Drug Administration (2005). FDA Alert [09/05]: Suicidal thinking in children and adolescents. Available at. Food and Drug Administration Website [On-line]. Available: http://www.fda.gov/cder/drug/infopage/atomoxetine/default.htm

  • 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 [see comments]. Archives of General Psychiatry, 56, 330–336.

    Article  PubMed  CAS  Google Scholar 

  • Gelperin, K. (2006). Psychiatric adverse events associated with drug treatment of ADHD: Review of post marketing safety data. Available at. Food and Drug Administration Website [On-line]. Available: http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210B-Index.htm

  • Greenhill, L. L., Biederman, J., Boellner, S. W., Rugino, T. A., Sangal, R. B., Earl, C. Q., et al. (2006a). A randomized, double-blind, placebo-controlled study of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 45, 503–511.

    Article  PubMed  Google Scholar 

  • Greenhill, L. L., Findling, R. L., & Swanson, J. M. (2002). A double-blind, placebo-controlled study of modified-release methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics, 109, E39.

    Article  PubMed  Google Scholar 

  • Greenhill, L. L., Muniz, R., Ball, R. R., Levine, A., Pestreich, L., & Jiang, H. (2006b). Efficacy and safety of dexmethylphenidate extended-release capsules in children with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 45, 817–823.

    Article  PubMed  Google Scholar 

  • Hammad, T. A., Laughren, T., & Racoosin, J. (2006). Suicidality in pediatric patients treated with antidepressant drugs. Archives of General Psychiatry, 63, 332–339.

    Article  PubMed  CAS  Google Scholar 

  • Jensen, P. S., Youngstrom, Y., Steiner, H., Findling, R. L., Meyer, R. E., Malone, R., et al. (in press) Consensus report: Impulsive aggression as a symptom across diagnostic categories in child psychiatry. Journal of the American Academy of Child and Adolescent Psychiatry.

  • Jonkman, L. M., Kemner, C., Verbaten, M. N., van Engeland, H., Camfferman, G., Buitelaar, J. K., et al. (2000). Attentional capacity, a probe ERP study: Differences between children with attention-deficit hyperactivity disorder and normal control children and effects of methylphenidate. Psychophysiology, 37, 334–346.

    Article  PubMed  CAS  Google Scholar 

  • Jucaite, A., Fernell, E., Halldin, C., Forssberg, H., & Farde, L. (2005). Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: Association between striatal dopamine markers and motor hyperactivity. Biological Psychiatry, 57, 229–238.

    Article  PubMed  CAS  Google Scholar 

  • Kim, B. N., Lee, J. S., Cho, S. C., & Lee, D. S. (2001). Methylphenidate increased regional cerebral blood flow in subjects with attention deficit/hyperactivity disorder. Yonsei Medical Journal, 42, 19–29.

    PubMed  CAS  Google Scholar 

  • Klein, R. G., Abikoff, H., Klass, E., Ganeles, D., Seese, L. M., & Pollack, S. (1997). Clinical efficacy of methylphenidate in conduct disorder with and without attention deficit hyperactivity disorder. Archives of General Psychiatry, 54, 1073–1080.

    PubMed  CAS  Google Scholar 

  • Klorman, R. (1991). Cognitive event-related potentials in attention deficit disorder. Journal of Learning Disabilities, 24, 130–140.

    Article  PubMed  CAS  Google Scholar 

  • Kok, A. (1986). Effects of degradation of visual stimuli on components of the event-related potential (ERP) in go/nogo reaction tasks. Biological Psychology, 23, 21–38.

    Article  PubMed  CAS  Google Scholar 

  • Kok, A. (1997). Event-related-potential (ERP) reflections of mental resources: A review and synthesis. Biological Psychology, 45, 19–56.

    Article  PubMed  CAS  Google Scholar 

  • Krause, K. H., Dresel, S. H., Krause, J., la Fougere, C., & Ackenheil, M. (2003). The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder. Neuroscience and Biobehavioral Reviews, 27, 605–613.

    Article  PubMed  CAS  Google Scholar 

  • Langleben, D. D., Acton, P. D., Austin, G., Elman, I., Krikorian, G., Monterosso, J. R., et al. (2002). Effects of methylphenidate discontinuation on cerebral blood flow in prepubescent boys with attention deficit hyperactivity disorder. Journal of Nuclear Medicine, 43, 1624–1629.

    PubMed  CAS  Google Scholar 

  • Loo, S. K. & Barkley, R. A. (2005). Clinical utility of EEG in attention deficit hyperactivity disorder. Applied Neuropsychology, 12, 64–76.

    Article  PubMed  Google Scholar 

  • Loo, S. K., Hopfer, C., Teale, P. D., & Reite, M. L. (2004). EEG correlates of methylphenidate response in ADHD: Association with cognitive and behavioral measures. Journal of Clinical Neurophysiology, 21, 457–464.

    Article  PubMed  Google Scholar 

  • Loo, S. K., Specter, E., Smolen, A., Hopfer, C., Teale, P. D., & Reite, M. L. (2003). Functional effects of the DAT1 polymorphism on EEG measures in ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 42, 986–993.

    Article  PubMed  Google Scholar 

  • Matochik, J. A., Liebenauer, L. L., King, A. C., Szymanski, H. V., Cohen, R. M., & Zametkin, A. J. (1994). Cerebral glucose metabolism in adults with attention deficit hyperactivity disorder after chronic stimulant treatment. American Journal of Psychiatry, 151, 658–664.

    PubMed  CAS  Google Scholar 

  • Matochik, J. A., Nordahl, T. E., Gross, M., Semple, W. E., King, A. C., Cohen, R. M., et al. (1993). Effects of acute stimulant medication on cerebral metabolism in adults with hyperactivity. Neuropsychopharmacology, 8, 377–386.

    PubMed  CAS  Google Scholar 

  • McGough, J. J., Biederman, J., Wigal, S. B., Lopez, F. A., McCracken, J. T., Spencer, T., et al. (2005). Long-term tolerability and effectiveness of once-daily mixed amphetamine salts (Adderall XR) in children with ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 44, 530–538.

    Article  PubMed  Google Scholar 

  • Michelson, D., Adler, L., Spencer, T., Reimherr, F. W., West, S. A., Allen, A. J., et al. (2003). Atomoxetine in adults with ADHD: Two randomized, placebo-controlled studies. Biological Psychiatry, 53, 112–120.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • Michelson, D., Faries, D., Wernicke, J., Kelsey, D., Kendrick, K., Sallee, 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, 1–9.

    Article  Google Scholar 

  • MTA Cooperative Group (2004). National institute of mental health multimodal treatment study of ADHD follow-up: Changes in effectiveness and growth after the end of treatment. Pediatrics, 113, 762–769.

    Article  Google Scholar 

  • MTA Cooperative Group (2006). Effects of stimulant medication on growth rates across three years in the MTA follow up. (in submission).

  • Muller, U., Clark, L., Lam, M. L., Moore, R. M., Murphy, C. L., Richmond, N. K., et al. (2005). Lack of effects of guanfacine on executive and memory functions in healthy male volunteers. Psychopharmacology (Berl.), 182, 205–213.

    Article  CAS  Google Scholar 

  • Newcorn, J. H., Spencer, T. J., Biederman, J., Milton, D. R., & Michelson, D. (2005). Atomoxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 44, 240–248.

    Article  PubMed  Google Scholar 

  • Pappadopulos, E., Macintyre Ii, J. C., Crismon, M. L., Findling, R. L., Malone, R. P., Derivan, A., et al. (2003). Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY). Part II. Journal of the American Academy of Child and Adolescent Psychiatry, 42, 145–161.

    Article  PubMed  Google Scholar 

  • Pliszka, S. R., Browne, R., Olvera, R. L., & Wynne, S. K. (2000). A double-blind placebo controlled trial of Adderall and methylphendiate in the treatment of Attention deficit hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 39, 619–626.

    Article  PubMed  CAS  Google Scholar 

  • Pliszka, S. R., Crismon, M. L., Hughes, C. W., Corners, C. K., Emslie, G. J., Jensen, P. S., et al. (2006a). The Texas Children’s Medication Algorithm Project: Revision of the algorithm for pharmacotherapy of attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 45, 642–657.

    Article  PubMed  Google Scholar 

  • Pliszka, S. R., Glahn, D. C., Semrud-Clikeman, M., Franklin, C., Perez, R., Xiong, J., et al. (2006b). Neuroimaging of inhibitory control areas in children with attention defict hyperactivity disorder who were treatment naive or in long term treatment. American Journal of Psychiatry, 163, 1052–1060.

    Article  PubMed  Google Scholar 

  • Pliszka, S. R., Liotti, M., & Woldorff, M. G. (2000). Inhibitory control in children with attention deficit/hyperactivity disorder: Event related potentials identify the processing component and timing of an impaired right-frontal response-inhibition mechanism. Biological Psychiatry, 48, 238–246.

    Article  PubMed  CAS  Google Scholar 

  • Pliszka, S. R., Matthews, T. L., Braslow, K. J., & Watson, M. A. (2006c). Comparative effects of methylphenidate and mixed salts amphetamine on height and weight in children with attention-deficit/hyperactivity disorder (ADHD). Journal of the American Academy of Child and Adolescent Psychiatry, 45, 520–526.

    Article  PubMed  Google Scholar 

  • Poulton, A. (2005). Growth on stimulant medication; clarifying the confusion: A review. Archives of Diseases of Childhood, 90, 801–806.

    Article  CAS  Google Scholar 

  • Rosa-Neto, P., Lou, H. C., Cumming, P., Pryds, O., Karrebaek, H., Lunding, J., et al. (2005). Methylphenidate-evoked changes in striatal dopamine correlate with inattention and impulsivity in adolescents with attention deficit hyperactivity disorder. Neuroimage, 25, 868–876.

    Article  PubMed  Google Scholar 

  • Rubia, K., Smith, A. B., Brammer, M. J., Toone, B., & Taylor, E. (2005). Abnormal brain activation during inhibition and error detection in medication-naive adolescents with ADHD. American Journal of Psychiatry, 162, 1067–1075.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Schmajuk, M., Liotti, M., Busse, L., & Woldorff, M. G. (2006). Electrophysiological activity underlying inhibitory control processes in normal adults. Neuropsychologia., 44, 384–395.

    Article  PubMed  Google Scholar 

  • Schur, S. B., Sikich, L., Findling, R. L., Malone, R. P., Crismon, M. L., Derivan, A., et al. (2003). Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY). Part I: A review. Journal of the American Academy of Child and Adolescent Psychiatry, 42, 132–144.

    Article  PubMed  Google Scholar 

  • Schweitzer, J. B., Lee, D. O., Hanford, R. B., Tagamets, M. A., Hoffman, J. M., Grafton, S. T., et al. (2003). A positron emission tomography study of methylphenidate in adults with ADHD: Alterations in resting blood flow and predicting treatment response. Neuropsychopharmacology, 28, 967–973.

    PubMed  CAS  Google Scholar 

  • Seifert, J., Scheuerpflug, P., Zillessen, K. E., Fallgatter, A., & Warnke, A. (2003). Electrophysiological investigation of the effectiveness of methylphenidate in children with and without ADHD. Journal of Neural Transmission, 110, 821–829.

    PubMed  CAS  Google Scholar 

  • Shafritz, K. M., Marchione, K. E., Gore, J. C., Shaywitz, S. E., & Shaywitz, B. A. (2004). The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder. American Journal of Psychiatry, 161, 1990–1997.

    Article  PubMed  Google Scholar 

  • Snyder, R., Turgay, A., Aman, M., Binder, C., Fisman, S., & Carroll, A. (2002). Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs. Journal of the American Academy of Child and Adolescent Psychiatry, 41, 1026–1036.

    Article  PubMed  Google Scholar 

  • Spencer, T., Biederman, J., Wilens, T., Harding, M., O’Donnell, D., & Griffin, S. (1996). Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 409–432.

    Article  PubMed  CAS  Google Scholar 

  • Spencer, T. J., Biederman, J., Madras, B. K., Faraone, S. V., Dougherty, D. D., Bonab, A. A., et al. (2005). In vivo neuroreceptor imaging in attention-deficit/hyperactivity disorder: A focus on the dopamine transporter. Biological Psychiatry, 57, 1293–1300.

    Article  PubMed  CAS  Google Scholar 

  • Spencer, T. J., Faraone, S. V., Biederman, J., Lerner, M., Cooper, K. M., & Zimmerman, B. (2006a). Does prolonged therapy with a long-acting stimulant suppress growth in children with ADHD? Journal of the American Academy of Child and Adolescent Psychiatry, 45, 527–537.

    Article  PubMed  Google Scholar 

  • Spencer, T. J., Wilens, T. E., Biederman, J., Weisler, R. H., Read, S. C., & Pratt, R. (2006b). Efficacy and safety of mixed amphetamine salts extended release (Adderall XR) in the management of attention-deficit/hyperactivity disorder in adolescent patients: A 4-week, randomized, double-blind, placebo-controlled, parallel-group study. Clinical Therapeutics, 28, 266–279.

    Article  PubMed  CAS  Google Scholar 

  • Sumner, C. S., Donnelly, C., Lopez, F. A., Sutton, V., Bakken, R., Paczkowski, M., et al. (2005). Atomoxetine treatment for pediatric patients with ADHD and comorbid anxiety. Presented at the annual meeting of the American Psychiatric Association, Altanta, GA (May).

  • Swanson, J. M., Greenhill, L. L., Lopez, F. A., Sedillo, A., Earl, C. Q., Jiang, J. G., et al. (2006). Modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: Results of a randomized, double-blind, placebo-controlled, fixed-dose study followed by abrupt discontinuation. Journal of Clinical Psychiatry, 67, 137–147.

    Article  PubMed  CAS  Google Scholar 

  • Swanson, J. M., McBurnett, K., Wigal, T., Pfiffner, L. J., Lerner, M. A., Williams, L., et al. (1993). Effect of stimulant medication on children with attention deficit disorder: A “review of reviews.”Exceptional Children, 60, 154–162.

    Google Scholar 

  • Swensen, A., Michelsen, D., Buesching, D., & Faries, D. E. (2001). Effects of atomoxetine on social and family functioning of ADHD children and adolescents. Presented at the 48th Annual Meeting of the American Academy of Child and Adolescent Psychiatry, Honolulu,HI, (Oct 23–28).

  • Szobot, C. M., Ketzer, C., Cunha, R. D., Parente, M. A., Langleben, D. D., Acton, P. D., et al. (2003). The acute effect of methylphenidate on cerebral blood flow in boys with attention-deficit/hyperactivity disorder. European Journal of Nuclear Medicine and Molecular Imaging, 30, 423–426.

    Article  PubMed  CAS  Google Scholar 

  • Tourette’s Syndrome Study Group (2002). Treatment of ADHD in children with tics: A randomized controlled trial. Neurology, 58, 527–536.

    Google Scholar 

  • Vaidya, C. J., Austin, G., Kirkorian, G., Ridlehuber, H. W., Desmond, J. E., Glover, G. H., et al. (1998). Selective effects of methylphenidate in attention deficit hyperactivity disorder: A functional magnetic resonance study. Proceedings of the National Academy of Science, 95, 14494–14499.

    Article  CAS  Google Scholar 

  • Villalaba, L. (2006). Follow up review of AERS search identifying cases of sudden death occuring with drugs used for the treatment of attention deficit hyperactivity disorder (ADHD). Available at. Food and Drug Administration Website [On-line]. Available: http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4210B-Index.htm

  • Vles, J. S., Feron, F. J., Hendriksen, J. G., Jolles, J., van Kroonenburgh, M. J., & Weber, W. E. (2003). Methylphenidate down-regulates the dopamine receptor and transporter system in children with attention deficit hyperkinetic disorder (ADHD). Neuropediatrics., 34, 77–80.

    Article  PubMed  CAS  Google Scholar 

  • Volkow, N. D., Wang, G., Fowler, J. S., Logan, J., Gerasimov, M., Maynard, L., et al. (2001). Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. Journal of Neuroscience, 21, RC121.

    PubMed  CAS  Google Scholar 

  • Volkow, N. D., Wang, G. J., Fowler, J. S., & Ding, Y. S. (2005). Imaging the effects of methylphenidate on brain dopamine: New model on its therapeutic actions for attention-deficit/hyperactivity disorder. Biological Psychiatry, 57, 1410–1415.

    Article  PubMed  CAS  Google Scholar 

  • Volkow, N. D., Wang, G. J., Fowler, J. S., Gatley, S. J., Logan, J., Ding, Y. S., et al. (1998). Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. American Journal of Psychiatry, 155, 1325–1331.

    PubMed  CAS  Google Scholar 

  • Volkow, N. D., Wang, G. J., Fowler, J. S., Telang, F., Maynard, L., Logan, J., et al. (2004). Evidence that methylphenidate enhances the saliency of a mathematical task by increasing dopamine in the human brain. American Journal of Psychiatry, 161, 1173–1180.

    Article  PubMed  Google Scholar 

  • Weisler, R. H., Biederman, J., Spencer, T. J., Wilens, T. E., Faraone, S. V., Chrisman, A. K., et al. (2006). Mixed amphetamine salts extended-release in the treatment of adult ADHD: A randomized, controlled trial. CNS Spectrum, 11, 625–639.

    Google Scholar 

  • Weiss, M., Wasdell, M., & Patin, J. (2004). A post hoc analysis of d-threo-methylphenidate hydrochloride (focalin) versus d,l-threo-methylphenidate hydrochloride (ritalin). Journal of the American Academy of Child and Adolescent Psychiatry, 43, 1415–1421.

    Article  PubMed  Google Scholar 

  • Wigal, S. B., McGough, J. J., McCracken, J. T., Biederman, J., Spencer, T. J., Posner, K. L., et al. (2005). A laboratory school comparison of mixed amphetamine salts extended release (Adderall XR) and atomoxetine (Strattera) in school-aged children with attention deficit/hyperactivity disorder. Journal of Attention Disorders, 9, 275–289.

    Article  PubMed  Google Scholar 

  • Wilens, T., McBurnett, K., Stein, M., Lerner, M., Spencer, T., & Wolraich, M. (2005). ADHD treatment with once daily OROS methylphendiate treatment: Final results from a long term open-label study. Journal of the American Academy of Child and Adolescent Psychiatry, 44, 1015–1023.

    Article  PubMed  Google Scholar 

  • Wilens, T. E., McBurnett, K., Bukstein, O., McGough, J., Greenhill, L., Lerner, M., et al. (2006). Multisite controlled study of OROS methylphenidate in the treatment of adolescents with attention-deficit/hyperactivity disorder. Archives of Pediatrics and Adolescent Medicine, 160, 82–90.

    Article  PubMed  Google Scholar 

  • Wolraich, M. L., Greenhill, L. L., Pelham, W., Swanson, J., Wilens, T., Palumbo, D., et al. (2001). Randomized, controlled trial of oros methylphenidate once a day in children with attention-deficit/hyperactivity disorder. Pediatrics, 108, 883–892.

    Article  PubMed  CAS  Google Scholar 

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  1. Division of Child and Adolescent Psychiatry, Department of Psychiatry, 7703 Floyd Curl Drive MC 7792, San Antonio, TX, 78229-3900, USA

    Steven R. Pliszka

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Pliszka, S.R. Pharmacologic Treatment of Attention-Deficit/Hyperactivity Disorder: Efficacy, Safety and Mechanisms of Action. Neuropsychol Rev 17, 61–72 (2007). https://doi.org/10.1007/s11065-006-9017-3

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