Hostname: page-component-77c89778f8-9q27g Total loading time: 0 Render date: 2024-07-24T02:43:57.696Z Has data issue: false hasContentIssue false
  • English
  • Français

Non-Stimulant Treatment of Attention-Deficit/Hyperactivity Disorder

Published online by Cambridge University Press:  07 November 2014

Steven R. Pliszka
Get access Rights & Permissions [Opens in a new window]

Abstract

Stimulants are a highly efficacious and safe treatment for attention-deficit/hyperactivity disorder (ADHD), with 75% to 90% of patients responding well if two different stimulants (amphetamine and methylphenidate) are used. Nonetheless, a subset of ADHD patients will either fail to respond to stimulants or have side effects that preclude their use (tics, severe loss of appetite, marked insomnia). For such patients, there are a number of non-stimulant agents that serve as second-line treatments. Tricyclic antidepressants (TCAs) are the most studied of these drugs. They are superior to placebo in the treatment of ADHD and may reduce abnormal movements in patients with ADHD/tic disorder. TCAs often produce side effects of sedation, dry mouth, and constipation. Bupropion is superior to placebo in the treatment of ADHD and has a more favorable side-effect profile than the TCAs. A new selective norepinephrine reuptake inhibitor, atomoxetine, has been shown to be efficacious in the treatment of ADHD and has recently received an approvable letter from the Food and Drug Administration. The α-agonists clonidine and guanfacine have also been used as alternative agents in ADHD, though the controlled data are more limited. A recent controlled clinical trial suggests a combination of methylphenidate and clonidine has advantages in the treatment of comorbid ADHD and tics over either medication alone. Clinical guidelines for each of these agents, as well as their use in combination with stimulants in comorbid conditions, will be discussed.

Type
Review
Information
CNS Spectrums , Volume 8 , Issue 4: Pediatric Psychopharmacology , April 2003 , pp. 253 - 258
Copyright
Copyright © Cambridge University Press 2003

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Bradley, C. The behavior of children receiving benzedrine. Am J Psychiatry. 1937;94:577–585.CrossRefGoogle Scholar
2.Barkley, RA. A review of stimulant drug research with hyperactive children. J Child Psychol Psychiatry. 1977;18:137–165.CrossRefGoogle ScholarPubMed
3.Swanson, JM, McBurnett, K, Christian, DL, Wigal, T. Stimulant medications and the treatment of children with ADHD. Adv Clin Child Psychol. 1995;17:232–265.Google Scholar
4.Elia, J, Borcherding, BG, Rapoport, JL, Keysor, CS. Methylphenidate and dextroamphetamine treatments of hyperactivity: are there true nonresponders? Psychiatry Res. 1991;36:141–155.CrossRefGoogle ScholarPubMed
5.Arnold, LE. Methylphenidate vs. amphetamine: a comparative review. J Attention Disord. 2000;3:200–211.CrossRefGoogle Scholar
6.Law, SF, Schachar, RJ. Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder? J Am Acad Child Adolesc Psychiatry. 1999;38:944–951.CrossRefGoogle ScholarPubMed
7.Gadow, KD, Sverd, J, Sprafkin, J, Nolan, EE, Ezor, SN. Efficacy of methylphenidate for attention-deficit hyperactivity disorder in children with tic disorder. Arch Gen Psychiatry. 1995;52:444–455.CrossRefGoogle ScholarPubMed
8.Spencer, TJ, Biederman, J, Faraone, S, et al.Impact of tic disorders on ADHD outcome across the life cycle: findings from a large group of adults with and without ADHD. Am J Psychiatry. 2001;158:611–617.CrossRefGoogle ScholarPubMed
9.Pliszka, SR, Carlson, CL, Swanson, JM. ADHD With Comorbid Disorders: Clinical Assessment and Management. New York, NY: Guilford Press; 1999.Google Scholar
10.Biederman, J. Resolved: mania is mistaken for ADHD in prepubertal children, affirmative. J Am Acad Child Adolesc Psychiatry. 1998;37:1091–1096.CrossRefGoogle Scholar
11.Klein, RG, Pine, DS, Klein, DF. Resolved: mania is mistaken for ADHD in prepubertal children, negative [discussion]. J Am Acad Child Adolesc Psychiatry. 1998;37:1096–1099.Google Scholar
12.Pliszka, SR. Antidepressants in the treatment of child and adolescent psychopathology. J Clin Child Psychol. 1991;20:313–320.CrossRefGoogle Scholar
13.Pliszka, SR. Tricyclic antidepressants in the treatment of children with attention deficit disorder. J Am Acad Child Adolesc Psychiatry. 1987;26:127–132.CrossRefGoogle ScholarPubMed
14.Biederman, J, Baldessarini, RJ, Wright, V, Knee, D, Harmatz, JS. A double-blind placebo controlled study of desipramine in the treatment of ADD: I. Efficacy. J Am Acad Child Adolesc Psychiatry. 1989;28:777–784.CrossRefGoogle ScholarPubMed
15.Riddle, MA, Nelson, JC, Kleinman, CS, et al.Sudden death in children receiving Norpramin: a review of three reported cases and commentary. J Am Acad Child Adolesc Psychiatry. 1991;30:104–108.CrossRefGoogle ScholarPubMed
16.Daly, JM, Wilens, T. The use of tricyclic antidepressants in children and adolescents. Pediatr Clin North Am. 1998;45:1123–1135.CrossRefGoogle ScholarPubMed
17.Prince, JB, Wilens, TE, Biederman, J, et al.A controlled study of nortriptyline in children and adolescents with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol. 2000;10:193–204.CrossRefGoogle ScholarPubMed
18.Singer, HS, Brown, J, Quaskey, S, Rosenberg, LA, Mellits, ED, Denckla, MB. The treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: a double-blind placebo-controlled study with clonidine and desipramine. Pediatrics. 1995;95:74–81.CrossRefGoogle ScholarPubMed
19.Spencer, T, Biederman, J, Coffey, B, et al.A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2002;59:649–656.CrossRefGoogle ScholarPubMed
20.Spencer, T, Biederman, J, Wilens, T, et al.Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 1998;155:693–695.CrossRefGoogle ScholarPubMed
21.Michelson, D, Faries, D, Wernicke, J, et al.Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics. 2001;108:E83.CrossRefGoogle ScholarPubMed
22.Heiligenstein, JH, Spencer, TJ, Faries, DE, Biederman, J, Kratochvil, C, Conners, CK. Tomoxetine, methylphenidate, placebo: comparison of treatment effects in children with ADHD. Paper presented at: Annual Meeting of the American Academy of Child and Adolescent Psychiatry; October 24-29, 2000; New York, NY.Google Scholar
23.Kratochvil, CJ, Heiligenstein, JH, Dittmann, R, et al.Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry. 2002;41:776–784.CrossRefGoogle ScholarPubMed
24.Conners, CK, Casat, CD, Gualtieri, CT, et al.Bupropion hydrochloride in attention deficit disorder with hyperactivity. J Am Acad Child Adolesc Psychiatry. 1996;35:1314–1321.CrossRefGoogle ScholarPubMed
25.Wilens, TE, Spencer, TJ, Biederman, J, et al.A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry. 2001;158:282–288.CrossRefGoogle ScholarPubMed
26.Wilens, TE, Prince, J, Spencer, TJ, et al. Bupropion SR for attention deficit hyperactivity disorder (ADHD) in adults with bipolar disorder (BPD) and ADHD. Paper presented at: Annual Meeting of the American Academy of Child and Adolescent Psychiatry; October 24-29, 2000; New York, NY.Google Scholar
27.Swanson, JM, Flockhart, D, Udrea, D, Cantwell, D, Connor, D, Williams, L. Clonidine in the treatment of ADHD: questions about safety and efficacy. J Child Adolesc Psychopharmacol. 1995;5:301–304.CrossRefGoogle Scholar
28.Pliszka, SR. Comparing the effects of stimulant and non-stimulant agents on catecholamine function: implications for theories of ADHD. In: Solanto, MV, Arnsten, AFT, Castellanos, FX, eds. Stimulant Drugs and ADHD: Basic and Clinical Neuroscience. New York, NY: Oxford University Press; 2001:332–352.Google Scholar
29.Connor, DF, Barkley, RA, Davis, HT. A pilot study of methylphenidate, clonidine, or the combination in ADHD comorbid with aggressive oppositional defiant disorder or conduct disorder. Clin Pediatr (Phila). 2000;39:15–25.CrossRefGoogle ScholarPubMed
30.Tourette's Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology. 2002;58:527–536.CrossRefGoogle Scholar
31.Arnsten, AF, Steere, JC, Hunt, RD. The contribution of α2-noradrenergic mechanisms of prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1996;53:448–455.CrossRefGoogle Scholar
32.Hunt, RD, Arnsten, AF, Asbell, MD. An open trial of guanfacine in the treatment of attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1995;34:50–54.CrossRefGoogle ScholarPubMed
33.Chappell, PB, Riddle, MA, Scahill, L, et al.Guanfacine treatment of comorbid attention-deficit hyperactivity disorder and Tourette's syndrome: preliminary clinical experience. J Am Acad Child Adolesc Psychiatry. 1995;34:1140–1146.CrossRefGoogle ScholarPubMed
34.Scahill, L, Chappell, PB, Kim, YS, et al.A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry. 2001;158:1067–1074.CrossRefGoogle ScholarPubMed
35.Ferraro, L, Tanganelli, S, O'Connor, WT, Antonelli, T, Rambert, F, Fuxe, K. The vigilance promoting drug modafinil increases dopamine release in the rat nucleus accumbens via the involvement of a local GABAergic mechanism. Eur J Pharmacol. 1996;306:33–39.CrossRefGoogle ScholarPubMed
36.Engber, TM, Dennis, SA, Jones, BE, Miller, MS, Contreras, PC. Brain regional substrates for the actions of the novel wake-promoting agent modafinil in the rat: comparison with amphetamine. Neuroscience. 1998;87:905–911.CrossRefGoogle ScholarPubMed
37.Rugino, TA, Copley, TC. Effects of modafinil in children with attention-deficit/hyperactivity disorder: an open-label study. J Am Acad Child Adolesc Psychiatry. 2001;40:230–235.CrossRefGoogle ScholarPubMed
38.Taylor, FB, Russo, J. Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults. J Child Adolesc Psychopharmacol. 2000;10:311–320.CrossRefGoogle ScholarPubMed
39. Cephalon reports no benefit from Provigil in study of adults with ADHD: plans for label expansion into other indications on track [press release]. West Chester, PA: Cephalon, Inc.; July 30, 2000.Google Scholar
40.Pliszka, SR, Greenhill, LL, Crismon, ML, et al.The Texas Children's Medication Algorithm Project: Report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. Part II: Tactics. Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2000;39:920–927.CrossRefGoogle ScholarPubMed
41.Pliszka, SR, Greenhill, LL, Crismon, ML, et al.The Texas Children's Medication Algorithm Project: Report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. Part I. Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2000;39:908–919.CrossRefGoogle ScholarPubMed