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Short- and Long-Term Cardiovascular Effects of Mixed Amphetamine Salts Extended-Release in Adolescents With ADHD

Published online by Cambridge University Press:  07 November 2014

Timothy E. Wilens ,
Thomas J. Spencer  and
Joseph Biederman
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Abstract

Objective

Assess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13–17 years of age) with attention-deficit/hyperactivity disorder (ADHD).

Methods

Blood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR(10, 20, 30, or 40 mg) was administered to subjects ≤75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study.

Findings

Changes in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P≤.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=.0252) and pulse (4.4 bpm; P<.0001) were statistically, but not clinically, significant diastolic BP was not significantly changed (0.6 mm Hg) A decrease in QTcB interval (-4.6±19.9 msec) was statistically (P=.009), but not clinically, significant. There were no serious cardiovascular adverse events.

Conclusion

Cardiovascular effects of short- and long-term MAS XR treatment (≤60 mg/day) were minimal in otherwise healthy adolescents with ADHD.

Type
Academic Supplement
Information
CNS Spectrums , Volume 10 , Issue S15: Mixed Amphetamine Salts Extended Release for the Treatment of ADHD in Adolescents: Current Evidence , October 2005 , pp. 22 - 30
Copyright
Copyright © Cambridge University Press 2005

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References

REFERENCES

1.Academy of Pediatrics, Committee on Quality Improvement and Subcommittee on Attention-Deficit/Hyperactivity Disorder. Clinical practice guideline: diagnosis and evaluation of the child with attention-deficit/hyperactivity disorder. Pediatrics. 2000;105:1158–1170.Google Scholar
2.Brown, TE, ed. Attention-Deficit Disorders and Comorbidities in Children, Adolescents, and Adults. Washington, DC: American Psychiatric Press, Inc.; 2000.Google Scholar
3.Barkley, RA, Fischer, M, Edelbrook, C, et al.The adolescent outcome of hyperactive children diagnosed by research criteria, I: an 8-year prospective follow-up study. J Am Acad Child Adoiesc Psychiatry. 1990;29:546–557.Google Scholar
4.Biederman, J, Faraone, S, Milberger, S, et al.Predictors of persistence and remission of ADHD into adolescence: results from a four-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry. 1996;35:343–351.Google Scholar
5.Greydanus, DE, Sloan, MA, Rappley, MD. Psychopharmacology of ADHD in adolescents. Adoiesc Med. 2002;13:599–624.Google ScholarPubMed
6.American Academy of Pediatrics, Committee on Quality Improvement and Subcommittee on Attention-Deficit/Hyperactivity Disorder. Clinical practice guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder. Pediatrics. 2001;108:1033–1044.Google Scholar
7.Swanson, JM, McBurnett, K, Wigal, T, et al.Effect of stimulant medication on children with attention deficit disorder: a review of reviews. Exceptional Children. 1993;60:154–162.Google Scholar
8.Greenhill, LL, Pliszka, S, Dulcan, MK, et al.Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry. 2002;41(suppl 2):26S–49S.Google Scholar
9.Findling, RL, Dogin, JW. Psychopharmacology of ADHD: children and adolescents. J Clin Psychiatry. 1998;59:42–49.Google Scholar
10.Findling, RL, Short, EJ, Manos, MJ. Short-term cardiovascular effects of methylphenidate and Adderall. J Am Acad Child Adolesc Psychiatry. 2001;40:525–529.Google Scholar
11.Gutgesell, H, Atkins, D, Barst, R, et al.AHA Scientific Statement: cardiovascular monitoring of children and adolescents receiving psychotropic drugs. J Am Acad Child Adolesc Psychiatry. 1999;38:1047–1050.Google Scholar
12.Findling, RL, Biederman, J, Wilens, TE, et al.Short- and long-term cardiovascular effects of mixed amphetamine salts extended release in children. J Pediatr. 2005;147. In press.Google Scholar
13.Spencer, TJ, Wilens, TE, Biederman, J, et al.Efficacy and safety of Adderall XR® in the management of attention-deficit/hyperactivity disorder in adolescent patients: a randomized, double-blind, placebo-controlled, parallel-group study. Ciin Ther. 2005. In press.Google Scholar
14.Wilens, T, McBurnett, K, Bukstetn, O, et al.A mukisite, controlled trial of OROS methylphenidate in the treatment of adolescents with ADHD. Arch Pediatr Adolesc Med. In press.Google Scholar
15.Wilens, TE, Biederman, J, Lerner, M, and the Concerta® Study Group. Effects of once-daily osmotic-release methylphenidate on blood pressure and heart rate in children with attention-deficit/hyperactivity disorder. Results from a one-year follow-up study. J Clin Psychopharmacol. 2004;24:36–41.Google Scholar
16.Spencer, TJ, Biederman, J, Wilens, TE. Efficacy and tolerability of long-term, open-label mixed amphetamine salts extended release in adolescents with ADHD. CNS Spectr. 2005;10(suppl 15):14–21.Google Scholar
17.Diagnostic and Statistical Manual for Mental Disorders. 4th ed text rev. Washington, DC: American Psychiatric Association; 2000.Google Scholar
18.Kaufman, J, Birmaher, B, Brent, D, et al.Schedule for Affective Disorders and Schizophrenia for School-aged Children-Present and Lifetime version (K-SADS-PL). J Am Acad Child Adolesc Psychiatry. 1997;36:980–988.Google Scholar
19.Bazett, H. An analysis of time relations of electrocardiogram. Heart. 1920;7:353–370.Google Scholar
20.SAS Institute. SAS/STAT Software: Changes and Enhancements Through Release 6.12. 1997; Cary, NC: SAS Institute.Google Scholar
21.Garson, A, Bricker, JT, McNamara, DG, eds. The Science and Practice of Pediatric Cardiology. Philadelphia, PA: Lea & Febiger; 1990.Google Scholar
22.Park, MK, ed. Pediatric Cardiology for Practitioners. Chicago, Ill: Year Book Medical Publishers; 1998.Google Scholar
23.Gunn, VL, Nechyba, C, eds. Trie Harriet Lane Handbook: A Manual for Pediatric House Officers. 16th ed. Philadelphia, PA: Mosby; 2002.Google Scholar
24.Committee for Proprietary Medicinal Products. The assessment of the potential for QT interval prolongation by non-cardiovascular medicinal products. London, UK: The European Agency for the Evaluation of Medicinal Products, Human Medicines Evaluation Unit; December 17, 1997. Report No. CPMP/986/96.Google Scholar
25.Rapport, MD, Moffitt, C. Attention deficit/hyperactivity disorder and methylphenidate. A review of height/weight, cardiovascular, and somatic complaint side effects. Ciin Psychol Rev. 2002;22:1107–1131.Google Scholar
26.Safet, DJ. Relative cardiovascular safety of psychostimulants used to treat attention-deficit hyperactivity disorder. J Child Adolesc Psychopharmacol. 1992;2:279–290.Google Scholar
27.Wilens, T, McBurnett, K, Stein, M, Lerner, M, Spencer, T, Wolraich, M. Attention-deficit/hyperactivity disorder treatment with once-daily OROS methylphenidate: final results from a long-term open-label study of up to 24 months. J Am Acad Child Adolesc Psychiatry. 2005. In press.Google Scholar
28.Wilens, T, Hamemess, P, Biederman, J, et al.Blood pressure changes associated with medication treatment of adults with ADHD. J Clin Psychiatry. 2005;66:253–259.Google Scholar
29.Biederman, J, Gastfriend, DR, Jellinek, MS. Desipramine in the treatment of children with attention deficit disorder. J Clin Psychopharmacol. 1986;6:359–363.Google Scholar
30.Wilens, TE, Biederman, J, Baldessarini, RJ, et al.Cardiovascular effects of therapeutic doses of tricyclic antidepressants in children and adolescents. J Am Acad Child Adolesc Psychiatry. 1996;35:1491–1501.Google Scholar
31.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.Google Scholar