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Long-Term Safety and Effectiveness of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder

Published online by Cambridge University Press:  07 November 2014

Richard Weisler ,
Joel Young ,
Greg Mattingly ,
Joseph Gao ,
Liza Squires ,
Lenard Adler  and
304 Study Group
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Abstract

Objective: To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score.

Results: A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P<.0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P<.0001).

Conclusions: LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months.

Type
Original Research
Information
CNS Spectrums , Volume 14 , Issue 10 , October 2009 , pp. 573 - 586
Copyright
Copyright © Cambridge University Press 2009

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References

REFERENCES

1.Polanczyk, G, de Lima, MS, Horta, BL, Biederman, J, Rohde, LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007;164:942–948.Google Scholar
2.Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. Text Revision. Washington, DC: American Psychiatric Association; 2000.Google Scholar
3.Barkley, RA, Fischer, M, Edelbrock, CS, Smallish, L. The adolescent outcome of hyperactive children diagnosed by research criteria: I. An 8-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry. 1990;29:546–557.CrossRefGoogle ScholarPubMed
4.Barkley, RA, Fischer, M, Smallish, L, Fletcher, K. The persistence of attention-deficit/hyperactivity disorder into young adulthood as a function of reporting source and definition of disorder. J Abnorm Psychol. 2002;111:279–289.Google Scholar
5.Biederman, J, Mick, E, Faraone, SV. Age-dependent decline of symptoms of attention deficit hyperactivity disorder: impact of remission definition and symptom type. Am J Psychiatry. 2000;157:816–818.Google Scholar
6.Kessler, RC, Adler, L, Barkley, R, et al.The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006;163:716–723.Google Scholar
7.Biederman, J, Faraone, SV, Spencer, TJ, Mick, E, Monuteaux, MC, Aleardi, M. Functional impairments in adults with self-reports of diagnosed ADHD: a controlled study of 1001 adults in the community. J Clin Psychiatry. 2006;67:524–540.Google Scholar
8.Biederman, J, Mick, E, Fried, R, Aleardi, M, Potter, A, Herzig, K. A simulated workplace experience for nonmedicated adults with and without ADHD. Psychiatr Serv. 2005;56:1617–1620.CrossRefGoogle ScholarPubMed
9.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(2 suppl):26S–49S.Google Scholar
10.Wilens, TE, Dodson, W. A clinical perspective of attention-deficit/hyperactivity disorder into adulthood. J Clin Psychiatry. 2004;65:1301–1313.Google Scholar
11.Faraone, SV, Spencer, TJ, Montano, CB, Biederman, J. Attention-deficit/hyperactivity disorder in adults: a survey of current practice in psychiatry and primary care. Arch Intern Med. 2004;164:1221–1226.CrossRefGoogle ScholarPubMed
12.Spencer, T, Wilens, T, Biederman, J, Faraone, SV, Ablon, JS, Lapey, K. A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1995;52:434–443.Google Scholar
13.Spencer, T, Biederman, J, Wilens, T, et al.Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2001;58:775–782.Google Scholar
14.Weisler, RH, Biederman, J, Spencer, TJ, et al, on behalf of the SLI381.303 Study Group. Mixed amphetamine salts extended-release in the treatment of adult ADHD: a randomized, controlled trial. CNS Spectr. 2006;11:625–639.Google Scholar
15.Fallu, A, Richard, C, Prinzo, R, Binder, C. Does OROS-methylphenidate improve core symptoms and deficits in executive function? Results of an open-label trial in adults with attention deficit hyperactivity disorder. Curr Med Res Opin. 2006;22:2557–2566.Google Scholar
16.Biederman, J, Mick, E, Surman, C, et al.A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder. Biol Psychiatry. 2006;59:829–835.Google Scholar
17.Weisler, RH, Biederman, J, Spencer, TJ, Wilens, TE. Long-term cardiovascular effects of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr. 2005;10(12 suppl 20):35–43.Google Scholar
18.Wilens, TE, Hammerness, PG, Biederman, J, et al.Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2005;66:253–259.Google Scholar
19.Nutt, DJ, Fone, K, Asherson, P, et al.Evidence-based guidelines for management of attention-deficit/hyperactivity disorder in adolescents in transition to adult services and in adults: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2007;21:10–41.Google Scholar
20.Adler, LA, Reingold, LS, Morrill, MS, Wilens, TE. Combination pharmacotherapy for adult ADHD. Curr Psychiatry Rep. 2006;8:409–415.CrossRefGoogle ScholarPubMed
21.Philipsen, A, Hornyak, M, Riemann, D. Sleep and sleep disorders in adults with attention deficit/hyperactivity disorder. Sleep Med Rev. 2006;10:399–405.CrossRefGoogle ScholarPubMed
22.Mick, E, Biederman, J, Jetton, J, Faraone, SV. Sleep disturbances associated with attention deficit hyperactivity disorder: the impact of psychiatric comorbidity and pharmacotherapy. J Child Adolesc Psychopharmacol. 2000;10:223–231.Google Scholar
23.Owens, JA. The ADHD and sleep conundrum: a review. J Dev Behav Pediatr. 2005;26:312–322.CrossRefGoogle ScholarPubMed
24.Carlson, GA, Kelly, KL. Stimulant rebound: how common is it and what does it mean? J Child Adolesc Psychopharmacol. 2003;13:137–142.Google Scholar
25.Mattingly, GW. ADHD, Psychostimulants and sleep disorders: is there a link? The Year in ADHD: 2008. 2009;1:32–37.Google Scholar
26.Pennick, M. Absorption of lisdexamfetamine dimesylate and hydrolysis to form the active moiety, d-amphetamine. Poster presented at: New Clinical Drug Evaluation Unit 49th Annual Meeting; June 29-July 2, 2009; Hollywood, FL.Google Scholar
27.Pennick, M. Hydrolytic conversion of lisdexamfetamine dimesylate to the active moiety, d-amphetamine. Poster presented at: Society of Biological Psychiatry's 64th Annual Scientific Convention and Meeting; May 14-16, 2009; Vancouver, British Columbia, Canada.Google Scholar
28.Shojaei, A, Ermer, JC, Krishnan, S. Lisdexamfetamine dimesylate as a treatment for ADHD: dosage formulation and pH effects. Poster presented at: 160th Annual Meeting of the American Psychiatric Association; May 19-24, 2007; San Diego, CA. Poster NR 740.Google Scholar
29.Krishnan, S, Zhang, Y. Relative bioavailability of lisdexamfetamine 70-mg capsules in fasted and fed healthy adult volunteers and in solution: a single-dose, crossover pharmacokinetic study. J Clin Pharmacol. 2008;48:293–302.Google Scholar
30.Ermer, J, Homolka, R, Martin, P, Buckwalter, M, Purkayastha, J, Roesch, BG. Linear dose proportionality, low inter- and intrasubject variability, and safety of lisdexamfetamine dimesylate in an open-label single-dose pharmacokinetic study in healthy adult volunteers. Poster presented at: 37th Annual Meeting of the American College of Clinical Pharmacy Annual Meeting; October 19-22, 2008; Louisville, KY. Poster 201.Google Scholar
31.Biederman, J, Krishnan, S, Zhang, Y, McGough, JJ, Findling, RL. Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forceddose, parallel-group study. Clin Ther. 2007;29:450–463.Google Scholar
32.Biederman, J, Boellner, SW, Childress, A, Lopez, FA, Krishnan, S, Zhang, Y. Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: a double-blind, placebo-controlled, crossover analog classroom study. Biol Psychiatry. 2007;62:970–976.Google Scholar
33.Wigal, SB, Kollins, SH, Childress, AC, Squires, L, for the 311 Study Group. A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. Child Adolesc Psychiatry Ment Health. 2009;3:17.Google Scholar
34.Adler, LA, Goodman, DW, Kollins, SH, et al, on behalf of the 303 Study Group. Double-blind, placebo-controlled study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2008;69:1364–1373.Google Scholar
35.Findling, RL, Childress, AC, Krishnan, S, McGough, JJ. Long-term effectiveness and safety of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. CNS Spectr. 2008;13:614–620.Google Scholar
36.Adler, L, Cohen, J. Diagnosis and evaluation of adults with attention-deficit/hyperactivity disorder. Psychiatr Clin North Am. 2004;27:187–201.Google Scholar
37. ADHD-RS Initial Evaluation. Available at: http://www.askdrjones.com/wp-content/uploads/patientforms/ADHD%20Screening-Initial%20Eval.pdf. Accessed August 12, 2009.Google Scholar
38.Buysse, DJ, Reynolds, CF III, Monk, TH, Berman, SR, Kupfer, DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193–213.CrossRefGoogle ScholarPubMed
39.Biederman, J, Spencer, TJ, Wilens, TE, Weisler, RH, Read, SC, Tulloch, SJ, on behalf of the SLI 381.304 Study Group. Long-term safety and effectiveness of mixed amphetamine salts extended release in adults with ADHD. CNS Spectr. 2005;10(12 Suppl 20):16–25.CrossRefGoogle ScholarPubMed
40.Adderall, XR [package insert]. Wayne, PA: Shire US Inc; 2009.Google Scholar
41. Concerta [package insert]. Titusville, NJ: McNeil Pediatrics; 2009.Google Scholar
42.Focalin, XR [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2009.Google Scholar
43.Adler, LA, Spencer, TJ, Williams, DW, Moore, RJ, Michelson, D. Long-term, open-label safety and efficacy of atomoxetine in adults with ADHD: final report of a 4-year study. J Atten Disord. 2008;12:248–253.Google Scholar
44. Vyvanse [package insert]. Wayne, PA: Shire US Inc; 2009.Google Scholar