Self-Reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study

Lenard A Adler, Bryan Dirks, Patrick Deas, Aparna Raychaudhuri, Matthew Dauphin, Keith Saylor, Richard Weisler, Lenard A Adler, Bryan Dirks, Patrick Deas, Aparna Raychaudhuri, Matthew Dauphin, Keith Saylor, Richard Weisler

Abstract

Background: This study examined the effects of lisdexamfetamine dimesylate (LDX) on quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) and clinically significant executive function deficits (EFD).

Methods: This report highlights QOL findings from a 10-week randomized placebo-controlled trial of LDX (30-70 mg/d) in adults (18-55 years) with ADHD and EFD (Behavior Rating Inventory of EF-Adult, Global Executive Composite [BRIEF-A GEC] ≥65). The primary efficacy measure was the self-reported BRIEF-A; a key secondary measure was self-reported QOL on the Adult ADHD Impact Module (AIM-A). The clinician-completed ADHD Rating Scale version IV (ADHD-RS-IV) with adult prompts and Clinical Global Impressions-Severity (CGI-S) were also employed. The Adult ADHD QoL (AAQoL) was added while the study was in progress. A post hoc analysis examined the subgroup having evaluable results from both AIM-A and AAQoL.

Results: Of 161 randomized (placebo, 81; LDX, 80), 159 were included in the safety population. LDX improved AIM-A multi-item domain scores versus placebo; LS mean difference for Performance and Daily Functioning was 21.6 (ES, 0.93, P<.0001); Impact of Symptoms: Daily Interference was 14.9 (ES, 0.62, P<.0001); Impact of Symptoms: Bother/Concern was 13.5 (ES, 0.57, P=.0003); Relationships/Communication was 7.8 (ES, 0.31, P=.0302); Living With ADHD was 9.1 (ES, 0.79, P<.0001); and General Well-Being was 10.8 (ES, 0.70, P<.0001). AAQoL LS mean difference for total score was 21.0; for subscale: Life Productivity was 21.0; Psychological Health was 12.1; Life Outlook was 12.5; and Relationships was 7.3. In a post hoc analysis of participants with both AIM-A and AAQoL scores, AIM-A multi-item subgroup analysis scores numerically improved with LDX, with smaller difference for Impact of Symptoms: Daily Interference. The safety profile of LDX was consistent with amphetamine use in previous studies.

Conclusions: Overall, adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A and AAQoL scales in line with medium/large ES; these improvements were paralleled by improvements in EF and ADHD symptoms. The safety profile of LDX was similar to previous studies.

Trial registration: ClinicalTrials.gov, NCT01101022.

Figures

Figure 1
Figure 1
Self-reported mean AIM-A multi-item global domain scores.
Figure 2
Figure 2
Mean self-reported AIM-A multi-item subscale scores.
Figure 3
Figure 3
Change from baseline at week 10/ET in AAQoL A) total and B) subscale scores.

References

    1. Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, Faraone SV, Greenhill LL, Howes MJ, Secnik K. 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(4):716–723. doi: 10.1176/appi.ajp.163.4.716.
    1. Brown TE. Executive functions and attention deficit hyperactivity disorder: implications of two conflicting views. Int J Disability Develop Educ. 2006;53(1):35–46. doi: 10.1080/10349120500510024.
    1. Willcutt EG, Doyle AE, Nigg JT, Faraone SV, Pennington BF. Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review. Biol Psychiatry. 2005;57(11):1336–1346. doi: 10.1016/j.biopsych.2005.02.006.
    1. Castellanos FX, Sonuga-Barke EJ, Milham MP, Tannock R. Characterizing cognition in ADHD: beyond executive dysfunction. Trends Cogn Sci. 2006;10(3):117–123. doi: 10.1016/j.tics.2006.01.011.
    1. Gioia GA, Isquith PK, Retzlaff PD, Espy KA. Confirmatory factor analysis of the Behavior Rating Inventory of Executive Function (BRIEF) in a clinical sample. Child Neuropsychol. 2002;8(4):249–257. doi: 10.1076/chin.8.4.249.13513.
    1. Gioia GA, Isquith PK, Guy SC, Kenworthy L. BRIEF: Behavior Rating Inventory of Executive Function: Professional Manual. Lutz, FL: Psychological Assessment Resources, Inc; 2000.
    1. Barkley RA. Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull. 1997;121(1):65–94.
    1. Lawrence V, Houghton S, Tannock R, Douglas G, Durkin K, Whiting K. ADHD outside the laboratory: boys’ executive function performance on tasks in videogame play and on a visit to the zoo. J Abnorm Child Psychol. 2002;30(5):447–462. doi: 10.1023/A:1019812829706.
    1. Biederman J, Petty CR, Fried R, Doyle AE, Spencer T, Seidman LJ, Gross L, Poetzl K, Faraone SV. Stability of executive function deficits into young adult years: a prospective longitudinal follow-up study of grown up males with ADHD. Acta Psychiatr Scand. 2007;116(2):129–136. doi: 10.1111/j.1600-0447.2007.01008.x.
    1. Biederman J, Petty CR, Doyle AE, Spencer T, Henderson CS, Marion B, Fried R, Faraone SV. Stability of executive function deficits in girls with ADHD: a prospective longitudinal followup study into adolescence. Dev Neuropsychol. 2008;33(1):44–61.
    1. Biederman J, Petty C, Fried R, Fontanella J, Doyle AE, Seidman LJ, Faraone SV. Impact of psychometrically defined deficits of executive functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry. 2006;163(10):1730–1738. doi: 10.1176/appi.ajp.163.10.1730.
    1. Biederman J, Monuteaux MC, Doyle AE, Seidman LJ, Wilens TE, Ferrero F, Morgan CL, Faraone SV. Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children. J Consult Clin Psychol. 2004;72(5):757–766.
    1. Brown TE. Brown Attention-Deficit Hyperactivity Disorder Scales for Adolescents and Adults. San Antonio, TX: The Psychological Corporation; 1996.
    1. Barkley RA. Barkley Deficits in Executive Functioning Scale (BDEFS) New York, NY: The Guilford Press; 2011.
    1. Roth RM, Isquith PK, Gioia GA. Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) Lutz, FL: Psychological Assessment Resources, Inc.; 1999.
    1. Shallice T, Burgess PW. Deficits in strategy application following frontal lobe damage in man. Brain. 1991;114(Pt 2):727–741.
    1. Barkley RA, Fischer M. Predicting impairment in major life activities and occupational functioning in hyperactive children as adults: self-reported executive function (EF) deficits versus EF tests. Dev Neuropsychol. 2011;36(2):137–161. doi: 10.1080/87565641.2010.549877.
    1. Coghill D. The impact of medications on quality of life in attention-deficit hyperactivity disorder: a systematic review. CNS Drugs. 2010;24(10):843–866. doi: 10.2165/11537450-000000000-00000.
    1. Adler LA, Spencer TJ, Levine LR, Ramsey JL, Tamura R, Kelsey D, Ball SG, Allen AJ, Biederman J. Functional outcomes in the treatment of adults with ADHD. J Atten Disord. 2008;11(6):720–727.
    1. Brown TE, Landgraf JM. Improvements in executive function correlate with enhanced performance and functioning and health-related quality of life: evidence from 2 large, double-blind, randomized, placebo-controlled trials in ADHD. Postgrad Med. 2010;122(5):42–51. doi: 10.3810/pgm.2010.09.2200.
    1. Matza LS, Johnston JA, Faries DE, Malley KG, Brod M. Responsiveness of the Adult Attention-Deficit/Hyperactivity Disorder Quality of Life Scale (AAQoL) Qual Life Res. 2007;16(9):1511–1520. doi: 10.1007/s11136-007-9254-9.
    1. Landgraf JM. Monitoring quality of life in adults with ADHD: reliability and validity of a new measure. J Atten Disord. 2007;11(3):351–362. doi: 10.1177/1087054707299400.
    1. Spencer TJ, Landgraf JM, Adler LA, Weisler RH, Anderson CS, Youcha SH. Attention-deficit/hyperactivity disorder–specific quality of life with triple-bead mixed amphetamine salts (SPD465) in adults: results of a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2008;69(11):1766–1775. doi: 10.4088/JCP.v69n1112.
    1. Brod M, Johnston J, Able S, Swindle R. Validation of the Adult Attention-Deficit/Hyperactivity Disorder Quality-of-Life Scale (AAQoL): a disease-specific quality-of-life measure. Qual Life Res. 2006;15(1):117–129. doi: 10.1007/s11136-005-8325-z.
    1. Wayne PA. Vyvanse [package insert] Wayne, PA: Shire US Inc; 2012.
    1. Adler LA, Goodman DW, Kollins SH, Weisler RH, Krishnan S, Zhang Y. Biederman J 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(9):1364–1373. doi: 10.4088/JCP.v69n0903.
    1. DuPaul GJ, Power TJ, Anastopoulos AD, Reid R. ADHD Rating Scale-IV: Checklists, Norms, and Clinical Interpretation. New York, NY: Guilford Press; 1998.
    1. Adler L, Cohen J. Diagnosis and evaluation of adults with attention-deficit/hyperactivity disorder. Psychiatr Clin North Am. 2004;27(2):187–201. doi: 10.1016/j.psc.2003.12.003.
    1. Sandra Kooij JJ, Marije Boonstra A, Swinkels SH, Bekker EM, de Noord I, Buitelaar JK. Reliability, validity, and utility of instruments for self-report and informant report concerning symptoms of ADHD in adult patients. J Atten Disord. 2008;11(4):445–458. doi: 10.1177/1087054707299367.
    1. Brown TE, Brams M, Gao J, Gasior M, Childress A. Open-label administration of lisdexamfetamine dimesylate improves executive function impairments and symptoms of attention-deficit/hyperactivity disorder in adults. Postgrad Med. 2010;122(5):7–17. doi: 10.3810/pgm.2010.09.2196.
    1. Brams M, Giblin J, Gasior M, Gao J, Wigal T. Effects of open-label lisdexamfetamine dimesylate on self-reported quality of life in adults with ADHD. Postgrad Med. 2011;123(3):99–108.
    1. Adler LA, Dirks BL, Deas P, Raychaudhuri A, Dauphin MR, Lasser R, Weisler RH. Lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2013;74(7):694–702. doi: 10.4088/JCP.12m08144.
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR, Fourth Edition. Text Revision. Fourth. Washington, DC: American Psychiatric Association; 2000. Attention-deficit and disruptive behavior disorders; pp. 85–93.
    1. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice E6(R1) 2013. . Accessed May 19, 2013.
    1. Guy W. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: US Department of Health, Education, and Welfare; Public Health Service, Alcohol, Drug Abuse and Mental Health Administration, NIMH Psychopharmacology Research Branch; 1976. Clinical global impressions; pp. 218–222.
    1. Barkley RA. Major life activity and health outcomes associated with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2002;63(Suppl 12):10–15.
    1. Biederman J, Faraone SV. The effects of attention-deficit/hyperactivity disorder on employment and household income. MedGenMed. 2006;8(3):12.
    1. Kupper T, Haavik J, Drexler H, Ramos-Quiroga JA, Wermelskirchen D, Prutz C, Schauble B. The negative impact of attention-deficit/hyperactivity disorder on occupational health in adults and adolescents. Int Arch Occup Environ Health. 2012;85(8):837–847. doi: 10.1007/s00420-012-0794-0.
    1. Spencer TJ, Adler LA, Weisler RH, Youcha SH. Triple-bead mixed amphetamine salts (SPD465), a novel, enhanced extended-release amphetamine formulation for the treatment of adults with ADHD: a randomized, double-blind, multicenter, placebo-controlled study. J Clin Psychiatry. 2008;69(9):1437–1448. doi: 10.4088/JCP.v69n0911.
    1. Adler LA, Liebowitz M, Kronenberger W, Qiao M, Rubin R, Hollandbeck M, Deldar A, Schuh K, Durell T. Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder and comorbid social anxiety disorder. Depress Anxiety. 2009;26(3):212–221. doi: 10.1002/da.20549.
    1. Ramos-Quiroga JA, Casas M. Achieving remission as a routine goal of pharmacotherapy in attention-deficit hyperactivity disorder. CNS Drugs. 2011;25(1):17–36. doi: 10.2165/11538450-000000000-00000.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren