TY - JOUR
T1 - Lisdexamfetamine dimesylate augmentation in adults with persistent executive dysfunction after partial or full remission of major depressive disorder
AU - Madhoo, Manisha
AU - Keefe, Richard S E
AU - Roth, Robert M.
AU - Sambunaris, Angelo
AU - Wu, James
AU - Trivedi, Madhukar H.
AU - Anderson, Colleen S.
AU - Lasser, Robert
N1 - Funding Information:
Under the direction of the authors, Elizabeth LaFlamme, PhD, employee of Complete Healthcare Communications (Chadds Ford, PA, USA), provided writing assistance for this publication. Editorial assistance in formatting, proofreading, copyediting, and fact checking was also provided by Craig Slawecki, PhD, from Complete Healthcare Communications. Brian Scheckner, PharmD, from Shire Development LLC also reviewed and edited the manuscript for scientific accuracy. Shire Development LLC also provided funding to Complete Healthcare Communications for support in writing and editing this manuscript. We wish to acknowledge all study investigators who worked at the sites at which the study was conducted. Clinical research was funded by Shire Development LLC (Wayne, PA, USA). Although the sponsor was involved in design, collection, analysis, interpretation, and fact checking of information, the content of this manuscript, the ultimate interpretation, and the decision to submit it for publication in Neuropsy-chopharmacology were made by the authors independently.
PY - 2014/5
Y1 - 2014/5
N2 - Evaluate lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy for executive dysfunction in partially or fully remitted major depressive disorder (MDD). This randomized, placebo-controlled study (NCT00985725) enrolled 143 adults (18-55 years) with mild MDD (Montgomery-Åsberg Depression Rating Scale (MADRS) score ≤18) and executive dysfunction (Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report Global Executive Composite (GEC) T score ≥60) on stable antidepressant monotherapy for ≥8 weeks. After 2 weeks of screening, participants were randomized to 9 weeks of double-blind LDX (20-70 mg/day) or placebo augmentation, followed by 2 weeks of single-blind placebo. The primary end point was change from baseline to week 9/end of study (EOS) in BRIEF-A Self-Report GEC T score; secondary assessments included the BRIEF-A Informant Report, MADRS, and treatment-emergent adverse events (TEAEs). Of 143 randomized participants, 119 completed double-blind treatment (placebo, n=59; LDX, n=60). Mean±standard deviation (SD) BRIEF-A GEC T scores decreased from baseline (placebo, 74.2±8.88; LDX, 76.8±9.66) to week 9/EOS (placebo, 61.4±14.61; LDX, 55.2±16.15); the LS mean (95% CI) treatment difference significantly favored LDX (-8.0 (-12.7, -3.3); P=0.0009). The LS mean (95% CI) treatment difference for MADRS total score also significantly favored LDX (-1.9 (-3.7, 0.0); P=0.0465). TEAE rates were 73.6% with placebo and 78.9% with LDX; serious TEAE rates were 4.2 and 2.8%. In this trial, LDX augmentation significantly improved executive dysfunction and depressive symptoms in participants with mild MDD. The safety profile of LDX was consistent with prior studies in adults with attention-deficit/hyperactivity disorder.
AB - Evaluate lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy for executive dysfunction in partially or fully remitted major depressive disorder (MDD). This randomized, placebo-controlled study (NCT00985725) enrolled 143 adults (18-55 years) with mild MDD (Montgomery-Åsberg Depression Rating Scale (MADRS) score ≤18) and executive dysfunction (Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report Global Executive Composite (GEC) T score ≥60) on stable antidepressant monotherapy for ≥8 weeks. After 2 weeks of screening, participants were randomized to 9 weeks of double-blind LDX (20-70 mg/day) or placebo augmentation, followed by 2 weeks of single-blind placebo. The primary end point was change from baseline to week 9/end of study (EOS) in BRIEF-A Self-Report GEC T score; secondary assessments included the BRIEF-A Informant Report, MADRS, and treatment-emergent adverse events (TEAEs). Of 143 randomized participants, 119 completed double-blind treatment (placebo, n=59; LDX, n=60). Mean±standard deviation (SD) BRIEF-A GEC T scores decreased from baseline (placebo, 74.2±8.88; LDX, 76.8±9.66) to week 9/EOS (placebo, 61.4±14.61; LDX, 55.2±16.15); the LS mean (95% CI) treatment difference significantly favored LDX (-8.0 (-12.7, -3.3); P=0.0009). The LS mean (95% CI) treatment difference for MADRS total score also significantly favored LDX (-1.9 (-3.7, 0.0); P=0.0465). TEAE rates were 73.6% with placebo and 78.9% with LDX; serious TEAE rates were 4.2 and 2.8%. In this trial, LDX augmentation significantly improved executive dysfunction and depressive symptoms in participants with mild MDD. The safety profile of LDX was consistent with prior studies in adults with attention-deficit/hyperactivity disorder.
KW - augmentation
KW - clinical drug studies
KW - executive function
KW - lisdexamfetamine dimesylate
KW - major depressive disorder
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U2 - 10.1038/npp.2013.334
DO - 10.1038/npp.2013.334
M3 - Article
C2 - 24309905
AN - SCOPUS:84900798015
SN - 0893-133X
VL - 39
SP - 1388
EP - 1398
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 6
ER -