title: Lisdexamfetamine dimesylate augmentation in adults with persistent executive dysfunction after partial or full remission of major depressive disorder.
abstract: 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.
authors: Shire Development LLC, Wayne, PA, USA.
authors: Manisha
authors: M
authors: Madhoo
authors: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
authors: Richard S E
authors: RS
authors: Keefe
authors: Adult Neuropsychological Services and Adult ADHD Program at Hanover Psychiatry, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
authors: Robert M
authors: RM
authors: Roth
authors: Atlanta Institute of Medicine and Research, Atlanta, GA, USA.
authors: Angelo
authors: A
authors: Sambunaris
authors: Shire Development LLC, Wayne, PA, USA.
authors: James
authors: J
authors: Wu
authors: Department of Psychiatry, University of Texas Southwestern Medical School, Dallas, TX, USA.
authors: Madhukar H
authors: MH
authors: Trivedi
authors: Shire Development LLC, Wayne, PA, USA.
authors: Colleen S
authors: CS
authors: Anderson
authors: F. Hoffman-La Roche Ltd, Basel, Switzerland.
authors: Robert
authors: R
authors: Lasser
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003913:Dextroamphetamine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D056344:Executive Function / Q000187:drug effects*; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D011619:Psychotropic Drugs; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine