Lisdexamfetamine dimesylate augmentation in adults with persistent executive dysfunction after partial or full remission of major depressive disorder

Manisha Madhoo, Richard S E Keefe, Robert M. Roth, Angelo Sambunaris, James Wu, Madhukar H. Trivedi, Colleen S. Anderson, Robert Lasser

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1388-1398
Number of pages11
JournalNeuropsychopharmacology
Volume39
Issue number6
DOIs
StatePublished - May 2014

Keywords

  • augmentation
  • clinical drug studies
  • executive function
  • lisdexamfetamine dimesylate
  • major depressive disorder

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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