title: A randomized controlled trial of the efficacy and safety of lisdexamfetamine dimesylate as augmentation therapy in adults with residual symptoms of major depressive disorder after treatment with escitalopram.
abstract: OBJECTIVE
  Evaluate the efficacy and safety of lisdexamfetamine dimesylate augmentation for major depressive disorder (MDD) in escitalopram nonremitters.
  
  
  METHODS
  In this proof-of-concept study (conducted from July 2009-August 2010) with a prespecified critical α = .10, adults with nonpsychotic MDD (DSM-IV-TR criteria) and residual depressive symptoms (17-item Hamilton Depression Rating Scale score ≥ 4) after 8 weeks of open-label escitalopram were randomized to 6 weeks of lisdexamfetamine dimesylate (20-50 mg/d) or placebo augmentation. The primary endpoint, Montgomery-Asberg Depression Rating Scale (MADRS) total score change in escitalopram nonremitters (MADRS total score > 10) from week 8 (augmentation baseline) to week 14/end of study, was assessed using analysis of covariance, with last observation carried forward.
  
  
  RESULTS
  For nonremitters (placebo, n = 64; lisdexamfetamine dimesylate, n = 65), the least squares (LS) mean (90% CI) treatment difference for MADRS total score reduction at week 14/end of study (-2.3 [-4.5 to -0.1]; P = .0902) met the prespecified criterion for lisdexamfetamine dimesylate superiority (adjusted effect size, -0.3); the number needed to treat for MADRS remission (MADRS total score ≤ 10) was 6.7. The LS mean treatment difference in remitters was not statistically significant (1.2 [-1.6 to 4.0]; P = .4726). Among randomized participants, 49.4% (42/85) receiving placebo and 60.2% (53/88) receiving lisdexamfetamine dimesylate had ≥ 1 treatment-emergent adverse event, the most frequent with lisdexamfetamine dimesylate being dry mouth and headache (both 11.4%). Mean (SD) vital sign and electrocardiogram changes (placebo vs lisdexamfetamine dimesylate) were 0.5 (8.98) versus 2.3 (9.04) mm Hg (systolic blood pressure), -1.0 (7.19) versus 0.9 (6.61) mm Hg (diastolic blood pressure), -0.4 (7.39) versus 4.8 (8.64) beats per minute (heart rate), and -1.6 (11.23) versus -4.9 (11.84) milliseconds (Fridericia-adjusted QTc).
  
  
  CONCLUSIONS
  Lisdexamfetamine dimesylate augmentation reduced depressive symptoms in participants with inadequate escitalopram response.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00905424.
authors.affiliation: Department of Psychiatry, Comprehensive Center for Depression, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9119 madhukar.trivedi@utsouthwestern.edu.
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cutler
authors.forename: Cynthia
authors.initials: C
authors.lastname: Richards
authors.forename: Robert
authors.initials: R
authors.lastname: Lasser
authors.forename: Brooke B
authors.initials: BB
authors.lastname: Geibel
authors.forename: Joseph
authors.initials: J
authors.lastname: Gao
authors.forename: Angelo
authors.initials: A
authors.lastname: Sambunaris
authors.forename: Ashwin A
authors.initials: AA
authors.lastname: Patkar
mesh_terms: D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage* / Q000009:adverse effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D015283:Citalopram / Q000008:administration & dosage* / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000188:drug therapy*; D003913:Dextroamphetamine / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory / Q000706:statistics & numerical data; D011594:Psychometrics; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000697:Central Nervous System Stimulants; D015283:Citalopram; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine