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.

METHOD:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT00905424.

• Authors: Madhukar H Trivedi, Andrew J Cutler, Cynthia Richards, Robert Lasser, Brooke B Geibel, Joseph Gao, Angelo Sambunaris, Ashwin A Patkar
• Journal: The Journal of clinical psychiatry (J Clin Psychiatry) Vol. 74 Issue 8 Pg. 802-9 (Aug 2013) ISSN: 1555-2101 [Electronic] United States
• PMID: 24021497 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Copyright 2013 Physicians Postgraduate Press, Inc.

Chemical References

• Antidepressive Agents, Second-Generation
• Central Nervous System Stimulants
• Citalopram
• Lisdexamfetamine Dimesylate
• Dextroamphetamine

Topics

• Adolescent
• Adult
• Antidepressive Agents, Second-Generation (administration & dosage, adverse effects)
• Central Nervous System Stimulants (administration & dosage, adverse effects)
• Citalopram (administration & dosage, adverse effects)
• Depressive Disorder, Major (drug therapy)
• Dextroamphetamine (administration & dosage, adverse effects)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Lisdexamfetamine Dimesylate
• Male
• Middle Aged
• Personality Inventory (statistics & numerical data)
• Psychometrics
• Young Adult