Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies

JOURNAL OF AFFECTIVE DISORDERS

卷:206

Article

Richards, Cynthia¹  McIntyre, Roger S.²  Weisler, Richard^3,4  Sambunaris, Angelo⁵  Brawman-Mintzer, Olga^6,7  Gao, Joseph¹  Geibel, Brooke¹  Dauphin, Matthew¹  Madhoo, Manisha¹ 

[1] Shire, 300 Shire Way, Lexington, MA 02421 USA

[2] Univ Toronto, Toronto, ON, Canada

[3] Duke Univ, Med Ctr, Durham, NC USA

[4] Univ North Carolina Chapel Hill, Chapel Hill, NC USA

[5] Atlanta Inst Med & Res, Atlanta, GA USA

[6] Med Univ South Carolina, Charleston, SC USA

[7] Ralph H Johnson VA Med Ctr, Charleston, SC USA

关键词: Augmentation;    Lisdexamfetamine dimesylate;    Major depressive disorder;    Selective serotonin reuptake inhibitors;    Serotonin-norepinephrine reuptake inhibitors;    Amphetamine;   

DOI  :  10.1016/j.jad.2016.07.006

来源: Elsevier

【 摘 要 】

Background: The efficacy, safety, and tolerability of lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy in adults with major depressive disorder (MDD) from two phase 3 studies are reported. Methods: Across study 1 (placebo, n=201; LDX, n=201) and study 2 (placebo, n=213; LDX, n=211), most participants (placebo and LDX) in the safety analysis set were female (study 1: 66.2% and 64.2%; study 2: 67.1% and 66.8%); mean +/- SD ages were 41.8 +/- 12.04 with placebo and 42.2 +/- 12.32 with LDX in study 1 and 42.6 +/- 11.41 with placebo and 42.0 +/- 11.63 with LDX in study 2. Participants (18-65 y) had DSM-IV-TR-diagnosed MDD and lead-in baseline Montgomery-Asberg Depression Rating Scale (MADRS) total scores >= 24. Eight-week antidepressant lead-in phases prospectively assessed antidepressant response. Then, 8 weeks of randomized (1:1), double-blind treatment with dose-optimized LDX (20-70 mg) or placebo in participants exhibiting inadequate antidepressant monotherapy responses (augmentation baseline MADRS total scores >= 18 and < 50% MADRS total score reductions from lead-in baseline to augmentation baseline) was initiated. The primary endpoint was MADRS total score change from augmentation baseline to week 16. Safety and tolerability measures included the occurrence of treatment-emergent adverse events (TEAE5). Results: Least squares mean (95% CI) treatment differences (LDX-placebo) for MADRS total score changes from augmentation baseline to week 16 were not statistically significant in study 1 (0.1 [-1.7, 2.0], P=0.883) or study 2 (-0.5 [-23, 1.3], P=0.583). The only TEAE reported by > 5% of LDX participants at twice the placebo rate in both studies was dry mouth. Limitations: Limitations include the exclusion of participants with psychiatric comorbidities/active medical disorders, the inability to assess specific MDD symptom domains (eg, anhedonia, cognition) or subtypes, the use of telephone-based depression assessments, and the potential influence of placebo response. Conclusion: Contrary to expectations, LDX augmentation was not superior to placebo in reducing

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