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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.
J Affect Disord. 2016 Dec; 206:151-160.JA

Abstract

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-Åsberg 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 (20-70mg) 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 (TEAEs).

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 [-2.3, 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 depressive symptoms in individuals with MDD exhibiting inadequate responses to antidepressant monotherapy.

Authors+Show Affiliations

Formerly of Shire, Lexington, MA, USA.University of Toronto, Toronto, ON, Canada.Duke University Medical Center, Durham, and the University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Atlanta Institute of Medicine & Research, Atlanta, GA, USA.Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston, SC, USA.Shire, Lexington, MA, USA.Formerly of Shire, Lexington, MA, USA.Formerly of Shire, Lexington, MA, USA.Shire, Lexington, MA, USA. Electronic address: mmadhoo@shire.com.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial

Language

eng

PubMed ID

27474961

Citation

Richards, Cynthia, et al. "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, vol. 206, 2016, pp. 151-160.
Richards C, McIntyre RS, Weisler R, et al. 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. J Affect Disord. 2016;206:151-160.
Richards, C., McIntyre, R. S., Weisler, R., Sambunaris, A., Brawman-Mintzer, O., Gao, J., Geibel, B., Dauphin, M., & Madhoo, M. (2016). 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, 206, 151-160. https://doi.org/10.1016/j.jad.2016.07.006
Richards C, et al. 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. J Affect Disord. 2016;206:151-160. PubMed PMID: 27474961.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Richards,Cynthia, AU - McIntyre,Roger S, AU - Weisler,Richard, AU - Sambunaris,Angelo, AU - Brawman-Mintzer,Olga, AU - Gao,Joseph, AU - Geibel,Brooke, AU - Dauphin,Matthew, AU - Madhoo,Manisha, Y1 - 2016/07/05/ PY - 2016/03/09/received PY - 2016/06/14/revised PY - 2016/07/03/accepted PY - 2016/10/25/pubmed PY - 2017/11/29/medline PY - 2016/7/31/entrez KW - Amphetamine KW - Augmentation KW - Lisdexamfetamine dimesylate KW - Major depressive disorder KW - Selective serotonin reuptake inhibitors KW - Serotonin-norepinephrine reuptake inhibitors SP - 151 EP - 160 JF - Journal of affective disorders JO - J Affect Disord VL - 206 N2 - 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-Åsberg 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 (20-70mg) 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 (TEAEs). 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 [-2.3, 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 depressive symptoms in individuals with MDD exhibiting inadequate responses to antidepressant monotherapy. SN - 1573-2517 UR - https://www.unboundmedicine.com/medline/citation/27474961/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-0327(16)30387-1 DB - PRIME DP - Unbound Medicine ER -