Effects of levomilnacipran extended-release on major depressive disorder patients with cognitive impairments: post-hoc analysis of a phase III study

Abstract

Performance-based cognitive data were collected using the Cognitive Drug Research System in a study of levomilnacipran extended-release (ER) 40-120 mg/day (NCT01034462) in adults with major depressive disorder. These data were analyzed post-hoc to explore the relationship between cognitive measures, depression symptoms (Montgomery-Åsberg Depression Rating Scale, MADRS), and self-reported psychosocial functioning (Sheehan Disability Scale; SDS). Changes from baseline were analyzed in the intent-to-treat population and subgroups with impaired attention, as indicated by baseline Cognitive Drug Research System scores for Power of Attention and Continuity of Attention. Path analyses evaluated the direct and indirect effects of levomilnacipran ER on SDS total score change. Significantly greater improvements were observed for levomilnacipran ER versus placebo for Power of Attention, Continuity of Attention, MADRS, and SDS score changes; the mean differences were larger in the impaired subgroups than in the overall intent-to-treat population. Path analyses showed that the majority of SDS total score improvement (≥50%) was attributable to an indirect treatment effect through MADRS total score change; some direct effect of levomilnacipran ER on SDS total score improvement was also observed. In adults with major depressive disorder, levomilnacipran ER effectively improved measures of depression and cognition, which contributed toward reductions in self-reported functional impairment.

Figures

Fig. 1

Mean changes from baseline in POA (a) and COA (b) scores. Subgroups were defined using the median POA and COA scores at baseline. For interaction analyses, §significance at the 0.1 level. *P<0.05; **P<0.01; ***P<0.001 for levomilnacipran ER versus placebo for score changes. COA, Continuity of Attention; ER, extended-release; ITT, intent-to-treat; n, number of patients with available assessments at baseline and end of treatment; LS, least squares; LSMD, least-squares mean difference between treatment groups; ns, not significant; POA, Power of Attention.

Fig. 2

Mean changes from baseline in MADRS (a) and SDS (b) total scores. Subgroups were defined using the median POA and COA scores at baseline. *P<0.05; **P<0.01; ***P=0.001 for levomilnacipran ER versus placebo for score changes. COA, Continuity of Attention; ER, extended-release; ITT, intent-to-treat; LS, least squares; LSMD, least-squares mean difference between treatment groups; MADRS, Montgomery–Åsberg Depression Rating Scale; n, number of patients with available assessments at baseline and end of treatment; ns, not significant; POA, Power of Attention; SDS, Sheehan Disability Scale.

Fig. 3

Mean changes from baseline in SDS subscale (a–c) scores. Subgroups were defined using the median POA and COA scores at baseline. For interaction analyses, §significance at the 0.1 level. *P<0.05; **P<0.01; ***P<0.001 for levomilnacipran ER versus placebo. COA, Continuity of Attention; ER, extended-release; ITT, intent-to-treat; LSM, least-squares mean; LSMD, least-squares mean difference between treatment groups; n, number of patients with available assessments at baseline and end of treatment; ns, not significant; POA, Power of Attention; SDS, Sheehan Disability Scale.