Effects of levomilnacipran extended-release on motivation/energy and functioning in adults with major depressive disorder

Abstract

The objective of this post-hoc analysis was to investigate the relationship between motivation/energy and functional impairment in patients with major depressive disorder (MDD). Data were taken from a phase 3 trial of levomilnacipran extended-release (ER) in adults with MDD (NCT01034462; N=429) that used the 18-item Motivation and Energy Inventory (MEI) to assess motivation/energy. Two subgroups with lower and higher motivation/energy were defined using baseline MEI total scores (≤28 and >28, respectively). Change from baseline in the Sheehan Disability Scale (SDS) total score was analyzed in the intent-to-treat (ITT) population and both subgroups. Path analyses were carried out in the ITT population and a lower MEI subgroup to assess the direct and indirect effects of levomilnacipran ER on SDS total score change. In the ITT population and the lower MEI subgroup, significant differences were found between levomilnacipran ER and placebo for changes in the SDS total score (-2.6 and -3.9, both P<0.01), but not in the higher MEI subgroup. The indirect effect of levomilnacipran ER on SDS total score improvement, as mediated by MEI total score change, was 79.9% in the lower MEI subgroup and 67.2% in the ITT population. Levomilnacipran ER was previously shown to improve motivation/energy in adults with MDD. The current analysis indicates that improvements in functional impairment were considerably mediated by improvements in motivation/energy, particularly in patients with lower motivation/energy at baseline.

Fig. 1

Change from baseline in MEI total score by study visit (ITT population, MMRM). Analysis includes all study visits at which MEI was evaluated. *P<0.05 versus placebo. ER, extended release; ITT, intent to treat; LSM, least squares mean; MEI, Motivation and Energy Inventory-Short Form; MMRM, mixed-effects model for repeated measures.

Fig. 2

Mean changes from baseline in (a) SDS total score and in (b, c, d) SDS subscale scores; analyzed in the ITT population and MEI subgroups using an MMRM approach. Lower and higher motivation/energy subgroups were defined by baseline MEI total scores less than or equal to 28 and greater than 28, respectively; n-values represent the number of patients with nonmissing SDS values at baseline and at week 8. *P<0.05; **P<0.01; ***P≤0.001 versus placebo. ER, extended release; ITT, intent to treat; LSM, least squares mean; LSMD, least squares mean difference between treatment groups; MEI, Motivation and Energy Inventory-Short Form; MMRM, mixed-effects model for repeated measures; SDS, Sheehan Disability Scale.

Fig. 3

Mean changes from baseline in (a) SF-36 MCS scores and (b) SF-36 PCS scores; analyzed in the ITT population and MEI subgroups using an LOCF approach. Lower and higher motivation/energy subgroups were defined by baseline MEI total scores less than or equal to 28 and greater than 28, respectively; n-values represent the number of patients with nonmissing SF-36 values at baseline and at the end of treatment. *P<0.05; **P<0.01 versus placebo. ER, extended release; ITT, intent to treat; LOCF, last observation carried forward; LSM, least squares mean; LSMD, least-squares mean difference between treatment groups; MCS, mental component summary; MEI, Motivation and Energy Inventory-Short Form; SF-36, Short Form-36 Health Survey; PCS, physical component summary.