Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

Abstract

Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales.

Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated.

Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P < .01). Depending on the SDS subscale, 48%-55% of levomilnacipran ER-treated patients with moderate-extreme impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%-47%) of levomilnacipran ER-treated patients versus only about one-third (29%-34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains.

Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant.

Trial registration: ClinicalTrials.gov identifiers: NCT00969709, NCT01377194, NCT00969150, and NCT01034462 and EudraCT identifier: 2006-002404-34.

Figures

Figure 1.

Patient Distribution by Baseline Functional Impairment Severity on the SDS Scores (completer population) aFor SDS subscales, analyses only include patients who had a valid assessment at baseline with at least 1 corresponding postbaseline assessment and who completed treatment (work/school: placebo, n = 744 and levomilnacipran ER, n = 1,055; social life and family life/home responsibilities: placebo, n = 832 and levomilnacipran ER, n = 1,178). bFor SDS average total scores, analysis is based on the mean of any available SDS subscale score(s) in patients who completed treatment (placebo: n = 806, levomilnacipran ER: n = 1,129). cSDS scores for impairment categories: none = 0, mild = 1–3, moderate = 4–6, marked = 7–9, extreme = 10, moderate-extreme = 4–10, marked-extreme = 7–10. Abbreviation: ER = extended release.

Figure 2.

Categorical Shifts in Functional Impairment Severity (completer population) aFor SDS subscales, analyses only include patients who had a valid assessment at baseline with at least 1 corresponding postbaseline assessment and who completed treatment. bFor SDS average total scores, analysis is based on the mean of any available SDS subscale score(s) in patients who completed treatment. cSDS scores for impairment categories: moderate-extreme = 4–10, marked-extreme = 7–10, moderate-none = 6–0, mild-none = 3–0. *P < .0001. †P < .001. ‡P < .01. Abbreviation: ER = extended release.