SAN ANTONIO, TX—Levomilnacipran extended-release (ER) significantly improved overall symptoms of depression in patients with major depressive disorder (MDD) and cognitive difficulties, according to results of post hoc analyses of a Phase 3 study reported at the U.S. Psychiatric & Mental Health Congress.
Also improved was functional impairment and cognition/attention, noted Roger S. McIntyre, MD, of the Mood Disorder Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada, and colleagues.
The 8-week multicenter, randomized, double-blind, placebo-controlled trial in 857 patients with MDD studied flexible dose levomilnacipran ER 40–120mg daily. Mean daily dose was approximately 75mg daily. Previously reported results showed a mean improvement in MADRS total score of -15.3 for levomilnacipran ER vs. -12.2 for placebo (P=0.0051).
Key inclusion criteria were adults with a DSM-IV-TR diagnosis for MDD, an ongoing major depressive episode of 4 weeks or greater in duration and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of ≥30.
Efficacy analyses included all patients who received 1 or more doses of double-blind treatment and had 1 or more post-baseline MADRS assessments.
The primary and secondary efficacy parameters were mean change from baseline to Week 8 in MADRS total score and Sheehan Disability Scale (SDS). The study also used Cognitive Drug Research Systems data to assess the effect of levomilnacipran ER on 2 composite measures of attention, the Power of Attention, which reflects the ability to temporarily focus attention and process information efficiently, and Continuity of Attention, which reflects the ability to sustain attention.
Using data from the study, two path analysis models were conducted to evaluate the direct effect of levomilnacipran ER on functional impairment, reflected in SDS total score change, and indirect effects the MADRS total score change and POA score change (Model 1) or COA score change (Model 2).
Patients had significantly greater improvements in POA and COA scores with levomilnacipran ER vs. placebo, with treatment group differences (by least squares mean) larger in the higher cognitive impairment subgroups (categorized as POA ≥1303 or COA <02; n=411) compared with the population overall.
Also, “in the higher cognitive impairment subgroups, placebo-treated patients had a mean worsening in cognitive impairment that was significantly different from the mean improvement in levomilnacipran ER-treated patients,” Dr. McIntyre noted.
In Model 1, 80.9% of the effect of levomilnacipran ER on SDS total score change was indirect (through MADRS total score change), while 11.1% of the effect was direct and 8.0% was indirect, through POA score change.
In Model 2, the 48.4% effect of the agent on SDS total score change was direct, with 51.2% an indirect effect through MADRS total score change and the remaining 0.3% also indirect, through COA score change.
“Future path analyses using objective measures of functional impairment are warranted,” the authors recommended. Also needing investigation is whether baseline differences in cognition scores impact treatment response.