Improving Rates of Functional Response in Major Depressive Disorder

San Francisco—Patients with major depressive disorder who received 80 mg or 120 mg of levomilnacipran sustained release had significant functional improvement and greater rates of functional response compared with a placebo group, according to post hoc analyses of a randomized, double-blind, phase 3 trial.

Results were presented during a poster session at the APA meeting. The poster was titled Effects of Levomilnacipran SR 40, 80, and 120 mg on Functional Outcomes in Major Depressive Disorder: Post Hoc Analyses of a Phase III Trial.

In July, the FDA approved levomilnacipran to treat major depressive disorder, which is associated with functional impairment and a negative impact on physical, social, and psychological well being. The drug is a potent and selective serotonin and norepinephrine reuptake inhibitor taken once daily. Levomilnacipran’s potency for norepinephrine is approximately 2 times greater than it is for serotonin reuptake inhibition.

The study included 3 phases: (1) a single-blind placebo run-in period lasting 1 week, (2) an 8-week double-blind treatment period, and (3) a 2-week double-blind down-taper period. During the double-blind treatment period, patients were randomized in a 1:1:1:1 ratio to receive placebo, 40 mg of levomilnacipran, 80 mg of levomilnacipran, or 120 mg of levomilnacipran once daily.

Patients were included if they were from 18 to 65 years of age and had major depressive disorder, an ongoing major depressive disorder lasting at least 8 weeks, normal physical examination findings, clinical laboratory results, and electrocardiogram results. At baseline, they were required to have a clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 30 as well as a score of at least 26 on the self-rated version of MADRS. Patients were excluded if they had a history of a depressive episode with psychotic features, manic or hypomanic episode, obsessive-compulsive disorder, schizophrenia, or other psychotic disorder.

Mean age of the 704 patients was approximately 41 years, 60% were women, and 75% were white. At baseline, the mean MADRS score was 36 and the mean Sheehan Disability Scale (SDS) score was 21.

Compared with the placebo group, patients in the 80-mg and 120-mg levomilnacipran groups had significantly greater improvements in SDS score after 8 weeks of treatment. In addition, significantly more patients in the 80-mg and 120-mg levomilnacipran groups met SDS response criteria compared with the placebo group. The rates of SDS remission were higher in the levomilnacipran groups, but the differences were not significant.

Among patients with severe depression, patients who received 120 mg of levomilnacipran had significant improvements in SDS score, a significantly greater response rate, and a significantly greater rate of functional remission compared with the placebo group.

The study also found that patients who received any dose of levomilnacipran had significantly greater improvements in MADRS total scores compared with patients in the placebo group. Further, patients in the 80-mg and 120-mg levomilnacipran groups had significant improvements on the 17-item Hamilton Depression Rating Scale and the Clinical Global Impression-Severity and Improvement scales.

Patients also tolerated the drug. The most common treatment-related adverse events were headache, nausea, and constipation.

This study was supported by Forest Laboratories, Inc.