• Psychopharmacology
• Mood Disorders
• Psychiatry Clinical Trials

• Psychopharmacology
• Mood Disorders
• Psychiatry
• Psychiatry Clinical Trials

Gregory M. Asnis, MD, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, USA, presented a poster with results of a Phase 3 trial to evaluate the efficacy and tolerability of levomilnacipran extended-release (ER) dose in adult patients with major depressive disorder (MDD)[APA2014 (poster NR6–087); NCT00969709]. The results of the study indicated that higher doses of levomilnacipran ER may benefit some patients, including those with moderate to severe depression.

Levomilnacipran ER, a potent, selective serotonin and norepinephrine reuptake inhibitor (SNRI), is approved for use in the treatment of MDD in adults, with dose-proportional pharmacokinetic effects demonstrated in some studies [Chen L et al. APA 2013 (poster NR9–37)].

To be included in the 8-week, double-blind, multicenter, parallel-group, placebo-controlled study, patients were required to be 18 to 65 years and meet DSM-IV-TR criteria for MDD, with a current major depressive episode ≥8 weeks, and a score of ≥30 on the Montgomery-Asberg Depression Rating Scale (MADRS). Patients were randomized to placebo (n=179) or once-daily levomilnacipran ER 40 mg (n=181), 80 mg (n=181), or 120 mg (n=183); doses were initiated at 20 mg and titrated to the target dose over 7 days.

Exclusion criteria included patients with various psychiatric conditions, as well as nonpsychiatric conditions that may interfere with the study. Those with a history of nonresponse to ≥2 antidepressants were also excluded.

In the intention-to-treat (ITT) patient population, the primary outcome was the change in MADRS total score from baseline to the end of Week 8. Secondary outcome was Sheehan Disability Scale (SDS) total score.

Least squares mean difference (LSMD) was used to assess the relationship between levomilnacipran dose and efficacy. Compared with placebo, the LSMD for depressive symptoms (MADRS total score change) was significantly different (p=0.0186; p=0.0038; p=0.0005) for all levomilnacipran ER dose groups (40 mg, −3.23; 80 mg, −3.99; 120 mg, −4.86). The data also suggested a linear relationship between dose and efficacy.

In patients with more severe MDD (baseline MADRS ≥35), LSMD values demonstrated that improvements in depressive symptoms were significantly greater in the 80 mg (−5.14; p=0.0098) and 120 mg (−6.21; p=0.0016) groups, but not in the 40 mg group (−3.81; p=0.0558).

On the SDS, the LSMD was also significantly different for the levomilnacipran ER 80 mg (−2.51; p=0.0151) and 120 mg (−2.57; p=0.0141) groups but not for the 40 mg group (−1.41; p=0.1687).

Levomilnacipran ER was generally well-tolerated across the dosage groups. Serious adverse events (AEs) occurred in ≤2% of patients in all treatment groups, with no deaths reported. The incidence of treatment-emergent adverse events (TEAEs) was 63.6% in the placebo group, and was similar across all three levomilnacipran ER dosage groups (40 mg, 75.8%; 80 mg, 82.7%; 120 mg, 76.7%). However, a dose-related effect was observed for urinary hesitation and erectile dysfunction, which occurred in 6.1% and 9.5% of patients in the 120-mg group, respectively.

In summary, higher doses of levomilnacipran ER are associated with greater improvements in MADRS and SDS, with no overall increase in the incidence of TEAEs with higher doses. Higher doses of levomilnacipran ER may therefore benefit some patients with MDD, including those with more severe symptoms, concluded Dr. Asnis.

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