HOLLYWOOD, FLA. – Levomilnacipran SR resulted in significant improvement in cognitive measures of attention and information processing in a phase 3 trial conducted in patients with major depressive disorder; the drug was approved July 25 by the Food and Drug Administration under the trade name Fetzima.*
Attention deficits are commonplace in patients with major depressive disorder (MDD). In the phase 3 study, improvement in MDD in levomilnacipran SR–treated patients was accompanied by gains in measures of attention. A question that will need to be addressed in future studies is whether the observed improvement in attention deficits results from a direct drug effect upon brain structures controlling attention or is a secondary by-product of reduced depressive symptoms, Keith A. Wesnes, Ph.D., noted at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.
Dr. Keith Wesnes
Levomilnacipran SR is a selective serotonin and norepinephrine reuptake inhibitor. Its norepinephrine reuptake potency is twice as great as its serotonin reuptake potency. In addition, levomilnacipran SR is greater than 10-fold more selective for norepinephrine reuptake inhibition than either duloxetine or venlafaxine.
The 8-week, double-blind, phase 3 clinical trial included 429 patients with MDD who were randomized to once-daily levomilnacipran SR at 40-120 mg or placebo. This was a severely depressed population as reflected in their mean baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score of 35, said Dr. Wesnes, professor of psychology at Northumbria University in Newcastle, England, and an employee of Bracket, a pharmaceutical industry consulting firm.
A MADRS total score reduction of at least 50% was achieved in 42% of the levomilnacipran SR group compared with 29% of controls. These MADRS responders on levomilnacipran SR also displayed significant improvement from baseline in several measures of attention. In contrast, placebo-treated controls and MADRS nonresponders on levomilnacipran SR did not.
During the course of the 8-week study, cognitive assessments carried out using the Cognitive Drug Research System for Attention demonstrated that MADRS responders on levomilnacipran SR had significant improvement over time on computerized tasks measuring power of attention, continuity of attention, reaction time variability, and digit vigilance task accuracy.
For example, levomilnacipran SR–treated MADRS responders improved their digit vigilance task accuracy by 3.1-U over baseline, while levomilnacipran SR–treated MADRS nonresponders had a 0.8-U decrease in performance, placebo-treated MADRS nonresponders averaged a 1.8-U decrease, and placebo-treated MADRS responders had a 1.5-U decline.
Arguing in favor of the possibility that the antidepressant medication improves attention deficits in MDD through direct action upon brain structures controlling attention is the observation that baseline measures of cognition correlated poorly with baseline MADRS depression symptoms or with changes in depressive symptoms during treatment, according to Dr. Wesnes.
He is an employee of Bracket, which was funded by Forest Laboratories and Pierre Fabre to conduct this analysis.
*This story was updated 7/29/2013.