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After years of disappointing clinical trial results for psychiatric drugs, many researchers believe that it is time to start thinking about mood disorders in terms of their composite symptoms. Major depressive disorder (MDD), for example, might need different drugs to manage fatigue, anhedonia and cognitive dysfunction. The FDA's rejection of Takeda and Lundbeck's application for a supplemental approval for vortioxetine deals a temporary delay to this approach.

Vortioxetine is a serotonin modulator and stimulator that the FDA approved for the treatment of MDD in 2013. Lundbeck and Takeda were seeking a supplemental approval to market the drug for the treatment of cognitive dysfunction in MDD, which would have helped it stand out from a crowded antidepressant market.

The application was based on data from three clinical trials, which showed improvements in the Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT), two measures of cognitive function. Although an independent panel of advisors to the FDA voted 8 to 2 that these data supported the efficacy claim in February, the agency rejected the application in March.

“We were disappointed to get a negative action from the FDA,” said Stevin Zorn, executive scientist in residence at Lundbeck Research USA, a subsidiary of Lundbeck. But he added that the discussion showed that the FDA recognizes the importance of cognitive dysfunction as a key component of MDD, and that they viewed it as a legitimate target for drug development. “This was just the beginning.” The next step, he says, is for the field to develop new clinical endpoints that are sensitive and robust enough to measure changes in the different symptoms of mood disorders.

Earlier this year, regulators in Europe supported the approval of vortioxetine for cognitive dysfunction in MDD.