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Current concepts of the mechanism of depressive illness have shifted from neurotransmitters to defects in nerve-cell growth (neurogenesis) in subcortical brain areas known to modulate mood and emotion. These researchers tested an experimental (non–FDA-approved) antidepressant, NSI-189, which has increased neurogenesis in the hippocampus in animal models of depression.
Primary outcomes in the manufacturer-funded study were safety and pharmacokinetics. The 24 participants, all with major depression, received 28 days of NSI-189 at one of three doses (40 mg daily, twice daily, or three times a day) or placebo. Analyses combined results from all three doses. The drug was well tolerated.
In exploratory analyses, the 18 NSI-189 recipients had signif…