The effects of JNJ-39393406 a positive allosteric nicotine modulator on mood and cognition in patients with unipolar depression: A double-blind, add-on, placebo-controlled trial

Nicotinic agonists have been shown to improve cognition and mood, but this improvement is inconsistent and short-lived, possibly due to receptor desensitization. Positive Allosteric Modulators (PAMs) of the nicotinic alpha-7 nicotinic-acetyl-choline receptor (a7nAChR) are hypothesized to change the configuration of the nicotinic receptor and delay desensitization, potentially increasing the duration of the activation of the receptor, and improving clinical efficacy. This was a randomized controlled trial (RCT) adding JNJ-39393406 9 (a PAM of the a7nAChR) (n=35) or placebo (n=36) to treatment as usual for two weeks in 71 patients with unipolar depression. Mixed models for repeated measures analyses were performed Primary outcome measures were the Brief Assessment of Cognition in Schizophrenia (BACS) composite and the Montgomery-Asperg Depression Rating Scale (MADRS) scores. The drug was well tolerated, however mixed models for repeated measures comparing JNJ-39393406 to placebo showed no significant difference for MADRS total score (p=0.78), BACS composite score (p=0.34), or any of the secondary outcome measures. There was no significant difference in adverse events between the study groups (p=0.44). In conclusion, this study's findings do not support the hypothesis that a positive nicotinic receptor modulator can improve cognitive or depressive symptomatology in patients with unipolar depression.