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.

Informations de copyright

Copyright © 2021. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Conflicts of Interest Michael Davidson: Dr. Davidson is an employee and owns stock options of Minerva Neurosciences, a Biotech developing CNS drugs. Linda Levi: Ms. Levi has no potential conflicts of interest to disclose. Jinyoung Park: Ms. Park has no potential conflicts of interest to disclose. Igor Nastas: Dr. Nastas has no potential conflicts of interest to disclose. Lisa Ford: Dr. Ford is an employee of Johnson and Johnson. Stefanie Rassnick: Dr. Rassnick is an employee of Johnson and Johnson. Carla Canuso: Dr. Canuso is an employee of Johnson and Johnson. John Davis: Dr. Davis has no potential conflicts of interest to disclose. Mark Weiser: Over the past 36 months Dr. Weiser has received payment for advisory boards/ fees/speaker fees/performed PANSS training from Teva, Jansen, Dexel and Lundbeck.