Depressed Mood Improvement Through Nicotine Dosing-3 (Depressed MIND3) Extension

Deficits in cognitive control are core features of late-life depression (LLD), contributing both to emotion dysregulation and problems with inhibiting irrelevant information, conflict detection, and working memory. Clinically characterized as executive dysfunction, these deficits are associated with poor response to antidepressants and higher levels of disability. Improvement of cognitive control network (CCN) dysfunction may benefit both mood and cognitive performance, however no current pharmacotherapy improves Cognitive Control Network deficits in LLD. The study examines the hypothesis that nicotine acetylcholine receptor agonists enhance Cognitive Control Network function. This effect may resultantly improve mood and cognitive performance in LLD. Small, open-label studies of transdermal nicotine (TDN) patches have supported potential clinical benefit and provided support that transdermal nicotine administration engages the Cognitive Control Network. This is an open-label, extension to the blinded Depressed MIND 3 (Depressed Mood Improvement through nicotine dosing) study. It will evaluate longer-term safety and efficacy of Transdermal Nicotine Patches for potential benefit in cognitive and depression outcomes in elderly depressed participants. Subjects complete blinded randomized trial of Depressed MIND-3 will be eligible for continuation in this extension. This extension study will consist of up to 12 weeks of treatment and a 3 -week safety follow-up period.

NCT Number	NCT05746546
Lead Sponsor	Vanderbilt University Medical Center Collaborators: National Institute of Mental Health (NIMH), University of North Carolina, Chapel Hill
Conditions	Depressive Disorder
Enrollment	25 participants
Start Date	2023-04-15
Primary Completion	2026-07-09 (estimated)
Study Completion	2026-07-09 (estimated)
Updated on ClinicalTrials.gov	2026-08-06