Depressed Mood Improvement Through Nicotine Dosing 2

• Status: Recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Deficits in cognitive control are core features of late-life depression, 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 CCN deficits in LLD. Supported by pilot data, Investigators propose that nicotine acetylcholine receptor agonists enhance CCN function and resultantly improve mood and cognitive performance in late-life depression. The objective of this initial R61-phase trial is to first determine whether transdermal nicotine enhances CCN neural activity in an exposure-dependent fashion during an emotional response inhibition task (the emotional Stroop task). Investigator's approach for the R61 phase is to examine in 36 older adults with Major Depressive Disorder whether transdermal nicotine patches enhance CCN activity over 12 weeks as measured during fMRI with the emotional Stroop task while measuring nicotine and nicotine metabolite levels. Transdermal nicotine has a mechanism of action that is distinct from current antidepressants, potentially making it a potentially important antidepressant augmentation agent. If hypotheses are correct, as patches are commercially available, this approach could be rapidly moved into definitive studies and may have applicability to other psychiatric disorders characterized by CCN dysfunction.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Treatments: Nicotine

Criteria

Inclusion Criteria:

1. Age > 60 years;

2. Diagnosis of major depressive disorder, single or recurrent episode (DSM5);

3. On a stable therapeutic dose of an allowed SSRI or SNRI for at least 8 weeks;

4. Severity: Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 15;

5. Cognition: Mini-Mental State Examination (MMSE) score ≥ 24;

6. Fluent in English

Exclusion Criteria:

1. Other Axis I psychiatric disorders, except for generalized anxiety disorder (GAD) symptoms occurring in a depressive episode;

2. Use of other medications for depression, e.g., bupropion or augmenting agents, although short-acting sedatives are allowed (see below);

3. Any use of tobacco or nicotine in the last year;

4. Living with a smoker or regular exposure to secondhand smoke;

5. History of alcohol use disorder or substance use disorder of moderate or greater severity (endorsing 4 or more of the 12 criteria) in the last 12 months;

6. Acute suicidality;

7. Acute grief (<1 month);

8. Current or past psychosis;

9. Primary neurological disorder, including dementia, stroke, epilepsy, etc.;

10. MRI contraindication;

11. Electroconvulsive therapy or transcranial magnetic stimulation in last 2 months;

12. Current or planned psychotherapy;

13. Allergy or hypersensitivity to nicotine patches;

14. In the last 4 weeks, regular use of drugs with central cholinergic or anticholinergic properties or moderate / severe CYP2A6 inhibitors /inducers.