Depressed Mood Improvement Through Nicotine Dosing 2
Condition: Depressive Disorder
MeSH terms: Depressive Disorder
Intervention: Transdermal Nicotine patch
Intervention description: Participants will begin a 12- week open label trial of transdermal nicotine patch during the day and remove it at night (16 hours). Dose titration starting at 3.5 mg patch/daily to maximum of 21mg patch/daily.
After week 12 , dose will be slowly tapered over 3 weeks.
Intervention MeSH terms: Nicotine
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No
Keywords: geriatrics; aging; elderly; cognition; memory; nicotine transdermal patch; depression

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.
    

Eligibility 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 selective serotonin reuptake inhibitor
             (SSRI) or serotonin-norepinephrine reuptake inhibitor (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.