Abstract
OBJECTIVE: Late-life depression (LLD) is characterized by poor antidepressant response and cognitive dysfunction. This study examined whether transdermal nicotine benefits mood symptoms and cognitive performance in LLD. METHODS: In a 12-week open-label outpatient study conducted between November 2016 and August 2017, transdermal nicotine was given to 15 nonsmoking older adults (≥ 60 years of age). Eligible participants met DSM-IV-TR criteria for major depressive disorder with ≥ 15 on the Montgomery-Asberg Depression Rating scale (MADRS) and endorsed subjective cognitive impairment. Transdermal nicotine patches were applied daily and titrated in a rigid dose escalation strategy to a maximum dose of 21.0 mg/d, allowing dose reductions for tolerability. The primary mood outcome was MADRS change measured every 3 weeks, with response defined as ≥ 50% improvement from baseline and remission as MADRS score ≤ 8. The primary cognitive outcome was the Conners Continuous Performance Test (CPT), a test of attention. RESULTS: Robust rates of response (86.7%; 13/15 subjects) and remission (53.3%; 8/15 subjects) were observed. There was a significant decrease in MADRS scores over the study (β = -1.51, P < .001), with improvement seen as early as 3 weeks (Bonferroni-adjusted P value = .004). We also observed improvement in apathy and rumination. We did not observe improvement on the CPT but did observe improvement in subjective cognitive performance and signals of potential drug effects on secondary cognitive measures of working memory, episodic memory, and self-referential emotional processing. Overall, transdermal nicotine was well tolerated, although 6 participants could not reach the maximum targeted dose. CONCLUSIONS: Nicotine may be a promising therapy for depressed mood and cognitive performance in LLD. A definitive placebo-controlled trial and establishment of longer-term safety are necessary before clinical usage. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02816138.