The effect of transdermal nicotine on mood and cognitive symptoms in late life depression

Background: Late Life Depression (LLD) is characterized by a poor antidepressant response and by poorer cognitive performance. Preliminary data suggest that nicotine may improve mood in midlife and may improve performance in cognitively impaired populations. We conducted a pilot trial to determine whether transdermal nicotine (TDN) might benefit mood and cognitive performance in LLD. Methods: Fifteen depressed older adults (14 completers) enrolled in a 12-week open-label trial of TDN. Participation required a > 15 score on the MADRS and subjective cognitive impairment, defined by the Cognitive Complaint Index. Participants were seen every three weeks with TDN titration dependent on tolerability, up to a maximum dose of 21.0 mg/ day. Primary outcomes included the MADRS for depression, the Memory Frequency Questionnaire (MFQ) for subjective cognitive complaints, and the Conner's Continuous Performance Task (CPT) for objective cognitive performance. Results: Thirteen participants were responders (87%) and 8 were remitters (53%; final MADRS < 7). MADRS score decreased over time (slope = -1.51, p-value < 0.001), with a mean change of 18.29 (SD=6.15) and change from baseline at week 3 (Bonferroni-adjusted p-value = 0.0036). MFQ score increased (better performance) over time by 23.64 (SD=40.96, t=2.16, p=0.0500). We did not observe a statistically significant change in the CPT, but did observe improvement in performance on secondary cognition outcomes, including the Cogstate shopping list task (immediate recall; 3.36, SD=5.80, p=0.0486) and the one-back test (working memory speed;-0.04 (0.07), p=0.0494). Conclusions: Nicotine may be a promising therapy for LLD. However, definitive target engagement and a controlled trial is necessary before clinical usage.