Transdermal Nicotine Boosts Mood and Cognitive Function in Late-Life Depression

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Results showed a significant change in depression severity with a mean MADRS reduction of 18.45 and a response rate of 86.7%.
Results showed a significant change in depression severity with a mean MADRS reduction of 18.45 and a response rate of 86.7%.

According to a study published in the Journal of Clinical Psychiatry, administration of transdermal nicotine in adults with late-life depression (LLD) reduced symptom severity and improved subjective cognitive performance. Robust response and remission rates for older nonsmoking adults using nicotine to treat depression were comparable to the effects of antidepressants.

Previous studies have characterized LLD by impaired cognitive function and a poor response to antidepressants. The investigators of this open-label outpatient study examined whether transdermal nicotine is efficacious in the treatment of LLD, especially in outcomes related to mood and cognitive performance.

The study sample included 15 nonsmokers aged 60 and older who met criteria for major depressive disorder and endorsed subjective cognitive decline. Participants were either antidepressant-free or stabilized on antidepressant monotherapy for at least 8 weeks. During the study, they wore transdermal nicotine patches daily for 12 weeks; the nicotine was administered in a rigid dose escalation strategy to a maximum of 21.0 mg/day with the ability to reduce dosage for tolerability.

Researchers measured mood outcomes every 3 weeks using the Montgomery-Asberg Depression Rating Scale (MADRS), in which a response was defined as ≥50% improvement from baseline and remission was defined as a score ≤8. They also measured objective cognitive outcomes at baseline and week 12 using the Conners Continuous Performance Test for attention and elements of the Cogstate battery for other cognitive domains (executive function, processing speed, episodic and working memory). Subjective cognitive outcomes were based on responses to the Memory Functioning Questionnaire (MFQ) and the PROMIS Applied Cognition–Abilities Questionnaire.

Results showed a significant change in depression severity with a mean MADRS reduction of 18.45 and a response rate of 86.7% (13 out of 15 participants); remission was achieved in 53.3% of the study sample (8 out of 15 participants). The investigators did not observe a significant change in objective cognitive performance. However, subjective cognitive function was significantly improved over time indicated by increases in both mean MFQ scores (23.64 points) and PROMIS scores (6.21). Overall, the study participants adhered to the medication and no serious adverse events were reported; only a single patient stopped the intervention, reporting feelings of confusion and anxiety.

Limitations of the study included the open-label design and a small sample size. The study investigators did not measure plasma levels to determine whether the nicotine dose had an effect on tolerability. Multiple comparisons further limited the study analysis.

Nicotine may be a promising pharmacotherapy, as it improved mood and cognitive symptoms in adults with for LLD. Future placebo-controlled trials are needed to establish long-term efficacy and safety of transdermal nicotine used to treat major depressive disorder in this population.

This study was supported by a grant from the National Institutes of Health, and the Clinical and Translational Science Award from the National Center for Advancing Translational Sciences.

Reference                                                                                                                       

Gandelman JA, Kang H, Antal A, et al. Transdermal nicotine for the treatment of mood and cognitive symptoms in nonsmokers with late-life depression. J Clin Psychiatry. 2018; 79:5. doi:10.4088/JCP.18m12137

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