Late-life depression (LLD) in adults 60 years and older is characterized by poor antidepressant response and cognitive decline. Even with successful antidepressant treatment, cognitive performance in LLD patients often does not return to previous levels. As the population ages, this has far-reaching implications for quality of life and for the healthcare burden associated with cognitive dysfunction.
A new study published in the Journal of Clinical Psychiatry looked at the benefits of transdermal nicotine for both mood symptoms and cognitive performance in LLD. It is the first trial testing transdermal nicotine in the context of LLD and supports its further investigation as a novel treatment for improving mood and preventing cognitive decline.
“We started studying nicotine in the context of memory disorders,” said Warren Taylor, M.D., director of Geriatric Psychiatry at Vanderbilt University Medical Center. “In addition to preliminary work on cognition in older adults, animal models show that nicotine has benefits for mood. We thought it would be interesting if it had the same impact in late-life depression. Based on our earlier work, we were really excited about it.”
Nicotine Improved Depression SYMPTOMS
In the 12-week, open-label outpatient study, transdermal nicotine was given to 15 older adults (≥ 60 years of age) with no tobacco or nicotine use in the last year. Eligible participants met DSM-IV-TR criteria for major depressive disorder with ≥15 on the MADRS scale and endorsed subjective cognitive impairment, meaning they felt their memory performance had deteriorated. Participants could be antidepressant-free or on monotherapy for depression for at least 8 weeks.
Additional exclusion criteria included other psychiatric disorders, history of alcohol or drug abuse over last three years, primary neurologic disorders including dementia, regular use of cholinergic or anticholinergic drugs in last four weeks and current psychotherapy. Depression severity by MADRS and neuropsychiatric assessments were conducted every three weeks. Secondary measures included specific symptom questionnaires administered at baseline and Week 12.
“Thirteen of 15 participants had a clinically relevant response and eight reached remission.”
“We actually saw a robust improvement in depression severity,” Taylor said. “Thirteen of 15 participants had a clinically relevant response and eight reached remission. It didn’t matter if you took the nicotine with another antidepressant medication — both groups did well. And it didn’t matter if you had a history of smoking.”
LLD and Cognitive Function
In general, people with LLD score lower on memory tests and have a higher risk of developing dementia. “It’s unclear why people with depression are prone to dementia,” Taylor said, “but we know that having repeated periods of depression over your life is not good for cognitive performance. If we can treat the depression earlier, maybe we can prevent some of the decline.”
Over the course of the trial, participants’ subjective cognitive performance significantly improved with nicotine treatment, with mean Memory Functioning Questionnaire (MFQ) score increasing by 23.64 points. Mean PROMIS score (representing improved subjective functioning) increased by 6.21 points from baseline to Week 12. Improvements were also observed in performance on some secondary cognitive measures, including working memory, episodic memory and immediate recall.
Some participants experienced expected side effects like dizziness and nausea with high doses of nicotine. “We kept people at a dose they could tolerate,” Taylor said. “Regardless of whether participants tolerated the higher dose or could only tolerate a moderate dose, dose didn’t seem to be related to improvement.”
Once taken off the nicotine patches, participants were followed for several weeks to track withdrawal symptoms, cravings or other adverse effects. “As this is a short-term study, we don’t know what the long-term effects would be,” Taylor said. “Addiction to nicotine may or may not be an issue.”
Next in Transdermal Nicotine Research
Taylor’s research team has submitted a proposal for a two-phase, multi-site study to include 90 participants. “Our next step is a more robust placebo-controlled trial to see if we can replicate this data,” he said. “We know there are genetic differences in how people metabolize nicotine; we plan to monitor drug levels to find out the optimal dose we need to use to get people really better.”