Nicotine Patch May Help Late-Life Depression

Deborah Brauser

March 21, 2018

HONOLULU, Hawaii — Transdermal nicotine treatment can decrease depressive symptoms in patients with late-life depression, new research suggests.

Jason Gandelman

An open-label pilot study of 15 nonsmoking older patients with major depressive disorder (MDD), as well as cognitive impairment, showed a significant decrease in score on the Montgomery-Åsberg Depression Rating Scale (MADRS) between baseline and week 12 of treatment (the primary mood outcome), with significant improvement seen as early as 3 weeks.

The primary cognitive outcome, improvement on the attention-assessing Conners Continuous Performance Test (CPT), was not statistically significant over time. However, there was a significant improvement for the secondary cognitive domains assessed, including executive function and working memory.

Lead author Jason A. Gandelman, a medical student at Vanderbilt University School of Medicine, Nashville, Tennessee, told Medscape Medical News that, to his knowledge, this is the first assessment of this treatment for depression in older patients.

"And we were pleasantly surprised with the results. We found an over 86% response to nicotine in our small sample and an over 50% remission rate. This is comparable if not better than open-label trials for currently available antidepressants," said Gandelman.

"It also targets a new mechanism and doesn't have some of the same side effects that other antidepressants have. Notably, we saw moderate weight loss with nicotine," rather than the weight gain commonly seen after use of antidepressants, he added.

The findings were presented here at American Association for Geriatric Psychiatry (AAGP) 2018.

Historically Poor Response

"Late-life depression has relatively poor treatment response, with less than 50% of people responding to their first antidepressant treatment. And late-life depression is different from normally developing depression in that there's both a mood and cognitive element to it. So we were looking for a treatment that could potentially benefit both of those things," said Gandelman.

Nicotine plays a neuromodulatory role in regions of the cognitive control network through nicotinic cholinergic receptor agonism, report the investigators.

"It's something that has been talked about in the literature, in some really small trials with animals and small trials in humans — but not in older adults. Because those studies did show some efficacy, we were interested in evaluating nicotine for late-life depression ourselves," Gandelman said.

The investigators enrolled 15 participants (66.7% women, 93.3% white) who were older than 60 years (mean age, 64.9 years), whose baseline MADRS score was greater than 15, and whose score on the Cognitive Complaint Index was greater than 20%. None had used tobacco or nicotine during the previous year.

The mean baseline MADRS score was 26.4, with 1.5 MDD episodes per year. Eight participants were past smokers.

The patients were told to wear the nicotine patch during the day and to take it off at bedtime. The initial dose was 3.5 mg/day for the first week. The dose was titrated to as high as 21.0 mg/day during the 12-week study.

The final patch dose was 21.0 mg/day for eight of the patients, 10.5 mg/day for four patients, and 7 mg/day for three patients. The mean final patch dose was 15.4 mg/day.

Mood Improvements

Primary mood results showed a significant change over time on the MADRS (P < .001), which persisted after controlling for smoking history, concurrent use of an antidepressant, and final patch dose.

Improvement in total MADRS score was significantly better at 3 weeks (P = .004), 6 weeks (P = .006), 9 weeks (P = .004), and 12 weeks (P = .004).

Two secondary mood measures also showed significant improvements at 12 weeks: the Apathy Evaluation Scale (P < .001) and the Ruminative Response Scale (P = .002).

Treatment response, defined as a decrease of at least 50% in the MADRS score, was achieved by 13 of the 15 participants. Eight participants experienced remission, defined as a final MADRS score of 8 or less.

Change on the CPT was not significant (P = .76). However, there were significant improvements on the eight-item PROMIS Applied Cognition–Abilities questionnaire (P = .001), the Memory Frequency Questionnaire, the One-Back speed test of working memory, and the Cogstate Shopping List Recall (for all, P = .049).

Gandelman noted that there were no serious adverse events (AEs). "The most significant AE was nausea — and most AEs were not dose-limiting," he said.

Preliminary "but Encouraging"

Seven patients reported nausea, which was dose-limiting in four patients. Dizziness was reported by four patients, and tension/anxiety was reported by three patients; these symptoms were dose-limiting in two patients in each group. Four patients also reported headache, which was dose-limiting in one. Three patients each reported vivid dreams and skin irritation, but these symptoms were not dose-limiting. One patient voluntarily withdrew from the study because of "light-headedness."

The only significant changes in vital signs were in weight loss (mean decrease, 6.7 pounds) and in body mass index (mean decrease, 1.0 kg/m2; for both, P < .001).

After the study ended, a few participants reported that their symptoms had improved to such an extent that they wanted to continue with the treatment, said Gandelman.

"They purchased the nicotine patch on their own, which is another advantage of this medication: it's already approved for smoking cessation and available over the counter," he said.

The investigators have now submitted grants for a "target engagement trial," which will involve assessment with functional MRI, and for a larger randomized, placebo-controlled trial.

"I think this study was promising, with some people showing real improvement," principal investigator Warren D. Taylor, MD, professor in the Department of Psychiatry and director of the Division of Geriatric Psychiatry at Vanderbilt, told Medscape Medical News.

"I'd caution others, 'Don't go out and do this in your own patients yet,' as we're going to do more definitive studies. But I think these preliminary data are very encouraging," said Taylor.

Compelling Concept

Approached for comment, Jeff Buenjemia, MD, a psychiatrist affiliated with Providence Milwaukie Hospital, Oregon, told Medscape Medical News that the poster highlighted a compelling concept.

"I thought this was very interesting, as it applies to late-life depression. I'd actually thought about doing the same thing in my own previous practice for patients with schizophrenia. However, since so many of them already smoke, it's hard to get a nicotine-free population," said Buenjemia.

Although the study was very small, the findings look promising, "except that the investigators showed improvements in mood but not in certain areas of cognition," he noted.

"Still, it's an interesting concept with a nice delivery system that's easily trackable. It's always nice to be able to have a larger armamentarium," Buenjemia concluded.

The study was funded by a grant from the National Institutes of Health and by a Clinical and Translational Science award from the National Center for Advancing Translational Sciences. Dr Gandelman and Dr Buenjemia have disclosed no relevant financial relationships.

American Association for Geriatric Psychiatry (AAGP) 2018 Annual Meeting. Abstract EI-14, presented March 16, 2018.

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