Transdermal nicotine in non-smokers: A systematic review to design COVID-19 clinical trials

Highlights

• It has been hypothesized that nicotine use has a protective effect against COVID-19 infection.

• Tobacco use will never be the solution or a way to prevent illness.

• 33 studies report useful data on the use of transdermal nicotine to treat non-smokers with a variety of medical conditions.

• In 7.1% of cases included in these 33 studies, side effects required treatment to be stopped.

• Treatment initiation with a low dose of nicotine (for example, 3.5 mg/24 h) is suitable.

• A 2-week gradual increase of dose increases acceptance.

• Final target dose of 14 mg/24 h seems safe.

• There is a need for better assessment of the risk of nicotine dependence in such situations.

Abstract

Recent data show an interaction between COVID-19 and nicotine and indicate the need for an assessment of transdermal nicotine use in non-smokers. Assessments have been conducted into the short-term cognitive effects of nicotine and into diseases such as Parkinson's, Tourette syndrome, ADHD or ulcerative colitis.

Methods

Analyses of nicotine administration protocols and safety were conducted after reviewing Medline and Science Direct databases performing a search using the words [transdermal nicotine] AND [non-smoker] AND selected diseases.

Results

Among 298 articles identified, there were 35 reviewed publications reporting on 33 studies of non-smokers receiving transdermal nicotine for > 48 hours. In the 16 randomized trials, 7 crossover, 1 case/control and 9 open studies patients received an initial nicotine dose of between 2.5 mg and 15 mg/day. In 22 studies, daily doses increased by 2 to 7 steps in 3 to 96 days until the dose was between 5 mg and 105 mg/day. The target nicotine dose was 19.06 ± 20.89 mg/day. The 987 non-smokers (534 never-smokers, 326 ex-smokers and 127 classified as “non-smokers”) received or did not receive nicotine. The most common side-effects were nausea and skin itching. Forty-three (7.1%) non-smokers stopped treatment because of an adverse event of nicotine. No hospitalization related to nicotine side-effects were reported.

Conclusion

Despite a relatively safe tolerance profile, transdermal nicotine therapy in non-smokers can only be used in clinical trials. There is a lack of formal assessment of the potential risk of developing a tobacco addiction. This review offers baseline data to set a transdermal nicotine protocol for non-smokers with a new purpose.