Combination nicotine replacement therapy for smoking cessation: Rationale, efficacy and tolerability

C. T. Sweeney, R. V. Fant, K. O. Fagerstrom, J. F. McGovern, J. E. Henningfield

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Currently available nicotine replacement therapy (NRT) medications provide effective treatment for tobacco dependence, typically doubling success rates compared with placebo. A strategy for further improving the efficacy of NRT is to combine one medication that allows for passive nicotine delivery (e.g. transdermal patch) with another medication that permits ad libitum nicotine delivery (e.g. gum, nasal spray, inhaler). The rationale for combining NRT medications is that smokers may need both a slow delivery system to achieve a constant concentration of nicotine to relieve cravings and tobacco withdrawal symptoms, as well as a faster acting preparation that can be administered on demand for immediate relief of breakthrough cravings and withdrawal symptoms. This article reviews 5 published studies that have examined the effectiveness of combination NRT compared with monotherapy in providing withdrawal relief and smoking cessation, and examines other factors relevant to the promotion of combination NRT for treating tobacco dependence. The data show that there are conditions under which combinations of NRT products provide greater efficacy in relieving withdrawal and enabling cessation than monotherapy, but the findings are not robust and additional research is warranted to better understand the magnitude and generality of the benefits of combination therapy. There are also regulatory and commercial obstacles that must be considered. Nonetheless, combination NRT has the potential to provide effective treatment of tobacco dependence in persons whose dependence is refractory to currently available treatments.

Original languageEnglish (US)
Pages (from-to)453-467
Number of pages15
JournalCNS Drugs
Issue number6
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Neuropsychology and Physiological Psychology
  • Pharmacology


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