, Volume 73, Issue 5, pp 407–426 | Cite as

Clinical Strategies to Enhance the Efficacy of Nicotine Replacement Therapy for Smoking Cessation: A Review of the Literature

  • Matthew J. Carpenter
  • Bianca F. Jardin
  • Jessica L. Burris
  • Amanda R. Mathew
  • Robert A. Schnoll
  • Nancy A. Rigotti
  • K. Michael Cummings
Review Article


A number of smoking cessation pharmacotherapies have led to increases in quitting and thus to significant benefits to public health. Among existing medications, nicotine replacement therapy (NRT) has been available the longest, has the largest literature base in support, and is the only option for over-the-counter access. While the short-term efficacy of NRT is well documented in clinical trials, long-term abstinence rates associated with using NRT are modest, as most smokers will relapse. This literature review examines emerging clinical strategies to improve NRT efficacy. After an initial overview of NRT and its FDA-approved indications for use, we review randomized trials in which clinical delivery of NRT was manipulated and tested, in an attempt to enhance efficacy, through (1) duration of use (pre-quit and extended use), (2) amount of use (high-dose and combination NRT), (3) tailoring to specific smoker groups (genotype and phenotype), or (4) use of NRT for novel purposes (relapse prevention, temporary abstinence, cessation induction). Outcomes vary within and across topic area, and we highlight areas that offer stronger promise. Combination NRT likely represents the most promising strategy moving forward; other clinical strategies offer conflicting evidence but deserve further testing (pre-quit NRT or tailored treatment) or offer potential utility but are in need of further, direct tests. Some areas, though based on a limited set of studies, do not offer great promise (high-dose and extended treatment NRT). We conclude with a brief discussion of emergent NRT products (e.g., oral nicotine spray, among others), which may ultimately offer greater efficacy than current formulations. In order to further lower the prevalence of smoking, novel strategies designed to optimize NRT efficacy are needed.


Nicotine Nicotine Replacement Therapy Nicotine Patch Abstinence Rate Point Prevalence Abstinence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by NIH Grants K23DA020482 (MJC) and R01DA021619 (MJC) and with additional support by P30CA138313 at the Hollings Cancer Center. Dr. Burris was supported by T32DA007288 from NIDA.

Conflicts of Interest

Dr. Schnoll serves as a consultant for GlaxoSmithKline and Pfizer. Dr. Rigotti has received royalties for chapters on smoking cessation from UpToDate, Inc., and is an unpaid consultant to Pfizer and Alere. Dr. Cummings has received grant funds from Pfizer and Nabi Pharmaceuticals, has served as consultant to Pfizer, and currently serves as a paid expert witness on behalf of plaintiffs in litigation against the tobacco industry. Drs. Scholl, Rigotti, and Cummings all receive funding from NIH, but funding from their consulting and grants was not used to support the present work. Drs. Carpenter, Jardin, and Burris, and Ms. Mathew do not report any conflicts of interest.


The authors thank Ms. Amy Wahlquist for assistance in preparation of tables.


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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Matthew J. Carpenter
    • 1
    • 2
    • 5
  • Bianca F. Jardin
    • 1
    • 2
  • Jessica L. Burris
    • 1
    • 2
  • Amanda R. Mathew
    • 1
  • Robert A. Schnoll
    • 3
  • Nancy A. Rigotti
    • 4
  • K. Michael Cummings
    • 1
    • 2
  1. 1.Department of Psychiatry and Behavioral SciencesMedical University of South Carolina (MUSC)CharlestonUSA
  2. 2.MUSC Hollings Cancer CenterCharlestonUSA
  3. 3.Department of PsychiatryUniversity of PennsylvaniaPhiladelphiaUSA
  4. 4.Department of Medicine, Harvard Medical SchoolTobacco Research and Treatment CenterBostonUSA
  5. 5.Department of Psychiatry, Clinical Neuroscience, Hollings Cancer CenterMedical University of South CarolinaCharlestonUSA

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