Randomized Comparative Trial of Nicotine Polacrilex, a Transdermal Patch, Nasal Spray, and an Inhaler.

Introduction
Multiple nicotine replacement therapy (NRT) products are available, but clinicians often lack direct evidence to guide product selection.
Prior studies evaluated NRT efficacy individually but rarely compared products head-to-head.
This study directly compared four NRT forms—nicotine gum, transdermal patch, nasal spray, and inhaler—to assess withdrawal relief, usability, compliance, and abstinence outcomes.
Key Points
Study design: Randomized comparative trial of 504 adult smokers seeking cessation assistance, with follow-up at 1, 4, and 12 weeks.
Products compared: Nicotine polacrilex gum (2–4 mg), 16-hour transdermal patch (15 mg), nasal spray, and inhaler.
Withdrawal symptoms: No significant differences between products in withdrawal discomfort, urges to smoke, or difficulty abstaining.
Abstinence rates:
12-week continuous abstinence ranged from ~20–24% across all products, with no statistically significant differences.
Compliance:
Highest with the patch (82% overall; 96% among abstainers).
Substantially lower with gum, nasal spray, and inhaler, especially the spray and inhaler.
Usability and acceptability:
Patch rated easiest to use and least embarrassing.
Inhaler and spray were more often considered embarrassing or impractical.
Adverse effects were a common reason for underuse of the nasal spray.
Nicotine exposure: Among nasal spray users, higher early use predicted better long-term abstinence, highlighting the importance of adequate dosing.
Behavioral aspects: Mimicking smoking behavior (e.g., inhaler use) did not confer added cessation benefit over nicotine delivery alone.
Conclusion
All four NRT products demonstrated similar overall efficacy for smoking cessation in a real-world clinical setting.
Differences in outcomes were driven more by compliance and usability than by pharmacologic effectiveness.
Clinicians should base NRT recommendations on patient preference, tolerability, and likelihood of proper use, rather than assuming superiority of any single product.

Hajek, Peter, et al. “Randomized Comparative Trial of Nicotine Polacrilex, a Transdermal Patch, Nasal Spray, and an Inhaler.” Archives of Internal Medicine, vol. 159, no. 17, 1999, pp. 2033–2038.