Use of low-dose varenicline in patients who do not tolerate standard-dose varenicline: A longitudinal case series.

Introduction: Although varenicline tartrate is the most effective monotherapy for smoking cessation, the standard-dose (1 mg twice daily) is associated with adverse events: gastrointestinal, sleep-related, and mood-related. Lower doses have demonstrated similar efficacy with lower adverse event incidence. The purpose of this study was to determine whether patients who previously discontinued standard-dose varenicline due to adverse events could tolerate and benefit from low-dose varenicline.

Methods: We conducted a prospective longitudinal pilot study of 22 adult daily smokers in Durham NC, USA, in 2022. All participants previously discontinued standard-dose varenicline due to adverse events. These patients were prescribed either 0.5 mg twice daily for varenicline-related nausea or 1 mg in the morning for sleep problems. The primary outcome was change in self-reported adverse event severity (scale: 0-7). Secondary outcomes were smoking abstinence at 6-week follow-up and tolerance of the lower dose.

Results: Patients with intolerable nausea reported significant severity reduction (6.00 to 0.00; p<0.001) as did patients with intolerable vivid dreams (3.27 to 0.27; p=0.001). Smoking abstinence rates were 28.6% for 0.5 mg twice daily and 26.7% for 1 mg once daily. Low-dose varenicline tolerance was 81.8%.

Conclusions: Patients who experience significant nausea with standard-dose varenicline may successfully make transition to a 0.5 mg low dose twice daily and those who experience vivid dreams to 1 mg varenicline in the morning. Treatment efficacy rates remained relatively high. This suggests a need for a future randomized controlled trial to establish low-dose varenicline as an approach for patients who do not tolerate the standard-dose varenicline.