Varenicline Combined with Oral Nicotine Replacement Therapy and Smartphone-Based Medication Reminders for Smoking Cessation: A Pilot and Feasibility Study (Preprint)

BACKGROUND Varenicline and oral nicotine replacement therapy (NRT) have each been shown to increase the likelihood of smoking cessation, but their combination has not been studied. Smoking cessation medication adherence is often poor, thus limiting the ability to evaluate medication efficacy. OBJECTIVE The current study examined the effects of combined varenicline and oral NRT; and smartphone medication reminders on daily pharmacotherapy adherence and smoking abstinence among adults enrolled in smoking cessation treatment. METHODS A 2x2 factorial design was employed. Participants (N=34) were randomized to 12 weeks of 1) varenicline + oral NRT (VAR+NRT; n=20) or varenicline alone (VAR; n=14) and 2) smartphone medication reminders messages (REM; n=11) or no reminder messages (NREM, n=23). Participants assigned to VAR+REM received varenicline reminder prompts, and those assigned to VAR+NRT+REM also received reminders to use oral NRT. Participants assigned to VAR+NREM and VAR+NRT+NREM did not receive medication reminders. All participants received tobacco cessation counseling. Daily smartphone assessments each morning assessed smoking as well as varenicline and NRT use (if applicable) during the previous day. Descriptive statistics were generated to characterize the relations between medication and reminder group assignments with daily smoking (yes/no), daily varenicline adherence (yes/no), and daily quantity of oral NRT used. RESULTS Participants were predominantly White (70.6%) or Black (15%), and half were female (50%). On average, participants were 54.2 years of age (SD=9.4), and smoked an average of 19.0 (SD=9.0) cigarettes per day for 34.6 (SD=12.7) years. Biochemically-verified 7-day point prevalence smoking abstinence rates were 20.6%, 17.6%, 26.5%, and 11.8% at 4, 8, 12, and 26 weeks, respectively. Participants assigned to VAR+NRT were abstinent on more days compared to VAR (29.8 days [41% of study days] vs. 26.6 days [37% of study days]). Descriptively, participants assigned to REM reported smoking abstinence on more days than those assigned to NREM (40.8 days [56% of study days] vs. 22.3 days [31% of study days]). Participants assigned to REM were adherent to varenicline on more days compared to those assigned to NREM (57.8 days [84% of days] vs. 39.9 days [66% of days]), and participants assigned to VAR were adherent to varenicline on more days (49.9 days [79% of days]) than those assigned to VAR + NRT (42.9 days [67% of days]). Average overall medication adherence (assessed via the Medication Adherence Questionnaire) showed the same pattern as the daily smartphone-based adherence assessments, with those assigned to REM reporting greater medication adherence than NREM, and those assigned to VAR reporting greater adherence than VAR + NRT. CONCLUSIONS Preliminary findings indicated that smoking cessation interventions may benefit from incorporating medication reminders and combining varenicline with oral NRT, though combining medications may be associated with reduced adherence. Further study is warranted. CLINICALTRIAL This trial is registered at Clinicaltrials.gov (NCT03722966).