ADHD symptoms impact smoking outcomes and withdrawal in response to Varenicline treatment for smoking cessation

Abstract

Introduction: Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with nicotine dependence and difficulty quitting smoking. Few cessation trials specifically consider the impact of ADHD on treatment outcomes, including those testing established pharmacological therapies, such as varenicline.

Methods: The current study focused on the impact of pretreatment ADHD inattention (IN) and hyperactivity-impulsivity (HI) symptoms on treatment outcome in a randomized controlled trial of varenicline [N=205, average age=34.13(10.07), average baseline cigarettes per day=14.71(7.06)]. Given that varenicline's putative therapeutic mechanism is attenuation of withdrawal severity during abstinence, we also tested changes in withdrawal as a mediator of treatment effects in high and low ADHD groups.

Results: ADHD symptom severity in this sample was in the subclinical range. Cessation was associated with HI, but not IN, such that high HI individuals on varenicline reported the lowest smoking levels at the end of treatment across all groups (3.06cig/day for high HI vs 4.02cig/day for low HI). Individuals with high HI who received placebo had the highest smoking at the end of treatment (7.69cigs/day for high HI vs 5.56cig/day for low HI). Patterns continued at follow-up. Varenicline significantly reduced withdrawal for those with high HI, but not low HI. However, path models did not support an indirect effect of medication on reducing smoking via withdrawal in either group, suggesting that unmeasured variables are involved in varenicline's effect on reducing smoking.

Conclusions: These data add to a gap in the smoking cessation literature regarding the impact of ADHD symptoms on the efficacy and mechanisms of frontline pharmacological treatments.

Keywords: Impulsivity; Inattention; Nicotine; Quitting smoking; Withdrawal.

Figure 1. Changes in Mean Cigarettes Smoked Per Day across Assessment Time Point By Medication Condition and ADHD Hyperactive-Impulsive (HI) Symptoms

Figure shows unadjusted average cigarettes per day at each assessment time for individuals with higher and lower ADHD Hyperactive/Impulsive (HI) symptoms in the two treatment conditions. Individuals with >= 5 HI symptoms who received varenicline smoked the fewest cigarettes per day at the end of treatment (Week 12) and individuals with >=5 HI symptoms who received the placebo treatment smoked the most cigarettes per day at the end of treatment (Week 12). At follow up (Week 36) the individuals with >= 5 HI symptoms who received placebo were smoking at the highest levels, over 9 cigs/day. In the placebo group, 59 individuals reported < 5 HI and 35 reported >= 5 HI symptoms. In the varenicline group, 69 individuals reported < 5 HI symptoms and 42 reported >= 5 HI symptoms.

Figure 2. Change in withdrawal as a mediator of treatment in individuals with high versus low hyperactivty-impulsivity (HI) symptoms

Standardized parameter estimates are presented. Parameter estimate before the slash is the low HI group, and the estimate after the slash is the high HI group (LOW/HIGH). Note. *p < .05; **p < .01. There were 51 males (26 females) in the high ADHD HI group (mean age=32.53 SD=9.70) and 81 males (46 females; 1 missing) in the low ADHD HI group (mean age=35.01 SD=10.19).