ADHD and Smoking Cessation Outcomes With Varenicline

CASE VIGNETTE

“Jill” is a 19-year-old African American female with a history of attention-deficit/hyperactivity disorder (ADHD), diagnosed at age 10 years. She presented with primarily inattentive symptoms and minimal issues with hyperactivity and impulsivity. She responded well to treatment with methylphenidate, which she continues to take.

At age 16 years, Jill started vaping with friends, typically after school. In the past 18 months, she has been smoking 10 cigarettes per day. She has motivation for smoking cessation. She reports that she received minimal benefit from a previous trial of nicotine replacement therapy, but she was unable to tolerate bupropion due to worsening anxiety.

She is interested in a trial of varenicline and asks her psychiatrist about her chances of success with this medication. As her psychiatrist, how does her comorbid ADHD impact on smoking cessation efforts?

The majority of adult users report first trying tobacco at ages 10 to 19 years.¹ Recently, there has been an increase in new smokers at ages 18 to 23 years.² Adolescent nicotine use is associated with increased risk of nicotine, alcohol, and psychostimulant use in adulthood.³

Adolescents and adults with ADHD are more likely to smoke.⁴ Given these associations, investigation of the impact of ADHD symptoms on the response to smoking cessation interventions is warranted.

Varenicline is an α4β2 nicotinic acetylcholine partial agonist that has limited evidence for efficacy in adolescents.⁵

The Current Study

Green and colleagues⁶ performed a secondary analysis of a recent clinical trial of varenicline for smoking cessation in adolescents and young adults.⁷ Although varenicline was well tolerated, it did not improve abstinence in this trial. The trial enrolled cigarette smokers ages 14 to 21 years. Inclusion criteria were daily smoking for at least 6 months, failing at least 1 prior attempt to quit, and interest in quitting.

At baseline, participants received smoking cessation brochures and brief counseling on cessation strategies and were instructed to set a quit date. They received weekly smoking cessation counseling. Participants were randomized 1:1 to a double-blind 12-week course of varenicline or placebo. In the varenicline group, patients >55 kg were titrated to 1 mg twice daily, and those ≤55 kg to 0.5 mg twice daily.

Self-reported smoking was collected via diary at weekly visits. Breath carbon monoxide was measured at all visits and urine cotinine at the end of treatment visit. ADHD symptoms were assessed at baseline and weeks 4, 8, and 12 with the ADHD—Rating Scale. Nicotine withdrawal was assessed weekly with the Minnesota Nicotine Withdrawal Scale.

The primary efficacy outcome was urine cotinine-confirmed, 7-day, self-reported abstinence at week 12. Study authors hypothesized that lower baseline ADHD symptoms would be associated with an increase in 7-day abstinence, which was analyzed using logistic regression.

Seventy-seven participants were randomized to varenicline and 80 to placebo, and 57% of participants attended the end-of-treatment visit. The mean age was 19 years, 60% were male, and 76% were white. Average smoking was 11.5 cigarettes/day and 4-year duration. The mean ADHD symptom count (9.0) was in the sub-clinical range.

Participants with low (versus high) ADHD inattentive item endorsement were almost 3 times more likely to have end-of-treatment abstinence (49% vs 17%, RR=2.9). Increases in continuous ADHD inattentive item scores were associated with decreased probability of both weekly and end-of-treatment abstinence.

When abstinence was not achieved, higher baseline ADHD inattentive symptoms were associated with more cigarettes per day. Increases in continuous ADHD hyperactivity-impulsivity scores were also associated with decreased probability of end-of-treatment abstinence.

Participants with low (versus high) ADHD hyperactive-inattentive item endorsement had twice the probability of end of treatment abstinence (38% versus 17%, RR=2.1), although findings failed to reach statistical significance. At study baseline, participants with increased ADHD item endorsement (both subtypes) had significantly higher nicotine withdrawal symptoms.

Study Conclusions

The authors concluded that there was a pattern such that greater ADHD inattentive symptoms at baseline were associated with decreased abstinence during treatment and more cigarettes per day. This pattern was not present for hyperactive-impulsive symptoms. The association with inattentive symptoms was not moderated by medication (varenicline or placebo). Participants with greater ADHD symptoms also had more severe nicotine withdrawal symptoms.

Study strengths included consideration of ADHD symptoms as both categorical and continuous measures, and cotinine-confirmed abstinence. Study limitations included the use of self-report ADHD symptoms, and that most participants did not meet diagnostic criteria for ADHD.

The Bottom Line

Smokers with higher ADHD inattentive symptoms are at greater risk for continued smoking, and varenicline does not modify treatment response. Greater ADHD symptoms are also associated with increased nicotine withdrawal.

Dr Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times®. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

References

1. National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health. Preventing Tobacco Use Among Youth and Young Adults: A Report of the Surgeon General. Atlanta (GA): Centers for Disease Control and Prevention (US); 2012.

2. Barrington-Trimis JL, Braymiller JL, Unger JB, et al. Trends in the age of cigarette smoking initiation among young adults in the US from 2002 to 2018. JAMA Netw Open. 2020;3(10):e2019022.

3. Ren M, Lotfipour S. Nicotine gateway effects on adolescent substance use. West J Emerg Med. 2019;20(5):696-709.

4. Mitchell JT, Howard AL, Belendiuk KA, et al. Cigarette smoking progression among young adults diagnosed with ADHD in childhood: a 16-year longitudinal study of children with and without ADHD [published correction appears in Nicotine Tob Res. 2019 Sep 19;21(10):1449]. Nicotine Tob Res. 2019;21(5):638-647.

5. Gray KM, Rubinstein ML, Prochaska JJ, et al. High-dose and low-dose varenicline for smoking cessation in adolescents: a randomised, placebo-controlled trial. Lancet Child Adolesc Health. 2020;4(11):837-845.

6. Green R, Baker NL, Ferguson PL, et al. ADHD symptoms and smoking outcomes in a randomized controlled trial of varenicline for adolescent and young adult tobacco cessation. Drug Alcohol Depend. 2023;244:109798.

7. Gray KM, Baker NL, McClure EA, et al. Efficacy and safety of varenicline for adolescent smoking cessation: a randomized clinical trial. JAMA Pediatr. 2019;173(12):1146-1153.