Efficacy and safety of pharmacotherapies for smoking cessation in anxiety disorders: Subgroup analysis of the randomized, active‐ and placebo‐controlled EAGLES trial

Abstract

Background Smoking rates are high in adults with anxiety disorders (ADs), yet little is known about the safety and efficacy of smoking‐cessation pharmacotherapies in this group. Methods Post hoc analyses in 712 smokers with AD (posttraumatic stress disorder [PTSD], n = 192; generalized anxiety disorder [GAD], n = 243; panic disorder [PD], n = 277) and in a nonpsychiatric cohort (NPC; n = 4,028). Participants were randomly assigned to varenicline, bupropion, nicotine‐replacement therapy (NRT), or placebo plus weekly smoking‐cessation counseling for 12 weeks, with 12 weeks follow‐up. General linear models were used to test the effects of treatment group, cohort, and their interaction on neuropsychiatric adverse events (NPSAEs), and continuous abstinence weeks 9–12 (treatment) and 9–24 (follow‐up). Results NPSAE incidence for PTSD (6.9%), GAD (5.4%), and PD (6.2%) was higher versus NPC (2.1%), regardless of treatment. Across all treatments, smokers with PTSD (odds ratio [OR] = 0.58), GAD (OR = 0.72), and PD (OR = 0.53) had lower continuous abstinence rates weeks 9–12 (CAR9–12) versus NPC. Varenicline demonstrated superior efficacy to placebo in smokers with GAD and PD, respectively (OR = 4.53; 95% confidence interval [CI] = 1.20–17.10; and OR = 8.49; 95% CI = 1.57–45.78); NRT was superior to placebo in smokers with PD (OR = 7.42; 95% CI = 1.37–40.35). While there was no statistically significant effect of any treatment on CAR9–12 for smokers with PTSD, varenicline improved 7‐day point prevalence abstinence at end of treatment in this subcohort. Conclusion Individuals with ADs were more likely than those without psychiatric illness to experience moderate to severe NPSAEs during smoking‐cessation attempts, regardless of treatment. While the study was not powered to evaluate abstinence outcomes with these subgroups of smokers with ADs, varenicline provided significant benefit for cessation in those with GAD and PD, while NRT provided significant benefit for those with PD.

Smoking cessation: Varenicline and the risk of neuropsychiatric adverse events

“…Of those with PTSD who received varenicline, there were no statistically significant differences in CAR from Week 9 to Week 12 vs placebo. 5 However, there was a significant difference in individuals with GAD (OR 4.53; 95% CI, 1.20 to 17.10), and panic disorder (OR 8.49; 95% CI, 1.57 to 45.78). 5 In contrast to CAR from Week 9 to Week 12, 7-day point prevalence abstinence at Week 12 for participants with PTSD was significant (OR 4.04; 95% CI, 1.39 to 11.74) when comparing varenicline to placebo.…”

“…5 However, there was a significant difference in individuals with GAD (OR 4.53; 95% CI, 1.20 to 17.10), and panic disorder (OR 8.49; 95% CI, 1.57 to 45.78). 5 In contrast to CAR from Week 9 to Week 12, 7-day point prevalence abstinence at Week 12 for participants with PTSD was significant (OR 4.04; 95% CI, 1.39 to 11.74) when comparing varenicline to placebo. Within the anxiety disorder cohort, there were no significant differences in moderate to severe NPSAE rates based on treatment group.…”

“…2 This article reviews the evidence regarding the use of varenicline and the risk of neuropsychiatric adverse events in patients with psychiatric illness. Table 2 [3][4][5][6] provides a summary of each varenicline trial we discuss.…”

“…In the psychiatric cohort, the varenicline and bupropion groups exhibited suggestive but not conclusive data that there was no increase in NPSAEs compared to placebo (Bayes factor 0.52 and 0.71, respectively). 4 Another EAGLES analysis by Ayers et al 5 evaluated participants with anxiety disorders (N = 712), including PTSD (N = 192), generalized anxiety disorder (GAD) (N = 243), and panic disorder (N = 277). Of those with PTSD who received varenicline, there were no statistically significant differences in CAR from Week 9 to Week 12 vs placebo.…”

Smoking cessation among people with mental illness: A South African perspective

“…Patients with schizophrenia smoke more cigarettes, take more frequent puffs over a shorter duration, extract more nicotine from a cigarette, suffer greater withdrawal and are more dependent on nicotine than those without mental illness. 6 , 9 , 22 , 41 Ayers et al 42 found that patients with anxiety disorders were more likely to suffer neuropsychiatric adverse events during smoking cessation than those without. Du Plooy et al 9 found that 87.8% of male smokers in a South African psychiatric hospital smoked daily.…”