Efficacy and Safety of Pharmacotherapeutic Smoking Cessation Aids in Schizophrenia Spectrum Disorders: Subgroup Analysis of EAGLES

Abstract

Objective: This study aimed to evaluate the efficacy and safety of varenicline, bupropion, and nicotine replacement therapy (NRT) among smokers with schizophrenia spectrum disorders in post hoc analyses of Evaluating Adverse Events in a Global Smoking Cessation Study data.

Methods: Smokers with schizophrenia spectrum disorder (N=390) and without a psychiatric illness (control group, N=4,028) were randomly assigned to receive varenicline, bupropion, NRT patch, or placebo for 12 weeks. Outcomes included abstinence rates during treatment and follow-up, number needed to treat (NNT) for abstinence, incidence of neuropsychiatric adverse events (NPSAEs), and temporal relationship between NPSAEs and abstinence status.

Results: Smokers with schizophrenia smoked more and had greater dependence and fewer prior trials of cessation pharmacotherapy at baseline. At each time point, smokers with schizophrenia assigned to varenicline had significantly greater odds of abstinence compared with their matched placebo group, with NNT comparable to the control group. Bupropion and NRT increased odds of abstinence; confidence intervals (CIs) included 1 for some comparisons, and NNT for smokers with schizophrenia was greater than for the control group. No treatment was associated with significantly more NPSAEs, compared with placebo, in either cohort. The estimated NPSAE rate was 5% (95% CI=3.0-7.7) for smokers with schizophrenia and 1% (95% CI=0.6-2.1) for the control group. Over one-third of NPSAEs occurred during partial or full abstinence, suggesting a multifactorial nature.

Conclusions: For smokers with schizophrenia, varenicline led to significantly higher abstinence rates, and NNT was comparable to the control group. A significant proportion of NPSAEs occurred during early abstinence. No treatment significantly increased NPSAE prevalence.

Trial registration: ClinicalTrials.gov NCT01456936.

Keywords: Schizophrenia; Smoking.

Figure 1. a) Observed 7-day point prevalence abstinence rates at each study visit, and b) number needed to treat for 7-day point prevalence abstinence at end of treatment and end of follow-up

NRT, nicotine replacement therapy (transdermal nicotine patch); PPA, point prevalence abstinence.

Figure 2. Risk differences for neuropsychiatric adverse events with varenicline, bupropion, NRT, and placebo

Period for ascertainment of neuropsychiatric adverse events was during 12 weeks’ treatment and ≤30 days after last dose. Model terms included: treatment group (varenicline, bupropion, NRT, placebo), cohort (schizophrenia spectrum disorders no psychiatric disorders), treatment by cohort interaction, region (US or non-US), and race (White, Black, Other). CI, confidence interval; NRT, nicotine replacement therapy (transdermal nicotine patch); RD, risk difference.