Trends in Incident Varenicline Prescribing Among Veterans Following the US Food and Drug Administration Drug Safety Warnings

OBJECTIVE: We sought to evaluate national trends in incident varenicline and nicotine replacement therapy (NRT) prescribing among Veterans Affairs (VA) beneficiaries before and after U.S. Food and Drug Administration (FDA) warnings regarding neuropsychiatric side effects with varenicline use. METHODS: We determined all adult VA patients identified as smokers from 2007–2019 (N=3,600,947) and calculated monthly counts of new varenicline and NRT users. An interrupted times series analysis estimated the effect of the FDA warnings on varenicline and NRT prescribing overall and among Veterans with and without mental health disorders. RESULTS: The incident use rate of varenicline decreased from a peak of 6.2 per 1,000 Veteran smokers in 10/2007 to 1.0 by 6/2009 following the first FDA warning (pre-warning monthly slope = −0.27; p=0.03). New NRT use increased from 10.7 per 1,000 Veteran smokers in 10/2007 to a peak of 12.6 in 7/2009 (slope change = 0.71, p=0.01) suggesting potential substitution. Following removal of the FDA boxed warning in 12/2016, varenicline prescribing increased but did not return to pre-warning levels by 12/2019. Among Veterans with and without mental health disorders, varenicline use decreased 90% and 88%, following the first FDA warning—both groups had comparable rates of new NRT use. CONCLUSIONS: Following the first FDA warning, incident use of varenicline declined significantly both among Veterans with and without mental health disorders. Despite removal of the FDA boxed warning in 12/2016, new use of varenicline had not returned to pre-warning levels 3 years following the removal.