Document Type



Medicine and Health Sciences



Varenicline carries a black box warning for neuropsychiatric adverse events.


We examined varenicline use and past history of major depressive disorder (MDD) on depressive symptoms during smoking cessation.


This is a secondary analysis of two smoking cessation studies in 152 postmenopausal women who received placebo or nicotine patch, or 78 women who received varenicline with relaxation. Lifetime history of MDD (LH-MDD) was assessed at baseline and women with current MDD were excluded. Center for Epidemiologic Study Depression scale (CESD) measured depressive symptoms at baseline, 6 and 12 weeks.


Baseline CESD scores were 5.3 + 4.4. Those with a LH-MDD reported higher CESD scores (p >.001). Those taking varenicline reported lower scores over all time periods compared to nicotine or placebo (p <.01). The differences between varenicline and the other treatments remained when controlling for LH-MDD, indicating an independent effect. CESD scores were associated with concurrent smoking status (p <.001), and with withdrawal symptoms (p <.001).


CESD score were lower in those receiving varenicline, whether this is due to an anti-depressant effect, subject selection, use of relaxation or another cause is unknown. Varenicline does not increase depressive symptoms during smoking cessation in postmenopausal women without current MDD. Subjects with a LH-MDD are susceptible to developing depressive symptoms during smoking cessation, regardless of pharmacologic aid.


Am J Addict. Author manuscript; available in PMC 2016 Oct 18. Published in final edited form as: Am J Addict. 2014 Sep-Oct; 23(5): 459–465. Published online 2014 Mar 15. doi: 10.1111/j.1521-0391.2014.12130.x PMCID: PMC5068915 NIHMSID: NIHMS790022