Varenicline (AKA Chantix®) is the latest smoking cessation medication approved by the U.S. Food and Drug Administration (FDA). It significantly increases abstinence rates compared to placebo, bupropion, and NRT1–7
. However, post-marketing surveillance and case reports have raised concerns about potential adverse effects associated with this medication while quitting smoking8–13
. Based on reports to the FDA, varenicline use may increase neuropsychiatric symptoms such as depressed mood, agitation, and suicidal ideation and behavior, particularly among persons with a psychiatric history. At this time, however, it is not clear if smokers with psychiatric history are, in fact, at greater risk for these disturbances compared to smokers with no prior psychiatric history. Individuals with psychiatric diagnoses were excluded from the initial efficacy trials and, to date, only one published trial has offered varenicline to persons with self-reported mental illness14
. This study found no greater medication side-effects or differential cessation outcomes among smokers with mental illness compared to persons with no history of mental illness, but the psychiatric sample was small (n
55) and included people with varying clinical diagnoses. A recent case series of smokers with stable schizophrenia also found no evidence of worsening mood or psychosis during varenicline treatment15
, but again the sample was small (n
19) and psychotic symptoms were not monitored with standardized measures. At present, more empirical data are needed to determine if persons with psychiatric history experience worse outcomes or side-effects when using varenicline, and if so, whether certain psychiatric groups are at greater risk than others. In the meantime, the FDA warns consumers to inform their providers of any prior psychiatric conditions before starting varenicline and to immediately report any changes in mood or behavior after beginning treatment8
The current paper examines mood, other self-reported symptoms commonly associated with varenicline use and/or nicotine withdrawal, and abstinence following varenicline initiation among smokers with and without a probable lifetime history of depression. In clinical cessation trials, as many as 35% to 60% of smokers have a positive depression history16–19
, and in a large epidemiological sample, 39% of smokers with moderate nicotine dependence had major depression20
. Thus, depression is prevalent among smokers. Smokers with a history of depression are also more likely to suffer recurrent major depression after quitting21
, have higher relapse and lower quit rates22–24
, and report more severe nicotine withdrawal symptoms25
. Based on these findings and the FDA warnings, we expected persons with a likely history of depression (DH+) would report worse treatment side-effects and lower abstinence rates than persons with no apparent history of depression (DH−). However, varenicline, α4β2 partial agonist, may also help attenuate negative affect and improve outcomes as it is thought to both block nicotine uptake and stimulate the dopaminergic reward pathway. A recent study found varenicline reduced negative affect and improved positive affect during active treatment compared to placebo26
. Persons with and without psychiatric history were not compared, so it is unclear if this effect would vary based on depression history. However, if varenicline improves mood among DH+ smokers, differences in treatment outcomes between DH+ and DH− smokers may not be as pronounced as in prior trials.
Data were collected as part of the COMPASS study, a randomized clinical smoking cessation trial. The purpose of COMPASS was to compare the effectiveness of three behavioral programs for smoking cessation, all offered with varenicline. Given the current warnings about varenicline use among smokers with prior psychiatric history, we report changes in mood which would indicate new or worsening depression post-medication exposure, as well as differences in a range of side-effects commonly associated with varenicline use and/or nicotine withdrawal. These include neuropsychiatric symptoms highlighted in the FDA warnings and other symptoms which might suggest DH+ have a qualitatively worse treatment experience. We are not able to discern which reported symptoms are due to medication use versus nicotine withdrawal, both because there is an overlap in the side-effects attributed to each and due to our study design, but we are able to comment on the overall subjective symptom experience reported by DH+ and DH− smokers and the observed abstinence rates among DH group participants treated with varenicline.