Varenicline Augmentation in Depressed Smokers

Abstract

Objective To assess possible antidepressant effects of varenicline augmentation in outpatients with treatment-resistant depressive disorders and nicotine dependence. Background Varenicline (Chantix) is a nicotinic acetylcholine receptor α4β2 partial agonist and α7 full agonist approved for smoking cessation. Studies of similar compounds have suggested evidence of antidepressant effects. Methods Eighteen patients were recruited from a general psychiatric outpatient clinic. Inclusion criteria were 1) primary Axis I depressive disorder, 2) persistent depressive symptoms despite adequate treatment, and 3) current cigarette smoking with nicotine dependence. Patients received varenicline in addition to stable doses of their regular psychotropic medications. Depression symptoms, side effects, clinical global impressions, anhedonia, daily cigarette consumption, and vitals signs were assessed every 2 weeks for 8 weeks. Baseline and endpoint ratings were compared, and the relationship between mood improvement and smoking cessation was examined. The primary outcome variable was mean improvement in depressive symptoms. Results Fourteen patients (78%) completed the study; 4 discontinued due to side effects, including gastrointestinal (n = 3) and worsened mood/irritability (n = 1). Patients demonstrated significant improvement in depression at endpoint (p < .001), with significant improvement as early as week 2. Eight (44%) patients met criteria for categorical response, and six (33%) reached remission criteria; the overall effect size was large. All patients were interested in smoking cessation, eight (44%) achieved abstinence, and nine (50%) had some reduction in smoking. Improvement in depressive symptoms was correlated with smoking cessation. There was no evidence of treatment-emergent suicidality. Conclusion Open-label varenicline augmentation was associated with significant improvement in mood in a small sample of outpatient smokers with persistent depressive symptoms. Larger, double-blind studies are needed to investigate potential antidepressant effects of varenicline augmentation.

Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior

“…In clinical studies, administration of varenicline during smoking cessation results in the improvement of both positive affect and cognitive function (Patterson et al, 2009). In addition, coadministration of varenicline was shown to positively enhance the effects of antidepressants in depressed smokers in a small open label study (Philip et al, 2009). However, despite its success, less than half of those using varenicline were able to quit smoking at a 3-month follow-up period (Garrison and Dugan, 2009).…”

“…Clinically, varenicline has demonstrated enhancement of both positive affect and cognitive function during smoking cessation (Patterson et al, 2009), and it was recently shown to augment the effects of antidepressants in depressed smokers (Philip et al, 2009). Despite its clinical success in smoking cessation (Nides et al, 2008), there have been a limited number of studies evaluating the behavioral effects of varenicline in animal models of depression (Rollema et al, 2009a) and none examining its effects on anxiety.…”

Multiple Nicotinic Acetylcholine Receptor Subtypes in the Mouse Amygdala Regulate Affective Behaviors and Response to Social Stress

“…Acetylcholine signals through muscarinic and nicotinic acetylcholine receptors (mAChRs and nAChRs, respectively) and many studies of depression have focused on mAChR signaling (Cannon et al, 2011;Riemann et al, 1994); however, blockade of either mAChRs or nAChRs can reverse the depression-like effects of increased cholinergic signaling in mice (Mineur et al, 2013) and it is likely that multiple receptors can mediate the effects of cholinergic signaling on depression (Drevets et al, 2013). The recent failure of a large clinical trial (Vieta et al, 2013) suggests that global antagonism of nAChRs will not be a viable strategy for antidepressant development; however, small human (Philip et al, 2009), and a number of rodent studies Rollema et al, 2009) suggest that targeting specific nAChR subtypes may be a potential strategy for treating depression. Numerous studies suggest that nAChRs are important for cellular and behavioral responses to stress, and that modulation of corticolimbic circuits by nAChRs may be particularly critical (Mansvelder et al, 2009).…”

Electroconvulsive therapy (ECT) effective for psychotic recrudescence and suicidality after varenicline adjunctive therapy for smoking cessation in a schizoaffective patient

“…Cigarette smoking decreases serotonin turnover and inhibits brain monoamine oxidase, increasing impulsivity and suicidality in a recently abstinent schizoaffective patient. Mood improving and antidepressant augmenting properties of varenicline have been previously described, 3 and such a drug might concur to generate unstable mood. Particular vulnerabilities to nicotine, nicotine abstinence, and varenicline might be determined by variants of the nAChR gene recently found in schizoaffective disorder, 4 which might favor fast built up of impulsivity and suicidality with varenicline use.…”