Depression Severity Moderates Reward Learning Among Smokers With Current or Past Major Depressive Disorder in a Smoking Cessation Randomized Clinical Trial.

Introduction: Behavioral and pharmacological smoking cessation treatments are hypothesized to increase patients' reward learning to reduce craving. Identifying changes in reward learning processes that support effective tobacco-dependence interventions among smokers who experience depression may guide patients toward efficient treatment strategies. The objective was to investigate the extent to which adult daily cigarette smokers with current or past major depressive disorder (MDD) learned to seek reward during 12 weeks of treatment combining behavioral activation and varenicline. We hypothesized that a decline in reward learning would be attenuated (least to most) in the following order: (1) behavioral activation integrated with ST (BASC) + varenicline, (2) BASC + placebo, (3) standard behavioral cessation treatment (ST) + varenicline, (4) ST + placebo.

Methods: We ran a phase IV, placebo-controlled, randomized clinical trial with 300 participants receiving 12 weeks of one of four conditions across two urban medical centers. Depressive symptoms were measured using the Beck Depression Inventory-II (BDI). Reward learning was ascertained at weeks 1, 7, and 14 using the Probabilistic Reward Task (PRT), a laboratory task that uses an asymmetric reinforcement schedule to assess (a) learning to seek reward (response bias), (b) differentiate between stimuli, and (c) time to react to cues.

Results: There was a significant interaction of BDI group × PRT response bias. Response bias declined from weeks 7 to 14 among participants with high baseline depression symptoms. The other two BDI groups showed no change in response bias.

Conclusions: Controlling for baseline depression, participants showed a decrease in response bias from weeks 1 to 14, and from weeks 7 to 14. Treatment condition and abstinence status were unassociated with change in reward learning.

Implications: Smokers who report greater depression severity show a decline in reward learning despite their participation in smoking cessation treatments, suggesting that depressed populations pose unique challenges with standard smoking cessation approaches.

Trial Registration: ClinicalTrials.gov Identifier: NCT02378714.