The effect of varenicline on mood and cognition in smokers with HIV



Barriers to smoking cessation, including negative affect and cognitive dysfunction, may contribute to high smoking rates among people living with HIV/AIDS (PLWH). Varenicline may help PLWH quit smoking by improving mood and cognition, yet this has not been explored.


The goal of this study was to evaluate the effect of varenicline on mood and cognition among PLWH enrolled in a smoking cessation clinical trial.


In this secondary analysis of a varenicline trial (NCT01710137), we assessed mood (depression, anxiety) and cognition (attention, working memory) at weeks 0 (baseline), 1, 3, and 12 (end-of-treatment, EOT). Primary outcomes were changes in mood and cognition from baseline to EOT. Secondarily, mood and cognition were evaluated as predictors of biochemically confirmed 7-day point-prevalence abstinence at EOT.


Overall, 173 subjects (87 varenicline, 86 placebo) were included. At EOT, varenicline reduced anxiety (P < 0.001), vs. placebo (P = 0.31; interaction P = 0.05). Across both treatment arms, reductions in anxiety from baseline to EOT were associated with a higher likelihood of abstinence (OR = 1.3, 95% CI 1.1 to 1.6, P = 0.01). There were no significant treatment by time interactions for cognition or depression.


These data suggest that varenicline operates, at least in part, by reducing anxiety. Anxiety should be an intervention target for smokers with HIV interested in quitting.

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The United States National Institutes of Health and Pfizer had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. The study principal investigator and members of the research team and co-authors had full access to all study data and final responsibility for the decision to submit this paper for publication. We would like to thank Sue Ware and Paul Sanborn for their assistance with data collection and management.

Funding information

This research was supported by grants from the National Institute on Drug Abuse (R01 DA033681, K24 DA045244, R01 DA042682, and R01 DA044906) and through core services and support from the Penn Center for AIDS Research (P30 AI045008) and the Penn Mental Health AIDS Research Center (P30 MH097488). Pfizer provided medication and placebo free of charge.

Author information

Rebecca Ashare co-drafted the manuscript with Morgan Thompson and handled aspects of the statistical analyses. Morgan Thompson and Katrina Serrano oversaw data collection. Frank Leone and Robert Gross ensured participant safety and helped with participant recruitment. Ronald Collman facilitated access to participants. Robert Schnoll is the overall study principal investigator. All authors reviewed and/or edited the manuscript for content and have approved the final version.

Correspondence to Rebecca L. Ashare.

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Conflict of interest

Dr. Schnoll receives medication and placebo free of charge from Pfizer for clinical trials and has provided consultation to Pfizer, GlaxoSmithKline, and Curaleaf. Dr. Gross serves on a Pfizer Data and Safety Monitoring Board for a drug unrelated to smoking or HIV. Dr. Ashare has an investigator-initiated grant from Novo Nordisk for a drug unrelated to the current study.

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Thompson, M., Schnoll, R., Serrano, K. et al. The effect of varenicline on mood and cognition in smokers with HIV. Psychopharmacology (2020).

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  • HIV
  • Smoking cessation
  • Cognition
  • Anxiety
  • Depression