Date of Award


Degree Type

Selective Evidence-Based Medicine Review

Degree Name

Master of Science in Health Sciences - Physician Assistant

Department Chair

John Cavenagh, PhD, PA-C


OBJECTIVE: The objective of this selective EBM review is to determine whether or not the use of varenicline for smoking-cessation therapy creates or increases depression in patients without existing depressive illness.

STUDY DESIGN: Review of two randomized controlled trials published in 2011 and one observational cohort study published in 2009, all English language.
DATA SOURCES: Two randomized, double-blind, controlled clinical trials comparing varenicline to placebo in smoking cessation, and one observational cohort study comparing varenicline use within subjects. All articles were found using PubMed and EBSCO.

OUTCOMES MEASURED: Changes in depression was evaluated using the MontgomeryÅsberg Depression Rating Scale (MADRS), and adverse events were recorded and classified into depression-related according to the Medical Dictionary for Regulatory Activities version 12 and, in the observational cohort study, the British Drug Safety Research Unit standards.

RESULTS: Bollinger et al. and Garza et al. demonstrated a present but nonsignificant increase in depressive adverse events associated with varenicline use. Garza et al, reported a similarly small and nonsignificant worsening in MADRS score in the varenicline arm. Kasliwal et al. reported a
nonsignificant change in depressive adverse events.

CONCLUSIONS: Results of the three studies show that there is inconclusive evidence regarding a link between varenicline and new-onset depression in smoking cessation. None of the studies demonstrated any significant relationship between varenicline and depression or depressive
adverse events, but limitations in study design prevent the results from convincingly addressing such a relationship. The results encourage further studies designed both to assess varenicline’s relationship with depression and to account for the varenicline’s higher quit rate as a possible source of depressive changes.