Lead Investigator: Kyle Greenway, McGill University
Title of Proposal Research: Antidepressant effects of bupropion, varenicline, nicotine replacement therapy, and placebo in tobacco users.
Vivli Data Request: 9081
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Major depressive disorder (MDD) is one of the most common psychiatric conditions, affecting around 20.6% of adults in the United States. It is characterized by a persistent low mood and/or a loss of interest in normally pleasurable activities. MDD can also lead to changes in appetite, sleep difficulties, fatigue, trouble concentrating, feelings of guilt, and thoughts of suicide. Additionally, people with depression often smoke cigarettes at higher rates and have a greater risk of becoming dependent on nicotine.
The EAGLES trial was the largest randomized clinical trial to date exploring smoking cessation treatments for people with psychiatric conditions, including MDD. The trial evaluated the comparative safety and efficacy of varenicline, bupropion, and nicotine replacement therapies. Varenicline (Champix/Chantix) is a non-nicotine-based medication used for smoking cessation. It provides relief from craving and withdrawal symptoms and diminishes the pleasurable sensation derived from smoking. Bupropion (Wellbutrin, Zyban) is an ‘atypical’ antidepressant that is also used for smoking cessation. It is known to act on two neurotransmitters called noradrenaline and dopamine, but its mechanism of action is not fully understood. Nicotine replacement therapies are alternative sources of nicotine (e.g. gum, nasal sprays, transdermal patches, sublingual tablets) that are used to reduce cravings and ease withdrawal symptoms. These three treatments were found to be well-tolerated and effective for helping the EAGLES trial participants quit smoking. In addition to the main analyses, several sub-analyses have been conducted, focusing on how well the treatments worked within specific groups of participants with different psychiatric conditions, most recently in MDD.
Our project aims to build upon these findings by investigating the differential antidepressant effects of these three treatments compared to a placebo (any treatment that has no active properties, such as a sugar pill). Based on the already-published EAGLES trial data, we hypothesize that none of the trial’s treatments will show significantly better antidepressant effects than placebo. This finding would be significant, since bupropion is an evidenced-based treatment for depression itself. To test our main hypothesis, we will use a statistical model (called “Mixed Effects Model”) that can account for individual variations in depression outcomes over time while also establishing whether or not there are differences between the three treatment groups compared to the placebo group. Our results will be valuable for physicians and researchers aiming to better understand the antidepressant effects of bupropion, in relation to other evidence-based treatments for tobacco use disorder, in a sample of smokers. We plan to publish our findings in a peer-reviewed scientific article and present any significant results at relevant academic conferences, such as the Canadian Psychiatric Association annual meeting.
A Phase 4, Randomized, Double-blind, Active And Placebo-controlled, Multicenter Study Evaluating The Neuropsychiatric Safety And Efficacy Of 12 Weeks Varenicline Tartrate 1mg Bid And Bupropion Hydrochloride 150mg Bid For Smoking Cessation In Subjects With And Without A History Of Psychiatric Disorders
Data Contributor: Pfizer Inc.
Study ID: NCT01456936
Sponsor ID: A3051123