Overview

The purpose of this research is to assess the effectiveness of two treatment strategies for smoking cessation in patients with acute recurrent pancreatitis or chronic pancreatitis who smoke cigarettes. All participants will receive varenicline, a commonly used medication that helps people stop smoking, at its standard dose. For those who are unable to stop smoking after 6 weeks of treatment, they will be randomly selected to either 1) increase their dose of varenicline, 2) combine varenicline with bupropion (another medication that helps with smoking cessation) or continue on the standard dose of varenicline. At the end of 12 weeks of treatment, participants will be asked if they have stopped smoking with confirmation done by measuring carbon monoxide levels in their breath.

Eligibility

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 or older
• Diagnosed with either recurrent acute pancreatitis or chronic pancreatitis as defined by the American Pancreatic Association:
  • Chronic Pancreatitis (any of the following): i. Moderate/marked pancreas imaging morphology (i.e. ductal and parenchymal abnormalities ii. Pancreatic calcifications iii. Histologic confirmation
  • Recurrent Acute Pancreatitis: i. Two or more documented attacks of acute pancreatitis, separated by 3 months from one another, defined by at least 2 of the following 3:
    1. amylase or lipase values, or both, that are greater than 3 times the upper limit of normal values
    2. characteristic cross-sectional imaging
    3. typically upper abdominal pain according to the revised Atlanta classification
• Currently smoking ≥ 5 cigarettes/day
• Explicitly express a desire to quit within 30 days
• Ability to take oral medication and be willing to adhere to the study intervention regimen
• Willing and able to comply with trial protocol and follow-up

Exclusion Criteria

• Age \< 18 years
• Ongoing acute pancreatitis or prior episode of pancreatitis in previous 30 days
• No desire to quit smoking
• Currently undergoing smoking cessation intervention (i.e. nicotine replacement therapy, varenicline, counseling, bupropion).
• Known allergic reactions to varenicline or bupropion SR
• History of seizures
• History of an eating disorder (anorexia or bulimia)
• Closed head trauma with any loss of consciousness or amnesia in the last 5 year
• Ever history of closed head trauma with \> 30 minutes of loss of consciousness or amnesia or resulting in skull fracture or subdural hematoma/brain contusion
• Ever history of alcohol withdrawal
• Ever history of chronic kidney disease (creatine clearance \< 30 mL/minute)
• Liver impairment (i.e. history of cirrhosis) with aminotransferase elevation ≥ 2 times the upper limit of normal and/or alkaline phosphatase elevation ≥ 2 times the upper limit of normal.
• History of bipolar disorder or psychosis
• Ongoing or recent use (prior 14 days) of any monoamine oxidase inhibitors (isocarboxazid, phenelzine, tranylcypromine, selegiline).
• Regular use of potent CYP2B6 inhibitors (i.e. clopidogrel, ticlopidine)
• Regular use of CYP2D6 substrates with narrow therapeutic indices (e.g. flecainide, propafenone, tricyclic antidepressants such as nortriptyline, thioridazine, vinblastine)
• History of acute angle closure glaucoma
• Meet criteria for depression as assessed by the Center for Epidemiologic Studies - Depression (CES-D) with a score of 16 or higher.
• Psychiatric hospitalization within 1 year of screening
• Participants who have a score of 3 or higher on the Columbus-Suicide Severity Rating Scale (C-SSRS) at enrollment or during any of the study assessments will be excluded
• Unable to provide consent for self Incarcerated
• Pregnant females. All female patients of childbearing potential must have a negative pregnancy test and must agree to use highly effective (failure rate \<1%) contraception during participation in the study.