Carcinogenicity Study of Bupropion

Post-marketing Carcinogenicity Study of Bupropion

There is a lack of toxicology data on one bupropion metabolite, and limited literature examining bupropion use and cancer risk. This study evaluates the association between bupropion exposure and the development of cancer of the prostate, breast, lung, colon/rectum, urinary bladder, and uterus by comparing the risk of cancer in bupropion users with other antidepressant users. Because there is no evidence that bupropion is associated with any particular cancer, we have chosen the six most common cancers diagnosed in the United States to optimize statistical power/precision for cancer-site specific comparisons. Two US population-based data resources with automated claims, pharmacy, and tumor registry data are included in this study. Using a nested case-control design, this study will compare the incidence of cancer in patients exposed to bupropion with the incidence in patients exposed to other antidepressants.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder; Cancer
• Intervention / Treatment: Drug: Regular bupropion use; Drug: Regular SSRI (Selective serotonin reuptake inhibitors) use; Drug: Regular TCA (Tricyclic antidepressants) use; Drug: Regular use of any other antidepressant

Detailed Description

Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.

• Study Type: Observational
• Enrollment (Actual): 50430

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

New users of antidepressants January 1, 1996 through December 31, 2006, regardless of indication for use (depression, smoking cessation, other) in Henry Ford Health System and Kaiser Permanente Health Plan of Northern California. The study population is limited to individuals 18 years of age or older with medical and pharmacy benefits and at least 6 months of health plan enrollment before the first antidepressant prescription. Patients with a history of any cancer (cancer diagnosis recorded in the tumor registries anytime before the first antidepressant prescription recorded during the study period) are excluded. Cases and controls will be selected from this cohort of antidepressant-exposed study subjects.

Description

Inclusion Criteria:

-

Exclusion Criteria:

• Cancers diagnosed within 12 months of initiation (i.e., new use) of antidepressant pharmacotherapy will be excluded to account for a minimum period for the development of cancer (cancer latency) and to be consistent with other studies of antidepressants and cancer.
• Patients with a history of any cancer (cancer diagnosis recorded in the tumor registries anytime before the first antidepressant prescription recorded during the study period)
• Any antidepressant use within 6 months of January 1, 1996

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

New users of antidepressants Jan. 1, 1996 to Dec. 31, 2006; All new users of antidepressants January 1, 1996 through December 31, 2006. Individuals 18 years of age or older with medical and pharmacy benefits and at least 6 months of health plan enrollment before the first antidepressant prescription.

Drug: Regular bupropion use; Regular use of bupropion is defined as use at least 4 times per week for at least 3 continuous months at least 12 months before index date.; Drug: Regular SSRI (Selective serotonin reuptake inhibitors) use; Regular use of SSRI is defined as use at least 4 times per week for at least 3 continuous months at least 12 months before index date.; Drug: Regular TCA (Tricyclic antidepressants) use; Regular use of TCA is defined as use at least 4 times per week for at least 3 continuous months at least 12 months before index date.; Drug: Regular use of any other antidepressant; Regular use of any other antidepressants is defined as use at least 4 times per week for at least 3 continuous months at least 12 months before index date. An "other antidepressant" would be any antidepressant other than bupropion, a SSRI or a TCA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Diagnosed With Any of the Cancers Under Investigation Who Were Regularly Exposed to the Indicated Antidepressant	The following are the cancers under investigation: colorectal, lung, bladder, uterus, breast, and prostate. Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.	January 1, 1996 - December 31, 2006

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Diagnosed With Colorectal Cancer Who Were Regularly Exposed to the Indicated Antidepressant	In this outcome, colorectal cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Colorectal cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.	January 1, 1996 - December 31, 2006
Number of Participants Diagnosed With Lung Cancer Who Were Regularly Exposed to the Indicated Antidepressant	In this outcome, lung cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Lung cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.	January 1, 1996 - December 31, 2006
Number of Participants Diagnosed With Bladder Cancer Who Were Regularly Exposed to the Indicated Antidepressant	In this outcome, bladder cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Bladder cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.	January 1, 1996 - December 31, 2006
Number of Participants Diagnosed With Uterine Cancer Who Were Regularly Exposed to the Indicated Antidepressant	In this outcome, uterine cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Uterine cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.	January 1, 1996 - December 31, 2006
Number of Participants Diagnosed With Breast Cancer Who Were Regularly Exposed to the Indicated Antidepressant	In this outcome, breast cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Breast cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.	January 1, 1996 - December 31, 2006
Number of Participants Diagnosed With Prostate Cancer Who Were Regularly Exposed to the Indicated Antidepressant	In this outcome, prostate cancer is under investigation: Cancer case were nested within a cohort of new antidepressant users. New antidepressant users were defined as no previous antidepressant prescription in the previous 6 months. Prostate cancer cases were identified and matched with controls from the same new-user cohort. Cal year, calendar year; dx, diagnosis; IBD, Inflammatory Bowel Disease; OC, oral contraceptive; HRT/ERT, hormone replacement therapy/estrogen replacement therapy; NSAID, non-steroidal anti-inflammatory drug.	January 1, 1996 - December 31, 2006

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: February 25, 2010
• First Submitted That Met QC Criteria: February 25, 2010
• First Posted (Estimate): March 1, 2010

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 25, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Bupropion; Carcinogenicity; Case control
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Dopamine Agents; Serotonin Receptor Agonists; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Bupropion; Serotonin; Antidepressive Agents; Serotonin Uptake Inhibitors; Antidepressive Agents, Tricyclic
• Other Study ID Numbers: 111982; EPI40463; WEUKSTV1113