Type II Diabetes Mellitus in Patients Exposed to Pravastatin and Paroxetine
Status:
Completed
Trial end date:
2012-05-01
Target enrollment:
Participant gender:
Summary
Type 2 Diabetes (T2DM) is a life-long, chronic condition affecting an individuals' ability to
regulate glucose levels in the blood. Diabetes can cause many severe complications if not
treated properly. Hyperglycemia is a regular effect of uncontrolled diabetes and can lead to
complications such as cardiovascular disease, chronic renal failure, diabetic retinopathy and
inability to maintain a healthy body weight.
Cardiovascular Disease (CVD) is now the leading cause of death worldwide, affecting millions
of people in both developed and non-developed countries. The buildup of cholesterol in the
bloodstream may cause the excess to be deposited in the coronary arteries of the heart and
the carotid arteries of the brain. The cholesterol deposits are a factor of the plaques that
cause blockage of the arteries which can in turn lead to heart disease and stroke. By
lowering the blood levels of cholesterol, risks of heart disease, strokes and heart attacks
are reduced. Medications such as HMG-CoA reductase inhibitors and fibrates are useful in the
prevention of CVD.
Pravastatin is a member of the drug class of statins, also known as HMG-CoA reductase
inhibitors, and is shown as an adjunctive therapy to diet. It is known to reduce the amount
of cholesterol and other fatty substances in the blood. In addition, pravastatin is indicated
to reduce the risk of myocardial infarction, revascularization and cardiovascular mortality
in hypercholesterolemic patients who do not have clinically apparent coronary heart disease.
The recommended starting dose for adults is 40 mg once daily. For patients who do not reach
the LDL-C goal with 40 mg, it is recommended to use an 80 mg dose. For persons with
significant renal impairment the recommended dose is 10 mg. Children aged 8-13 years have a
recommended starting dose of 20 mg daily. Adolescents aged 14 to 18 years have a recommended
starting dose of 40 mg daily.
Depression is known as the most common mental disorder and most prevalent type of mood
disorder today. It can be seen as a state of mood, a symptom, a syndrome or as a clinical
diagnosis. Depression is a common disorder, affecting about 121 million people worldwide.
Depression is more likely to co-occur with medical illnesses such as stroke, heart disease,
cancer and diabetes. Up to one-quarter of people with diabetes are estimated to experience
depression which is two times more than those who do not suffer from diabetes. Studies have
shown that major depression mainly occurs in 2¬4 percent of people in the community, in 5-10
percent of primary care patients and 10-14 percent of medical inpatients. Also, recent
studies have estimated that the symptoms continue over a 6 month to one year period in
patients with major depression. The severity of the symptoms and the incidence of medical
illness are expected to predict the persistence of depression. Depression can be treated
effectively by a variety of antidepressants and/or psychotherapies. If treated appropriately,
over 80 percent of people who suffer from depression can be helped.
Paroxetine is an orally administered selective serotonin reuptake inhibitor (SSRI)
antidepressant. It was the first antidepressant that was formally approved in the United
States for the treatment of panic attacks, major depression, post¬traumatic stress disorder,
social anxiety, generalized anxiety disorder, panic disorder and obsessive-compulsive
disorder. Paroxetine has a well-established safety profile and it shares the common side
effects and contraindications of other SSRI's which include nausea and somnolence and is
associated with weight gain.
This study proposes to conduct a retrospective cohort study to assess the risk of new onset
diabetes among patients undergoing treatment with Pravastatin or other statins, and
Paroxetine or other SSRI's. This study will compare the risk of co administration of two drug
classes versus the use of each agent alone. In addition, the risk among patients prescribed
Paroxetine and fibrates in combination, relative to the use of Paroxetine singly, will be
examined to determine whether any interaction found between Paroxetine and statins extends to
other drugs indicated for hypercholesterolemia.
The first primary objective of the study is to estimate the incidence of Type 2 Diabetes
(T2DM) among patients newly exposed to pravastatin in combination with paroxetine, or other
SSRIs, compared to those newly exposed to pravastatin alone. The second primary objective is
to estimate the incidence of Type 2 Diabetes (T2DM) among patients newly exposed to
paroxetine in combination with pravastatin, other statins, or fibrates, compared to those
newly exposed to paroxetine alone.