Warfarin is also highly protein-bound; therefore when used concomitantly with other medications that are highly protein-bound, it has the potential to be displaced from serum protein, leading to increased free warfarin concentration and an increased risk of bleeding. Although warfarin is approximately 99% protein-bound, there is little clinical evidence that this pharmacodynamic interaction produces a meaningful drug-drug interaction, even among antidepressants that are noted to be highly protein-bound (i.e., sertraline, duloxetine). 4,6
Each of the antidepressants has varying effects on the CYP450 system as it relates to warfarin (TABLE 1). 4,6-8
Mechanism of Drug Interactions With Warfarin
The updated CHEST guidelines from the American College of Chest Physicians provide new recommendations on the frequency of INR monitoring. 17 If patients consistently maintain a stable, therapeutic INR, the guidelines recommend checking the INR every 12 weeks instead of the previously recommended monthly testing. However, if the INR is not within a stable therapeutic range, it is still recommended to monitor the INR every 4 weeks until stable. Patients who present with a single INR out of range of ≤0.5, who normally present with stable INR values, are no longer recommended to receive a warfarin dosage change. Instead, the guidelines now recommend continuing the current dose and rechecking the INR within 1 to 2 weeks. Additionally, bridging with enoxaparin is no longer recommended for single out-of-range INR values of ≤0.5. 17
ABSTRACT: When used as monotherapy, warfarin is associated with an increased risk of bleeding. When warfarin is used concomitantly with other drugs that may also increase the risk of bleeding or affect the concentration of warfarin, the bleeding risk may be further increased. The combined use of warfarin and antidepressants, particularly the selective serotonin reuptake inhibitors, may lead to drug-drug interactions via pharmacodynamic and pharmacokinetic mechanisms. Limited data exist concerning the potential for drug-drug interactions between warfarin and antidepressants. When it is necessary to use both warfarin and an antidepressant, it is recommended to select an agent with minimal effect on the CYP450 system and a lower degree of inhibition of serotonin reuptake, as well as to increase the frequency of monitoring of the international normalized ratio and signs and symptoms of bleeding.
Studies reporting adverse effects of bleeding with antidepressant use have been mostly observational in design. Meijer et al conducted a case-control study of first-time antidepressant users investigating the relationship between serotonin reuptake inhibition and bleeding risks. 16 A greater degree of serotonin reuptake inhibition, which was categorized as high, intermediate, or low, was associated with a higher risk of abnormal bleeding (TABLE 2). 16
Our Coumadin Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
Coumadin may interact with other medications to prevent blood clots, antibiotics, antifungals, sulfa drugs, medicines to treat tuberculosis, antidepressants, herbal (botanical) products (including coenzyme Q10, cranberry, echinacea, garlic, ginkgo biloba, ginseng, goldenseal, or St. John’s wort), secobarbital, barbiturates, seizure medications, and other drugs. Tell your doctor all medications and supplements you use.
Coumadin has a wide range of tablets: 2, 2.5, 3, 4, 5, 6, 7.5 and 10 mg tablets are available. An injectable form of the drug (5 mg) is also available. The dose of Coumadin is determined in each individual by administering a trial dose and ten measuring the patient’s INR (International Normalized Ratio), a lab test that is standardized by the WHO (world Health Organization) and recognized worldwide. Therapeutic ranges for this test are between 2.0 to 3.0 when a patient is taking Coumadin. INR levels below 2 may allow easier blood clotting to occur while levels above 3 may cause excessive tendency for the patient to bleed.
Coumadin During Pregnancy and Breastfeeding
Common side effects of Coumadin include
Pregnant women should not be given Coumadin; lactating women may need to be closely monitored and their breastfed infants should have their INR checked, according to some investigators. Although Coumadin has been used in pediatric patients to prevent clot formations, children under 18 have not been well studied with this drug and some investigators suggest achieving stable INR levels seems more difficult in the pediatric population.
Coumadin (warfarin) is a blood anticoagulant that inhibits the function of Vitamin K dependent coagulation used to inhibit the coagulation of blood to reduce or prevent the chance of developing heart attacks (myocardial infarctions), strokes, and venous and other blood clots (deep venous thromboses, pulmonary emboli and thrombi produced with atrial fibrillation). Coumadin is also used to treat these conditions if they develop. Coumadin is available as a generic.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Severe or Chronic Medical Conditions. Any chronic or serious illness, such as diabetes or multiple sclerosis, can lead to depression. Many medications taken for chronic medical problems can also cause depression.
ACOG and the American Psychiatric Association (APA) recommend that women who are pregnant or thinking about becoming pregnant should not stop taking antidepressants without first talking to their doctors. Women who have mild or no depressive symptoms for at least 6 months before becoming pregnant may be able to taper off or discontinue antidepressant medication, under supervision of their doctor. Stopping medication may be more difficult for women with a history of severe recurrent depression. Psychotherapy (preferably cognitive behavioral therapy or interpersonal therapy) may be helpful in addition to, or in replacement of, antidepressant medication. Electroconvulsive therapy (ECT) may be an option for pregnant women with severe depression.
Depression in Men
Tips for selecting a therapist:
Mental Decline. Depression in the elderly is associated with a decline in mental functioning, regardless of the presence of dementia.
According to major surveys, major depressive disorder affects nearly 15 million Americans (about 7% of the adult population) in a given year. While depression is an illness that can affect anyone at any time in their life, the average age of onset is 32 (although adults ages 49 – 54 years are the age group with the highest rates of depression.). Other major risk factors for depression include being female, being African-American, and living in poverty.