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A Critical Review of Selective Serotonin Reuptake Inhibitor-Associated Bleeding: Balancing the Risk of Treating Hepatitis C-Infected Patients

Robert M. Weinrieb, M.D.; Marc Auriacombe, M.D., M.Sc.; Kevin G. Lynch, Ph.D.; Kyong-Mi Chang, M.D.; and James D. Lewis, M.D., M.S.C.E.

Background: Selective serotonin reuptake inhibitors (SSRIs) are increasingly being used to treat interferon-associated side effects in patients receiving hepatitis C virus (HCV) therapy. Because there is an increased risk of bleeding in HCV-infected patients who have developed cirrhosis and either portal hypertension or hepatic failure or both, we critically reviewed the literature on SSRI-associated bleeding.

Data Sources and Study Selection: We performed a MEDLINE search of literature from 1966 to the present using hemorrhage, SSRI, and antidepressants as search terms and followed up on relevant citations. We reviewed 6 retrospective studies, 5 of which were case-control studies, and 18 case reports of bleeding in 37 people. Our review is supplemented with a case report of a possible connection between SSRI treatment and a fatal gastrointestinal bleed in an HCV-infected man.

Data Synthesis: Bleeding events in 12/18 reports (67%) describing 19/24 people (79%) were closely associated with the use of SSRIs.

Conclusion: Combining aspirin or nonsteroidal anti-inflammatory drugs with SSRIs for the treatment of interferon-associated neuropsychiatric side effects increases the risks of hemorrhage in patients with HCV who have developed cirrhosis and either portal hypertension or hepatic failure or both. We recommend that clinicians exercise caution when prescribing medications that can promote spontaneous bleeding to patients with multiple risk factors for internal hemorrhage.

(J Clin Psychiatry 2003;64:1502-1510)

Received Jan. 21, 2003; accepted May 13, 2003. From the Department of Psychiatry (Drs. Weinrieb, Auriacombe, and Lynch) and the Division of Gastroenterology, Department of Medicine (Drs. Chang and Lewis), University of Pennsylvania, Philadelphia; the Philadelphia Veterans Administration Medical Center, Philadelphia, Pa. (Drs. Weinrieb, Lynch, Chang, and Lewis); and the Groupe d'Étude des Addictions, Department of Psychiatry, Victor Pachon Medical School, Victor Segalen University of Bordeaux, Bordeaux, France (Dr. Auriacombe).

Drs. Weinrieb and Lynch are supported by grant 1R01AA12299-01 and Drs. Weinrieb and Chang are supported by grant RO1-AA12849-01 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Md. Dr. Weinrieb is funded by the Mental Illness, Research, Education and Clinical Care (MIRECC) of the Veterans Administration Medical Center (funding source is NIAAA, Bethesda, Md.). Dr. Chang is supported by grant RO1-AI47519 from the National Institute of Allergy and Infectious Diseases, Bethesda, Md.

Dr. Lewis has consulted for Merck, Bayer, GlaxoSmith Kline, and Wyeth and has received grant funding from Centocor, Wyeth, Whitehall-Robins, GlaxoSmithKline, and Bayer in recent years. Dr. Auriacombe has no grant support or competing interests to report.

The authors gratefully acknowledge A. Thomas McLellan, Ph.D., for editorial assistance.

Corresponding author and reprints: Robert M. Weinrieb, M.D., The Treatment and Evaluation Center of the University of Pennsylvania, 3440 Market St., Suite 380, Philadelphia, PA 19104