paroxetine for the treatment of interferon related side effects for hepatitis c

Conditions: Hepatitis C; Depression; Interferon-alpha Associated Side Effects

Summary: a.overview this is a 26 week study examining the ability of paroxetine (paxil) to prevent the development of depression and neurotoxicity in patients receiving either 3 million units of subcutaneous ifn(interferon-alpha-2b) 3 times/week (plus ribavirin, 1000-1200 mg/d)) or peg (polyethylene glycol) interferon-alpha-2b (1.5 micrograms/kg one time a week) and ribavirin (800 to 1,400 mg a day) for chronic hepatitis c (chc). the ifn plasma half life (t1/2 of 24 to 34 hours) of peg, a chc treatment recently approved by the fda, is significantly prolonged allowing for once a week dosing. studies indicate that the side effect profile of the two forms of ifn-alpha treatment are very similar. chc patients will be screened for study eligibility, and a total of 100 chc patients between the ages of 18 and 65 years old will be enrolled across three sites (30 at emory site and a combination of 30 from the university of pennsylvania, rush-presbyterian-saint lukes medical center in chicago and montefiore medical center in new york.) two weeks prior to treatment with subcutaneous ifn-alpha-2b, patients who meet inclusion and exclusion criteria will be stratified on the basis of a history of major depression and then randomly assigned to paroxetine or placebo in double blind fashion.


Eligibility criteria:
inclusion criteria: * age 18-65 years including males, females and minorities * serum positive for either anti-hcv antibodies or hcv-rna positive by pcr * compensated liver disease with the following minimum hematologic and biochemical criteria: hemoglobin 3 g/dl for males; 12 g/dl for females, white blood cell count \> 3,000/mm3, neutrophil count \>1,5000/mm3, platelets \> 100,000/mm3, prothrombin time 2 seconds prolonged compared to control, or equivalent inr ratio, albumin stable and within normal limits, serum creatinine within normal limits, thyroid-stimulating hormone (tsh) within normal limits, direct bilirubin 0.3 mg/dl or within 20% of upper limit of normal (uln) for local laboratory, indirect bilirubin 0.8 mg/dl or within 20% of uln for local laboratory, fasting blood sugar 115 mg/dl or within 20% of uln for non-diabetic patients * serum hepatitis b surface antigen (hbsag) negative, antinuclear antibodies (ana) 1:320 * normal pre-therapy ocular examination if a history of diabetes or hypertension * hemoglobin a1c \<8.5% if a history of diabetes * negative pregnancy test for women of childbearing potential, and consent to adhere to adequate contraception or monogamous relationship with a male partner who has had a vasectomy during the treatment period and for 6 months after discontinuation of therapy * not breast feeding * documentation and confirmation of adequate contraception in sexually active males * free from all psychotropic medications for a minimum of 14 days prior to baseline visit (8 weeks for fluoxetine) exclusion criteria: * actively meet criteria for major depression within the past six months * active, effective treatment of depression with an antidepressant within the past three months * meet criteria for schizophrenia or bipolar disorder (mania) past or present * actively meet dsm iv criteria for substance abuse/dependence within the past six months * psychotropic medications within 14 days prior to baseline visit (8 weeks for fluoxetine) * evidence of untreated or poorly controlled endocrine, cardiovascular, hematological, renal, or neurological disease * evidence of decompensated liver disease (such as a history or presence of ascites, bleeding varices, spontaneous encephalopathy) * history of cns trauma or active seizure disorder requiring medication * any cause for liver disease other than chronic hepatitis c, such as co-infection with hepatitis b virus and/or human immunodeficiency virus, hemochromatosis, or wilson's disease * prior treatment with other (other than ifn-alpha or ribavirin) immunomodulatory drugs, including corticosteroids within 6 months of entry into protocol * clinical gout * known hypersensitivity to alpha interferon or ribavirin * hemoglobinopathies (e.g. thalassemia) * a positive pregnancy test * clinically significant retinal abnormalities * organ transplants * a score of \<24 on the mini mental status exam (mmse) * prior history of severe adverse events associated with paroxetine * any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with participating in or completing the protocol

Keywords: hepatitis c interferon-alpha associated side effects antidepressants prevention