Paroxetine for prevention of depressive symptoms induced by interferon-alpha and ribavirin for hepatitis C.

BACKGROUND: Whether antidepressants prevent depression during interferon-alpha/ribavirin treatment for hepatitis C virus infection has yet to be established. AIM: To investigate the use of paroxetine in a prospective, double-blind, placebo-controlled study for this indication. METHODS: Sixty-one hepatitis C virus-infected patients were randomly assigned to the antidepressant, paroxetine (n = 28), or placebo (n = 33), begun 2 weeks before and continued for 24 weeks during interferon-alpha/ribavirin treatment. Primary endpoints included development of major depression and severity of depressive symptoms measured by the Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: Rates of major depression during the study were low (17%) and did not differ between groups. Nevertheless, using published MADRS cut-off scores, the percent of subjects who met criteria for mild, moderate or severe depression during interferon-alpha/ribavirin therapy was significantly lower in paroxetine- vs. placebo-treated subjects (P = 0.02, Fisher's exact test). Assignment to paroxetine was also associated with significantly reduced depressive symptom severity. This effect was largely accounted for by participants with depression scores above the median (MADRS > 3) at baseline in whom paroxetine was associated with a maximal reduction in MADRS scores of 10.3 (95% CI: 2.1-18.5) compared with placebo at 20 weeks (P < 0.01). Study limitations included a small sample size and high drop-out rate. CONCLUSION: This double-blind, placebo-controlled trial provides preliminary data in support of antidepressant pre-treatment in hepatitis C virus patients with elevated depressive symptoms at baseline.

Liver transplantation at the University of Pennsylvania and the Children's Hospital of Philadelphia.

The liver transplant program at the University of Pennsylvania and the Children's Hospital of Philadelphia experienced healthy growth in its clinical activity in the past 5 years. Patterns of referral and patient evaluation were established, care of patients while waiting on the list or being followed after transplantation was streamlined. We are now achieving excellent outcomes while transplanting relatively sicker patients. Innovative surgical procedures are implemented resulting in more efficient utilization of cadaveric and living-donor liver grafts. The protocols that are used for patient care are more standard, yet flexible and accommodate recent advancement in transplantation immunobiology. This progress of the clinical program was enhanced by careful preservation of the academic mission of the institution, which encourages the liver transplant faculty to be involved in NIH-supported clinical and basic science research.

Ritanserin in the treatment of alcohol dependence--a multi-center clinical trial. Ritanserin Study Group.

Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT2 receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects' QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence.