Serotonergic function in major depression and effect of sertraline and paroxetine treatment

We investigated platelet [C-14]serotonin (5-HT) uptake and lysergic acid di ethylamide [N-methyl-H-3] ([H-3]LSD)- and phenyl-6'-paroxetine ([H-3]paroxe tine) binding in 30 patients with major depression at baseline and after 6 months of treatment with either paroxetine or sertraline. The study was of a double-blind design. Baseline data was compared with an age- and gender m atched group of healthy volunteers. Baseline V-max was significantly lower in patients than in controls. B-max for [H-3]paroxetine binding were simila r in patients and controls, but patients who suffered their first depressio n had significantly lower B-max for [H-3]paroxetine binding than patients w ho had suffered multiple depressions. Twenty-three patients (76%) (13 in th e paroxetine group and 10 in the sertraline group) responded to treatment a s judged by a 50% or more reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores after 6 months of treatment. There were no significant differences between the paroxetine and sertraline treated groups. Both par oxetine and sertraline caused a significant reduction in V-max and a signif icant increase in K-m. There was a strong correlation between K-m and:plasm a drug concentration in patients who experienced their first depression but not in patients who had suffered multiple episodes. B-max for [H-3]paroxet ine binding increased after paroxetine treatment while the opposite occurre d after sertraline treatment. There was a significant interaction between t he impact of drug and earlier depressions. All patients included in the stu dy had been drug free for at least 2 months. Earlier antidepressant treatme nt may have long withstanding effects on the serotonin uptake machinery but it cannot be excluded that the sensitivity of the uptake mechanism may bec ome more resistant to change in patients with recurrent depressive episodes . (C) 2001 Lippincott Williams & Wilkins.