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

We investigated platelet [14C]serotonin (5-HT) uptake and lysergic acid diethylamide [N-methyl-3H] ([3H]LSD)- and phenyl-6'-paroxetine ([3H]paroxetine) 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-matched group of healthy volunteers. Baseline Vmax was significantly lower in patients than in controls. Bmax for [3H]paroxetine binding were similar in patients and controls, but patients who suffered their first depression had significantly lower Bmax for [3H]paroxetine binding than patients who had suffered multiple depressions. Twenty-three patients (76%) (13 in the paroxetine group and 10 in the sertraline group) responded to treatment as 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 paroxetine and sertraline caused a significant reduction in Vmax and a significant increase in Km. There was a strong correlation between Km and plasma drug concentration in patients who experienced their first depression but not in patients who had suffered multiple episodes. Bmax for [3H]paroxetine binding increased after paroxetine treatment while the opposite occurred after sertraline treatment. There was a significant interaction between the impact of drug and earlier depressions. All patients included in the study had been drug free for at least 2 months. Earlier antidepressant treatment may have long withstanding effects on the serotonin uptake machinery but it cannot be excluded that the sensitivity of the uptake mechanism may become more resistant to change in patients with recurrent depressive episodes.