Maprotiline in the treatment of endogenous depression: comparison of therapeutic effect with serotonin level in blood platelets.

In blood platelets of untreated patients with endogenous depression a significantly lower concentration of serotonin (5-HT) was found than in healthy persons (P less than 0.05). The patients were afterwards divided into two groups: group I with mild symptoms of depression (total scores by Hamilton Depression Rating Scale below 40) and group II with severe depression (total scores above 40). The gradual diminishing of symptoms in both groups was accompanied by no change in 5-HT level in the first group and by progressive and well marked increases in platelet 5-HT content in the second one, attaining average normal values at the end of week 3 of treatment with maprotiline. In in vitro experiments maprotiline inhibited the uptake of 5-HT into blood platelets of healthy persons less than doxepin. After injection of maprotiline in rats (50 mg/kg IP) the turnover rate of 5-HT in the brain was only marginally affected if measured by 5-HT rise and 5-hydroxyindoleacetic acid (5-HIAA) decline after administration of the MAO inhibitor pargyline, or by estimation of 5-HIAA increase after blocking active transport with probenecid. However, after treatment with maprotiline alone, the 5-HIAA level in the rat brain was significantly increased, although the concentration of 5-HT was not altered. These results suggest: a) the possibility of an action of maprotiline on serotoninergic neurons and b) the suitability of blood platelets as a model for such an investigation.