Biochemical effects of antidepressant treatment--studies of monoamine metabolites in cerebrospinal fluid and platelet [3H]imipramine binding.

Two putative markers of serotonergic function, the concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the binding parameters of [3H]imipramine to blood platelets, are discussed. Pretreatment concentrations of 5-HIAA in the cerebrospinal fluid (CSF) are lower in depressed patients than in normal controls, and a low concentration of the metabolite is associated with an increased risk of suicide. Many studies have attempted to use pretreatment concentrations of 5-HIAA, of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and of the dopamine metabolite homovanillic acid (HVA) as predictors of therapeutic effect. On the whole, HVA appears to predict the effects of diverse treatments rather better than 5-HIAA. Treatment with antidepressant drugs changes the amine metabolite concentrations in the CSF in a relatively predictable way. Thus, administration of selective inhibitors of serotonin uptake has a more profound effect on CSF 5-HIAA, while noradrenaline uptake inhibitors preferentially reduce CSF MHPG concentrations. The Bmax of [3H]imipramine binding to blood platelets has been found to be lower in untreated depressed patients than in healthy controls in several studies. In a study from our group, three weeks' treatment with the serotonin uptake blockers zimeldine and alaproclate increased Bmax, while neither nortriptyline nor electroconvulsive treatment caused any change in Bmax after this time period. One year after initiation of treatment, patients who had clinically recovered and were no longer taking drugs still had a low Bmax of [3H]imipramine platelet binding. Prophylactic lithium caused a significant, but transient decrease in the Bmax of platelet [3H]imipramine binding in euthymic bipolar patients.