Fluvoxamine treatment of mixed anxiety and depression: Evidence for serotonergically mediated anxiolysis

Although increasing evidence suggests that selective serotonin reuptake inhibitor (SSRI) treatment may be effective for anxiety in addition to depression, SSRI anxiolysis has not been definitively related to the inhibition of serotonin (5-HT) transport. The gene that encodes for the human serotonin transporter (5-HTT) expresses its protein in neurons and in blood platelets, and both tissues respond to transport inhibition similarly in response to SSRI treatment. This study examined the relationship between the change in the 5-HTT's apparent affinity for 5-HT and the anxiolytic response in a group of 18 fluvoxamine-treated patients meeting Structured Clinical Interview for DSM-IV criteria for both generalized anxiety disorder and major depression. Significant decreases were found in both Hamilton anxiety and Hamilton depression scores over a 2-month treatment period. Robust increases were found in the apparent affinity constant (K_m) for platelet 5-HT transport with treatment, and the increases covaried significantly with the decrease in anxiety (F = 4.97,p < 0.03). The pretreatment 5HTT K_m significantly correlated with the improvement in depression scores (r = 0.53,p < 0.03), consistent with the Hypothesis of Initial Conditions. These results suggest that the therapeutic effect of SSRI treatment can be linked to the magnitude and time-course of 5-HT transport inhibition effected with fluvoxamine, a drug that seems to have an antianxiety effect of the same magnitude as its effect on depression.