Displacement of Serotonin and Dopamine Transporters by Venlafaxine Extended Release Capsule at Steady State

Both positron emission tomography and single photon emission computed tomography (SPECT) studies suggest that saturation of serotonin transporters (SERT) is present during treatment with therapeutic doses of selective serotonin reuptake inhibitors (SSRIs). Selective serotonin reuptake inhibitors also appear to increase the availability of dopamine transporters (DAT). The current study measured SERT occupancy and modulation of DAT by the serotonin/norepinephrine reuptake inhibitor (SNRI) venlafaxine using [123I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane SPECT. Eight healthy subjects were administered open-label venlafaxine extended release capsules (75 mg/d for 4 days followed by 150 mg/d for 5 days). Venlafaxine significantly inhibited [123I]beta-CIT binding to SERT in the brainstem (55.4%) and the diencephalon (54.1%). In contrast, venlafaxine increased [123I]beta-CIT binding to DAT in the striatum (10.1%) after 5 days of administration of 150 mg/d. The displacement of [123I]beta-CIT from brain SERT and the increase in striatal [123I]beta-CIT binding to DAT appear similar to previous work with the SSRI citalopram (40 mg/d). A literature review of SERT occupancy by marketed SSRIs and the SNRI venlafaxine using SPECT ([123I]beta-CIT) or positron emission tomography ([11C](N, N-Dimethyl-2-(2-amino-4-cyanophenylthio)-benzylamine) imaging suggests that therapeutic doses of SNRI are associated with virtual saturation of the serotonin transporter.