Altered serotonin 1B receptor binding after escitalopram for depression is correlated with treatment effect

Abstract

Background Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT) but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI-administration in primates and rodents respectively. The effect of SSRI treatment on 5-HT1B receptor binding in MDD subjects has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect. Methods Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand [11C]AZ10419369 before and after 3-4 weeks of treatment with the SSRI escitalopram 10mg daily. Depression severity was assessed at time of PET and after 6-7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale (MADRS). Results We observed a significant reduction in [11C]AZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (p = 0.036). Change in DBS [11C]AZ10419369 binding correlated with MADRS reduction after three (r = 0.78, p = 0.021) and seven (r = 0.94, p < 0.001) weeks’ treatment. Conclusions Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker.