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 patients with MDD 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 to 4 weeks of treatment with the SSRI escitalopram 10 mg daily. Depression severity was assessed at time of PET and after 6 to 7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale.

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 = .036). Change in DBS [11C]AZ10419369 binding correlated with Montgomery-Åsberg Depression Rating Scale reduction after 3-4 (r = 0.78, P = .021) and 6-7 (r = 0.94, P < .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.

Keywords: 5-HT1B receptor; Positron emission tomography; SSRI; major depressive disorder.

Figure 2.

Parametric positron emission tomography (PET) image of [¹¹C]AZ10419369 BP_ND before (PET 1) and after (PET 2) treatment with escitalopram 10mg. Parametric images of averaged [¹¹C]AZ10419369 binding at PET 1 and PET 2 normalized to MNI space. Closeup of brainstem area, with an outline of the summed dorsal brainstem (DBS) region of interest (ROI) for the eight participants normalized to MNI space. Normalization was performed using SPM12.

Figure 1.

DBS BP_ND–MADRS correlation. Scatterplots of change in MADRS to change in DBS [¹¹C]AZ10419369 BP_ND after treatment with escitalopram 10 mg at PET 2 and at 6 to 7 weeks. Regression line in blue with shaded 95% CI. Color represents dorsal brainstem (DBS) [¹¹C]AZ10419369 BP_ND at PET 1. MADRS, Montgomery-Åsberg Depression Rating Scale.