The Effect of Escitalopram on Central Serotonergic and Dopaminergic Systems in Patients with Cervical Dystonia, and Its Relationship with Clinical Treatment Effects: A Double-Blind Placebo-Controlled Trial.

Evelien Zoons,Yasmine E.M Dreissen,Jan Booij,Marina A.J Tijssen,Marenka Smit

doi:10.3390/biom10060880

Abstract

Purpose: The pathophysiology of cervical dystonia (CD) is thought to be related to changes in dopamine and serotonin levels in the brain. We performed a double-blind trial with escitalopram (selective serotonin reuptake inhibitor; SSRI) in patients with CD. Here, we report on changes in dopamine D2/3 receptor (D2/3R), dopamine transporter (DAT) and serotonin transporter (SERT) binding potential (BPND) after a six-week treatment course with escitalopram or placebo. Methods: CD patients had [123I]FP-CIT SPECT (I-123 fluoropropyl carbomethoxy-3 beta-(4-iodophenyltropane) single-photon emission computed tomography) scans, to quantify extrastriatal SERT and striatal DAT, and [123I]IBZM SPECT (I-123 iodobenzamide SPECT) scans to quantify striatal D2/3R BPND before and after six weeks of treatment with either escitalopram or placebo. Treatment effect was evaluated with the Clinical Global Impression scale for dystonia, jerks and psychiatric symptoms, both by physicians and patients. Results: In both patients treated with escitalopram and placebo there were no significant differences after treatment in SERT, DAT or D2/3R BPND. Comparing scans after treatment with escitalopram (n = 8) to placebo (n = 8) showed a trend (p = 0.13) towards lower extrastriatal SERT BPND in the SSRI group (median SERT occupancy of 64.6%). After treatment with escitalopram, patients who reported a positive effect on dystonia or psychiatric symptoms had significantly higher SERT occupancy compared to patients who did not experience an effect. Conclusion: Higher extrastriatal SERT occupancy after treatment with escitalopram is associated with a trend towards a positive subjective effect on dystonia and psychiatric symptoms in CD patients.

Highlights

Cervical dystonia (CD) is the most common form of adult-onset, isolated, focal dystonia [1]
There were no significant differences in baseline extrastriatal serotonin transporter (SERT), striatal dopamine transporter (DAT) or striatal D2/3 receptor (D2/3R) BPND between patients randomized to be treated with escitalopram first and patients randomized to be treated with placebo first
We found no significant difference in SERT, DAT and D2/3R BPND before and after treatment with either escitalopram or placebo

Summary

Introduction

Cervical dystonia (CD) is the most common form of adult-onset, isolated, focal dystonia [1]. The pathophysiology of CD and other forms of dystonia is not fully understood, but alterations in neurotransmitters such as dopamine and serotonin are hypothesized to play an important role [5,6]. In line with this hypothesis, in two recent single-photon emission computed tomography (SPECT) studies in CD, we have shown that abnormalities in central dopaminergic and serotonergic systems are mainly related to depressive symptoms [7,8]. Increasing the SSRI dose leads to higher plasma levels but SERT occupancy does not further increase (ceiling effect). It was found that the striatal DAT binding is significantly increased by approximately 20% during a successful six-week treatment course with an SSRI, this effect is smaller in older patients [11]

Methods

Results

Conclusion