I only did research on this after ex dubio from mind mucle posting evidence it indeed was, so credits go to him.
While escitalopram is slightly more effective it is significant enough to make its own thread for it, HOWEVER response to ssris is mostly just highly individual, effexor acts on the opiate system, fluvoxamine is a sigma agonist and so forth.. so a thread dedicated to most available antidepressants might be a good idea, as an example.
Also guys while it may be superior, ssris are still not much better then placebo for depression, but we cant deny they work
Quote
Pharmacol Biochem Behav. 2016 Feb;141:50-7. doi: 10.1016/j.pbb.2015.11.010. Epub 2015 Nov 24.
In vivo investigation of escitalopram's allosteric site on the serotonin transporter.
Murray KE1, Ressler KJ2, Owens MJ3.
Abstract
Escitalopram is a commonly prescribed antidepressant of the selective serotonin reuptake inhibitor class. Clinical evidence and mapping of the serotonin transporter (SERT) identified that escitalopram, in addition to its binding to a primary uptake-blocking site, is capable of binding to the SERT via an allosteric site that is hypothesized to alter escitalopram's kinetics at the SERT. The studies reported here examined the in vivo role of the SERT allosteric site in escitalopram action. A knockin mouse model that possesses an allosteric-null SERT was developed. Autoradiographic studies indicated that the knockin protein was expressed at a lower density than endogenous mouse SERT (approximately 10-30% of endogenous mouse SERT), but the knockin mice are a viable tool to study the allosteric site. Microdialysis studies in the ventral hippocampus found no measurable decrease in extracellular serotonin response after local escitalopram challenge in mice without the allosteric site compared to mice with the site (p=0.297). In marble burying assays there was a modest effect of the absence of the allosteric site, with a larger systemic dose ofescitalopram (10-fold) necessary for the same effect as in mice with intact SERT (p=0.023). However, there was no effect of the allosteric site in the tail suspension test. Together these data suggest that there may be a regional specificity in the role of the allosteric site. The lack of a robust effect overall suggests that the role of the allosteric site for escitalopram on the SERT may not produce meaningful in vivo effects.
Copyright © 2015 Elsevier Inc. All rights reserved.
QuoteQuote
Changes in the regional cerebral blood flow detected by arterial spin labeling after 6-week escitalopramtreatment for major depressive disorder.
Kaichi Y1, Okada G2, Takamura M2, Toki S3, Akiyama Y4, Higaki T5, Matsubara Y6, Okamoto Y2, Yamawaki S2, Awai K5.
Abstract
BACKGROUND:
A few studies have used pseudo-continuous arterial spin labeling (pCASL) to assess the regional cerebral blood flow (rCBF) in patients with major depressive disorder (MDD). However, rCBF changes during treatment with escitalopram have not been studied in detail. We used pCASL to investigate the effect of 6-week escitalopram treatment on the rCBF in MDD patients.
METHODS:
We subjected 53 MDD patients and 36 controls to pCASL (T1, baseline). The patients then received treatment with escitalopram for 6 weeks and 27 were scanned again (T2). We used selected regions of interest that exhibited differences between the controls and patients at T1 and compared the T2 rCBF in the patients with the T1 rCBF of the controls. We also compared the T1 and T2 rCBF in the patients to assess their response to escitalopram.
RESULTS:
After 6-week treatment with escitalopram, the rCBF in the patients' left inferior temporal gyri, the middle- and inferior frontal gyri, and the subgenual anterior cingulate, which had been higher at T1 than in the controls, was decreased. Their rCBF in the right lingual gyrus remained significantly lower at T2.
LIMITATION:
We did not have a placebo-control group and the number of patients available at T2 was small.
CONCLUSION:
In MDD patients, 6-week escitalopram treatment elicited significant rCBF changes toward normalization in most of the areas that had shown significant differences between the patients and the controls at T1. The persistence of rCBF anomalies in the right lingual gyrus may be a trait marker of MDD.
Copyright © 2015 Elsevier B.V. All rights reserved.
Quote
Pharmacol Biochem Behav. 2016 Feb 15. pii: S0091-3057(16)30018-1. doi: 10.1016/j.pbb.2016.02.005. [Epub ahead of print]
Effects of escitalopram, R-citalopram, and reboxetine on serum levels of tumor necrosis factor-α, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration.
Dong C1, Zhang JC1, Yao W1, Ren Q1, Yang C1, Ma M1, Han M1, Saito R2, Hashimoto K3.
Abstract
Inflammation plays a role in the pathophysiology of depression. The purpose of this study is to examine whether the selective serotonin reuptake inhibitor (SSRI) escitalopram, its inactive enantiomer R-citalopram, and selective noradrenaline reuptake inhibitor (NRI) reboxetine, show anti-inflammatory and antidepressant effects in an inflammation-induced model of depression. Pretreatment with escitalopram (1, 3, or 10mg/kg, i.p.) markedly blocked an increase in the serum levels of pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), after a single administration of lipopolysaccharide (LPS; 0.5mg/kg). Furthermore, escitalopram (3 or 10mg/kg) significantly increased the serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) by a single administration of LPS. In contrast, pretreatment with R-citalopram (10mg/kg, i.p.) or reboxetine (10mg/kg, i.p.) did not affect the alterations in serum levels of TNF-α and IL-10 after LPS administration. Co-administration of reboxetine with escitalopram did not show anti-inflammatory effects. Pretreatment with escitalopram (10mg/kg) significantly attenuated LPS-induced increase of the immobility time in the tail-suspension test (TST) and forced swimming test (FST). In contrast, pretreatment with R-citalopram (10mg/kg), or reboxetine (10mg/kg) did not alter LPS-induced increase of immobility time of TST and FST. Interestingly, co-administration of reboxetine with escitalopram did not show antidepressant effect in this model. These findings suggest that escitalopram, but not R-citalopram and reboxetine, has anti-inflammatory and antidepressant effects in LPS-treated model of depression, and that reboxetine can antagonize the effects of escitalopram in the inflammation model. Therefore, it is likely that serotonergic system plays a key role in the pathophysiology of inflammation-induced depression.
Copyright © 2015. Published by Elsevier Inc.
QuoteQuote
J Pharmacol Pharmacother. 2015 Oct-Dec;6(4):198-203. doi: 10.4103/0976-500X.171883.
A comparative study of the clinical efficacy and safety of agomelatine with escitalopram in major depressive disorder patients: A randomized, parallel-group, phase IV study.
Urade CS1, Mahakalkar SM1, Tiple PG2.
Abstract
OBJECTIVE:
To compare the efficacy of agomelatine with escitalopram in the treatment of major depressive disorder (MDD), improve sleep in MDD patients and study the adverse effects of agomelatine.
MATERIALS AND METHODS:
Randomized, parallel-group, open-label study. The primary efficacy outcome was change from baseline to last post-baseline value in Hamilton depression rating scale and Leeds sleep evaluation questionnaire scale. Both parametric and nonparametric tests were applied for analysis.
RESULTS:
Within-group and between-groups comparison of the mean HAMD17 scores showed statistically significant changes (P < 0.0001).Escitalopram showed early onset of response and remission compared to agomelatine at 10(th) week (P < 0.0001) and 14(th) week (P < 0.0001), respectively. In agomelatine, within-group and between-groups change of the mean LSEQ score was statistically significant at subsequent follow-up visits (P < 0.0001).
CONCLUSION:
Escitalopram is superior to agomelatine in efficacy, considering the early response, early remission, and better relief from symptoms of MDD in adults. Agomelatine may be preferred in MDD patients having insomnia as a predominant symptom. Liver function monitoring should be done in patients on long-term agomelatine therapy.
KEYWORDS:
Agomelatine; antidepressants; escitalopram; insomnia; major depressive disorder
QuoteQuote
Pharmacopsychiatry. 2016 Jan;49(1):26-31. doi: 10.1055/s-0035-1565241. Epub 2016 Jan 20.
The Effects of Antidepressants on Neuropeptide Y in Patients with Depression and Anxiety.
Ozsoy S1, Olguner Eker O2, Abdulrezzak U3.
Abstract
INTRODUCTION:
This study aimed to investigate the neuropeptide Y (NPY) levels in patients with anxiety and depression and also the effects of antidepressants on this neuropeptide.
MATERIALS AND METHODS:
The study included 40 outpatients who presented with depressive and anxiety symptoms, and 32 healthy controls. The patients received antidepressant treatment for 6 months. Serum levels of neuropeptide Y were measured before treatment in 40 patients, after 8 weeks of treatment in 32 patients, after 6 months in 10 patients, and once in the controls.
RESULTS:
Serum NPY levels were lower in the patients than in the controls. NPY levels were increased and normalized by antidepressant treatment. While there was no change in NPY levels in the patients using fluoxetine and sertraline for 8 weeks, an increase was found in patients using escitalopram and venlafaxine. Serum NPY levels were increased by treatment for 8 weeks in the patients with depression, but not in the patients with anxiety.
DISCUSSION:
The findings suggest that NPY may be related to pathophysiology in depression and anxiety, and antidepressants influence NPY levels.
© Georg Thieme Verlag KG Stuttgart · New York.
QuoteQuote
Int Clin Psychopharmacol. 2015 Dec 8. [Epub ahead of print]
Measuring citalopram in blood and central nervous system: revealing a distribution pattern that differs from other antidepressants.
Paulzen M1, Lammertz SE, Gründer G, Veselinovic T, Hiemke C, Tauber SC.
· 1aDepartment of Psychiatry, Psychotherapy and Psychosomatics, JARA - Translational Brain Medicine bDepartment of Neurology, RWTH Aachen University, Aachen cDepartment of Psychiatry and Psychotherapy, University Medical Center of Mainz, Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany.
Abstract
The aim of this study was to measure blood and cerebrospinal fluid concentrations of citalopram and its weakly active N-demethylated metabolite desmethylcitalopram to account for the distribution between the two compartments. The findings are discussed in the context with own preceding studies on the distribution pattern of different antidepressants. Concentrations of citalopram were measured in blood serum and cerebrospinal fluid of 18 patients treated with daily doses of 10-40 mg. Daily doses were correlated with serum and cerebrospinal fluid concentrations, and serum concentrations were correlated with concentrations in cerebrospinal fluid. Serum concentrations of citalopram and desmethylcitalopram showed no significant correlation to the daily dose, r=0.164, P=0.515, and r=0.174, P=0.505, respectively, whereas citalopram concentrations in serum and cerebrospinal fluid were highly correlated (r=0.763, P<0.001). The cerebrospinal fluid/serum ratio for citalopram (total=bound+unbound concentration) varied between 0.14 and 0.86 (mean 0.35, SD 0.16). By correcting the mean cerebrospinal fluid/serum ratio for 80% plasma protein binding, cerebrospinal fluid concentrations of citalopram were on average 77% higher than the calculated unbound serum concentration with a ratio of 1.77 (SD 0.81, range 0.68-4.29). Findings indicate a very good ability of citalopram to cross the blood-brain and cerebrospinal fluid barrier. High concentrations of citalopram in the cerebrospinal fluid are indicative of active transport of citalopram into or missing active transport out of the cerebrospinal fluid. The results suggest a high ability of citalopram to enter the brain with sufficiently high drug concentrations at the target sites within the brain, contributing toward clinical efficacy.
QuoteQuote
J Psychopharmacol. 2016 Jan;30(1):33-9. doi: 10.1177/0269881115620462. Epub 2015 Dec 8.
Effect of short-term escitalopram treatment on neural activation during emotional processing.
Maron E1, Wall M2, Norbury R3, Godlewska B4, Terbeck S5, Cowen P4, Matthews P2, Nutt DJ2.
Abstract
Recent functional magnetic resonance (fMRI) imaging studies have revealed that subchronic medication with escitalopram leads to significant reduction in both amygdala and medial frontal gyrus reactivity during processing of emotional faces, suggesting that escitalopram may have a distinguishable modulatory effect on neural activation as compared with other serotonin-selective antidepressants. In this fMRI study we aimed to explore whether short-term medication with escitalopram in healthy volunteers is associated with reduced neural response to emotional processing, and whether this effect is predicted by drug plasma concentration. The neural response to fearful and happy faces was measured before and on day 7 of treatment with escitalopram (10mg) in 15 healthy volunteers and compared with those in a control unmedicated group (n=14). Significantly reduced activation to fearful, but not to happy facial expressions was observed in the bilateral amygdala, cingulate and right medial frontal gyrus following escitalopram medication. This effect was not correlated with plasma drug concentration. In accordance with previous data, we showed thatescitalopram exerts its rapid direct effect on emotional processing via attenuation of neural activation in pathways involving medial frontal gyrus and amygdala, an effect that seems to be distinguishable from that of other SSRIs.
QuoteQuote
Pharmacol Biochem Behav. 2016 Feb;141:50-7. doi: 10.1016/j.pbb.2015.11.010. Epub 2015 Nov 24.
In vivo investigation of escitalopram's allosteric site on the serotonin transporter.
Murray KE1, Ressler KJ2, Owens MJ3.
Abstract
Escitalopram is a commonly prescribed antidepressant of the selective serotonin reuptake inhibitor class. Clinical evidence and mapping of the serotonin transporter (SERT) identified that escitalopram, in addition to its binding to a primary uptake-blocking site, is capable of binding to the SERT via an allosteric site that is hypothesized to alter escitalopram's kinetics at the SERT. The studies reported here examined the in vivo role of the SERT allosteric site in escitalopram action. A knockin mouse model that possesses an allosteric-null SERT was developed. Autoradiographic studies indicated that the knockin protein was expressed at a lower density than endogenous mouse SERT (approximately 10-30% of endogenous mouse SERT), but the knockin mice are a viable tool to study the allosteric site. Microdialysis studies in the ventral hippocampus found no measurable decrease in extracellular serotonin response after local escitalopram challenge in mice without the allosteric site compared to mice with the site (p=0.297). In marble burying assays there was a modest effect of the absence of the allosteric site, with a larger systemic dose ofescitalopram (10-fold) necessary for the same effect as in mice with intact SERT (p=0.023). However, there was no effect of the allosteric site in the tail suspension test. Together these data suggest that there may be a regional specificity in the role of the allosteric site. The lack of a robust effect overall suggests that the role of the allosteric site for escitalopram on the SERT may not produce meaningful in vivo effects.
Copyright © 2015 Elsevier Inc. All rights reserved.
I only did research on this after ex dubio from mind mucle posting evidence it indeed was, so credits go to him.
While escitalopram is slightly more effective it is significant enough to make its own thread for it, HOWEVER response to ssris is mostly just highly individual, effexor acts on the opiate system, fluvoxamine is a sigma agonist and so forth.. so a thread dedicated to most available antidepressants might be a good idea, as an example.
Also guys while it may be superior, ssris are still not much better then placebo for depression, but we cant deny they work
Quote
Pharmacol Biochem Behav. 2016 Feb;141:50-7. doi: 10.1016/j.pbb.2015.11.010. Epub 2015 Nov 24.
In vivo investigation of escitalopram's allosteric site on the serotonin transporter.
Murray KE1, Ressler KJ2, Owens MJ3.
Abstract
Escitalopram is a commonly prescribed antidepressant of the selective serotonin reuptake inhibitor class. Clinical evidence and mapping of the serotonin transporter (SERT) identified that escitalopram, in addition to its binding to a primary uptake-blocking site, is capable of binding to the SERT via an allosteric site that is hypothesized to alter escitalopram's kinetics at the SERT. The studies reported here examined the in vivo role of the SERT allosteric site in escitalopram action. A knockin mouse model that possesses an allosteric-null SERT was developed. Autoradiographic studies indicated that the knockin protein was expressed at a lower density than endogenous mouse SERT (approximately 10-30% of endogenous mouse SERT), but the knockin mice are a viable tool to study the allosteric site. Microdialysis studies in the ventral hippocampus found no measurable decrease in extracellular serotonin response after local escitalopram challenge in mice without the allosteric site compared to mice with the site (p=0.297). In marble burying assays there was a modest effect of the absence of the allosteric site, with a larger systemic dose ofescitalopram (10-fold) necessary for the same effect as in mice with intact SERT (p=0.023). However, there was no effect of the allosteric site in the tail suspension test. Together these data suggest that there may be a regional specificity in the role of the allosteric site. The lack of a robust effect overall suggests that the role of the allosteric site for escitalopram on the SERT may not produce meaningful in vivo effects.
Copyright © 2015 Elsevier Inc. All rights reserved.
QuoteQuote
Changes in the regional cerebral blood flow detected by arterial spin labeling after 6-week escitalopramtreatment for major depressive disorder.
Kaichi Y1, Okada G2, Takamura M2, Toki S3, Akiyama Y4, Higaki T5, Matsubara Y6, Okamoto Y2, Yamawaki S2, Awai K5.
Abstract
BACKGROUND:
A few studies have used pseudo-continuous arterial spin labeling (pCASL) to assess the regional cerebral blood flow (rCBF) in patients with major depressive disorder (MDD). However, rCBF changes during treatment with escitalopram have not been studied in detail. We used pCASL to investigate the effect of 6-week escitalopram treatment on the rCBF in MDD patients.
METHODS:
We subjected 53 MDD patients and 36 controls to pCASL (T1, baseline). The patients then received treatment with escitalopram for 6 weeks and 27 were scanned again (T2). We used selected regions of interest that exhibited differences between the controls and patients at T1 and compared the T2 rCBF in the patients with the T1 rCBF of the controls. We also compared the T1 and T2 rCBF in the patients to assess their response to escitalopram.
RESULTS:
After 6-week treatment with escitalopram, the rCBF in the patients' left inferior temporal gyri, the middle- and inferior frontal gyri, and the subgenual anterior cingulate, which had been higher at T1 than in the controls, was decreased. Their rCBF in the right lingual gyrus remained significantly lower at T2.
LIMITATION:
We did not have a placebo-control group and the number of patients available at T2 was small.
CONCLUSION:
In MDD patients, 6-week escitalopram treatment elicited significant rCBF changes toward normalization in most of the areas that had shown significant differences between the patients and the controls at T1. The persistence of rCBF anomalies in the right lingual gyrus may be a trait marker of MDD.
Copyright © 2015 Elsevier B.V. All rights reserved.
Quote
Pharmacol Biochem Behav. 2016 Feb 15. pii: S0091-3057(16)30018-1. doi: 10.1016/j.pbb.2016.02.005. [Epub ahead of print]
Effects of escitalopram, R-citalopram, and reboxetine on serum levels of tumor necrosis factor-α, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration.
Dong C1, Zhang JC1, Yao W1, Ren Q1, Yang C1, Ma M1, Han M1, Saito R2, Hashimoto K3.
Abstract
Inflammation plays a role in the pathophysiology of depression. The purpose of this study is to examine whether the selective serotonin reuptake inhibitor (SSRI) escitalopram, its inactive enantiomer R-citalopram, and selective noradrenaline reuptake inhibitor (NRI) reboxetine, show anti-inflammatory and antidepressant effects in an inflammation-induced model of depression. Pretreatment with escitalopram (1, 3, or 10mg/kg, i.p.) markedly blocked an increase in the serum levels of pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), after a single administration of lipopolysaccharide (LPS; 0.5mg/kg). Furthermore, escitalopram (3 or 10mg/kg) significantly increased the serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) by a single administration of LPS. In contrast, pretreatment with R-citalopram (10mg/kg, i.p.) or reboxetine (10mg/kg, i.p.) did not affect the alterations in serum levels of TNF-α and IL-10 after LPS administration. Co-administration of reboxetine with escitalopram did not show anti-inflammatory effects. Pretreatment with escitalopram (10mg/kg) significantly attenuated LPS-induced increase of the immobility time in the tail-suspension test (TST) and forced swimming test (FST). In contrast, pretreatment with R-citalopram (10mg/kg), or reboxetine (10mg/kg) did not alter LPS-induced increase of immobility time of TST and FST. Interestingly, co-administration of reboxetine with escitalopram did not show antidepressant effect in this model. These findings suggest that escitalopram, but not R-citalopram and reboxetine, has anti-inflammatory and antidepressant effects in LPS-treated model of depression, and that reboxetine can antagonize the effects of escitalopram in the inflammation model. Therefore, it is likely that serotonergic system plays a key role in the pathophysiology of inflammation-induced depression.
Copyright © 2015. Published by Elsevier Inc.
QuoteQuote
J Pharmacol Pharmacother. 2015 Oct-Dec;6(4):198-203. doi: 10.4103/0976-500X.171883.
A comparative study of the clinical efficacy and safety of agomelatine with escitalopram in major depressive disorder patients: A randomized, parallel-group, phase IV study.
Urade CS1, Mahakalkar SM1, Tiple PG2.
Abstract
OBJECTIVE:
To compare the efficacy of agomelatine with escitalopram in the treatment of major depressive disorder (MDD), improve sleep in MDD patients and study the adverse effects of agomelatine.
MATERIALS AND METHODS:
Randomized, parallel-group, open-label study. The primary efficacy outcome was change from baseline to last post-baseline value in Hamilton depression rating scale and Leeds sleep evaluation questionnaire scale. Both parametric and nonparametric tests were applied for analysis.
RESULTS:
Within-group and between-groups comparison of the mean HAMD17 scores showed statistically significant changes (P < 0.0001).Escitalopram showed early onset of response and remission compared to agomelatine at 10(th) week (P < 0.0001) and 14(th) week (P < 0.0001), respectively. In agomelatine, within-group and between-groups change of the mean LSEQ score was statistically significant at subsequent follow-up visits (P < 0.0001).
CONCLUSION:
Escitalopram is superior to agomelatine in efficacy, considering the early response, early remission, and better relief from symptoms of MDD in adults. Agomelatine may be preferred in MDD patients having insomnia as a predominant symptom. Liver function monitoring should be done in patients on long-term agomelatine therapy.
KEYWORDS:
Agomelatine; antidepressants; escitalopram; insomnia; major depressive disorder
QuoteQuote
Pharmacopsychiatry. 2016 Jan;49(1):26-31. doi: 10.1055/s-0035-1565241. Epub 2016 Jan 20.
The Effects of Antidepressants on Neuropeptide Y in Patients with Depression and Anxiety.
Ozsoy S1, Olguner Eker O2, Abdulrezzak U3.
Abstract
INTRODUCTION:
This study aimed to investigate the neuropeptide Y (NPY) levels in patients with anxiety and depression and also the effects of antidepressants on this neuropeptide.
MATERIALS AND METHODS:
The study included 40 outpatients who presented with depressive and anxiety symptoms, and 32 healthy controls. The patients received antidepressant treatment for 6 months. Serum levels of neuropeptide Y were measured before treatment in 40 patients, after 8 weeks of treatment in 32 patients, after 6 months in 10 patients, and once in the controls.
RESULTS:
Serum NPY levels were lower in the patients than in the controls. NPY levels were increased and normalized by antidepressant treatment. While there was no change in NPY levels in the patients using fluoxetine and sertraline for 8 weeks, an increase was found in patients using escitalopram and venlafaxine. Serum NPY levels were increased by treatment for 8 weeks in the patients with depression, but not in the patients with anxiety.
DISCUSSION:
The findings suggest that NPY may be related to pathophysiology in depression and anxiety, and antidepressants influence NPY levels.
© Georg Thieme Verlag KG Stuttgart · New York.
QuoteQuote
Int Clin Psychopharmacol. 2015 Dec 8. [Epub ahead of print]
Measuring citalopram in blood and central nervous system: revealing a distribution pattern that differs from other antidepressants.
Paulzen M1, Lammertz SE, Gründer G, Veselinovic T, Hiemke C, Tauber SC.
· 1aDepartment of Psychiatry, Psychotherapy and Psychosomatics, JARA - Translational Brain Medicine bDepartment of Neurology, RWTH Aachen University, Aachen cDepartment of Psychiatry and Psychotherapy, University Medical Center of Mainz, Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany.
Abstract
The aim of this study was to measure blood and cerebrospinal fluid concentrations of citalopram and its weakly active N-demethylated metabolite desmethylcitalopram to account for the distribution between the two compartments. The findings are discussed in the context with own preceding studies on the distribution pattern of different antidepressants. Concentrations of citalopram were measured in blood serum and cerebrospinal fluid of 18 patients treated with daily doses of 10-40 mg. Daily doses were correlated with serum and cerebrospinal fluid concentrations, and serum concentrations were correlated with concentrations in cerebrospinal fluid. Serum concentrations of citalopram and desmethylcitalopram showed no significant correlation to the daily dose, r=0.164, P=0.515, and r=0.174, P=0.505, respectively, whereas citalopram concentrations in serum and cerebrospinal fluid were highly correlated (r=0.763, P<0.001). The cerebrospinal fluid/serum ratio for citalopram (total=bound+unbound concentration) varied between 0.14 and 0.86 (mean 0.35, SD 0.16). By correcting the mean cerebrospinal fluid/serum ratio for 80% plasma protein binding, cerebrospinal fluid concentrations of citalopram were on average 77% higher than the calculated unbound serum concentration with a ratio of 1.77 (SD 0.81, range 0.68-4.29). Findings indicate a very good ability of citalopram to cross the blood-brain and cerebrospinal fluid barrier. High concentrations of citalopram in the cerebrospinal fluid are indicative of active transport of citalopram into or missing active transport out of the cerebrospinal fluid. The results suggest a high ability of citalopram to enter the brain with sufficiently high drug concentrations at the target sites within the brain, contributing toward clinical efficacy.
QuoteQuote
J Psychopharmacol. 2016 Jan;30(1):33-9. doi: 10.1177/0269881115620462. Epub 2015 Dec 8.
Effect of short-term escitalopram treatment on neural activation during emotional processing.
Maron E1, Wall M2, Norbury R3, Godlewska B4, Terbeck S5, Cowen P4, Matthews P2, Nutt DJ2.
Abstract
Recent functional magnetic resonance (fMRI) imaging studies have revealed that subchronic medication with escitalopram leads to significant reduction in both amygdala and medial frontal gyrus reactivity during processing of emotional faces, suggesting that escitalopram may have a distinguishable modulatory effect on neural activation as compared with other serotonin-selective antidepressants. In this fMRI study we aimed to explore whether short-term medication with escitalopram in healthy volunteers is associated with reduced neural response to emotional processing, and whether this effect is predicted by drug plasma concentration. The neural response to fearful and happy faces was measured before and on day 7 of treatment with escitalopram (10mg) in 15 healthy volunteers and compared with those in a control unmedicated group (n=14). Significantly reduced activation to fearful, but not to happy facial expressions was observed in the bilateral amygdala, cingulate and right medial frontal gyrus following escitalopram medication. This effect was not correlated with plasma drug concentration. In accordance with previous data, we showed thatescitalopram exerts its rapid direct effect on emotional processing via attenuation of neural activation in pathways involving medial frontal gyrus and amygdala, an effect that seems to be distinguishable from that of other SSRIs.
QuoteQuote
Pharmacol Biochem Behav. 2016 Feb;141:50-7. doi: 10.1016/j.pbb.2015.11.010. Epub 2015 Nov 24.
In vivo investigation of escitalopram's allosteric site on the serotonin transporter.
Murray KE1, Ressler KJ2, Owens MJ3.
Abstract
Escitalopram is a commonly prescribed antidepressant of the selective serotonin reuptake inhibitor class. Clinical evidence and mapping of the serotonin transporter (SERT) identified that escitalopram, in addition to its binding to a primary uptake-blocking site, is capable of binding to the SERT via an allosteric site that is hypothesized to alter escitalopram's kinetics at the SERT. The studies reported here examined the in vivo role of the SERT allosteric site in escitalopram action. A knockin mouse model that possesses an allosteric-null SERT was developed. Autoradiographic studies indicated that the knockin protein was expressed at a lower density than endogenous mouse SERT (approximately 10-30% of endogenous mouse SERT), but the knockin mice are a viable tool to study the allosteric site. Microdialysis studies in the ventral hippocampus found no measurable decrease in extracellular serotonin response after local escitalopram challenge in mice without the allosteric site compared to mice with the site (p=0.297). In marble burying assays there was a modest effect of the absence of the allosteric site, with a larger systemic dose ofescitalopram (10-fold) necessary for the same effect as in mice with intact SERT (p=0.023). However, there was no effect of the allosteric site in the tail suspension test. Together these data suggest that there may be a regional specificity in the role of the allosteric site. The lack of a robust effect overall suggests that the role of the allosteric site for escitalopram on the SERT may not produce meaningful in vivo effects.
Copyright © 2015 Elsevier Inc. All rights reserved.
