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Plasma serotonin levels are associated with antidepressant response to SSRIs

Holck, Amanda LU ; Wolkowitz, Owen M. LU ; Mellon, Sindy H.; Reus, Victor I.; Nelson, J. Craig; Westrin, Åsa LU and Lindqvist, Daniel LU (2019) In Journal of Affective Disorders 250. p.65-70
Abstract

Background: Less than half of patients with major depressive disorder (MDD) respond to their first antidepressant trial. Our understanding of the underlying mechanisms of selective serotonin reuptake inhibitors (SSRIs) remains poor, and there is no reliable method of predicting treatment response. Methods: Thirty-seven MDD subjects and 41 healthy controls, somatically healthy and medication-free for at least six weeks, were recruited, and plasma serotonin (5-HT) levels were assessed at baseline. Twenty-six of the MDD subjects were then treated in an open-label manner with clinically appropriate doses of sertraline for 8 weeks, after which plasma 5-HT levels were again assessed. Response to treatment was defined as an improvement of 50%... (More)

Background: Less than half of patients with major depressive disorder (MDD) respond to their first antidepressant trial. Our understanding of the underlying mechanisms of selective serotonin reuptake inhibitors (SSRIs) remains poor, and there is no reliable method of predicting treatment response. Methods: Thirty-seven MDD subjects and 41 healthy controls, somatically healthy and medication-free for at least six weeks, were recruited, and plasma serotonin (5-HT) levels were assessed at baseline. Twenty-six of the MDD subjects were then treated in an open-label manner with clinically appropriate doses of sertraline for 8 weeks, after which plasma 5-HT levels were again assessed. Response to treatment was defined as an improvement of 50% or more on the Hamilton Depression Rating Scale. Results: Non-responders to sertraline treatment had significantly lower pre-treatment 5-HT levels compared to both healthy controls and responders (F = 4.4, p = 0.004 and p = 0.036, respectively). There was a significant decrease in 5-HT levels over treatment in all MDD subjects (t = 6.2, p = 0.000003). The decrease was significantly more prominent in responders compared to non-responders (t = 2.1, p = 0.047). There was no significant difference in post-treatment 5-HT levels between responders and non-responders. Limitations: The study had a modest sample size. 5-HT levels in plasma may not reflect 5-HT levels in the brain. Conclusions: The results indicate that SSRI response may be facilitated by adequate baseline plasma 5-HT content and that successful SSRI treatment is associated with greater decreases in circulating 5-HT. Plasma 5-HT content may be a predictor of SSRI treatment outcome. Potential underlying mechanisms are discussed.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antidepressant, Major depressive disorder, Selective serotonin reuptake inhibitor (SSRI), Serotonin, Treatment response
in
Journal of Affective Disorders
volume
250
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:85062170718
ISSN
0165-0327
DOI
10.1016/j.jad.2019.02.063
language
English
LU publication?
yes
id
3ecc2735-fd77-4a62-bde5-a8fe687d0e96
date added to LUP
2019-03-11 10:53:12
date last changed
2019-04-02 04:14:44
@article{3ecc2735-fd77-4a62-bde5-a8fe687d0e96,
  abstract     = {<p>Background: Less than half of patients with major depressive disorder (MDD) respond to their first antidepressant trial. Our understanding of the underlying mechanisms of selective serotonin reuptake inhibitors (SSRIs) remains poor, and there is no reliable method of predicting treatment response. Methods: Thirty-seven MDD subjects and 41 healthy controls, somatically healthy and medication-free for at least six weeks, were recruited, and plasma serotonin (5-HT) levels were assessed at baseline. Twenty-six of the MDD subjects were then treated in an open-label manner with clinically appropriate doses of sertraline for 8 weeks, after which plasma 5-HT levels were again assessed. Response to treatment was defined as an improvement of 50% or more on the Hamilton Depression Rating Scale. Results: Non-responders to sertraline treatment had significantly lower pre-treatment 5-HT levels compared to both healthy controls and responders (F = 4.4, p = 0.004 and p = 0.036, respectively). There was a significant decrease in 5-HT levels over treatment in all MDD subjects (t = 6.2, p = 0.000003). The decrease was significantly more prominent in responders compared to non-responders (t = 2.1, p = 0.047). There was no significant difference in post-treatment 5-HT levels between responders and non-responders. Limitations: The study had a modest sample size. 5-HT levels in plasma may not reflect 5-HT levels in the brain. Conclusions: The results indicate that SSRI response may be facilitated by adequate baseline plasma 5-HT content and that successful SSRI treatment is associated with greater decreases in circulating 5-HT. Plasma 5-HT content may be a predictor of SSRI treatment outcome. Potential underlying mechanisms are discussed.</p>},
  author       = {Holck, Amanda and Wolkowitz, Owen M. and Mellon, Sindy H. and Reus, Victor I. and Nelson, J. Craig and Westrin, Åsa and Lindqvist, Daniel},
  issn         = {0165-0327},
  keyword      = {Antidepressant,Major depressive disorder,Selective serotonin reuptake inhibitor (SSRI),Serotonin,Treatment response},
  language     = {eng},
  pages        = {65--70},
  publisher    = {Elsevier},
  series       = {Journal of Affective Disorders},
  title        = {Plasma serotonin levels are associated with antidepressant response to SSRIs},
  url          = {http://dx.doi.org/10.1016/j.jad.2019.02.063},
  volume       = {250},
  year         = {2019},
}