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Trends Pharmacol Sci. 2016 Nov;37(11):933-944. doi: 10.1016/j.tips.2016.09.001. Epub 2016 Sep 28.

Adjunctive 5-Hydroxytryptophan Slow-Release for Treatment-Resistant Depression: Clinical and Preclinical Rationale.

Author information

1
Department of Cell Biology, Duke University, Durham, NC 27710, USA.
2
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27710, USA.
3
Rush Medical College, Chicago, IL 60612, USA.
4
Department of Cell Biology, Duke University, Durham, NC 27710, USA; Department of Medicine, Duke University, Durham, NC 27710, USA; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: marc.caron@dm.duke.edu.

Abstract

Serotonin transporter (SERT) inhibitors treat depression by elevating brain extracellular 5-hydroxytryptamine (5-HTExt). However, only one-third of patients respond adequately. Treatment-resistant depression (TRD) is a major unmet need. Interestingly, elevating 5-HTExt beyond what is achieved by a SERT inhibitor appears to treat TRD. Adjunctive administration of 5-hydroxytryptophan (5-HTP) safely elevates 5-HTExt beyond the SERT inhibitor effect in humans; however, 5-HTP cannot be a clinically viable drug because of its poor pharmacokinetics. A slow-release (SR) delivery mode would be predicted to overcome the pharmacokinetic limitations of 5-HTP, substantially enhancing the pharmacological action and transforming 5-HTP into a clinically viable drug. Animal studies bear out this prediction. Thus, adjunct 5-HTP SR could be an important new treatment for TRD. Here, we review the clinical and preclinical evidence for this treatment.

KEYWORDS:

5-hydroxytryptophan; Antidepressant; depression; treatment-resistant depression

PMID:
27692695
PMCID:
PMC5728156
DOI:
10.1016/j.tips.2016.09.001
[Indexed for MEDLINE]
Free PMC Article

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