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

Journal Article (Journal Article;Review)

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.

Full Text

Duke Authors

Cited Authors

  • Jacobsen, JPR; Krystal, AD; Krishnan, KRR; Caron, MG

Published Date

  • November 2016

Published In

Volume / Issue

  • 37 / 11

Start / End Page

  • 933 - 944

PubMed ID

  • 27692695

Pubmed Central ID

  • PMC5728156

Electronic International Standard Serial Number (EISSN)

  • 1873-3735

Digital Object Identifier (DOI)

  • 10.1016/


  • eng

Conference Location

  • England