Comparative antidepressant effects of intravenous and intrathecal thyrotropin-releasing hormone: Confounding effects of tolerance and implications for therapeutics

Ann M. Callahan, Mark A. Frye, Lauren B. Marangell, Mark S. George, Terence A. Ketter, Todd L'Herrou, Robert M. Post

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

A significant amount of preclinical and human data indicate that thyrotropin-releasing hormone (TRH) has antidepressant effects. Although early studies showing these effects using intravenous TRH were not consistently replicated, it has been suggested that this could be explained by its poor blood-brain barrier penetration. For this reason we compared the antidepressant effect of intrathecal and intravenous TRH administered in a double-blind design to 2 treatment-refractory patients with bipolar II disorder. Each experienced a robust antidepressant response by both routes; subsequent open trials of intravenous TRH also were effective until apparent tolerance developed. Intrathecal TRH was readministered and both subjects again experienced robust antidepressant responses. These preliminary data suggest a differential mechanism of tolerance to the two routes of administration and raise the possibility that a subgroup of patients may be responsive to the antidepressant effects of TRH independent of its route of administration.

Original languageEnglish (US)
Pages (from-to)264-272
Number of pages9
JournalBiological psychiatry
Volume41
Issue number3
DOIs
StatePublished - Feb 1 1997

Keywords

  • bipolar disorder
  • depression
  • intrathecal administration
  • intravenous administration
  • thyrotropin-releasing hormone
  • tolerance

ASJC Scopus subject areas

  • Biological Psychiatry

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