COMPARATIVE ANTIDEPRESSANT EFFECTS OF INTRAVENOUS AND INTRATHECAL THYROTROPIN-RELEASING-HORMONE - CONFOUNDING EFFECTS OF TOLERANCE AND IMPLICATIONS FOR THERAPEUTICS

A significant amount of preclinical and human data indicate that thyro tropin-releasing hormone (TRH) has antidepressant effects. Although ea rly studies showing these effects using intravenous TRH were not consi stently replicated, it has been suggested that this could be explained by its poor blood-brain barrier penetration, For this reason we compa red the antidepressant effect of intrathecal and intravenous TRH admin istered in a double-blind design to 2 treatment-refractory patients wi th bipolar II disorder. Each experienced a robust antidepressant respo nse by both routes; subsequent open trials of intravenous TRH also wer e effective until apparent tolerance developed. Intrathecal TRH was re administered 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 possibili ty that a subgroup of patients may be responsive to the antidepressant effects of TRH independent of its route of administration. (C) 1997 S ociety of Biological Psychiatry.