EFFECTS OF INTRATHECAL THYROTROPIN-RELEASING-HORMONE (PROTIRELIN) IN REFRACTORY DEPRESSED-PATIENTS

Background: Therapeutic effects of the tripeptide protirelin (thyrotro pin-releasing hormone) have been postulated in the affective disorders , but direct assessment in humans has been hindered by poor blood-brai n barrier permeability. Methods: Eight medication-free inpatients with refractory depression received 500 mu g of protirelin via a lumbar in trathecal injection and an identical sham lumbar puncture procedure, s eparated by 1 week, in a double-blind crossover design. Results: Five of eight patients responded to intrathecal protirelin, defined asa 50% or greater reduction in an abbreviated Hamilton Rating Scale for Depr ession score. Suicidality also was reduced significantly (P<.05). Resp onses were rapid and clinically robust, but short-lived. Conclusion: A dministration of protirelin by an intrathecal route induced a rapid im provement in mood and suicidality in these refractory depressed patien ts, supporting the hypothesis that thyrotropin-releasing hormone could be a positive modulator of mood.