March 1997

Effects of Intrathecal Thyrotropin-Releasing Hormone (Protirelin) in Refractory Depressed Patients

Author Affiliations

From the Biological Psychiatry Branch, National Institutes of Mental Health, Bethesda, Md (Drs Marangell, George, Callahan, Ketter, Pazzaglia, and Post and Messrs L'Herrou and Leverich); the Department of Psychiatry, Baylor College of Medicine, Houston, Tex (Dr Marangell); the Department of Psychiatry, Medical University of South Carolina, Charleston (Dr George); the Department of Psychiatry, Mount Sinai Medical Center, New York, NY (Dr Callahan); the Electronic Village Systems, Centreville, Va (Mr L'Herrou); the Department of Psychiatry, Stanford School of Medicine, Stanford, Calif (Dr Ketter); and the Department of Psychiatry, University of Mississippi Medical School, Jackson (Dr Pazzaglia).

Arch Gen Psychiatry. 1997;54(3):214-222. doi:10.1001/archpsyc.1997.01830150034007

Background:  Therapeutic effects of the tripeptide protirelin (thyrotropin-releasing hormone) have been postulated in the affective disorders, but direct assessment in humans has been hindered by poor blood-brain barrier permeability.

Methods:  Eight medication-free inpatients with refractory depression received 500 μg of protirelin via a lumbar intrathecal injection and an identical sham lumbar puncture procedure, separated by 1 week, in a doubleblind crossover design.

Results:  Five of eight patients responded to intrathecal protirelin, defined as a 50% or greater reduction in an abbreviated Hamilton Rating Scale for Depression score. Suicidality also was reduced significantly (P<.05). Responses were rapid and clinically robust, but shortlived.

Conclusion:  Administration of protirelin by an intrathecal route induced a rapid improvement in mood and suicidality in these refractory depressed patients, supporting the hypothesis that thyrotropin-releasing hormone could be a positive modulator of mood.