Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients

Arch Gen Psychiatry. 1997 Mar;54(3):214-22. 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 micrograms of protirelin via a lumbar intrathecal injection and an identical sham lumbar puncture procedure, separated by 1 week, in a double-blind 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 short-lived.

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Affect / drug effects
  • Cross-Over Studies
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Double-Blind Method
  • Female
  • Hospitalization
  • Humans
  • Injections, Spinal
  • Male
  • Middle Aged
  • Personality Inventory
  • Psychiatric Status Rating Scales
  • Thyrotropin-Releasing Hormone / administration & dosage
  • Thyrotropin-Releasing Hormone / pharmacology
  • Thyrotropin-Releasing Hormone / therapeutic use*
  • Treatment Outcome


  • Thyrotropin-Releasing Hormone