Thyrotropin-TRH

How a course is commonly described

1. 1
   Minutes 0-30: the stimulation testClinical

   The labeled use is a single 500 mcg intravenous bolus with the patient lying down, a TSH sample before injection and another at 30 minutes. Flushing, nausea, an urge to urinate and a metallic taste begin within a minute or two and fade within about ten.

2. 2
   Hours 0-48: single-dose mood studiesClinical

   In the antidepressant studies, a single 500 mcg dose given intravenously at midnight or intrathecally produced mood changes within 24 hours that had faded by about 48 hours. The peptide itself is gone from blood within an hour, so whatever drives the effect outlasts the drug.

3. 3
   Day 1: the only multi-dose course in a large trialClinical

   The antenatal trial gave four 400 mcg infusions 8 hours apart over a single day, the longest schedule tested in a large controlled human study, and found no benefit for the infants. No human trial has given TRH daily for weeks.

4. 4
   Repeat dosing: toleranceClinical

   The label requires at least seven days between stimulation tests because the TSH response shrinks with repeated administration. In two treatment-resistant bipolar patients given repeated open-label intravenous doses, the antidepressant effect also faded as tolerance developed, although intrathecal re-dosing still worked, which argues against the daily schedules sold with research vials.

5. 5
   Community protocolsCommunity-reported

   Research-chemical pages describe 1-10 mg subcutaneously or 0.5-5 mg intranasally, repeated because of the short half-life, with no course length or break defined. No human study has used a subcutaneous dose, and the milligram figures are 2 to 20 times the labeled intravenous dose.

• The only validated human use is a single intravenous diagnostic dose. The TSH response blunts with repetition, which is why the label spaces tests a week apart and why no evidence supports daily courses.
• Measured human pharmacokinetics give a 6.5-minute plasma half-life after intravenous injection and much lower blood levels after a 2 mg nasal dose; no subcutaneous pharmacokinetic data have been published, so the vendor subcutaneous figures are untested.
• Protirelin has no approved therapeutic indication in the United States, the branded diagnostic has been off the market since 2002, and the largest controlled trial of repeated dosing (antenatal, 996 women) found no benefit.