Therapeutic failure of oral thyrotropin-releasing hormone in depression.

A double-blind investigation of the psychological and hormonal responses to orally administered thyrotropin-releasing hormone (TRH) in a dosage range of 200 to 300 mg daily was conducted in a group of 11 depressed patients hospitalized for an initial 10-day period and followed as outpatients for the balance of a 30-day period of observation. The study was purposely restricted to depressives conventionally classed as reactive, neurotic, or characterologic, the groups most commonly encountered clinically. Contrary to some reports of TRH as an effective antidepressant, our results indicated not only failure of benefit but actual antitherapeutic effects in 3 of 6 treated patients as compared with placebo controls. Excessive CNS arousal with psychomotor activation produced dysphoric mental and behavioral effects in these patients.