PILOT INVESTIGATION OF THYROTROPIN-RELEASING HORMONE-INDUCED THYROTROPIN AND PROLACTIN-RELEASE IN ANXIOUS PATIENTS TREATED WITH DIAZEPAM

Benzodiazepines have been reported to inhibit thyrotropin (TSH) and pr olactin (PRL.) secretion in response to stressful and pharmacologic st imuli in experimental animals. The current study investigates basal an d thyrotropin-releasing hormone (TRH)-stimulated TSH and PRL release i n anxious patients treated with diazepam. Six hospitalized patients ha ving generalized anxiety or adjustment disorder with anxious mood (DSM III-R criteria) were treated during 1 week with diazepam (mean daily dose 33.3 mg). TRH testing was performed comparatively before and afte r 7 days of diazepam administration (with 250 mu g protirelin and bloo d sampling at 15-min intervals over 60 min). Steady-state plasma level s of diazepam and its metabolite nordazepam (desmethyldiazepam) were d etermined by high-performance liquid chromatography. After 7 days of d iazepam treatment, basal plasma levels of TSH and PRL were not affecte d compared with pretreatment values. Similarly, the time-course of TRH -induced TSH release was not modified by the treatment. By contrast, t here was a trend to decrease in the TRH-induced PRL release, and the d ecrease in the PRL response to TRH on day 7 was significantly correlat ed with plasma nordazepam concentrations (r(s) = 8.943, p = 0.02). The se preliminary results suggest that benzodiazepines, at therapeutic do ses for the treatment of anxiety, may alter TRH-induced PRL release in humans.