Rapid antidepressant response after nocturnal TRH administration in patients with bipolar type I and bipolar type II major depression

Thyrotropin-releasing hormone (TRH) is a tripeptide that produces endocrine and behavioral effects in animals and humans. Some studies have shown transient antidepressant activity after morning administration of TRH. We hypothesized that nocturnal administration of TRH, when the circadian sensitivity of the TRH receptor is at its peak, may result in a more robust antidepressant effect. Twenty patients with bipolar (BP) type I or BP type II major depressive episode (MDE) were given nocturnal intravenous TRH 500 microg (n = 10) or saline (n = 10) at midnight in a randomized, double-blind fashion. Antidepressant activity was assessed using the Hamilton Depression Rating (HAM-D), Young Mania Rating (YMR), and Profile of Mood (POMS) scales over a 48-hour period. Thyrotropin (TSH), total T4, and free T3 concentrations were measured before and after TRH administration. Data were analyzed using chi test, Fisher exact test, and repeated-measures ANOVA. Sixty percent of the TRH group and 10% of the saline group showed a > or =50% reduction in baseline total HAM-D score within 24 hours (P = 0.03). HAM-D ratings fell by an average of 52% after TRH administration versus 12% after saline administration (P = 0.038). There was a modest increase in YMR scores after TRH compared with saline (P < 0.032). No manic or hypomanic episodes were observed. Antidepressant effects of TRH lasted up to 48 hours. There was no correlation between DeltaTSH, DeltaT4, or DeltaT3 measures after TRH (or saline) administration and the change in HAM-D scores. Nocturnal TRH administration may produce a rapid antidepressant effect in some patients with BP I and BP II MDE.