Effects of methysergide and ritanserin on the prolactin and thyrotropin responses to TRH in depressed patients

Despite extensive study of the effects of various pharmacological agents on the thyrotropin (TSH) and prolactin (PRL) responses to TRH challenge, the effect of serotoninergic agents remains inconclusive. We studied the effect of the serotonin antagonists methysergide (non-selective 5-HT 1/5-HT 2 blocker with dopaminergic properties) and ritanserin (selective 5-HT 2 blocker) on the TSH and PRL responses to TRH stimulation in two groups of medication-free female depressed patients in a double-blind, within-subject design. Methysergide was found to decrease significantly the PRL response to TRH, while ritanserin had no effect. Neither compound influenced the TSH response. Results suggest that 5-HT 2 mechanisms do not mediate the PRL and TSH responses to TRH challenge in depression. The reduction in PRL observed after methysergide is probably due to either 5-HT 1 or dopaminergic mechanisms.