Abnormal 5-HT1D receptor function in major depression:: A neuropharmacological challenge study using sumatriptan

Background. Sumatriptan, a specific agonist at 5-HT1D receptors, stimulates release of growth hormone (GH) and inhibits release of prolactin (PRL). Methods. We gave sumatriptan (6 mg subcutaneously) to 11 patients with unipolar major depression and 11 control subjects matched for age, sex, weight and menstrual cycle phase. Serum GH and PRL were measured at 0, 15, 30, 45, 60 and 90 min after injection. Results. The maximal rise in GH was significantly reduced in the depressed patients, with 60% showing no increase over baseline compared with 18% of controls. There were no significant differences in PRL responses. Conclusions. These results suggest reduced sensitivity of 5-HT1D receptors in major depression. Our results and those of studies investigating 5-HT1A receptors imply that both 5-HT1A and 5-HT1D autoreceptors may show reduced function in major depression.