Decreased sensitivity of 5-HT1D receptors in melancholic depression

BackgroundBrain serotonin (5-HT) function is abnormal in major depression, but the involvement of different 5-HT receptor subtypes has been little studied. The availability of selective ligands now makes it possible to test the sensitivity of 5-HT1D receptors in patients with depression.AimsThe aim of the study was to use the 5-HT1D receptor agonist, zolmitriptan, to test the sensitivity of 5-HT1D receptors in patients with depression before and after treatment with selective serotonin reuptake inhibitors (SSRIs).MethodWe measured the growth hormone response to zolmitriptan (5 mg orally) in patients with major depression before and after SSRI treatment. A matched sample of healthy subjects acted as a control group.ResultsThe growth hormone response to zolmitriptan was blunted in patients with a melancholic depressive syndrome. SSRI treatment produced a marked reduction in zolmitriptan-induced growth hormone release.ConclusionsPatients with melancholic depression have impaired sensitivity of the post-synaptic 5-HT1D receptors that mediate growth hormone release. The reduction in 5-HT1D receptor sensitivity following SSRI treatment is probably an adaptive response to increased levels of synaptic 5-HT.