title: Double-blind, placebo-controlled study of single-dose metergoline in depressed patients with seasonal affective disorder.
abstract: A role for serotonin in season affective disorder (SAD) has been explored with a variety of serotonergic pharmacologic agents. The authors initially hypothesized that metergoline, a nonspecific serotonin antagonist, would exacerbate depressive symptoms. In a small, open-label pilot study, the authors observed the opposite effect. They decided to follow up on this finding with this formal study. The study followed a double-blind, randomized cross-over design. Sixteen untreated, depressed patients with SAD received single oral doses of metergoline 8 mg and of placebo, spaced 1 week apart. Fourteen patients were restudied after 2 weeks of light treatment. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder Version were performed at baseline and at 3 and 6 days after each intervention. These data were analyzed by baseline-corrected repeated measures with analysis of variance. In the off-lights condition, severity of depression was diminished after metergoline compared with placebo administration (p = 0.001). Patient daily self-ratings suggested that the peak effect occurred 2 to 4 days after study drug administration. In contrast, after 2 weeks of treatment with bright artificial light, metergoline did not demonstrate a significant effect on mood. These data suggest that single doses of metergoline may have antidepressant effects that last several days. Possible mechanisms include 5-hydroxytryptamine(2) receptor downregulation and dopamine agonism.
authors.affiliation: Section on Biological Rhythms, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland, USA. Erick.Turner@med.va.gov
authors.forename: Erick H
authors.initials: EH
authors.lastname: Turner
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Schwartz
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Lowe
authors.forename: Stefan S
authors.initials: SS
authors.lastname: Nawab
authors.forename: Susana
authors.initials: S
authors.lastname: Feldman-Naim
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Drake
authors.forename: Frances S
authors.initials: FS
authors.lastname: Myers
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Barnett
authors.forename: Norman E
authors.initials: NE
authors.lastname: Rosenthal
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008711:Metergoline / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010789:Phototherapy; D011985:Receptors, Serotonin / Q000187:drug effects; D016574:Seasonal Affective Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D012702:Serotonin Antagonists / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000928:Antidepressive Agents; D018491:Dopamine Agonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D008711:Metergoline