title: Noradrenergic function in generalized anxiety disorder: impact of treatment with venlafaxine on the physiological and psychological responses to clonidine challenge.
abstract: Serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressants have evidence of efficacy in the treatment of generalized anxiety disorder (GAD); however, it is not clear whether there is an advantage over selective serotonin reuptake inhibitor (SSRI) medicines and there is limited evidence for noradrenergic dysfunction in GAD. We tested whether a dysfunctional alpha-2 adrenoceptor system is present in patients with GAD and the effects of SNRI treatment on this system. The method used was an infusion of clonidine (a selective alpha-2 adrenergic receptor agonist) on psychological and physiological outcomes in three subject groups: 10 untreated GAD patients, five SNRI-treated GAD patients and seven normal controls. The clonidine challenge elicited sedation, a rise in growth hormone, decrease in blood pressure, decline in saccadic eye movement (SEM) variables, and improvement in verbal fluency as anticipated in the 22 subjects examined. Lower cortisol levels were found in controls and higher blood pressure readings in GAD-treated subjects, as well as evidence that GAD-treated subjects had SEMs that were intermediate between control and GAD subjects' scores and have less clonidine-induced sedation. The implications of these findings with reference to the study hypothesis in this small study are discussed.
authors.affiliation: Psychopharmacology Unit, University of Bristol, Bristol, UK. sean.hood@uwa.edu.au
authors.forename: S D
authors.initials: SD
authors.lastname: Hood
authors.forename: J K
authors.initials: JK
authors.lastname: Melichar
authors.forename: L G
authors.initials: LG
authors.lastname: Taylor
authors.forename: N
authors.initials: N
authors.lastname: Kalk
authors.forename: T R
authors.initials: TR
authors.lastname: Edwards
authors.forename: D A
authors.initials: DA
authors.lastname: Hince
authors.forename: A
authors.initials: A
authors.lastname: Lenox-Smith
authors.forename: A R
authors.initials: AR
authors.lastname: Lingford-Hughes
authors.forename: D J
authors.initials: DJ
authors.lastname: Nutt
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D001008:Anxiety Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology*; D005133:Eye Movements / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009638:Norepinephrine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D000069470:Venlafaxine Hydrochloride
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D003000:Clonidine; D003511:Cyclohexanols; D019382:Human Growth Hormone; D006854:Hydrocortisone; D009638:Norepinephrine; D011941:Receptors, Adrenergic; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride