Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder.
The catecholamine norepinephrine is a critical effector of the mammalian stress response and has been implicated in the pathophysiology of posttraumatic stress disorder (PTSD)-a syndrome intrinsically related to the experience of extraordinary stress. Symptom-linked hypernoradrenergic derangements have been observed in PTSD and several studies have examined the potential therapeutic effects of agents that dampen the centrally hyperactive noradrenergic state. These agents include compounds that decrease norepinephrine release (e.g. centrally acting alpha(2) agonists such as clonidine) and those which block post-synaptic norepinephrine receptors (e.g. centrally acting alpha(1) or beta receptor antagonists such as prazosin or propranolol). In this article, we review studies of central noreadrenergic hyperactivity under both basal and challenge conditions and explore the evidence for these derangements as potential psychopharmacologic targets in patients with PTSD. Given the significant involvement of CNS norepinephrine hyperactivity in PTSD, and its link to intrusive and hyperarousal symptoms, it is not surprising that interventions directed at this system have therapeutic potential in PTSD. The utility of these anti-adrenergics in the clinical treatment of PTSD remains to be determined, though it is possible that they may prove to have primary roles in a disorder that is only modestly responsive to antidepressant treatment.
Strawn
J R
JR
Department of Psychiatry, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267-0559, USA. strawnjr@uc.edu
Geracioti
T D
TD
D018674:Adrenergic Antagonists / Q000627:therapeutic use; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D003000:Clonidine / Q000627:therapeutic use; D006801:Humans; D008016:Life Change Events; D009638:Norepinephrine / Q000502:physiology*; D011224:Prazosin / Q000627:therapeutic use; D011433:Propranolol / Q000627:therapeutic use; D011600:Psychopharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000503:physiopathology*
D018674:Adrenergic Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011433:Propranolol; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin