title: Targeting the Noradrenergic System in Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis of Prazosin Trials.
abstract: Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that may develop after exposure to a life-threatening trauma. As veterans and armed forces may deal with diverse health problems compared with civilians, they have a greater risk for psychiatric disorders, including PTSD, than civilians, even if the disorder may be also frequent in the general population. PTSD is associated with significant comorbidity, especially with mood disorders and substance abuse. Moreover, the suicide risk is higher in PTSD patients than in the general population. Selective Serotonin Reuptake Inhibitors (SSRIs), atypical antipsychotics and benzodiazepines are commonly employed in the management of PTSD, but often these treatments fail or are discontinued due to adverse effects. It has been demonstrated that high noradrenergic activity may be associated with hyperarousal, trauma nightmares and sleep disturbances in PTSD subjects, probably through the stimulation of α -1 adrenergic receptors in the brain prefrontal cortex. The α -1 adrenoreceptor antagonist prazosin decreases noradrenaline effects at brain α-1 adrenoreceptors and may be a promising agent in the treatment of PTSD, as some studies have found it effective and well tolerated. Therefore, the present review is aimed to examine the role of noradrenergic system in the pathophysiology of PTSD. Moreover, we conducted a systematic review to evaluate the effectiveness and tolerability of prazosin in PTSD patients. Meta-analysis was used to combine data from multiple studies and better estimate the effect of prazosin on specific outcomes. We found prazosin to be significantly more efficacious than placebo in reducing distressing dreams in PTSD patients, even though our results should be interpreted with caution due to the small number of studies included in our quantitative synthesis.
authors.affiliation: National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "G. Mazzini" Hospital, p.zza Italia 1, 64100 Teramo (Italy). dodebera@aliceposta.it.
authors.forename: Domenico
authors.initials: D
authors.lastname: De Berardis
authors.forename: Stefano
authors.initials: S
authors.lastname: Marini
authors.forename: Nicola
authors.initials: N
authors.lastname: Serroni
authors.forename: Felice
authors.initials: F
authors.lastname: Iasevoli
authors.forename: Carmine
authors.initials: C
authors.lastname: Tomasetti
authors.forename: Andrea
authors.initials: A
authors.lastname: de Bartolomeis
authors.forename: Monica
authors.initials: M
authors.lastname: Mazza
authors.forename: Daniela
authors.initials: D
authors.lastname: Tempesta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valchera
authors.forename: Michele
authors.initials: M
authors.lastname: Fornaro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pompili
authors.forename: Gianna
authors.initials: G
authors.lastname: Sepede
authors.forename: Federica
authors.initials: F
authors.lastname: Vellante
authors.forename: Laura
authors.initials: L
authors.lastname: Orsolini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinotti
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Giannantonio
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D059906:Neuroimaging; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012893:Sleep Wake Disorders / Q000378:metabolism / Q000517:prevention & control / Q000523:psychology; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D016896:Treatment Outcome
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D009638:Norepinephrine; D011224:Prazosin