Title:Targeting the Noradrenergic System in Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis of Prazosin Trials
Volume: 16
Issue: 10
Author(s): Domenico De Berardis, Stefano Marini, Nicola Serroni, Felice Iasevoli, Carmine Tomasetti, Andrea de Bartolomeis, Monica Mazza, Daniela Tempesta, Alessandro Valchera, Michele Fornaro, Maurizio Pompili, Gianna Sepede, Federica Vellante, Laura Orsolini, Giovanni Martinotti and Massimo Di Giannantonio
Affiliation:
Keywords:
Efficacy, hyperarousal, nightmares, post-traumatic stress disorder, prazosin, noradrenergic system, tolerability.
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.
