Inflammatory markers and chronic exposure to fluoxetine, divalproex, and placebo in intermittent explosive disorder.
Intermittent Explosive Disorder (IED) is a disorder of impulsive aggression affecting 4-7% of the U.S. population during some period of life. In addition to other biological correlates, elevations of plasma inflammatory markers have been reported in IED, compared with control, subjects. In this study we sought to explore if treatment exposure to anti-aggressive agents, compared with placebo, would be associated with a reduction in circulating levels of inflammatory markers. Thirty IED subjects, from a 12-week, double-blind, randomized, placebo-controlled trial of fluoxetine and divalproex, in which both pre- and post-treatment levels of C-Reactive Protein (CRP), interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α were obtained. Efficacy measures included the Overt Aggression Scale-Modified (OAS-M) score for Aggression and for Irritability, rate of Clinical Global Impression of Improvement (CGI-I), and rate of IED Remitters at study completion. As compared to placebo, neither fluoxetine nor divalproex reduced any of the measures of aggression. In addition, levels of CRP and pro- and anti-inflammatory cytokines showed no changes from pre- to post-treatment for any treatment condition. Correlations between pre- and post- treatment plasma CRP/cytokines were substantial (mean r=0.71, r(2)=0.50, p<0.001). Overall, circulating markers of inflammation markers were unaffected by treatment with fluoxetine or divalproex, consistent with the absence of change in measures of impulsive aggression.
Clinical Neuroscience & Psychopharmacology Research Unit, Department of Psychiatry and Behavioral Neuroscience, University of Chicago, USA.
Emil F
EF
Coccaro
Clinical Neuroscience & Psychopharmacology Research Unit, Department of Psychiatry and Behavioral Neuroscience, University of Chicago, USA.
Royce
R
Lee
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, USA; Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine, USA.
Elizabeth C
EC
Breen
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, USA; Department of Psychiatry and Biobehavioral Sciences, UCLA David Geffen School of Medicine, USA; Department of Psychology, UCLA, USA.
Michael R
MR
Irwin
D000328:Adult; D000374:Aggression; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007378:Interleukins / Q000097:blood; D007508:Irritable Mood; D008297:Male; D008875:Middle Aged; D011619:Psychotropic Drugs / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects; D014635:Valproic Acid / Q000627:therapeutic use*
D015415:Biomarkers; D018836:Inflammation Mediators; D007378:Interleukins; D011619:Psychotropic Drugs; D014409:Tumor Necrosis Factor-alpha; D005473:Fluoxetine; D014635:Valproic Acid; D002097:C-Reactive Protein
Aggression; Divalproex; Fluoxetine; Inflammation