A double-blind, randomized, placebo-controlled trial of fluoxetine in patients with intermittent explosive disorder.
ABSTRACT Intermittent explosive disorder (IED) is a disorder of impulsive aggression that affects as many as 7.3% of the U.S. population during some period of life. Since central serotonergic (5-HT) system dysfunction is related to impulsive aggressive behavior, pharmacologic enhancement of 5-HT activity should reduce impulsive aggressive behavior in individuals with IED.
A double-blind, randomized, placebo-controlled trial of the selective 5-HT uptake inhibitor fluoxetine was conducted in 100 individuals with IED (research diagnostic criteria) and current histories of impulsive aggressive behavior. The primary efficacy measure was the aggression score from the Overt Aggression Scale-Modified (OAS-M) for Outpatient Use. Secondary efficacy measures included the irritability score from the OAS-M and the Clinical Global Impressions-Improvement scale (CGI-I) score. The study took place between July 1990 and July 1999.
Fluoxetine treatment resulted in a sustained reduction in OAS-M aggression, and OAS-M irritability scores, apparent as early as week 2 (p < .01 for aggression and p < .001 for irritability at endpoint). Fluoxetine was also superior to placebo in the proportion of responders on the CGI-I (p < .001). Closer examination of the data revealed that full or partial remission of impulsive aggressive behaviors, as reflected by the A criteria for IED, occurred in 46% of fluoxetine-treated subjects. Fluoxetine did not exert an antidepressant or antianxiety effect, and its effects on impulsive aggression were not influenced by presence of current symptoms of depression or anxiety.
Fluoxetine treatment has a clear antiaggressive effect in impulsive aggressive individuals with IED. However, while fluoxetine's antiaggressive effects appear robust, they lead to full or partial remission of IED in less than 50% of subjects treated with fluoxetine.
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ABSTRACT: Aggressive manifestations and their consequences are a major issue of mankind, highlighting the need for understanding the contributory factors. Still, aggression-related genetic analyses have so far mainly been conducted on small population subsets such as individuals suffering from a certain psychiatric disorder or a narrow-range age cohort, but no data on the general population is yet available. In the present study, our aim was to identify polymorphisms in genes affecting neurobiological processes that might explain some of the inter-individual variation between aggression levels in the non-clinical Caucasian adult population. 55 single nucleotide polymorphisms (SNP) were simultaneously determined in 887 subjects who also filled out the self-report Buss-Perry Aggression Questionnaire (BPAQ). Single marker association analyses between genotypes and aggression scores indicated a significant role of rs7322347 located in the HTR2A gene encoding serotonin receptor 2a following Bonferroni correction for multiple testing (p = 0.0007) both for males and females. Taking the four BPAQ subscales individually, scores for Hostility, Anger and Physical Aggression showed significant association with rs7322347 T allele in themselves, while no association was found with Verbal Aggression. Of the subscales, relationship with rs7322347 was strongest in the case of Hostility, where statistical significance virtually equaled that observed with the whole BPAQ. In conclusion, this is the first study to our knowledge analyzing SNPs in a wide variety of genes in terms of aggression in a large sample-size non-clinical adult population, also describing a novel candidate polymorphism as predisposal to aggressive traits.PLoS ONE 02/2015; 10(2):e0117792. DOI:10.1371/journal.pone.0117792 · 3.53 Impact Factor
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ABSTRACT: En la búsqueda de evidencias indicativas de una lesión en los animales y en el ser humano, los estudios de neuroimagen están identificando de manera creciente anomalías de los circuitos corticolímbicos que intervienen en la conducta agresiva. Esta revisión se centra en 3 sistemas neurales que participan en la agresividad impulsiva/reactiva: a) los sistemas neurales subcorticales responsables de la producción de los impulsos agresivos; b) los circuitos de toma de decisión y los circuitos de procesamiento de información social-emocional, que evalúan las consecuencias de realizar o no una agresión, y c) las regiones frontoparietales que intervienen en la regulación de las emociones y las tendencias motivacionales impulsivas. Revisamos los trastornos psiquiátricos, como el trastorno límite de la personalidad y el trastorno de personalidad antisocial, que se caracterizan por una agresividad reactiva elevada, centrándonos en las anomalías de estos 3 sistemas neurales.04/2012; 19(2):46-53. DOI:10.1016/j.psiq.2012.06.001
12/2015; 2(1). DOI:10.1186/s40479-015-0028-7