title: Chronic tiagabine administration and aggressive responding in individuals with a history of substance abuse and antisocial behavior.
abstract: Anticonvulsants, notably those which modulate GABA activity, have shown efficacy in reducing aggressive behavior. Previously, we found dose-related decreases in human aggressive responding following acute tiagabine administration. Here, we examined the effects of chronic tiagabine over a 5-week period. Twelve individuals at increased risk for aggressive and violent behavior (currently on parole/probation with personality and/or substance use disorders) were randomly assigned to placebo (n = 6) or an escalating dose sequence of placebo, 4 mg, 8 mg, 12 mg, placebo (n = 6). Data were analyzed using both frequentist and Bayesian mixed models, evaluating aggressive behavior as a function of time, dose condition, and their interaction. For aggressive responding, there was a significant interaction of drug condition and time. Aggression in the tiagabine condition decreased for each additional week in the study, while participants in the placebo condition failed to demonstrate similar change over time. For monetary-reinforced responding, no drug or drug by time interactions were observed, suggesting specificity of drug effects on aggression. The small number of subjects limits the generality of the findings, and previous studies with tiagabine are limited to acute dosing and case report investigations. However, the present data provide an indication that tiagabine merits further examination as an agent for management of impulsive aggression.
authors: Program in Neuroscience, Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, TX, USA.
authors: Joshua L
authors: JL
authors: Gowin
authors: Charles E
authors: CE
authors: Green
authors: Joseph L
authors: JL
authors: Alcorn
authors: Alan C
authors: AC
authors: Swann
authors: F Gerard
authors: FG
authors: Moeller
authors: Scott D
authors: SD
authors: Lane
mesh_terms: D000328:Adult; D000374:Aggression / Q000187:drug effects*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000987:Antisocial Personality Disorder / Q000150:complications / Q000188:drug therapy*; D001499:Bayes Theorem; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D005260:Female; D058805:GABA Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007175:Impulsive Behavior / Q000517:prevention & control; D008297:Male; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010352:Patient Dropouts; D011569:Psychiatric Status Rating Scales; D019966:Substance-Related Disorders / Q000150:complications / Q000188:drug therapy*; D013781:Texas; D000078308:Tiagabine; D013997:Time Factors; D014754:Violence / Q000517:prevention & control; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D058805:GABA Uptake Inhibitors; D009557:Nipecotic Acids; D000078308:Tiagabine