Fluoxetine treatment of alcoholic perpetrators of domestic violence: a 12-week, double-blind, randomized, placebo-controlled intervention study.

OBJECTIVE: Behaviorally based therapies for the treatment of perpetrators who initiate intimate partner violence (IPV) have generally shown minimal therapeutic efficacy. To explore a new treatment approach for IPV, we examined the effects of a selective serotonin reuptake inhibitor on the irritability subscale score of the Modified Overt Aggression Scale. This score served as a surrogate marker for the anger and physical aggression that characterize perpetrators of IPV. METHOD: A 12-week, double-blind, randomized, placebo-controlled intervention study employing fluoxetine, alcohol treatment, and cognitive-behavioral therapy was performed. Sixty (46 men) non-court-mandated, DSM-IV-diagnosed alcoholic perpetrators of IPV with a history of at least 2 episodes of IPV in the year prior to participation in the study were evaluated. The primary outcome measure was the score on the irritability subscale of the Modified Overt Aggression Scale. Secondary measures included anxiety, depression, and ratings by the perpetrator's spouse/significant other. The study was conducted from January 2002 through December 2007. RESULTS: A repeated-measures analysis of variance using the irritability subscale scores obtained from perpetrators who completed the 12-week study (n = 24) showed a significant drug effect (F(1,21) = 12.09, P = .002). Last observation carried forward (F(1,32) = 4.24, P = .048) as well as intent-to-treat analysis (F(1,54) = 5.0, P = .034) also showed a significant drug effect. Spouses'/significant others' physical and nonphysical Partner Abuse Scale ratings showed a significant reduction of abuse over time (F(1,11) = 10.2, P = .009 and F(1,11) = 24.2, P = .0005, respectively). CONCLUSION: This is the first controlled study to show that a pharmacologic intervention employing a selective serotonin reuptake inhibitor, in conjunction with alcohol treatment and cognitive-behavioral therapy, can reduce measures of anger and physical aggression in alcoholic perpetrators of IPV.

Effect of acamprosate on magnetic resonance spectroscopy measures of central glutamate in detoxified alcohol-dependent individuals: a randomized controlled experimental medicine study.

CONTEXT: Acamprosate is approved for the treatment of alcoholism, but its mechanism of action remains unclear. Results of animal studies suggest that a persistent hyperglutamatergic state contributes to the pathogenesis of alcoholism and that acamprosate may exert its actions by intervening in this process. Human translation of these findings is lacking. OBJECTIVE: To examine whether acamprosate modulates indices of central glutamate levels in recently abstinent alcohol-dependent patients as measured using proton nuclear magnetic resonance spectroscopy (¹H-MRS). DESIGN: A 4-week, double-blind, placebo-controlled, randomized controlled experimental medicine study, with ¹H-MRS measures obtained on days 4 and 25. SETTING: An inpatient research unit at the NIH Clinical Center. Patients Thirty-three patients who met the DSM-IV criteria for alcohol dependence and who were admitted for medically supervised withdrawal from ongoing alcohol use. Intervention Four weeks of acamprosate (initial oral loading followed by 1998 mg daily) or matched placebo, initiated at the time of admission. MAIN OUTCOME MEASURES: The glutamate to creatine ratio as determined using single-voxel ¹H-MRS in the anterior cingulate. Exploratory neuroendocrine, biochemical, and behavioral outcomes were also collected, as were safety- and tolerability-related measures. RESULTS: There was a highly significant suppression of the glutamate to creatine ratio across time by acamprosate (time × treatment interaction: F1(,)29 = 13.5, P < .001). Cerebrospinal fluid levels of glutamate obtained in a subset of patients 4 weeks into abstinence were uncorrelated with the MRS measures and unaffected by treatment but were strongly correlated (R² = 0.48, P < .001) with alcohol dependence severity. Other exploratory outcomes, including repeated dexamethasone-corticotropin-releasing hormone tests, and psychiatric ratings were unaffected. Among tolerability measures, gastrointestinal symptoms were significantly greater in acamprosate-treated individuals, in agreement with the established profile of acamprosate. CONCLUSION: The MRS measures of central glutamate are reduced across time when acamprosate therapy is initiated at the onset of alcohol abstinence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00106106.

A model linking biology, behavior and psychiatric diagnoses in perpetrators of domestic violence.

Research indicates that perpetrators of domestic violence have abnormalities in central serotonin and testosterone metabolism, an increased sensitivity to anxiogenic stimuli, and an impaired neuro-connection between their cortex and the amygdala. Clinical evaluations show that perpetrators of domestic violence also have a distinguishing set of behaviors and diagnoses related to anxiety, depression, intermittent explosive disorder, and borderline personality disorder. In this paper we propose a model to understand how the biological abnormalities can potentially explain the behaviors and diagnoses exhibited by the perpetrators. Changes in the perpetrator's neurotransmitters lead to a heightened sensitivity to environmental stimuli, anxiety, and conditioned fear. Lack of cortical input to the amygdala impairs the perpetrator's ability to extinguish anxiety and/or conditioned fear and gives rise to either innate behaviors (e.g., fight, flight, and shut down) or learned fear avoidant behaviors designed to avoid anxiety (e.g., alcohol consumption, self-injurious acts, and obsessive behaviors). Linking conditioned fear and fear avoidance to the behaviors and psychiatric diagnoses will serve to change the way the medical community perceives and treats perpetrators of domestic violence.