The pharmacodynamic effects of combined administration of flibanserin and alcohol.

WHAT IS KNOWN AND OBJECTIVE: Flibanserin is a serotonin 5-HT1A agonist and 5-HT2A antagonist approved for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. Because of the increased risk of hypotension- and syncope-related adverse events (AEs) observed with coadministration of flibanserin and alcohol, alcohol use is contraindicated. To provide a more comprehensive understanding of the interaction between flibanserin and alcohol, the results of a dedicated phase 1 alcohol-interaction study and a pooled analysis of phase 3 studies of premenopausal women with HSDD are presented. METHODS: In the phase 1 study, healthy participants (males [n=23] and females [n=2]) were randomly assigned to one of five sequence groups, which determined the order in which they were to receive flibanserin 100 mg or placebo, with or without ethanol 0.4 g/kg or 0.8 g/kg. Change from baseline in seated blood pressure, orthostatic vital signs, AEs and visual analogue scale sedation outcomes were examined. Blood samples were collected at baseline and for up to 4 hours after dosing to determine flibanserin area under the plasma concentration-time curve from 0 to 4 hours (AUC0-4 ). Pooled data from five phase 3 studies of patients receiving flibanserin 100 mg once daily (n=1543), or placebo (n=1905), were analysed. RESULTS: In the phase 1 study, the incidence of hypotension and syncope increased when flibanserin was coadministered with ethanol. Sedation increased 20% and 27% from baseline with flibanserin plus ethanol 0.4 g/kg and 0.8 g/kg, respectively, at 4 hours post-dose. In the pooled analysis of phase 3 studies, 58.2% and 63.6% of participants receiving flibanserin or placebo, respectively, reported baseline alcohol use. In patients receiving flibanserin, fatigue and dizziness occurred more frequently in patients with vs. without alcohol use. WHAT IS NEW AND CONCLUSION: Results from this study suggest that increased incidence of hypotension- and syncope-related events may result from a pharmacodynamic interaction between flibanserin and alcohol, although the clinical significance of these interactions in real-world populations remains unclear.

Articulated thoughts of maritally violent and nonviolent men during anger arousal.

The cognitive correlates of anger arousal were investigated in community-based samples of maritally violent (MV), maritally distressed-nonviolent (DNV), and maritally satisfied-nonviolent (SNV) husbands. Participants performed the Articulated Thoughts in Simulated Situations (ATSS) paradigm while listening to anger-arousing audiotapes. Trained raters coded for irrational beliefs, cognitive biases, hostile attributional biases, and anger control statements. Results indicated that MV men articulated significantly more irrational thoughts and cognitive biases than DNV and SNV men. MV men articulated more hostile attributional biases than DNV and SNV men across all ATSS scenarios. SNV men, however, articulated more anger control statements during ATSS anger arousal than MV or DNV participants. Discriminant function analyses indicated that specific thoughts discriminated between the groups and differentiated mildly from severely violent participants. ATSS cognitive distortions (a) were not correlated with questionnaire measures of cognitive distortion, and (b) were superior to questionnaire measures in discriminating between the groups. The findings are interpreted in light of recent advances in understanding the relationship between information processing, anger, and marital aggression.

Anger and hostility in maritally violent men: conceptual distinctions, measurement issues, and literature review.

Marital violence researchers have generally used the terms anger and hostility interchangeably. However, there are important differences between anger and hostility that may be vital to understanding the relationship between these constructs and marital violence. The present manuscript highlights the advantages of distinguishing between anger and hostility. In order to investigate the role of anger and hostility in marital violence, we provide a comprehensive review of 26 empirical studies in addition to critically examining researchers' definitions of anger and hostility and the methods of assessment utilized in this body of research. While many researchers have presented data suggesting that maritally violent men are higher in anger and hostility than maritally nonviolent men, the findings are not consistent and vary in accordance with the construct assessed and the assessment strategy used.