Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder.

OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. METHODS: In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. RESULTS: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. CONCLUSIONS: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.

A holistic understanding of the effect of stress on adolescent well-being: A conditional process analysis.

Although traditional assumptions tend to conceptualize stress as inherently dysfunctional, psychological theory suggests that it is not intrinsically maladaptive. Contemporary models emphasize that the stress response can be differentiated into both negative and positive aspects, known as distress and eustress. Research examining the differential effect of positive and negative stress on adolescent well-being is limited and has been hindered by a lack of appropriate measurement tools. The aim of the present study was to utilize the recently developed Adolescent Distress-Eustress Scale to provide a balanced understanding of the impact of stress on positive mental health, holistically considering the effect of both distress and eustress on adolescent well-being. One thousand eighty-one Australian adolescents (Mage = 15.14, 54.03% female) completed an online survey composed of the Adolescent Distress-Eustress Scale alongside measures of well-being, self-efficacy, psychological ill-being, physical activity, and daytime sleepiness. Conditional process analysis suggested that distress exerted no direct influence on well-being, with the observed negative relationship fully mediated by psychological and behavioural variables. Contrastingly, eustress was both directly related to increased well-being and exerted an indirect effect through relationships with mediating variables. These results demonstrate that stress can have profoundly positive consequences. Theoretical contributions, implications for practice, and perspectives for future research are discussed.