Hypothalamic-pituitary-adrenocortical response in alcohol-dependent patients during baclofen treatment and association with clinical outcome: Preliminary results.

Baclofen has been shown to reduce alcohol consumption in some individuals with alcohol use disorder. This preliminary study aimed to evaluate i) the effect of baclofen versus placebo on hypothalamic-pituitary-adrenocortical activity (HPA axis), as measured by cortisol, and ii) the relationship between clinical outcomes such as alcohol consumption on a randomized controlled trial of baclofen (BAC) versus placebo (PL) (Kirsten C. Morley et al., 2018; K. C. Morley, Leung, Baillie, & Haber, 2013). We hypothesized that baclofen will reduce HPA-axis activity following a mild stressor in patients with alcohol dependence. Plasma cortisol levels were taken from N = 25 alcohol-dependent patients at two time points, approximately 60 (pre-MRI scan: PreCortisol) and 180 min (post MRI scan: PostCortisol) following administration of PL, BAC 10 mg, or BAC 25 mg. Participants were followed up for the remaining 10 weeks as part of the trial for clinical outcome (percentage days abstinent). Mixed models revealed a significant main effect of medication on cortisol levels (F = 3.88, p = 0.037), no significant effect of time (F = 0.04, p = 0.84), and a significant time × medication interaction (F = 3.54, p = 0.049). Linear regression (F = 6.98, p = 0.01, R2 = 0.66) revealed that abstinence at follow-up, weighted by gender, was predicted by blunted cortisol response (β = -0.48 p = 0.023), in addition to medication (β = 0.73 p = 0.003). In conclusion, our preliminary data suggest that baclofen moderates HPA-axis activity, as measured by blood cortisol, and that these alterations may play a role in long-term treatment response.