FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study

Abstract

Pharmacological treatment in alcohol use disorder suffers from modest effect sizes. Efforts have been undertaken to identify patient characteristics that help to select individuals that benefit from pharmacological treatment. Previous studies indicated that neural alcohol cue-reactivity (CR) might provide a marker that identifies patients, which benefit from naltrexone treatment.We investigated the reproducibility of the association between ventral striatum (VS) activation and naltrexone (NTX) treatment response by analyzing data from a recent longitudinal clinical trial in N = 44 abstinent treatment-seeking alcohol-dependent patients. A follow-up was conducted over 3 months. We computed the percentage of significant voxels in VS and tested main effects and interactions with NTX treatment on relapse risk using Cox Regression models.We found a significant interaction effect between pre-treatment cue reactivity in the VS and NTX treatment on time to first heavy relapse (Hazard Ratio = 7.406, 95% CI 1.17–46.56, p = 0.033), such that the patient group with high VS activation (defined by a mean split) showed a significant medication effect (Hazard Ratio = 0.140, 95% CI 0.02–0.75, p = 0.022) with a number needed to treat of 3.4 [95% CI 2.413.5], while there was no significant effect in the group with low VS activation (Hazard Ratio = 0.726, p = 0.454).Thus, using an independent sample we replicated the previously described positive association between VS activation and NTX efficacy. Although our results should be considered cautiously in light of the small sample size, our results support the potential of neural alcohol CR as a tool for precision medicine approaches in alcohol dependence.

Are we compulsively chasing rainbows?

“…Compulsive drug use occurs after chronic drug use and is often associated with mild to severe SUD, whereas continued drug use despite negative consequences (e.g., innapropriate behavior, belligerence, mood lability, impaired judgment) can be observed in individuals with limited drug intoxication history and is frequently observed in the absence of an SUD diagnosis. While one may argue that the neurobiological mechanisms underlying so-called compulsive-like responding in an individual with limited prior intoxication are relevant for addiction, there is abundant evidence that compulsivelike drug responding with limited drug intoxication may not be driven by the same mechanisms [12] and may not be responsive to the same treatments as compulsive-like drug responding with a history of chronic drug intoxication [13][14][15][16]. In addition, the neurobiological substrates underlying action-outcome associations are likely to differ according to (1) the extent of prior drug exposure and (2) whether or not acute intoxication is associated with negative consequences (which may be immediate or delayed).…”

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity

“…Then, the COU specification should clarify whether the FDCR-derived biomarker is to be used for diagnostic or prognostic purposes, to select or assess interventions, or as an intervention target (Table; eFigure 8 in the Supplement). This choice should guide the design and interpretation of the biomarker and, ultimately, its validation.…”

Deep brain stimulation of the nucleus accumbens in treatment-resistant alcohol use disorder: a double-blind randomized controlled multi-center trial

“…Previous studies in depressed patients reported significant effects of NAc DBS on depressive symptoms, including anhedonia [ 72 – 74 ]. Furthermore, neuroimaging studies in AUD showed that alcohol-cue-induced brain response in the NAc and the striatum can predict both relapse risk [ 16 ] as well as treatment response to naltrexone [ 18 , 19 ].…”

“…Past neuroimaging studies have uncovered evidence of alcohol-cue exposure increasing brain activation in the NAc and striatum [11][12][13][14]. Brain activation in these areas has been repeatedly demonstrated to be correlated to subjective alcohol craving [11,15], to predict relapse in AUD patients after withdrawal treatment [16,17] and to be associated with a better treatment response to naltrexone, an opioid antagonist [18][19][20].…”