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Interaction of Heavy Drinking Patterns and Depression Severity Predicts Efficacy of Quetiapine Fumarate XR in Lowering Alcohol Intake in Alcohol Use Disorder Patients.

ABSTRACT: Background:Shared etiological pathways of dopamine and serotonin neurotransmission play a central role in heavy alcohol intake and exacerbation in the symptoms of depression.We investigated the treatment efficacy of Quetiapine fumarate extended release (XR) in lowering alcohol intake in alcohol use disorder (AUD) patients indicated by the shared alleviation of depression ratings and patterns of heavy drinking. Methods:Hundred and eight male and female heavy drinking AUD patients in the age range of 18 to 64 years. participated in a randomized clinical trial (RCT) to receive 12?weeks of quetiapine XR or placebo (N?=?115). Participants were sub-grouped by the severity grading of depression using Montgomery-Asberg Depression Rating Scale (MADRS) (clinically relevant ?8 [CR], clinically non-relevant ?7 [CNR]) at baseline in both the groups. Drinking history and depression ratings were assessed at the patients' visits. Results:Heavy drinking days (HDD) and total drinks (TD) were significantly fewer in CR patients at the treatment end. A true positive response in AUROC analysis supported the lowering of TD in CR patients. The number of drinking days (NDD) and average drinks per drinking day (AvgD) were lower in the CNR patients at treatment-end. Significant associations with increasing effect sizes were observed for all the heavy drinking measures (HDD, TD, NDD, and AvgD) and MADRS scores by the end of the treatment course. Conclusions:Baseline elevated depressive symptoms could likely predict the course of heavy alcohol drinking during the treatment, and efficacy outcome of a treatment. AUD patients with baseline clinically significant depression had a progressive lowering in heavy drinking markers significantly corresponding to the lowering of depression symptoms by the end of treatment with Quetiapine fumarate XR.ClinicalTrials.gov: NCT#0049862 (https://clinicaltrials.gov/ct2/show/NCT00498628?term=litten&draw=2&rank=3).

SUBMITTER: Vatsalya V

PROVIDER: S-EPMC7488613 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Interaction of Heavy Drinking Patterns and Depression Severity Predicts Efficacy of Quetiapine Fumarate XR in Lowering Alcohol Intake in Alcohol Use Disorder Patients.

Vatsalya Vatsalya V Kong Maiying M Marsano Luis M LM Kurlawala Zimple Z Chandras Kan V KV Schwandt Melanie L ML Ramchandani Vijay A VA McClain Craig J CJ

Substance abuse : research and treatment 20200909

<h4>Background</h4>Shared etiological pathways of dopamine and serotonin neurotransmission play a central role in heavy alcohol intake and exacerbation in the symptoms of depression.We investigated the treatment efficacy of Quetiapine fumarate extended release (XR) in lowering alcohol intake in alcohol use disorder (AUD) patients indicated by the shared alleviation of depression ratings and patterns of heavy drinking.<h4>Methods</h4>Hundred and eight male and female heavy drinking AUD patients i ...[more]

PMID: 32963470

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Project description:ObjectivesTo evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD).Patients and methodsThis was a 10-week (8-week active treatment/2-week post-treatment) randomized, double-blind, placebo- and active-controlled study (D1448C00004). Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery-Åsberg Depression Rating Scale [MADRS] total score) at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (≥50% improvement) and remission (score ≤8); Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions - Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI) global; and Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form percentage maximum total scores. Tolerability was assessed throughout.ResultsA total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward) with either active treatment (quetiapine XR, -17.21 [P=0.174]; escitalopram, -16.73 [P=0.346]) versus placebo (-15.61). There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, -4.96 [P<0.01] versus placebo, -3.37). Mixed-model repeated-measures analysis of observed-case data suggested that the primary analysis may not be robust. Most commonly reported adverse events included dry mouth, somnolence, and dizziness for quetiapine XR, and headache and nausea for escitalopram.ConclusionIn this study, neither quetiapine XR (150/300 mg/day) nor escitalopram (10/20 mg/day) showed significant separation from placebo. Both compounds have been shown previously to be effective in the treatment of MDD; possible reasons for this failed study are discussed. Quetiapine XR was generally well tolerated, with a profile similar to that reported previously.

Project description:BackgroundBehavioral economic theory predicts that low access to environmental reward is a risk factor for alcohol use disorder (AUD). The Substance-Free Activity Session (SFAS) is a behavioral economic supplement to standard brief alcohol interventions that attempts to increase environmental reward and may therefore have beneficial effects, particularly for individuals with low levels of environmental reward.MethodsParticipants were 393 college students who reported at least 2 heavy-drinking episodes in the past month. Participants were randomly assigned to 1 of 3 conditions following a baseline assessment: a standard alcohol-focused brief motivational intervention plus relaxation training session (BMI + RT), BMI plus Substance-Free Activity Session (BMI + SFAS), or an assessment-only control condition (AO). In a secondary analysis of the data from this study, we used person-centered statistical techniques to describe trajectories of alcohol severity and environmental reward over a 16-month follow-up and examined whether environmental reward levels moderated the effectiveness of the interventions.ResultsPiecewise growth mixture modeling identified 2 trajectories of reward availability: low increasing (LR; n = 120) and high stable (HR; n = 273). Depressive symptoms, cannabis use, sensation seeking, and low life satisfaction were associated with a greater probability of classification in the LR trajectory. Alcohol severity was greater in the LR trajectory than the HR trajectory. For students in the LR trajectory, at 1, 6, and 12 months, BMI + SFAS led to greater increases in reward availability and reduced levels of alcohol severity compared with the BMI + RT and AO conditions and at 16 months compared with AO.ConclusionsYoung adults with low levels of environmental reward are at heightened risk for greater alcohol severity and may show greater benefit from brief alcohol interventions that focus on increasing substance-free reward than individuals who are not deficient in reward availability.

Project description:BackgroundMost physiological studies interested in alcohol-dependence examined ethanol as a pharmacological agent rather than a nutrient. We conducted two studies, which assessed the metabolic and endocrine factors involved in the regulation of alcohol and nutrient intake in alcohol-dependent (AD) subjects. We also examined the potential role of a disruption in energy balance in alcohol-dependence.Methods and resultsIn Study-1, quantitative dietetic interviews of eating and drinking habits were conducted with 97 AD subjects. The population was split around a median alcohol intake value of 12.5 kcal/kg/day. The results showed that the "low alcohol" drinking AD subjects had high Body Mass Index (BMI) and Fat Mass (FM) and alcohol intake was compensated for by a decrease in non-alcoholic intakes. "High alcohol" drinking AD subjects, on the other hand, had low BMI and FM and the total caloric intakes were largely above norms. In Study-2, 24 AD inpatients were submitted to dietetic interviews, calorimetry and blood samplings for the measurement of biomarkers of the regulation of metabolism and satiety, on day 2, 5 and 16 of abstinence. These patients were compared with 20 controls matched for age and gender. We observed in AD patients an increase in cortisol, leptin and PYY plasma levels and a decrease in ghrelin, which might explain the observed decrease in non-alcoholic intakes. However, alcoholic and non-alcoholic intakes correlated positively with basal metabolism and negatively with leptin and leptin/BMI.ConclusionFor individuals consuming below 12.5 kcal/kg/day of alcohol, alcohol intake is compensated for by a decrease in non-alcoholic nutrient intakes, probably due to changes in metabolic and satiety factors. For individuals consuming above 12.5 kcal/kg/day of alcohol, alcohol accelerates metabolism and decreases fat mass and leptin levels, and the total caloric intake largely exceeds norms. A dual model for regulation of energy intake in AD subjects is proposed.

Dataset Information

Interaction of Heavy Drinking Patterns and Depression Severity Predicts Efficacy of Quetiapine Fumarate XR in Lowering Alcohol Intake in Alcohol Use Disorder Patients.

Publications

Interaction of Heavy Drinking Patterns and Depression Severity Predicts Efficacy of Quetiapine Fumarate XR in Lowering Alcohol Intake in Alcohol Use Disorder Patients.

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