title: Safety Assessment of Liver Injury with Quetiapine Fumarate XR Management in Very Heavy Drinking Alcohol-Dependent Patients.
abstract: BACKGROUND
  Studies have reported liver injury as a consequence of antipsychotic treatment. Very heavy alcohol drinking (ten or more drinks/day for men and eight for women) also causes liver injury. This study aims to evaluate liver injury with quetiapine extended release (XR) in very heavy drinking alcohol-dependent (AD) patients.
  
  
  METHODS
  Two hundred and eighteen AD patients, 18-65 years of age, received 12 weeks of quetiapine XR or placebo treatment in a dose-escalated manner reaching the full dose of 400 mg/day during week 4. Blood chemistry and hematology were assessed at baseline (W0), post-titration at the end of week 3 (W4), week 8 (W8), and end of week 12 (W13). Patients were further grouped as GR.1 (no liver injury, ALT ≤40) and GR.2 (pre-existing liver injury, ALT >40) within each treatment. Drinking history, fasting blood glucose concentration (FBG), and lipid panel were used as covariates in the analyses.
  
  
  RESULTS
  Liver injury and total drinks and average drinking measures from the Timeline follow-back questionnaire (TLFB) were highly associated. No significant exacerbation in liver injury was observed in patients treated with quetiapine XR in GR.2. Liver injury as determined by elevated alanine aminotransaminase (ALT) was reported in a few patients in GR.1 who received quetiapine XR; however, the occurrence was low, and the level of liver injury was not significant. FBG and lipid measures showed some elevation, but did not show any significant association with liver injury.
  
  
  CONCLUSIONS
  Quetiapine XR did not show any significant exacerbation of liver injury in very heavy drinking alcohol-dependent patients with pre-existing liver injury. Frequency and severity of new liver injury cases in quetiapine XR-treated patients without any pre-existing liver injury was also low. Study findings support medical management of AD patients with heavy drinking profile using quetiapine XR formulation.
authors: Department of Medicine, University of Louisville School of Medicine, 505 S. Hancock St., CTR Room 521A, Louisville, KY, 40202, USA. v0vats01@exchange.louisville.edu.|Laboratory of Clinical and Translational Studies, Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA. v0vats01@exchange.louisville.edu.
authors: Vatsalya
authors: http://orcid.org/0000-0001-6764-6891
authors: V
authors: Vatsalya
authors: Department of Pediatric Gastroenterology, Maria Fareri Children's Hospital - Westchester Medical Center, Valhalla, NY, USA.
authors: Akash
authors: A
authors: Pandey
authors: Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors: Melanie L
authors: ML
authors: Schwandt
authors: Department of Medicine, University of Louisville School of Medicine, 505 S. Hancock St., CTR Room 521A, Louisville, KY, 40202, USA.
authors: Matthew C
authors: MC
authors: Cave
authors: Department of Medicine, University of Louisville School of Medicine, 505 S. Hancock St., CTR Room 521A, Louisville, KY, 40202, USA.|Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.
authors: Shirish S
authors: SS
authors: Barve
authors: Laboratory of Clinical and Translational Studies, Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
authors: Vijay A
authors: VA
authors: Ramchandani
authors: Department of Medicine, University of Louisville School of Medicine, 505 S. Hancock St., CTR Room 521A, Louisville, KY, 40202, USA.|Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.|Robley Rex VA Medical Center, Louisville, KY, USA.
authors: Craig J
authors: CJ
authors: McClain
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D000437:Alcoholism / Q000150:complications*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069348:Quetiapine Fumarate / Q000009:adverse effects*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D000069348:Quetiapine Fumarate