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Safety Assessment of Liver Injury with Quetiapine Fumarate XR Management in Very Heavy Drinking Alcohol-Dependent Patients

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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.

Conclusion

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.

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Author Contribution

VV is the project PI, and designed this study. VV and MS were responsible for data management. VV conducted the data analysis. VV interpreted the data analysis. VV wrote this manuscript. MS, SSB, AP, MCC, VAR, and CJM provided significant scientific input into this project. All authors have approved the final submission version of this manuscript.

Vijay A Ramchandani and Craig J. McClain are senior authors.

Acknowledgments

Study evaluation was conducted at UofL Alcohol Research Center. We thank Ms. Marion McClain for editing the manuscript.

Author information

Authors and Affiliations

  1. Department of Medicine, University of Louisville School of Medicine, 505 S. Hancock St., CTR Room 521A, Louisville, KY, 40202, USA

    Vatsalya Vatsalya, Matthew C. Cave, Shirish S. Barve & Craig J. McClain

  2. Department of Pediatric Gastroenterology, Maria Fareri Children’s Hospital - Westchester Medical Center, Valhalla, NY, USA

    Akash Pandey

  3. Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA

    Melanie L. Schwandt

  4. Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA

    Shirish S. Barve & Craig J. McClain

  5. Laboratory of Clinical and Translational Studies, Section on Human Psychopharmacology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA

    Vatsalya Vatsalya & Vijay A. Ramchandani

  6. Robley Rex VA Medical Center, Louisville, KY, USA

    Craig J. McClain

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  1. Vatsalya Vatsalya
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Corresponding author

Correspondence to Vatsalya Vatsalya.

Ethics declarations

Funding

This study was supported by the NIH - National Institute of Alcohol Abuse and Alcoholism: CSP-1027 (VV) and Z99-AA999999 (VV); P50-AA024337-01, U01-AA021901 and R37-AA010762 (CJM); and ZIA AA000466 (VAR).

Declaration/Conflict of interest

Vatsalya Vatsalya, Akash Pandey, Melanie L. Schwandt, Shirish S. Barve, Matthew C. Cave, Vijay A. Ramchandani, and Craig J. McClain declare that they have no conflicts of interest.

Ethical Approval

All procedures in this study were in accordance with the 1964 Helsinki Declaration (and its amendments).

Ethics Committee

This study was approved by the IRB of specific sites that recruited patients.

Informed Consent

All study patients enrolled in this study consented to participate in this treatment study.

NIH and Public Access Policy

This article is a US Government-sponsored work and is in the public domain in the USA.

Electronic supplementary material

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40261_2016_439_MOESM1_ESM.pdf

Supplement Figure 1. Evaluation of liver injury by incidence and level of elevated ALT values in patients at each assessment timeline during the study period in quetiapine and placebo arm. “Total” shows records included in the study from the baseline number of participants at each study phase. Data presented as Mean ± Standard Error. Q: in Quetiapine treatment group. P: in Placebo treatment group. ALT normal range: 6–40 IU/L. Gr.1: Non-elevated group from baseline. Gr.2: Elevated group from baseline. (PDF 182 kb)

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Vatsalya, V., Pandey, A., Schwandt, M.L. et al. Safety Assessment of Liver Injury with Quetiapine Fumarate XR Management in Very Heavy Drinking Alcohol-Dependent Patients. Clin Drug Investig 36, 935–944 (2016). https://doi.org/10.1007/s40261-016-0439-2

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