title: A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial.
abstract: Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group.
  
  
  
  This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life.
  
  
  
  This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems.
  
  
  
  ClinicalTrials.gov, NCT02649231 . Registered on 5 January 2016.
authors.affiliation: Psychopharmacology and Addiction Research Centre (PARC), College of Life and Environmental Science, University of Exeter, Washington Singer Building, Perry Road, Exeter, EX4 4QG, UK. a.mcandrew@exeter.ac.uk.
authors.forename: Amy
authors.identifier: 0000-0001-8021-3257
authors.initials: A
authors.lastname: McAndrew
authors.affiliation: Clinical Psychopharmacology Unit, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK.
authors.forename: Will
authors.initials: W
authors.lastname: Lawn
authors.affiliation: Psychopharmacology and Addiction Research Centre (PARC), College of Life and Environmental Science, University of Exeter, Washington Singer Building, Perry Road, Exeter, EX4 4QG, UK.
authors.forename: Tobias
authors.initials: T
authors.lastname: Stevens
authors.affiliation: Clinical Psychopharmacology Unit, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK.
authors.forename: Lilla
authors.initials: L
authors.lastname: Porffy
authors.affiliation: Anaesthetics Department, Podium 3, maple Link corridor, Unviersity College Hospital, 235 Euston Road, London, NW1 2BU, UK.
authors.forename: Brigitta
authors.initials: B
authors.lastname: Brandner
authors.affiliation: Psychopharmacology and Addiction Research Centre (PARC), College of Life and Environmental Science, University of Exeter, Washington Singer Building, Perry Road, Exeter, EX4 4QG, UK.
authors.forename: Celia J A
authors.initials: CJ
authors.lastname: Morgan
mesh_terms: D000293:Adolescent; D000328:Adult; D064829:Alcohol Abstinence; D000428:Alcohol Drinking / Q000517:prevention & control* / Q000523:psychology; D000437:Alcoholism / Q000175:diagnosis / Q000523:psychology / Q000628:therapy*; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004739:England; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010353:Patient Education as Topic; D000075082:Proof of Concept Study; D011613:Psychotherapy / Q000379:methods*; D011788:Quality of Life; D012008:Recurrence; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007649:Ketamine
keywords: Alcoholism; Depression; Ketamine; Relapse