Risk-factors for methadone-specific deaths in Scotland’s methadone-prescription clients between 2009 and 2013*

Highlights • Powerful analysis of a national cohort’s 362 methadone-specific deaths.• Scottish cohort of 33,128 methadone-prescription clients in 2009–2013.• Steeper age-gradient than for all drugs-related deaths.• No gender differential in the hazard of methadone-specific deaths.• Increased hazard at the highest quintile for quantity of methadone prescribed.

[1]  A. Dahan,et al.  Gender Differences in Opioid-mediated Analgesia: Animal and Human Studies , 2000, Anesthesiology.

[2]  M. Valenstein,et al.  Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths , 2012 .

[3]  L. Thabane,et al.  Sex differences in outcomes of methadone maintenance treatment for opioid addiction: a systematic review protocol , 2014, Systematic Reviews.

[4]  D. Randall,et al.  Mortality risk of opioid substitution therapy with methadone versus buprenorphine: a retrospective cohort study. , 2015, The lancet. Psychiatry.

[5]  J. Oliver,et al.  The role of methadone in drug-related deaths in the west of Scotland. , 2003, Addiction.

[6]  Cynthia Wei-Sheng Lee,et al.  Sex differences in opioid analgesia and addiction: interactions among opioid receptors and estrogen receptors , 2013, Molecular pain.

[7]  A. B. Hill.  The Environment and Disease: Association or Causation? , 1965, Proceedings of the Royal Society of Medicine.

[8]  Wojciech Zareba,et al.  Drug induced QT prolongation. , 2007, Cardiology journal.

[9]  K. Reinier,et al.  A community-based evaluation of sudden death associated with therapeutic levels of methadone. , 2008, The American journal of medicine.

[10]  R. Chou,et al.  Research gaps on methadone harms and comparative harms: findings from a review of the evidence for an American Pain Society and College on Problems of Drug Dependence clinical practice guideline. , 2014, The journal of pain : official journal of the American Pain Society.

[11]  D. Roden.  Long QT syndrome: reduced repolarization reserve and the genetic link , 2006, Journal of internal medicine.

[12]  Drug Misuse Information Scotland.  The Road to Recovery: A New Approach to Tackling Scotland's Drug Problem , 2003 .

[13]  M. Stark.  Drug misuse and dependence — guidelines on clinical management , 1999 .

[14]  Marcia Valenstein,et al.  Association between Opioid Prescribing Patterns and Opioid Overdose-related Deaths Downloaded From: Http://jama.jamanetwork.com/ by a Penn State Milton S Hershey Med Ctr User on 08/01/2013 , 2022 .

[15]  S. Bird.  Everyone counts—so count everyone in England and Wales , 2016, The Lancet.

[16]  J. Marsden,et al.  Fatal opioid poisoning: a counterfactual model to estimate the preventive effect of treatment for opioid use disorder in England. , 2015, Addiction.

[17]  Stephen Pavis,et al.  Unleashing the power of administrative health data: the Scottish model. , 2015, Public health research & practice.

[18]  W. Hall,et al.  Impact of supervision of methadone consumption on deaths related to methadone overdose (1993-2008): analyses using OD4 index in England and Scotland , 2010, BMJ : British Medical Journal.

[19]  Stephen Evans,et al.  Medicines and Healthcare Products Regulatory Agency (MHRA) (Formerly MCA) , 2005 .

[20]  H. Jones,et al.  Methadone and Buprenorphine for the Management of Opioid Dependence in Pregnancy , 2012, Drugs.

[21]  R. Chou,et al.  Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society. , 2014, The journal of pain : official journal of the American Pain Society.

[22]  B. Turner,et al.  Assessing risk for drug overdose in a national cohort: role for both daily and total opioid dose? , 2015, The journal of pain : official journal of the American Pain Society.

[23]  O. Drummer,et al.  A review of methadone deaths between 2001 and 2005 in Victoria, Australia. , 2013, Forensic science international.

[24]  T. Fahey,et al.  Risk of mortality on and off methadone substitution treatment in primary care: a national cohort study. , 2016, Addiction.

[25]  Dennis Andersson,et al.  A retrospective cohort study , 2018 .

[26]  R. Chou,et al.  Methadone overdose and cardiac arrhythmia potential: findings from a review of the evidence for an American Pain Society and College on Problems of Drug Dependence clinical practice guideline. , 2014, The journal of pain : official journal of the American Pain Society.

[27]  T Fahey,et al.  Factors associated with mortality in Scottish patients receiving methadone in primary care: retrospective cohort study , 2009, BMJ : British Medical Journal.

[28]  S. Bird,et al.  Effectiveness of Scotland's National Naloxone Programme for reducing opioid‐related deaths: a before (2006–10) versus after (2011–13) comparison , 2016, Addiction.

[29]  J. Mørland,et al.  Methadone-related deaths in Norway. , 2013, Forensic science international.

[30]  Rosie P Cornish,et al.  Risk of death during and after opiate substitution treatment in primary care: prospective observational study in UK General Practice Research Database , 2010, BMJ : British Medical Journal.

[31]  R. Nisticò,et al.  Gender differences in pharmacokinetics and pharmacodynamics of methadone substitution therapy , 2015, Front. Pharmacol..

[32]  Jeff Ward,et al.  Role of maintenance treatment in opioid dependence , 1999, The Lancet.

[33]  T. Buclin,et al.  Interindividual Variability of the Clinical Pharmacokinetics of Methadone , 2002, Clinical pharmacokinetics.

[34]  Marion Bennie,et al.  Data Resource Profile: The Scottish National Prescribing Information System (PIS) , 2016, International journal of epidemiology.

[35]  G. Dunn,et al.  Quantifying crime associated with drug use among a large cohort of sanctioned offenders in England and Wales , 2015, Drug and alcohol dependence.

[36]  Zunyou Wu,et al.  Who uses methadone services in China? Monitoring the world's largest methadone programme. , 2015, Addiction.

[37]  I. Maremmani,et al.  QTc interval screening for cardiac risk in methadone treatment of opioid dependence. , 2013, The Cochrane database of systematic reviews.

[38]  T. Gomes,et al.  Opioid dose and drug-related mortality in patients with nonmalignant pain. , 2011, Archives of internal medicine.

[39]  Dara Ganoczy,et al.  Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study , 2015, BMJ : British Medical Journal.

[40]  Antony M. Overstall,et al.  Estimating prevalence of injecting drug users and associated heroin‐related death rates in England by using regional data and incorporating prior information , 2014 .

[41]  J. Strang,et al.  Take-home naloxone to prevent fatalities from opiate-overdose: Protocol for Scotland's public health policy evaluation, and a new measure to assess impact , 2014, Drugs.

[42]  M. Lehmann,et al.  Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. , 1993, JAMA.

[43]  J. Strang,et al.  Take-home emergency naloxone to prevent deaths from heroin overdose , 2014, BMJ : British Medical Journal.

[44]  G. Perugi,et al.  QTc Interval Prolongation in Patients on Long-Term Methadone Maintenance Therapy , 2004, European Addiction Research.

[45]  A. Uchtenhagen.  Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence , 2009 .

[46]  S. Sunjic,et al.  Deaths in methadone maintenance treatment in New South Wales, Australia 1990-1995. , 2000, Addiction.

[47]  A. McAuley,et al.  The National Drug-Related Deaths Database ( Scotland ) Report : Analysis of Deaths occurring in 2014 , 2014 .

[48]  G. Jensen,et al.  Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen , 2007, Heart.

[49]  Ruth King,et al.  Injecting drug users in Scotland, 2006: Listing, number, demography, and opiate-related death-rates , 2012, Addiction research & theory.

[50]  T. Gomes,et al.  Predictors of Opioid-Related Death During Methadone Therapy. , 2015, Journal of substance abuse treatment.

[51]  Ariel Porat,et al.  Risk of Death , 2010 .

[52]  S. Bird,et al.  National record linkage study of mortality for a large cohort of opioid users ascertained by drug treatment or criminal justice sources in England, 2005–2009 , 2015, Drug and alcohol dependence.

[53]  H. Thaler,et al.  QTc interval prolongation associated with intravenous methadone , 2003, Pain.

[54]  A. Gal‐Oz,et al.  Methadone-associated Torsades de Pointes (polymorphic ventricular tachycardia) in opioid-dependent patients. , 2006, Addiction.

[55]  S. Bird,et al.  Modeling the current and future disease burden of hepatitis C among injection drug users in Scotland , 2005, Hepatology.

[56]  H. Druid,et al.  Opioid-related mortality and filled prescriptions for buprenorphine and methadone. , 2014, Drug and alcohol review.

[57]  S. Bird.  Editorial: Counting the dead properly and promptly , 2013 .

[58]  L. Degenhardt,et al.  Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta-analysis of cohort studies. , 2011, Addiction.

[59]  D. De Angelis,et al.  Survival and cessation in injecting drug users: prospective observational study of outcomes and effect of opiate substitution treatment , 2010, BMJ : British Medical Journal.

[60]  M. Kreek,et al.  Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment (MMT) patients: a cross-sectional study. , 2007, Addiction.

[61]  S. Bird,et al.  A record-linkage study of the development of hepatocellular carcinoma in persons with hepatitis C infection in Scotland , 2008, British Journal of Cancer.

[62]  S. Bird,et al.  Toxicology of Scotland's drugs-related deaths in 2000–2007: Presence of heroin, methadone, diazepam and alcohol by sex, age-group and era , 2011 .

[63]  S. Bird,et al.  Mortality of those who attended drug services in Scotland 1996–2006: Record-linkage study , 2012, The International journal on drug policy.

[64]  G. Bigelow,et al.  QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. , 2007, Archives of internal medicine.

[65]  S. Bird,et al.  Hospitalization of hepatitis C-diagnosed individuals in Scotland for decompensated cirrhosis: a population-based record-linkage study , 2010, European journal of gastroenterology & hepatology.

[66]  G. Dunn,et al.  Impact of treatment for opioid dependence on fatal drug‐related poisoning: a national cohort study in England , 2015, Addiction.

[67]  A. Dahan,et al.  Gender Differences in Opioid-mediated Analgesia , 2000 .

[68]  D. Randall,et al.  The increasing mortality burden of liver disease among opioid-dependent people: cohort study. , 2011, Addiction.

[69]  U. Gundert-Remy,et al.  Gender differences in pharmacokinetics , 1996, European Journal of Drug Metabolism and Pharmacokinetics.

[70]  Sir John Strang.  Drug misuse and dependence: UK guidelines on clinical management , 2015 .

[71]  C. Teljeur,et al.  Risk of drug-related mortality during periods of transition in methadone maintenance treatment: a cohort study. , 2011, Journal of substance abuse treatment.