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- 1 National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW
- 2 Currumbin Clinic, Gold Coast, QLD
- 3 Griffith University, Gold Coast, QLD
- 4 University of South Australia, Adelaide, SA
- 5 Southern Adelaide Local Health Network, Adelaide, SA
Suzanne Nielsen holds a National Health and Medical Research Council Research Fellowship (1132433).
Suzanne Nielsen is a named investigator on untied educational grants from Reckitt–Benckiser and Indivior. Tim MacDonald has received honoraria, fees and professional development resources from Servier, the Australian and New Zealand Mental Health Association, and Healthe Care; he works in the private sector and receives income for clinical services.
- 1. International Narcotics Control Board. Narcotic drugs estimated world requirements for 2015 — statistics for 2013. New York: International Narcotics Control Board, 2015. https://www.incb.org/documents/Narcotic-Drugs/Technical-Publications/2014/Narcotic_Drugs_Report_2014.pdf (viewed Apr 2017).
- 2. Gisev N, Nielsen S, Cama E, et al. An ecological study of the extent and factors associated with the use of prescription and over-the-counter codeine in Australia. Eur J Clin Pharmacol 2016; 72: 469-494.
- 3. Van Hout MC, Bergin M, Foley M, et al. A scoping review of codeine use, misuse and dependence; final report. Brussels: CODEMISUSED Project European Commission 7th Framework Programme, 2014. http://codemisused.org/uploads/files/Van_Hout_et_al_Scoping_Report_23-03-2015.pdf (viewed Apr 2017).
- 4. Coller JK, Christrup LL, Somogyi AA. Role of active metabolites in the use of opioids. Eur J Clin Pharmacol 2009; 65: 121-439.
- 5. Iedema J. Cautions with codeine. Aust Prescr 2011; 34: 133-135.
- 6. Somogyi AA, Barratt DT, Coller JK. Pharmacogenetics of opioids. Clin Pharmacol Ther 2007; 81: 429-444.
- 7. Mattoo SK, Basu D, Sharma A, et al. Abuse of codeine-containing cough syrups: a report from India. Addiction 1997; 92: 1783-1787.
- 8. Orriols L, Gaillard J, Lapeyre-Mestre M, Roussin A. Evaluation of abuse and dependence on drugs used for self-medication: a pharmacoepidemiological pilot study based on community pharmacies in France. Drug Saf 2009; 32: 859-873.
- 9. Nielsen S, Cameron J, Pahoki S. Over the counter codeine dependence [report]. Melbourne: Turning Point Alcohol and Drug Centre, 2010. http://atdc.org.au/wp-content/uploads/2011/02/OTC_CODEINE_REPORT.pdf (viewed Dec 2017).
- 10. Murnion BP. Combination analgesics in adults. Aust Prescr 2010; 33: 113-115.
- 11. McQuay HJ, Carroll D, Watts PG, et al. Does adding small doses of codeine increase pain relief after third molar surgery? Clin J Pain 1986; 2: 197-202.
- 12. Zhang WY, Po A. Do codeine and caffeine enhance the analgesic effect of aspirin? A systematic overview. J Clin Pharm Ther 1997; 22: 79-97.
- 13. Nielsen S, Tobin CL, Dobbin MDH. OTC codeine: examining the evidence for and against. Aust Pharmacist 2012; (Mar): 236-240.
- 14. Baratta JL, Gandhi K, Viscusi ER. Limited evidence that single-dose oral ibuprofen plus codeine is more effective than either drug alone. Evid Based Nurs 2014; 17: 51-52.
- 15. Derry S, Karlin SM, Moore R. Single dose oral ibuprofen plus codeine for acute postoperative pain in adults. Cochrane Database Syst Rev 2015; (2): CD01017.
- 16. MacDonald N, MacLeod SM. Has the time come to phase out codeine? CMAJ 2010; 182: 1825.
- 17. Anderson BJ. Is it farewell to codeine? Arch Dis Child 2013; 98: 986-988.
- 18. Babalonis S, Lofwall MR, Nuzzo PA, et al. Abuse liability and reinforcing efficacy of oral tramadol in humans. Drug Alcohol Depend 2013; 129: 116-124.
- 19. Frei MY, Nielsen S, Dobbin MD, Tobin CL. Serious morbidity associated with misuse of over-the-counter codeine-ibuprofen analgesics: a series of 27 cases. Med J Aust 2010; 193: 294-296. <MJA full text>
- 20. Sproule BA, Busto UE, Somer G, Romach MK. Characteristics of dependent and nondependent regular users of codeine. J Clin Psychopharmacol 1999; 19: 367-372.
- 21. Mill D, Johnson JL, Cock V, et al. Counting the cost of over-the-counter codeine containing analgesic misuse: a retrospective review of hospital admissions over a 5 year period. Drug Alcohol Rev 2017; doi: 10.1111/dar.12595 [Epub ahead of print].
- 22. Pilgrim JL, Dobbin M, Drummer OH. Fatal misuse of codeine–ibuprofen analgesics in Victoria, Australia. Med J Aust 2013; 199: 329-331. <MJA full text>
- 23. Australian Government Department of Health, Therapeutic Goods Administration. Scheduling delegate’s final decision: codeine, December 2016. Updated Jan 2017. http://www.tga.gov.au/scheduling-decision-final/scheduling-delegates-final-decision-codeine-december-2016 (viewed Dec 2017).
- 24. Manitoba College of Pharmacists. Practice direction: exempted codeine preparations [effective Feb 2016]. http://mpha.in1touch.org/uploaded/web/Legislation/Practice%20Resources/Exempted%20Codeine%20Products%20Council%20Approved.pdf (viewed May 2017).
- 25. Cracknell C. Codeine now restricted to prescription-only. The Connexion [website] 13 July 2017. https://www.connexionfrance.com/French-news/Codeine-now-restricted-to-prescription-only (viewed July 2017).
- 26. Myers B, Siegfried N, Parry CD. Over-the-counter and prescription medicine misuse in Cape Town: findings from specialist treatment centres. S Afr Med J 2003; 93: 367-370.
- 27. Nielsen S, Murnion B, Dunlop A, et al. Comparing treatment-seeking codeine users and strong opioid users: findings from a novel case series. Drug Alcohol Rev 2015; 34: 304-311.
- 28. Nielsen S, Roxburgh A, Bruno R, et al. Changes in non-opioid substitution treatment episodes for pharmaceutical opioids and heroin from 2002 to 2011. Drug Alcohol Depend 2015; 149: 212-219.
- 29. Joanna Briggs Institute. Critical appraisal checklist for analytical cross sectional studies. Adelaide: Joanna Briggs Institute, 2016. http://joannabriggs-webdev.org/assets/docs/critical-appraisal-tools/JBI_Critical_Appraisal-Checklist_for_Analytical_Cross_Sectional_Studies.pdf (viewed Apr 2017).
- 30. Glynn L. A critical appraisal tool for library and information research. Library Hi Tech 2006; 24: 387-339.
- 31. Guyatt G, Oxman A, Akl E, et al. GRADE guidelines. Introduction: GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64: 383-394.
- 32. Gossop M, Darke S, Griffiths P, et al. The Severity of Dependence Scale (SDS): psychometric properties of the SDS in English and Australian samples of heroin, cocaine and amphetamine users. Addiction 1995; 90: 607-614.
- 33. Nielsen S, Cameron J, Lee N. Characteristics of a nontreatment-seeking sample of over-the-counter codeine users: implications for intervention and prevention. J Opioid Manag 2011; 7: 363-370.
- 34. Van Hout MC, Horan A, Santlal K, et al. “Codeine is my companion”: misuse and dependence on codeine containing medicines in Ireland. Ir J Psychol Med 2015; 9: 1-14.
- 35. Fredheim O, Skurtveit S, Moroz A, et al. Prescription pattern of codeine for non-malignant pain: a pharmacoepidemiological study from the Norwegian Prescription Database. Acta Anaesthesiol Scand 2009; 53: 627-633.
- 36. Dada S, Burnhams NH, Van Hout MC, Parry CDH. Codeine misuse and dependence in South Africa: learning from substance abuse treatment admissions. S Afr Med J 2015; 105: 776-779.
- 37. Qiu YW, Su HH, Lv XF, Jiang GH. Abnormal white matter integrity in chronic users of codeine-containing cough syrups: a tract-based spatial statistics study. AJNR Am J Neuroradiol 2015; 36: 50-56.
- 38. Cooper RJ. “I can’ t be an addict. I am.” Over-the-counter medicine abuse: a qualitative study. BMJ Open 2013; 3: e002913.
- 39. Nielsen S, Cameron J, Pahoki S. Opportunities and challenges: over-the-counter codeine supply from the codeine consumer’s perspective. Int J Pharm Pract 2013; 21: 161-168.
- 40. McAvoy BR, Dobbin MD, Tobin CL. Over-the-counter codeine analgesic misuse and harm: characteristics of cases in Australia and New Zealand. N Z Med J 2011; 124: 29-33.
- 41. McDonough MA. Misuse of codeine-containing combination analgesics. Med J Aust 2011; 194: 486. <MJA full text>
- 42. Thekiso TB, Farren C. Over the counter (OTC) opiate abuse treatment. Ir J Psychol Med 2010; 27: 189-191.
- 43. Nielsen S, Bruno R, Murnion B, et al. Treating codeine dependence with buprenorphine: dose requirements and induction outcomes from a retrospective case series in New South Wales, Australia. Drug Alcohol Rev 2015; 35: 70-75.
- 44. Ammit M. Over-the-counter codeine dependency: a case analysis of an inpatient nursing intervention. Aust Nurs Midwifery J 2016; 23: 28-31.
- 45. Bedi RS. Dependence on a common cough linctus. Indian J Chest Dis Allied Sci 1991; 33: 227-228.
- 46. Dutch MJ. Nurofen Plus misuse: an emerging cause of perforated gastric ulcer. Med J Aust 2008; 188: 56-57. <MJA full text>
- 47. Dyer BT, Martin JL, Mitchell JL, et al. Hypokalaemia in ibuprofen and codeine phosphate abuse. Int J Clin Pract 2004; 58: 1061-1062.
- 48. Eng EL, Lachenmeyer J. Codeine self-medication in a headache patient. Headache 1996; 36: 452-455.
- 49. Evans C, Chalmers-Watson TA, Gearry RB. Combination NSAID-codeine preparations and gastrointestinal toxicity. N Z Med J 2010; 123: 92-93.
- 50. Faierman D, Jacobs S. Liver injury from elixir of terpin hydrate with codeine. Mt Sinai J Med 1973; 40: 56-59.
- 51. Gruber CM, Nelson GM. Codeine addiction. Ann Intern Med 1948; 29: 151-153.
- 52. Hard B. Management of opioid painkiller dependence in primary care: ongoing recovery with buprenorphine/naloxone. BMJ Case Rep 2014; doi: 10.1136/bcr-2014-207308.
- 53. Karamatic R, Croese J, Roche E. Serious morbidity associated with misuse of over-the-counter codeine–ibuprofen analgesics. Med J Aust 2011; 195: 516. <MJA full text>
- 54. Kean J. Illicit and over-the-counter codeine dependence after acute back pain-successful treatment and ongoing recovery after buprenorphine/naloxone taper. Heroin Addict Relat Clin Probl 2016; 18: 21-24.
- 55. Lake IAE. Screening and behavioral management: medication overuse headache — the complex case. Headache 2008; 48: 26-31.
- 56. Lake H. Ibuprofen belly: a case of small bowel stricture due to non-steroidal anti-inflammatory drug abuse in the setting of codeine dependence. Aust N Z J Psychiatry 2013; 47: 1210-1211.
- 57. Marr E, Hill D. Optimising service provision for prescribed opioid analgesic dependence. Heroin Addict Relat Clin Probl 2015; 17: 13-18.
- 58. Ng JL, Morgan DJR, Loh NKM, et al. Life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis. Med J Aust 2011; 194: 313-316. <MJA full text>
- 59. Page CB, Wilson PA, Foy A, et al. Life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis. Med J Aust 2011; 194: 613-614. <MJA full text>
- 60. Robinson GM, Robinson S, McCarthy P, Cameron C. Misuse of over-the-counter codeine-containing analgesics: dependence and other adverse effects. N Z Med J 2010; 123: 59-64.
- 61. Roussin A, Bouyssi A, Pouche L, et al. Misuse and dependence on non-prescription codeine analgesics or sedative H1 antihistamines by adults: a cross-sectional investigation in France. PLoS One 2013; 8: e76499.
- 62. Senjo M. Obsessive–compulsive disorder in people that abuse codeine. Acta Psychiatr Scand 1989; 79: 619-620.
- 63. Vaughan JV, Fleischl P, Nathan M, Taylor RC. Chronic renal disease and analgesic abuse. N Z Med J 1967; 66: 794-797.
- 64. Wylie AS, Fraser AA. Hazards of codeine plus paracetamol compounds. Br J Gen Pract 1994; 44: 376.
- 65. Van Hout MC, Delargy I, Ryan G, et al. Dependence on over the counter (OTC) codeine containing analgesics: treatment and recovery with buprenorphine naloxone. Int J Ment Health Addict 2016; 14: 873-883.
- 66. Romach MK, Otton SV, Somer G, et al. Cytochrome P450 2D6 and treatment of codeine dependence. J Clin Psychopharmacol 2000; 20: 43-45.
- 67. Nilsen HK, Stiles TC, Landro NI, et al. Patients with problematic opioid use can be weaned from codeine without pain escalation. Acta Anaesthesiol Scand 2010; 54: 571-579.
- 68. Fernandes LC, Kilicarslan T, Kaplan HL, et al. Treatment of codeine dependence with inhibitors of cytochrome P450 2D6. J Clin Psychopharmacol 2002; 22: 326-329.
- 69. Norman IJ, Bergin M, Parry CD, Van Hout MC. Best practices and innovations for managing codeine misuse and dependence. J Pharm Pharm Sci 2016; 19: 367-381.
- 70. Nielsen S, Larance B, Degenhardt L, et al. Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database Syst Rev 2016; (5): CD011117.
- 71. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2014; (2): CD002207.
- 72. Gowing L, Ali R, Dunlop A, et al. National guidelines for medication-assisted treatment of opioid dependence. Canberra: National Drug Strategy, 2014. http://www.nationaldrugstrategy.gov.au/internet/drugstrategy/Publishing.nsf/content/AD14DA97D8EE00E8CA257CD1001E0E5D/$File/National_Guidelines_2014.pdf (viewed Dec 2017).
- 73. Amato L, Minozzi S, Davoli M, Vecchi S. Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification. Cochrane Database Syst Rev 2011; (9): CD005031.
- 74. Amato L, Minozzi S, Davoli M, Vecchi S. Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence. Cochrane Database Syst Rev 2011; (10): CD004147.
- 75. Quello SB, Brady KT, Sonne SC. Mood disorders and substance use disorder: a complex comorbidity. Sci Pract Perspect 2005; 3: 13-21.
- 76. Evers S, Jensen R. Treatment of medication overuse headache: guideline of the EFNS headache panel. Eur J Neurol 2011; 18: 1115-1121.
- 77. Chiang C, Schwedt T, Wang S, Dodick D. Treatment of medication-overuse headache: a systematic review. Cephalalgia 2016; 36: 371-386.
- 78. Tassorelli C, Jensen R, Allena M, et al. A consensus protocol for the management of medication-overuse headache: evaluation in a multicentric, multinational study. Cephalalgia 2014; 34: 645-655.
- 79. Katsarava Z, Fritsche G, Muessig M, et al. Clinical features of withdrawal headache following overuse of triptans and other headache drugs. Neurology 2001; 57: 1694-1698.
- 80. Dodick DW, Silberstein SD. How clinicians can detect, prevent and treat medication overuse headache. Cephalalgia 2008; 28: 1207-1217.
- 81. Katsarava Z, Muessig M, Dzagnidze A, et al. Medication overuse headache: rates and predictors for relapse in a 4-year prospective study. Cephalalgia 2005; 25: 12-15.
Abstract
Objectives: Codeine dependence is a significant public health problem, motivating the recent rescheduling of codeine in Australia (1 February 2018). To provide information for informing clinical responses, we undertook a systematic review of what is known about identifying and treating codeine dependence.
Study design: Articles published in English that described people who were codeine-dependent or a clinical approach to treating people who were codeine-dependent, without restriction on year of publication, were reviewed. Articles not including empirical data were excluded. One researcher screened each abstract; two researchers independently reviewed full text articles. Study quality was assessed, and data were extracted with standardised tools.
Data sources: MEDLINE and EMBASE were searched for relevant publications on 22 November 2016. The reference lists of eligible studies were searched to identify further relevant publications. 2150 articles were initially identified, of which 41 were eligible for inclusion in our analysis.
Data synthesis: Studies consistently reported specific characteristics associated with codeine dependence, including mental health comorbidity and escalation of codeine use attributed to psychiatric problems. Case reports and series described codeine dependence masked by complications associated with overusing simple analgesics and delayed detection. Ten studies described the treatment of codeine dependence. Three reports identified a role for behavioural therapy; the efficacy of CYP inhibitors in a small open label trial was not confirmed in a randomised controlled trial; four case series/chart reviews described opioid agonist therapy and medicated inpatient withdrawal; two qualitative studies identified barriers related to perceptions of codeine-dependent people and treatment providers, and confirmed positive perceptions and treatment outcomes achieved with opioid agonist treatments.
Conclusion: Strategies for identifying problematic codeine use are needed. Identifying codeine dependence in clinical settings is often delayed, contributing to serious morbidity. Commonly described approaches for managing codeine dependence include opioid taper, opioid agonist treatment, and psychological therapies. These approaches are consistent with published evidence for pharmaceutical opioid dependence treatment and with broader frameworks for treating opioid dependence.
PROSPERO registration: CRD42016052129.