Year 2020 / Volume 27 / Number 5

Review

Opioid misuse in patients with cancer pain: an integrative systematic review of the literature

Rev. Soc. Esp. Dolor. 2020; 27(5): 306-315 / DOI: 10.20986/resed.2020.3801/2020

María Labori, Rosa Hernández, Josep Porta


ABSTRACT

Background: Opioids are widely used for the treatment of cancer pain and non-malignant pain. There is a lot of information about opioid misuse (OM) in patients with non-malignant pain, however in cancer patients there is less evidence.
Objectives: To identify, appraise and synthesize existing evidence about epidemiology, risk factors, clinical tools and evolution of OM in patients with cancer pain.
Methods: Integrative systematic review with data extraction and narrative synthesis. PubMed, Web of Science y PsychINFO databases were searched for articles published through 31 December 2017. Study inclusion criteria were as follows: 1) published in English, Spanish or French language; and 2) containing data on the prevalence or incidence of OM in patients with cancer pain; or/and 3) providing information about OM risk factors, mortality, duration and remission.
Results: The search yielded 3520 articles, of which 40 met the inclusion criteria. Four themes were identified: 1) epidemiology, 2) risk factors, 3) patient’s and professional’s opinion, and 4) specific policies. The obtained results were very heterogeneous; the prevalence of OM varied from 0 up to 26 % and the prevalence of opioid-associated aberrant behaviours from 12 to 85 %. Different risk factors for OM were identified, highlighting young age and history of psychiatric disorders or substance abuse, and different tools for risk assessment or diagnosis of OM were described. Regarding professional’s opinion, it seems to be more awareness about OM but nevertheless policies regarding this problem are scarce.
Conclusions: Even though there is a greater awareness among professionals about OM in cancer patients, the current information is very heterogeneous and does not allow clear conclusions. For this reason, it will be necessary to carry out new studies trying to standardize criteria and establish better protocols and policies for detection and management of OM.



RESUMEN

Introducción: Los opioides son ampliamente utilizados para el control del dolor oncológico y no oncológico. Existe mucha información sobre el uso inadecuado de opioides (UIO) en pacientes no oncológicos, sin embargo en pacientes oncológicos existe menos evidencia.
Objetivos: Identificar, analizar y sintetizar la evidencia disponible sobre la epidemiología, los factores de riesgo, instrumentos clínicos y evolución del UIO en pacientes con dolor oncológico.
Material y métodos: Revisión sistemática integradora de la literatura con extracción de datos y síntesis narrativa. Las fuentes utilizadas para buscar artículos publicados hasta el 31 de diciembre de 2017 fueron las bases de datos PubMed, Web of Science y PsychINFO. Se eligieron aquellos artículos que siguieran los siguientes criterios de inclusión: 1) publicados en lengua inglesa, española o francesa, y 2) que incluyesen información sobre la prevalencia o incidencia del UIO en pacientes con dolor oncológico, o/y 3) que aportasen información sobre factores de riesgo, mortalidad, duración del UIO y su remisión.
Resultados: De la búsqueda surgieron 3520 artículos, de los cuales 40 cumplieron los criterios de inclusión. Se identificaron cuatro áreas temáticas: 1) epidemiología, 2) factores de riesgo, 3) opinión de pacientes y profesionales, y 4) políticas específicas. Los resultados obtenidos fueron muy heterogéneos, identificándose una prevalencia que oscila entre el 0 y el 26 % en el UIO y entre el 12 y el 85 % en las conductas aberrantes relacionadas con opioides. Se identificaron diferentes factores de riesgo de UIO, destacando la edad joven y la presencia de antecedentes psiquiátricos o de abuso de sustancias, y se describieron diferentes instrumentos dirigidos a la evaluación del riesgo o bien al diagnóstico del UIO. En cuanto a la opinión de los profesionales, parece haber un incremento de la sensibilización al respecto, pero las políticas de los centros en relación con esta problemática suelen ser casi inexistentes.
Conclusiones: A pesar de que existe una mayor sensibilización de los profesionales acerca del UIO en pacientes oncológicos, la información de que disponemos es muy heterogénea y no nos permite extraer conclusiones claras. Por esta razón será necesaria la realización de nuevos estudios intentando homogeneizar criterios y establecer mejores protocolos y políticas de detección e intervención frente al UIO.





Complete Article

Bibliografía

1. Manual Diagnóstico y Estadístico de los Trastornos Mentales. 5ª ed. Arlington, VA: Asociación Americana de Psiquiatría; 2014.
3. Webster L, St Marie B, McCarberg B, Passik SD, Panchal SJ, Voth E. Current status and evolving role of abuse-deterrent opioids in managing patients with chronic pain. J Opioid Manag. 2011;7(3):235-45. DOI: 10.5055/jom.2011.0066.
4. Passik SD, Weinreb HJ. Managing chronic nonmalignant pain: overcoming obstacles to the use of opioids. Adv Ther. 2000;17(2):70-83. DOI: 10.1007/BF02854840.
5. Del Fabbro E. Assessment and management of chemical coping in patients with cancer. J Clin Oncol. 2014;32(16):1734-8. DOI: 10.1200/JCO.2013.52.5170.
6. Brown RL, Rounds LA. Conjoint screening questionnaires for alcohol and other drug abuse: criterion validity in a primary care practice. Wis Med J. 1995;94(3):135-40.
7. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool. Pain Med. 2005;6(6):434-42. DOI: 10.1111/j.1526-4637.2005.00072.x.
8. Akbik H, Butler SF, Budman SH, Fernandez K, Katz NP, Jamison RN. Validation and clinical application of the Screener and Opioid Assessment for Patients with Pain (SOAPP). J Pain Symptom Manage. 2006;32(3):287-93. DOI: 10.1016/j.jpainsymman.2006.03.010.
9. Butler SF, Budman SH, Fernandez KC, Houle B, Benoit C, Katz N, et al. Development and validation of the Current Opioide Misuse Measure. Pain. 2007;130(1-2):144-56. DOI: 10.1016/j.pain.2007.01.014.
10. Manchikanti L, Singh A. Therapeutic opioids: a ten-year perspective on the complexities and complications of the escalating use, abuse, and nonmedical use of opioids. Pain Physician. 2008; 11(2 Suppl):S63-88.
11. Jay GW, Barkin RL. Perspectives on the opioid crisis from pain medicine clinicians. Dis Mon. 2018;64(10):451-66. DOI: 10.1016/j.disamonth.2018.07.002.
12. Shipton EA, Shipton EE, Shipton AJ. A Review of the opioid epidemic: What do we do about it? Pain Ther. 2018;7(1):23-36. DOI: 10.1007/s40122-018-0096-7.
13. U.S. Department of Justice – Drug enforcement administration – Diversion control division [Internet]. Springfield, VA. Disponible en: http://www.deadiversion.usdoj.gov/arcos/retail_drug_summary/index.html.
15. Madadi P, Hildebrandt D, Lauwers AE, Koren G. Characteristics of opioid-users whose death was related to opioid-toxicity: a population-based study in Ontario, Canada. PLoS One. 2013;8(4):e60600. DOI: 10.1371/journal.pone.0060600.
16. Schubert I, Ihle P, Sabatowski R. Increase in opiate prescription in Germany between 2000 and 2010: a study based on insurance data. Dtsch Arztebl Int. 2013;110(4):45-51. DOI: 10.3238/arztebl.2013.0045.
17. Carmichael AN, Morgan L, Del Fabbro E. Identifying and assessing the risk of opioid abuse in patients with cancer: an integrative review. Subst Abuse Rehabil. 2016;7:71-9.
18. Sociedad científica española de estudios sobre el alcohol, el alcoholismo y las otras toxicomanías (Socidrogalcohol). Guía de consenso para el buen uso de analgésicos opioides en el dolor crónico. 1ª ed, 2017. ISBN: 978-84-945737-4-3.
19. Miaskowski C, Dodd MJ, West C, Paul SM, Tripathy D, Koo P, et al. Lack of adherence with the analgesic regimen: a significant barrier to effective cancer pain management. J Clin Oncol. 2001;19(23):4275-9. DOI: 10.1200/JCO.2001.19.23.4275.
20. Nguyen LM, Rhondali W, De la Cruz M, Hui D, Palmer L, Kang DH, et al. Frequency and predictors of patient deviation from prescribed opioids and barriers to opioid pain management in patients with advanced cancer. J Pain Symptom Manage. 2013;45(3):506-16. DOI: 10.1016/j.jpainsymman.2012.02.023.
21. Mayahara M, Foreman MD, Wilbur J, Paice JA, Fogg LF. Effect of hospice nonprofessional caregiver barriers to pain management on adherence to analgesic administration recommendations and patient outcomes. Pain Manag Nurs. 2015;16(3):249-56. DOI: 10.1016/j.pmn.2014.07.001.
22. Hojsted J, Sjogren P. Addiction to opioids in chronic pain patients: a literature review. Eur J Pain. 2007;11(5):490-518. DOI: 10.1016/j.ejpain.2006.08.004.
23. Minozzi S, Amato L, Davoli M. Development of dependence following treatment with opioid analgesics for pain relief: a systematic review. Addiction. 2013;108(4):688-98. DOI: 10.1111/j.1360-0443.2012.04005.x.
24. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006-12. DOI: 10.1016/j.jclinepi.2009.06.005.
25. Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs. 2005;52(5):546-53. DOI: 10.1111/j.1365-2648.2005.03621.x.
26. Carroll C, Booth A, Lloyd-Jones M. Should we exclude inadequately reported studies from qualitative systematic reviews? An evaluation of sensitivity analyses in two case study reviews. Qual Health Res. 2012;22(10):1425-34. DOI: 10.1177/1049732312452937.
27. Kanner RM, Foley KM. Patterns of narcotic drug use in a cancer pain clinic. Ann N Y Acad Sci. 1981;362:161-72. DOI: 10.1111/j.1749-6632.1981.tb12804.x.
28. Sun WZ, Chen TL, Fan SZ, Peng WL, Wang MS, Huang FY. Can cancer pain attenuate the physical dependence on chronic long-term morphine treatment? J Formos Med Assoc. 1992;91(5):513-20.
29. Ljungman G, Gordh T, Sörensen S, Kreuger A. Pain in paediatric oncology: interviews with children, adolescents and their parents. Acta Paediatr. 1999;88(6):623-30. DOI: 10.1080/08035259950169279.
30. Vainio A. Practising physicians’ experiences of treating patients with cancer pain. Acta Oncol. 1989;28(2):177-82. DOI: 10.3109/02841868909111243.
31. Tabei SZ, Heydari ST, Mehrabani D, Shamsina SJ, Ahmadi J, Firouzi SM. Current substance use in patients with gastric cancer in Southern Iran. J Cancer Res Ther. 2006;2(4):182-5. DOI: 10.4103/0973-1482.29828.
32. Santana Pineda MM, Jover López-Rodrigálvarez R, Rodríguez Sainz P, Gómez Cortes MD, Rodríguez Huertas F, Morgado Muñoz I. Uso y abuso de opioides en el área norte de la provincia de Cádiz. Rev Soc Esp Dolor. 2016;23(3):127-34.
33. Payne R, Coluzzi P, Hart L, Simmonds M, Lyss A, Rauck R, et al. Long-term safety of oral transmucosal fentanyl citrate for breakthrough cancer pain. J Pain Symptom Manage. 2001;22(1):575-83. DOI: 10.1016/s0885-3924(01)00306-2.
34. Taylor D, Radbruch L, Revnic J, Torres LM, Ellershaw JE, Perelman M. A report on the long-term use of fentanyl pectin nasal spray in patients with recurrent breakthrough pain. J Pain Symptom Manage. 2014;47(6):1001-7. DOI: 10.1016/j.jpainsymman.2013.07.012.
35. Kwon JH, Tanco K, Park JC, Wong A, Seo L, Liu D, et al. Frequency, predictors, and medical record documentation of chemical coping among advanced cancer patients. Oncologist. 2015;20(6):692-7. DOI: 10.1634/theoncologist.2015-0012.
36. Reddy A, de la Cruz M, Rodriguez EM, Thames J, Wu J, Chisholm G, et al. Patterns of storage, use, and disposal of opioids among cancer outpatients. Oncologist. 2014;19(7):780-5. DOI: 10.1634/theoncologist.2014-0071.
37. Silvestre J, Reddy A, de la Cruz M, Wu J, Liu D, Bruera E, et al. Frequency of unsafe storage, use, and disposal practices of opioids among cancer patients presenting to the emergency department. Palliat Support Care. 2017;15(6):638-43. DOI: 10.1017/S1478951516000158.
38. Anghelescu DL, Ehrentraut JH, Faughnan LG. Opioid misuse and abuse: risk assessment and management in patients with cancer pain. J Natl Compr Canc Netw. 2013;11(8):1023-31. DOI: 10.6004/jnccn.2013.0120.
39. Ehrentraut JH, Kern KD, Long SA, An AQ, Faughnan LG, Anghelescu DL. Opioid misuse behaviors in adolescents and young adults in a hematology/oncology setting. J Pediatr Psychol. 2014;39(10):1149-60. DOI: 10.1093/jpepsy/jsu072.
40. Evans PJ. Narcotic addiction in patients with chronic pain. Anaesthesia 1981;36(6):597-602. DOI: 10.1111/j.1365-2044.1981.tb10323.x.
41. Macaluso C, Weinberg D, Foley KM. Opioid abuse and misuse in a cancer pain population. J Pain Symptom Manage 1988;3:S24.
42. Schug SA, Zech D, Grond S, Jung H, Meuser T, Stobbe B. A long-term survey of morphine in cancer pain patients. J Pain Symptom Manage. 1992;7(5):259-66. DOI: 10.1016/0885-3924(92)90059-q.
43. Passik SD, Kirsh KL, McDonald MV, Ahn S, Russak SM, Martin L, et al. A pilot survey of aberrant drug-taking attitudes and behaviors in samples of cancer and AIDS patients. J Pain Symptom Manage. 2000;19:274-86. DOI: 10.1016/s0885-3924(00)00119-6.
44. Passik SD, Schreiber J, Kirsh KL. A chart review of the ordering of urine toxicology screen in a cancer center: do they influence on pain management. J Pain Symptom Manage. 2000;19(1):40-4. DOI: 10.1016/s0885-3924(99)00137-2.
45. Passik SD, Kirsh KL, Donaghy KB, Portenoy RK. Pain and aberrant drug-related behaviors in medically ill patients with and without histories of substance abuse. Clin J Pain. 2006;22(2):173-81. DOI: 10.1097/01.ajp.0000161525.48245.aa.
46. Hojsted J, Nielsen PR, Guldstrand SK, Frich L, Sjogren P. Classification and identification of opioid addiction in chronic pain patients. Eur J Pain. 2010;14(10):1014-20. DOI: 10.1016/j.ejpain.2010.04.006.
47. Bohnert AS, Valenstein M, Bair MJ, Ganoczy D, McCarthy JF, Ilgen MA, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305(13):1315-21. DOI: 10.1001/jama.2011.370.
48. Novy DM, Lam C, Gritz ER, Hernandez M, Driver LC, Koyyalagunta D. Distinguishing features of cancer patients who smoke: pain, symptom burden, and risk for opioid misuse. J Pain. 2012;13(11):1058-67. DOI: 10.1016/j.jpain.2012.07.012.
49. Koyyalagunta D, Bruera E, Aigner C, Nusrat H, Driver L, Novy D. Risk stratification of opioid misuse among patients with cancer pain using the SOAPP-SF. Pain Med. 2013;14(5):667-75. DOI: 10.1111/pme.12100.
50. Barclay JS, Owens JE, Blackhall LJ. Screening for substance abuse risk in cancer patients using the Opioid Risk Tool and urine drug screen. Support Care Cancer. 2014;22(7):1883-8. DOI: 10.1007/s00520-014-2167-6.
51. Ma JD, Horton JM, Hwang M, Atayee RS, Roeland EJ. A single-center, retrospective analysis evaluating the utilization of the opioid risk tool in opioid-treated cancer patients. J Pain Palliat Care Pharmacother. 2014;28(1):4-9. DOI: 10.3109/15360288.2013.869647.
52. Childers JW, King LA, Arnold RM. Chronic pain and risk factors for opioid misuse in a palliative care clinic. Am J Hosp Palliat Care. 2015;32(6):654-9. DOI: 10.1177/1049909114531445.
53. Kwon JH, Hui D, Bruera E. A pilot study to define chemical coping in cancer patients using the Delphi method. J Palliat Med. 2015;18(8):703-6. DOI: 10.1089/jpm.2014.0446.
54. Arthur JA, Edwards T, Lu Z, Reddy S, Hui D, Wu J, et al. Frequency, predictors, and outcomes or urine drug testing among patients with advanced cancer on chronic opioid therapy at an outpatient supportive care clinic. Cancer. 2016;122(23):3732-9. DOI: 10.1002/cncr.30240.
55. Kim YJ, Dev R, Reddy A, Hui D, Tanco K, Park M, et al. Association between tobacco use, symptom expression, and alcohol and illicit drug use in advanced cancer patients. J Pain Symptom Manage. 2016;51(4):762-8. DOI: 10.1016/j.jpainsymman.2015.11.012.
56. Reyes-Gibby CC, Anderson KO, Todd KH. Risk for opioid misuse among emergency department cancer patients. Acad Emerg Med. 2016;23(2):151-8. DOI: 10.1111/acem.12861.
57. Von Roenn JH, Cleeland CS, Gonin R, Hatfield AK, Pandya KJ. Physician attitudes and practice in cancer pain management. A survey from the Eastern Cooperative Oncology Group. Ann Intern Med. 1993;119(2):121-6. DOI: 10.7326/0003-4819-119-2-199307150-00005.
58. Serra E, Marchand F, Mimassi N, Ganry H. Point de vue des médecins généralistes sur les risques de survenue d'une dépendance lors de la prescription d'opioïdes forts. Ann Med Psychol (Paris). 2014;172(4):323-9.
59. Paice JA, Toy C, Shott S. Barriers to cancer pain relief: fear of tolerance and addiction. J Pain Symptom Manage. 1998;16(1):1-9. DOI: 10.1016/s0885-3924(98)00025-6.
60. Wills BS, Wootton YS. Concerns and misconceptions about pain among Hong Kong Chinese patients with cancer. Cancer Nurs. 1999;22(6):408-13. DOI: 10.1097/00002820-199912000-00002.
61. Davies AN, Vriens J, Kennett A, McTaggart M. An observational study of oncology patients’ utilization of breakthrough pain medication. J Pain Symptom Manage. 2008;35(4):406-11. DOI: 10.1016/j.jpainsymman.2007.05.010.
62. Reid CM, Gooberman-Hill R, Hanks GW. Opioid analgesics for cancer pain: symptom control for the living or comfort for the dying? A qualitative study to investigate the factors influencing the decision to accept morphine for pain caused by cancer. Ann Oncol. 2008;19(1):44-8. DOI: 10.1093/annonc/mdm462.
63. Jacobsen R, Samsanaviciene J, Liuabarskiene Z, Sciupokas A. Barriers to pain management among Lithuanian cancer patients. Pain Pract. 2010;10(2):145-57. DOI: 10.1111/j.1533-2500.2009.00333.x.
64. Alsirafy SA, Saleh RN, Fawzy R, Alnagar AA, Hammad AM, El-Sherief W, et al. The fear of using tramadol for pain control (tramadolophobia) among Egyptian patients with cancer. J Opioid Manag. 2015;11(6):474-80. DOI: 10.5055/jom.2015.0300.
65. Cella IF, Trindade LCT, Sanvido LV, Skare TL. Prevalence of opiophobia in cancer pain treatment. Rev Dor. Sao Paulo. 2016;17(4):245-7.
66. Levin DN, Cleeland CS, Dar R. Public attitudes toward cancer pain. Cancer. 1985;56(9):2337-9. DOI: 10.1002/1097-0142(19851101)56:92337::aid-cncr2820560935>3.0.co;2-w.
67. Grant M, Ugalde A, Vafiadis P, Philip J. Exploring the myths of morphine in cancer: views of the general practice population. Support Care Cancer. 2015;23(2):438-9. DOI: 10.1007/s00520-014-2379-9.
68. Blackhall LJ, Alfons ED, Barclay JS. Screening for substance abuse and diversion in Virginia hospices. J Palliat Med. 2013;16(3):237-42. DOI: 10.1089/jpm.2012.0263.
69. De la Cruz M, Reddy A, Balankari V, Epner M, Frisbee-Hume S, Wu J, et al. The impact of an educational program on patient practices for safe use, storage, and disposal of opioids at a comprehensive cancer center. Oncologist. 2017;22(1):115-21. DOI: 10.1634/theoncologist.2016-0266.
70. Rosón B, Corbella X, Perney P, Santos A, Stauber R, Lember M, et al. Prevalence, Clinical Characteristics, and Risk Factors for Non-recording of Alcohol Use in Hospitals across Europe: The ALCHIMIE Study. Alcohol Alcohol. 2016;51(4):457-64. DOI: 10.1093/alcalc/agv142.
71. Ferrel BR, Temel JS, Temin S, Alesi ER, Balboni TA, Basch EM, et al. Integration of palliative care into standard oncology care: american society of clinical oncology clinical practice guideline update. J Clin Oncol. 2017;35(1):96-112.
72. Kaasa S, Loge JH, Aapro M, Albreht T, Anderson R, Bruera E, et al. Integration of oncology and palliative care: a Lancet Oncology Comission. Lancet Oncol. 2018;19(11):e588-e653. DOI: 10.1016/S1470-2045(18)30415-7.
73. Higginson IJ, Evans CJ, Grande G, Preston N, Morgan M, McCrone P, et al. Evaluating complex interventions in end of life care: the MORECare statement on good practice generated by a synthesis of transparent expert consultations and systematic reviews. BMC Med. 2013;11:111. DOI: 10.1186/1741-7015-11-111.

Tablas y Figuras

Table I

Figure 1

Anexos

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Labori M, Hernández R, Porta J. Opioid misuse in patients with cancer pain: an integrative systematic review of the literature. Rev Soc Esp Dolor 2020; 27(5): 306-315 / DOI: 1020986/resed20203801/2020


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