Strategies to Identify Patient Risks of Prescription Opioid Addiction When Initiating Opioids for Pain: A Systematic Review
Open accessAbstract
Importance: Although prescription opioid use disorder is associated with substantial harms, strategies to identify patients with pain among whom prescription opioids can be safely prescribed have not been systematically reviewed. Objective: To review the evidence examining factors associated with opioid addiction and screening tools for identifying adult patients at high vs low risk of developing symptoms of prescription opioid addiction when initiating prescription opioids for pain. Data Sources: MEDLINE and Embase (January 1946 to November 2018) were searched for articles investigating risks of prescription opioid addiction. Study Selection: Original studies that were included compared symptoms, signs, risk factors, and screening tools among patients who developed prescription opioid addiction and those who did not. Data Extraction and Synthesis: Two investigators independently assessed quality to exclude biased or unreliable study designs and extracted data from higher quality studies. The Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Accuracy Studies (PRISMA-DTA) reporting guideline was followed. Main Outcomes and Measures: Likelihood ratios (LRs) for risk factors and screening tools were calculated. Results: Of 1287 identified studies, 6 high-quality studies were included in the qualitative synthesis and 4 were included in the quantitative synthesis. The 4 high-quality studies included in the quantitative synthesis were all retrospective studies including a total of 2 888 346 patients with 4470 cases that met the authors' definitions of prescription opioid addiction. A history of opioid use disorder (LR range, 17-22) or other substance use disorder (LR range, 4.2-17), certain mental health diagnoses (eg, personality disorder: LR, 27; 95% CI, 18-41), and concomitant prescription of certain psychiatric medications (eg, atypical antipsychotics: LR, 17; 95% CI, 15-18) appeared useful for identifying patients at high risk of opioid addiction. Among individual findings, only the absence of a mood disorder (negative LR, 0.50; 95% CI, 0.45-0.52) was associated with a lower risk of opioid addiction. Despite their widespread use, most screening tools involving combinations of questions were based on low-quality studies or, when diagnostic performance was assessed among high-quality studies, demonstrated poor performance in helping to identify patients at high vs low risk. Conclusions and Relevance: While a history of substance use disorder, certain mental health diagnoses, and concomitant prescription of certain psychiatric medications appeared useful for identifying patients at higher risk, few quality studies were available and no symptoms, signs, or screening tools were particularly useful for identifying those at lower risk.
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Use of prescribed opioids for pain can lead to opioid addiction.
“Use of prescribed opioids for pain can lead to opioid addiction [61].”
From Substance and Behavioral Addictions among American Indian and Alaska Native Populations (2022) · cites this paper as [61]
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Trends in prescription opioid analgesic use in Australia from 2015 to 2022
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Annis, I., Jordan, R., & Thomas, K. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-059414 · Cited by 10 · see citing works
Categorization of Opioid Use Among Pregnant People and Association With Overdose or Death
Camden, A., To, T. M., Ray, J. G., Gomes, T., Bai, L., & Guttmann, A. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.14688 · Cited by 12 · see citing works
‘First Do No Harm’: physician discretion, racial disparities and opioid treatment agreements
Beck, A., Svirsky, L., & Howard, D. (2021) · Journal of Medical Ethics · doi:10.1136/medethics-2020-107030 · Cited by 10 · see citing works
Predictive Models to Assess Risk of Persistent Opioid Use, Opioid Use Disorder, and Overdose
Song, S. L., Dandapani, H. G., Estrada, R. S., Jones, N. W., Samuels, E. A., & Ranney, M. L. (2024) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000001276 · Cited by 7 · see citing works
The Role of Pharmacists in Opioid Addiction Management
Dave, P. (2024) · Asian Journal of Dental and Health Sciences · doi:10.22270/ajdhs.v4i1.71 · Cited by 10 · see citing works
“22,23 Coincidentally, individuals who experience chronic pain have higher rates of SUDs.”
BackgroundPrimary care management of Long-Term opioid therapy
Coffin, P., Martinez, R. S., Wylie, B., & Ryder, B. (2022) · Annals medicus · doi:10.1080/07853890.2022.2121417 · Cited by 9 · see citing works
Skoy, E., Frenzel, O. C., Eukel, H. N., Lothspeich, E., Steig, J., Strand, M., & Werremeyer, A. B. (2022) · Preventing Chronic Disease · doi:10.5888/pcd19.220028 · Cited by 9 · see citing works
Blair, A., & Siddiqi, A. (2022) · Social Psychiatry and Psychiatric Epidemiology · doi:10.1007/s00127-022-02281-3 · Cited by 9 · see citing works
How I Treat Hematologic Malignancies Safely with Opioid Therapy.
Geyer, H., Gazelka, H., & Mesa, R. (2020) · Blood · doi:10.1182/blood.2019003116 · Cited by 9 · see citing works
Morris, C. J., Mills-Huffnagle, S. L., & Zgierska, A. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.07.018 · Cited by 8 · see citing works
Engineering Approaches for Addressing Opioid Use Disorder in the Community
Griffin, P. M. (2020) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-082719-040832 · Cited by 14 · see citing works
“Several more in-depth and validated survey instruments, such as the Current Opioid Misuse Measure, can help define specific OUD patient characteristics (16).”
BackgroundThe Role of TRP Channels in Sepsis and Colitis
Dvornikova, K., Platonova, O. N., & Bystrova, E. Y. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094784 · Cited by 7 · see citing works
“Opioids are known to be beneficial pain relievers, but their effects on the brain can be addictive [21].”
BackgroundPrescription stimulant use during long-term opioid therapy and risk for opioid use disorder
Scherrer, J. F., Salas, J., Grucza, R., Wilens, T., Quinn, P. D., Sullivan, M. D., Rossom, R., Wright, E. A., Piper, B., Sanchez, K., et al. (2022) · Drug and Alcohol Dependence Reports · doi:10.1016/j.dadr.2022.100122 · Cited by 7 · see citing works
Poirrier, J., DeMartino, J., Nagar, S., Carrico, J., Hicks, K., Meyers, J., & Stoddard, J. (2022) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2022.2040328 · Cited by 7 · see citing works
“Identifying patients who are at greater risk of addiction after initiation of opioid treatment for pain has proven difficult.(39) Future interventions should focus on prevention of HZ and PHN, especially in those patients with comorbidities and immunocompromised status.”
BackgroundKlimas, J., Hamilton, M., Carney, G., Cooper, I., Croteau, N., Dong, H., Dormuth, C., Maclure, M., Socías, M., Ti, L., et al. (2021) · Contemporary Clinical Trials · doi:10.1016/j.cct.2021.106462 · Cited by 7 · see citing works
Self-citationTop Ten Tips Palliative Care Clinicians Should Know About Opioid Use Disorder
Haley, E., Stone, J., Childers, J., Davis, A., Ehrman, S., Houser, M. W., Olenik, J., Roche, M., Jones, C. A., & Skarf, L. (2020) · Journal of Palliative Medicine · doi:10.1089/jpm.2020.0409 · Cited by 7 · see citing works
Prescribing opioids to patients with chronic pain: translation of the opioid rsk tool into Italian.
Miceli, L., Bednarova, R., Cuomo, A., Cascella, M., Guardamagna, V., Romualdi, P., & Marinangeli, F. (2020) · Minerva Anestesiologica · doi:10.23736/s0375-9393.20.14312-8 · Cited by 7
Santo, T., Larance, B., Bruno, R., Gisev, N., Nielsen, S., Degenhardt, L., & Campbell, G. (2019) · Drug and Alcohol Review · doi:10.1111/dar.13021 · Cited by 7 · see citing works
McNeilage, A., Browne, E., Nielsen, S., Ashton-James, C., & Murnion, B. (2025) · European Journal of Pain · doi:10.1002/ejp.70116 · Cited by 6 · see citing works
Held, U., Forzy, T., Signorell, A., Deforth, M., Burgstaller, J., & Wertli, M. (2023) · Pain · doi:10.1097/j.pain.0000000000003023 · Cited by 6 · see citing works
Mind-body approaches for reducing the need for post-operative opioids: Evidence and opportunities
Pester, B., Edwards, R. R., Martel, M. O., Gilligan, C. J., & Meints, S. M. (2023) · Journal of Clinical Anesthesia and Intensive Care · doi:10.46439/anesthesia.3.016 · Cited by 9 · see citing works
Opioid risk stratification in the community pharmacy: The utility of the Opioid Risk Tool.
Strand, M., Eukel, H. N., Frenzel, O. C., Skoy, E., Steig, J., & Werremeyer, A. B. (2022) · Research in Social and Administrative Pharmacy · doi:10.1016/j.sapharm.2022.07.009 · Cited by 6
Neighborhood disadvantage and prescription drug misuse in low-income urban mothers.
Bernhardt, C., & King, C. (2021) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2021.109245 · Cited by 6 · see citing works
Opioid Prescribing at Discharge in Opioid-Naïve Trauma Patients
Johnston, J. P., Lapietra, A., Elsawy, O. A., Wang, A.-T., Richards, L., Yee, S., Foran, L. A., Hlayhel, A. F., Fahey, R. A., & Nerenberg, S. F. (2021) · The American surgeon · doi:10.1177/00031348211011105 · Cited by 6
Assessing Patients’ Risk for Opioid Use Disorder
Marie, B. S. (2019) · AACN Advanced Critical Care · doi:10.4037/aacnacc2019931 · Cited by 6 · see citing works
Associations Among Sleep, Pain, and Medications for Opioid Use Disorder: a Scoping Review
Hsaio, C., DiMeola, K. A., Jegede, O. O., Funaro, M. C., Langstengel, J., Yaggi, H. K., & Barry, D. T. (2024) · Current Addiction Reports · doi:10.1007/s40429-024-00606-7 · Cited by 4 · see citing works
“Additionally, people with opioid “misuse” and “pre-OUD” may offer significant insights into risk factors associated with sleep and pain in developing OUD [98–101].”
Marel, C., Afzali, M. H., Sunderland, M., Teesson, M., & Mills, K. L. (2024) · International Journal of Mental Health and Addiction · doi:10.1007/s11469-024-01257-5 · Cited by 5 · see citing works
“A small number of risk-prediction models have been developed in relation to opioid use; however, these have largely been restricted to examinations of the risk of overdose among people using prescription opioids for pain (Glanz et al., 2018; Klimas et al., 2019; Lo-Ciganic et al., 2019).”
Quality use of publicly subsidised tapentadol in Australia: a population‐based analysis
Camacho, X., Schaffer, A., Brett, J., Pratt, N., Buckley, N., Henry, D., & Pearson, S. (2024) · Internal medicine journal (Print) · doi:10.1111/imj.16335 · Cited by 5 · see citing works
U-PAIN cohort study among patients with chronic pain in specialised pain care: a feasibility study
Ljungvall, H., Lind, A., Zetterberg, H., Wagner, S., Ekselius, L., Karlsten, R., Heilig, M., & Åsenlöf, P. (2022) · BMJ Open · doi:10.1136/bmjopen-2022-062265 · Cited by 5 · see citing works
Elsamadicy, A., Sandhu, M., Reeves, B. C., Freedman, I. G., Koo, A. B., Jayaraj, C., Hengartner, A. C., Havlik, J., Hersh, A., Pennington, Z., et al. (2022) · Spine Deformity · doi:10.1007/s43390-022-00609-2 · Cited by 5
“General risk factors for baseline opioid dependence prior to surgical intervention in patients with chronic pain include mental illness [40], younger age, and male sex [41].”
BackgroundCharacterizing OPRM1 DNA methylation in prescription opioid users with chronic musculoskeletal pain
Sheikh, S., Smotherman, C., Patel, M., Langaee, T., Wang, D.-X., Swaray, E., Velasquez, E., Schmidt, S., Hendry, P., Cavallari, L., et al. (2022) · PAIN Reports · doi:10.1097/pr9.0000000000001046 · Cited by 5 · see citing works
The impact of opioid prescribing report cards in Medicaid
Candon, M., Xue, L.-S., Shen, S., Cole, E., Donohue, J., & Rothbard, A. (2022) · Journal of Managed Care & Specialty Pharmacy · doi:10.18553/jmcp.2022.28.8.862 · Cited by 5 · see citing works
Mallow, P. J., & Belk, K. W. (2021) · Journal of Comparative Effectiveness Research · doi:10.2217/cer-2021-0115 · Cited by 9 · see citing works
Keller, M., Jusufagic, A., Nuckols, T., Needleman, J., & Heilemann, M. V. (2021) · Substance Use & Misuse · doi:10.1080/10826084.2021.1926514 · Cited by 5 · see citing works
“The evidence on whether risk mitigation strategies are effective in decreasing patients’ risk of misuse, abuse, or overdose is limited and mixed (Appendix Table 1) (Dowell et al., 2016; Fink et al., 2018; Klimas et al., 2019; Joanna L. Starrels et al., 2010).”
BackgroundJones, K., White, G. E., Bennett, A. V., Bulls, H., Escott, P., Orris, S., Escott, E., Fischer, S. M., Hamm, M. E., Krishnamurti, T., et al. (2023) · JMIR Research Protocols · doi:10.2196/54953 · Cited by 4 · see citing works
“…this long-term opioid use definition also excludes individuals who are receiving methadone or buprenorphine/naloxone (suboxone) for the treatment of opioid use disorder, as the potential benefits and harms of opioid therapy in this population are unique and merit separate investigation [36].”
BackgroundChamoun, K., Mouawad, J., Salameh, P., Sacre, H., Haddad, R., Khabbaz, L., Mégarbane, B., & Hajj, A. (2023) · BMC Psychiatry · doi:10.1186/s12888-023-05304-8 · Cited by 4 · see citing works
“Therefore, it is essential to accurately evaluate and identify psychiatric disorders before starting an opioid treatment for pain management [81].”
BackgroundTeam Approach: Use of Opioids in Orthopaedic Practice
Pasqualini, I., Rullán, P. J., Deren, M., Krebs, V., Molloy, R., Nystrom, L., & Piuzzi, N. (2023) · JBJS Reviews · doi:10.2106/jbjs.rvw.22.00209 · Cited by 4
Accelerating Opioid Use Disorders Research by Integrating Multiple Data Modalities
Bianchi, S. B., Jeffery, A. D., Samuels, D. C., Schirle, L. M., Palmer, A. A., & Sanchez‐Roige, S. (2022) · Complex Psychiatry · doi:10.1159/000525079 · Cited by 5 · see citing works
Ljungvall, H., Öster, C., Katila, L., & Åsenlöf, P. (2022) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2021-0171 · Cited by 2 · see citing works
Lee, C., Gandotra, S., Bliss, A., Jenkins, G., Dyalram, D., Hatten, K. M., Moyer, K., Mehra, R., Molitoris, J., Ferris, M., et al. (2025) · Head and Neck · doi:10.1002/hed.70089 · Cited by 3 · see citing works
Picco, L., Xia, T., Bell, J. S., Pearce, C., Buchbinder, R., Lubman, D. I., & Nielsen, S. (2023) · Drug and Alcohol Review · doi:10.1111/dar.13754 · Cited by 3 · see citing works
“OUD is often associated with both long-term and high-dose opioid use [35 – 37].”
BackgroundSkeer, M., Yang, J.-E., Booth, M., Robison, E., Hajinazarian, G., Boyadjian, T., Sabelli, R. A., Chui, K., & Stopka, T. (2023) · SSM - Qualitative Research in Health · doi:10.1016/j.ssmqr.2023.100281 · Cited by 3 · see citing works
Answering a Call to Action on American Workplace and Community Opioid Concerns
Harnett, P., Hindman, J., Dueñas, M., Coogan, M., & Misicko, H. (2021) · New solutions : a journal of environmental and occupational health policy : NS · doi:10.1177/10482911211037573 · Cited by 3
“This decrease in initial prescription supply and duration further reduces the likelihood of an employee developing an OUD.15 Additionally, ESI is educating members and providers.”
BackgroundInfluentialChronic Pain Management in the Homeless Population
Pangarkar, S., & Chang, L. (2021) · Springer eBooks · doi:10.1007/978-3-030-70135-2_4 · Cited by 3 · see citing works
Ethnic Identity and Past 30-Day Opioid Misuse: Mediating Effect of Relational Support
Miller-Roenigk, B. D., & Stevens-Watkins, D. J. (2025) · Substance Use & Misuse · doi:10.1080/10826084.2025.2509262 · Cited by 2 · see citing works
“While limited research examines the effect of ethnic identity on opioid misuse specifically, Halfon et al. (2022) reveal that higher ethnic identity is associated with pain resilience among Latinx populations, and pain is a major reason for opioid use (Klimas et al., 2019).”
Kaufman, M. J., & Meloni, E. (2025) · Medical Gas Research · doi:10.4103/mgr.medgasres-d-24-00063 · Cited by 2 · see citing works
Chandrashekarappa, S. B., Assi, S., Jayabalan, M., Al-Hamid, A., & Obe, D. A. (2024) · Emerging Trends in Drugs, Addictions, and Health · doi:10.1016/j.etdah.2024.100165 · Cited by 2
Assessing suicide risk in chronic pain management: a narrative review across drug classes
Brezić, N., Gligorevic, S., Candido, K. D., & Knežević, N. N. (2024) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2024.2391999 · Cited by 2 · see citing works
Houghton, D. C., Merritt, C. R., Miller, S., Mitchell, J. M., Parker, D., Hommel, J. D., Cunningham, K. A., & Wilkes, D. M. (2024) · Journal of Pain Research · doi:10.2147/jpr.s436898 · Cited by 2 · see citing works
“6,7 Therefore, even when providers utilize the best available measures, many instances of non-adherence are likely undetected.”
BackgroundNøst, T. H., Skurtveit, S., Odsbu, I., Pedersen, L., Borchgrevink, P. C., & Handal, M. (2024) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2024-0059 · Cited by 2 · see citing works
Angarita-Fonseca, A., Lacasse, A., Choinière, M., Kaboré, J.-L., Sylvestre, M., Dinkou, G. D. T., Bruneau, J., Martel, M., Hovey, R., Motulsky, A., et al. (2023) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.5706 · Cited by 2 · see citing works
“Our findings are consistent with previous literature showing an association between mental health symptoms and prescription opioid use among patients with CP. 65 – 67 Additionally, prolonged pain war-ranting opioids may increase the risk of developing depression.”
ResultProlonged opioid use after distal radius fracture
Pardo, F. L., Bondesson, E., Petersson, I., Schelin, M., & Jöud, A. (2023) · European Journal of Pain · doi:10.1002/ejp.2114 · Cited by 2
“The relation between prior mental illness and the risk for prolonged opioid use has been shown in previous studies which have reported increased risk for both prolonged opioid use after surgery and risk of opioid addiction (Kent et al., 2019; Klimas et al., 2019).”
BackgroundOpioid Use Disorder Among the Economically Disadvantaged in the Rural South
Albright, D. L., Suntai, Z., McDaniel, J. T., Johnson, K., Henson, H., Robertson, E., & McIntosh, S. (2023) · Journal of Addiction Medicine · doi:10.1097/adm.0000000000001142 · Cited by 2 · see citing works
Klimas, J., Hamilton, M., Carney, G., Cooper, I., Croteau, N., Dong, H.-R., Dormuth, C., Maclure, M., Socías, M., Ti, L., et al. (2022) · Canadian Journal of Addiction · doi:10.1097/cxa.0000000000000135 · Cited by 2 · see citing works
“As many as 26% of all patients initiated on opioids for the treatment of non-cancer pain may develop a prescription opioid use disorder (OUD), which suggests a substantial proportion of opioid-treated patients at high risk for developing a prescription OUD.(4) But despite this risk, and the overall prescription opioid…”
BackgroundInfluentialSelf-citation
- Authors
- Klimas, J., Gorfinkel, L., Fairbairn, N., Amato, L., Ahamad, K., Nolan, S., Simel, D. L., & Wood, E.
- Affiliations
- School of Medicine, University College Dublin, Health Sciences Centre, Belfield, Dublin, Ireland
- Columbia University (US)
- University of British Columbia (CA)
- Regione Lazio (IT)
- Duke University (US)
- Venue
- JAMA Network Open
- Publisher
- American Medical Association (AMA)
- Published
- 2019-05-03
- Volume
- 2
- Issue
- 5
- Pages
- e193365
- ISSN
- 2574-3805 (ISSN-L)
- PMC
- PMC6503484
- OpenAlex
- W2942730080
- Cited by
- 162
- References
- 38
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 21 · 2023: 20 · 2022: 33 · 2021: 33 · 2020: 17 · 2019: 8 · 2018: 1
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- JAMA Network Open (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Repository UCD (University College Dublin) (submittedVersion, cc-by-nc-nd)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (CIN 13–410)
- Bond University
- Michael Smith Health Research BC
- European Commission (701698)
- Canada Research Chairs (Tier1)
- University of British Columbia
- Canadian Institutes of Health Research (397968)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- prescription opioid use disorder, opioid addiction risk, pain management, opioid initiation, risk screening tool, risk factors, substance use disorders, mental health diagnoses, personality disorders, atypical antipsychotics, psychiatric medication, mood disorders, diagnostic accuracy, likelihood ratios
- MeSH terms
- Analgesics, Opioid, Female, Humans, Male, Opioid-Related Disorders, Practice Patterns, Physicians', Retrospective Studies, Risk Factors, Risk Assessment, Mood Disorders, Chronic Pain
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