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Association of Dose Tapering With Overdose or Mental Health Crisis Among Patients Prescribed Long-term Opioids

Educational Objective
To learn about adverse health outcomes associated with opioid dose tapering.
1 Credit CME
Key Points

Question  In patients prescribed stable, long-term, high-dose opioid therapy, is dose tapering associated with an increased risk of overdose or mental health crisis?

Findings  In this retrospective cohort study that included 113 618 patients prescribed stable, high-dose opioid therapy, patients in periods following dose tapering, compared with patients before or without tapering, had an adjusted incidence rate ratio of 1.68 for overdose and 2.28 for mental health crisis; both risks were statistically significant.

Meaning  Opioid dose tapering was associated with increased risk for overdose and mental health crisis, but interpretation of these findings is limited by the study design.

Abstract

Importance  Opioid-related mortality and national prescribing guidelines have led to tapering of doses among patients prescribed long-term opioid therapy for chronic pain. There is limited information about risks related to tapering, including overdose and mental health crisis.

Objective  To assess whether there are associations between opioid dose tapering and rates of overdose and mental health crisis among patients prescribed stable, long-term, higher-dose opioids.

Design, Setting, and Participants  Retrospective cohort study using deidentified medical and pharmacy claims and enrollment data from the OptumLabs Data Warehouse from 2008 to 2019. Adults in the US prescribed stable higher doses (mean ≥50 morphine milligram equivalents/d) of opioids for a 12-month baseline period with at least 2 months of follow-up were eligible for inclusion.

Exposures  Opioid tapering, defined as at least 15% relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period. Maximum monthly dose reduction velocity was computed during the same period.

Main Outcomes and Measures  Emergency or hospital encounters for (1) drug overdose or withdrawal and (2) mental health crisis (depression, anxiety, suicide attempt) during up to 12 months of follow-up. Discrete time negative binomial regression models estimated adjusted incidence rate ratios (aIRRs) of outcomes as a function of tapering (vs no tapering) and dose reduction velocity.

Results  The final cohort included 113 618 patients after 203 920 stable baseline periods. Among the patients who underwent dose tapering, 54.3% were women (vs 53.2% among those who did not undergo dose tapering), the mean age was 57.7 years (vs 58.3 years), and 38.8% were commercially insured (vs 41.9%). Posttapering patient periods were associated with an adjusted incidence rate of 9.3 overdose events per 100 person-years compared with 5.5 events per 100 person-years in nontapered periods (adjusted incidence rate difference, 3.8 per 100 person-years [95% CI, 3.0-4.6]; aIRR, 1.68 [95% CI, 1.53-1.85]). Tapering was associated with an adjusted incidence rate of 7.6 mental health crisis events per 100 person-years compared with 3.3 events per 100 person-years among nontapered periods (adjusted incidence rate difference, 4.3 per 100 person-years [95% CI, 3.2-5.3]; aIRR, 2.28 [95% CI, 1.96-2.65]). Increasing maximum monthly dose reduction velocity by 10% was associated with an aIRR of 1.09 for overdose (95% CI, 1.07-1.11) and of 1.18 for mental health crisis (95% CI, 1.14-1.21).

Conclusions and Relevance  Among patients prescribed stable, long-term, higher-dose opioid therapy, tapering events were significantly associated with increased risk of overdose and mental health crisis. Although these findings raise questions about potential harms of tapering, interpretation is limited by the observational study design.

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Article Information

Corresponding Author: Alicia Agnoli, MD, MPH, MHS, Department of Family and Community Medicine, University of California, Davis, 4860 Y St, Ste 2300, Sacramento, CA 95817 (aagnoli@ucdavis.edu).

Accepted for Publication: June 21, 2021.

Author Contributions: Drs Agnoli and Fenton had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Agnoli, Magnan, Jerant, Fenton.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Agnoli, Jerant, Fenton.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Xing, Tancredi, Magnan, Fenton.

Obtained funding: Agnoli, Fenton.

Administrative, technical, or material support: Agnoli, Magnan, Jerant.

Supervision: Agnoli, Magnan, Jerant, Fenton.

Conflict of Interest Disclosures: Dr Agnoli reported receiving grants from the University of California Davis School of Medicine Dean's Office (scholar in women's health research; BIRCWH/K12) during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was supported by a University of California–OptumLabs Research Credit and the Department of Family and Community Medicine, University of California, Davis. Dr Agnoli was supported by the University of California, Davis School of Medicine Dean’s Office (Dean’s Scholarship in Women’s Health Research).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Rudd  RA , Seth  P , David  F , Scholl  L .  Increases in drug and opioid-involved overdose deaths—United States, 2010-2015.   MMWR Morb Mortal Wkly Rep. 2016;65(50-51):1445-1452. doi:10.15585/mmwr.mm655051e1PubMedGoogle Scholar
2.
Jeffery  MM , Hooten  WM , Henk  HJ ,  et al.  Trends in opioid use in commercially insured and Medicare Advantage populations in 2007-16: retrospective cohort study.   BMJ. 2018;362:k2833. doi:10.1136/bmj.k2833PubMedGoogle Scholar
3.
Chou  R , Turner  JA , Devine  EB ,  et al.  The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop.   Ann Intern Med. 2015;162(4):276-286. doi:10.7326/M14-2559PubMedGoogle ScholarCrossref
4.
Dowell  D , Haegerich  TM , Chou  R .  CDC guideline for prescribing opioids for chronic pain—United States, 2016.   JAMA. 2016;315(15):1624-1645. doi:10.1001/jama.2016.1464PubMedGoogle ScholarCrossref
5.
Fenton  JJ , Agnoli  AL , Xing  G ,  et al.  Trends and rapidity of dose tapering among patients prescribed long-term opioid therapy, 2008-2017.   JAMA Netw Open. 2019;2(11):e1916271. doi:10.1001/jamanetworkopen.2019.16271PubMedGoogle Scholar
6.
Bohnert  ASB , Guy  GPJ  Jr , Losby  JL .  Opioid prescribing in the United States before and after the Centers for Disease Control and Prevention’s 2016 opioid guideline.   Ann Intern Med. 2018;169(6):367-375. doi:10.7326/M18-1243PubMedGoogle ScholarCrossref
7.
Wilson  N , Kariisa  M , Seth  P , Smith  H  IV , Davis  NL .  Drug and opioid-involved overdose deaths—United States, 2017-2018.   MMWR Morb Mortal Wkly Rep. 2020;69(11):290-297. doi:10.15585/mmwr.mm6911a4PubMedGoogle ScholarCrossref
8.
FDA identifies harm reported from sudden discontinuation of opioid pain medicines and requires label changes to guide prescribers on gradual, individualized tapering. US Food and Drug Administration. Published April 12, 2019. Accessed July 6, 2021. https://www.fda.gov/drugs/drug-safety-and-availability/fda-identifies-harm-reported-sudden-discontinuation-opioid-pain-medicines-and-requires-label-changes
9.
HHS guide for clinicians on the appropriate dosage reduction or discontinuation of long-term opioid analgesics. US Dept of Health and Human Services. Published October 2019. Accessed November 1, 2019. https://www.hhs.gov/opioids/sites/default/files/2019-10/Dosage_Reduction_Discontinuation.pdf
10.
Sullivan  MD , Turner  JA , DiLodovico  C , D’Appollonio  A , Stephens  K , Chan  YF .  Prescription opioid taper support for outpatients with chronic pain: a randomized controlled trial.   J Pain. 2017;18(3):308-318. doi:10.1016/j.jpain.2016.11.003PubMedGoogle ScholarCrossref
11.
Oliva  EM , Bowe  T , Manhapra  A ,  et al.  Associations between stopping prescriptions for opioids, length of opioid treatment, and overdose or suicide deaths in US veterans: observational evaluation.   BMJ. 2020;368:m283. doi:10.1136/bmj.m283PubMedGoogle Scholar
12.
Binswanger  IA , Glanz  JM , Faul  M ,  et al.  The association between opioid discontinuation and heroin use: a nested case-control study.   Drug Alcohol Depend. 2020;217:108248. doi:10.1016/j.drugalcdep.2020.108248PubMedGoogle Scholar
13.
Mark  TL , Parish  W .  Opioid medication discontinuation and risk of adverse opioid-related health care events.   J Subst Abuse Treat. 2019;103:58-63. doi:10.1016/j.jsat.2019.05.001PubMedGoogle ScholarCrossref
14.
James  JR , Scott  JM , Klein  JW ,  et al.  Mortality after discontinuation of primary care-based chronic opioid therapy for pain: a retrospective cohort study.   J Gen Intern Med. 2019;34(12):2749-2755. doi:10.1007/s11606-019-05301-2PubMedGoogle ScholarCrossref
15.
Pitt  AL , Humphreys  K , Brandeau  ML .  Modeling health benefits and harms of public policy responses to the US opioid epidemic.   Am J Public Health. 2018;108(10):1394-1400. doi:10.2105/AJPH.2018.304590PubMedGoogle ScholarCrossref
16.
Fenton  JJ , Magnan  EM , Agnoli  AL , Henry  SG , Xing  G , Tancredi  DJ .  Longitudinal dose trajectory among patients tapering long-term opioids.   Pain Med. Published online March 19, 2021. doi:10.1093/pm/pnaa470PubMedGoogle Scholar
17.
Vivolo-Kantor  A , Pasalic  E , Liu  S , Martinez  PD , Gladden  RM ; Overdose Morbidity Team.  Defining indicators for drug overdose emergency department visits and hospitalisations in ICD-10-CM coded discharge data.   Inj Prev. 2021;27(S1):i56-i61. doi:10.1136/injuryprev-2019-043521PubMedGoogle Scholar
18.
Green  CA , Perrin  NA , Janoff  SL , Campbell  CI , Chilcoat  HD , Coplan  PM .  Assessing the accuracy of opioid overdose and poisoning codes in diagnostic information from electronic health records, claims data, and death records.   Pharmacoepidemiol Drug Saf. 2017;26(5):509-517. doi:10.1002/pds.4157PubMedGoogle ScholarCrossref
19.
Slavova  S , Quesinberry  D , Costich  JF ,  et al.  ICD-10-CM-based definitions for emergency department opioid poisoning surveillance: electronic health record case confirmation study.   Public Health Rep. 2020;135(2):262-269. doi:10.1177/0033354920904087PubMedGoogle ScholarCrossref
20.
Fiest  KM , Jette  N , Quan  H ,  et al.  Systematic review and assessment of validated case definitions for depression in administrative data.   BMC Psychiatry. 2014;14:289. doi:10.1186/s12888-014-0289-5PubMedGoogle ScholarCrossref
21.
Swain  RS , Taylor  LG , Braver  ER , Liu  W , Pinheiro  SP , Mosholder  AD .  A systematic review of validated suicide outcome classification in observational studies.   Int J Epidemiol. 2019;48(5):1636-1649. doi:10.1093/ije/dyz038PubMedGoogle ScholarCrossref
22.
US Department of Agriculture.  Documentation: 2010 Rural-Urban Commuting Area (RUCA) Codes. Economic Research Service; 2016.
23.
Chronic conditions data warehouse: condition categories. Centers for Medicare & Medicaid Services; 2019. Accessed January 28, 2019. https://www.ccwdata.org/web/guest/condition-categories
24.
Moore  BJ , White  S , Washington  R , Coenen  N , Elixhauser  A .  Identifying increased risk of readmission and in-hospital mortality using hospital administrative data: the AHRQ Elixhauser comorbidity index.   Med Care. 2017;55(7):698-705. doi:10.1097/MLR.0000000000000735PubMedGoogle ScholarCrossref
25.
Henry  SG , Paterniti  DA , Feng  B ,  et al.  Patients’ experience with opioid tapering: a conceptual model with recommendations for clinicians.   J Pain. 2019;20(2):181-191. doi:10.1016/j.jpain.2018.09.001PubMedGoogle ScholarCrossref
26.
Frank  JW , Levy  C , Matlock  DD ,  et al.  Patients’ perspectives on tapering of chronic opioid therapy: a qualitative study.   Pain Med. 2016;17(10):1838-1847. doi:10.1093/pm/pnw078PubMedGoogle ScholarCrossref
27.
Morgan  MM , Christie  MJ .  Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human.   Br J Pharmacol. 2011;164(4):1322-1334. doi:10.1111/j.1476-5381.2011.01335.xPubMedGoogle ScholarCrossref
28.
Dowell  D , Haegerich  T , Chou  R .  No shortcuts to safer opioid prescribing.   N Engl J Med. 2019;380(24):2285-2287. doi:10.1056/NEJMp1904190PubMedGoogle ScholarCrossref
29.
Kertesz  SG , Manhapra  A .  The drive to taper opioids: mind the evidence, and the ethics.   Spinal Cord Ser Cases. 2018;4:64. doi:10.1038/s41394-018-0092-5PubMedGoogle ScholarCrossref
30.
Manhapra  A , Arias  AJ , Ballantyne  JC .  The conundrum of opioid tapering in long-term opioid therapy for chronic pain: A commentary.   Subst Abus. 2018;39(2):152-161. doi:10.1080/08897077.2017.1381663PubMedGoogle ScholarCrossref
31.
Lovejoy  TI , Morasco  BJ , Demidenko  MI , Meath  THA , Frank  JW , Dobscha  SK .  Reasons for discontinuation of long-term opioid therapy in patients with and without substance use disorders.   Pain. 2017;158(3):526-534. doi:10.1097/j.pain.0000000000000796PubMedGoogle ScholarCrossref
32.
Frank  JW , Lovejoy  TI , Becker  WC ,  et al.  Patient outcomes in dose reduction or discontinuation of long-term opioid therapy: a systematic review.   Ann Intern Med. 2017;167(3):181-191. doi:10.7326/M17-0598PubMedGoogle ScholarCrossref
33.
Demidenko  MI , Dobscha  SK , Morasco  BJ , Meath  THA , Ilgen  MA , Lovejoy  TI .  Suicidal ideation and suicidal self-directed violence following clinician-initiated prescription opioid discontinuation among long-term opioid users.   Gen Hosp Psychiatry. 2017;47:29-35. doi:10.1016/j.genhosppsych.2017.04.011PubMedGoogle ScholarCrossref
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