Review
Effects of hydrocodone rescheduling on opioid use outcomes: A systematic review

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Abstract

Objective

To evaluate opioid prescribing, dispensing, and use in relation to hydrocodone-containing product (HCP) rescheduling.

Methods

Seven biomedical databases and grey literature sources were searched with keywords and database-specific controlled vocabulary relevant to HCP rescheduling for items published between January 2014 and July 2019. We included English-language quasi-experimental studies that assessed changes in HCP and other opioid prescribing, dispensing, utilization, and opioid-related health outcomes before and after HCP rescheduling. A data extraction sheet was created for this review. Two authors evaluated risk of bias for each included study. Two of 4 authors each independently extracted patient demographics and opioid-related outcomes from the included studies. Conflicts were resolved by a third author.

Results

All studies identified (n = 44) were quasi-experimental in design with 10 using an interrupted time series approach. A total of 24 studies reported a decrease in HCP prescribing by 3.1%-66.0%. Six studies reported a decrease in HCP days’ supply or doses by 14.0%-80.8%. There was increased prescribing of oxycodone-containing products by 4.5%-13.9% in 5 studies, tramadol by 2.7%-53.0% in 9 studies, codeine-containing products by 0.8%-1352.9% in 8 studies). Five studies reported a decrease in morphine equivalents by at least 10%, whereas 2 studies reported an increase in morphine equivalents. Differences in populations, sample sizes, and approaches did not allow for a meta-analysis. Details regarding approach and findings were limited in published conference abstracts (n = 16).

Conclusions

Hydrocodone rescheduling was associated with reductions in prescribing and use of HCPs but was also associated with increased prescribing and use of other opioids, both schedule II and nonschedule II.

Section snippets

Background

According to the Centers for Disease Control and Prevention (CDC), opioids contributed to 67.8% of the 70,237 overdose deaths observed in 2017, representing a 12% increase over the previous year.1 Numerous regulations have been enacted in an effort to mitigate opioid-related harms. On October 6, 2014, the Drug Enforcement Administration (DEA) put into effect a rule that rescheduled hydrocodone-containing product (HCPs) from schedule III to II.2, 3 For schedule II drugs, prescribing requirements

Objective

The primary aim of this systematic review was to evaluate the existing body of evidence related to prescribing, dispensing, use by the patient, and other opioid-related outcomes affected by HCP rescheduling.

Data sources and searches

This review followed the internationally accepted gold standard guidelines for systematic reviews as stated in the Cochrane Handbook for Systematic Reviews of Interventions.4

The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement was used for reporting this review. Institutional review board approval was not required. An initial search was performed on April 19, 2019 of 5 bibliographic databases and 2 gray literature sources. According to the Cochrane Handbook

Description of included studies

A total of 539 articles were screened for this review, and 44 studies comprising 28 published manuscripts and 16 published refereed conference abstracts met the inclusion criteria for data extraction (Figure 1).

When reported (n = 24), the size of the populations studied ranged from 300 people to 11.5 million people. A total of 83% of articles (n = 20) reported a study population of 1000 subjects or greater.10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 7, 8, 9 Of those

Discussion

On the basis of the findings of this systematic review of 44 quasi-experimental studies, the rescheduling of HCPs to schedule II in the United States led to an overall reduction in the use of these medications across all population sizes and as measured by a variety of metrics. Although this change is arguably one of the intended effects for the policy, the change in rescheduling also resulted in the potential unanticipated consequence of increasing the use of other opioids, specifically

Conclusion

The rescheduling of HCPs appears to have resulted in decreased HCP use in doses, days’ supply, and MMEs, across a variety of settings, data sources, population sizes, and locations. This decrease appears to be matched with an unanticipated increase in the prescribing, use, and days’ supply or doses of other opioids, such as oxycodone-containing products, codeine-containing products, and tramadol. Information on deaths, abuse, and other opioid exposures was limited in the included studies,

Silken A. Usmani, PharmD, Assistant Scientist, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL; and University of Florida Health Physicians, Gainesville, FL

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    Silken A. Usmani, PharmD, Assistant Scientist, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL; and University of Florida Health Physicians, Gainesville, FL

    Josef Hollmann, Pharmacy Intern, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL

    Amie Goodin, PhD, MPP, Assistant Professor, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL; and Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL

    Juan M. Hincapie-Castillo, PharmD, MS, PhD, Assistant Professor, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL; Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL; and Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL

    Lauren E. Adkins, MLIS, AHIP, Assistant University Librarian, University of Florida Health Science Center Libraries, Gainesville, FL

    Natalie Ourhaan, Pharmacy Student, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL

    Razanne Oueini, MSc, Pharmay Student, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL

    Hemita Bhagwandass, Pharmacy Student, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL

    Taylor Easey, BS, Pharmacy Student, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL

    Scott Martin Vouri, PharmD, PhD, Clinical Assistant Professor, Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL; Assistant Director of Pharmacy Services, University of Florida Health Physicians, Gainesville, FL; and Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL

    Disclosure: The authors declare no relevant conflicts of interest or financial relationships.

    Previous presentation: An abstract of this research was presented as a poster at the Addiction Health Services Research 2019 conference at Park City, Utah in October 17, 2019.

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