The impact of hydrocodone rescheduling on utilization, abuse, misuse, and overdose deaths

Abstract

Purpose: To evaluate the impact of increased federal restrictions on hydrocodone combination product (HCP) utilization, misuse, abuse, and overdose death.

Methods: We assessed utilization, misuse, abuse, and overdose death trends involving hydrocodone versus select opioid analgesics (OAs) and heroin using descriptive and interrupted time-series (ITS) analyses during the nine quarters before and after the October 2014 rescheduling of HCPs from a less restrictive (CIII) to more restrictive (CII) category.

Results: Hydrocodone dispensing declined >30% over the study period, and declines accelerated after rescheduling. ITS analyses showed that immediately postrescheduling, quarterly hydrocodone dispensing decreased by 177M dosage units while codeine, oxycodone, and morphine dispensing increased by 49M, 62M, and 4M dosage units, respectively. Postrescheduling, hydrocodone-involved misuse/abuse poison center (PC) case rates had a statistically significant immediate drop but a deceleration of preperiod declines. There were small level increases in codeine-involved PC misuse/abuse and overdose death rates immediately after HCP's rescheduling, but these were smaller than level decreases in rates for hydrocodone. Heroin-involved PC case rates and overdose death rates increased across the study period, with exponential increases in PC case rates beginning 2015.

Conclusions: HCP rescheduling was associated with accelerated declines in hydrocodone dispensing, only partially offset by smaller increases in codeine, oxycodone, and morphine dispensing. The net impact on hydrocodone and other OA-involved misuse/abuse and fatal overdose was unclear. We did not detect an immediate impact on heroin abuse or overdose death rates; however, the dynamic nature of the crisis and data limitations present challenges to causal inference.

Keywords: abuse; codeine; hydrocodone rescheduling; misuse; opioids; overdose deaths; utilization.

Figure 1.

Estimated Number of Prescriptions and Dosage Units Dispensed from U.S. Retail Pharmacies by Quarter for Hydrocodone and Select Opioid Analgesics Prior to and Following the Rescheduling of Hydrocodone Combination Products Abbreviations: ER/LA- extended-release/long-acting; IR- immediate-release; SE- single-entity. Source: IQVIA National Prescription Audit^™, 2012–2016. Data extracted November 2019. Period prior to rescheduling: July 1, 2012 through September 30, 2014. Period after rescheduling: October 1, 2014 through December 31, 2016. Quarterly trends and patterns are displayed for select formulations given that similar trends and patterns were observed between: (1) any oral solid hydrocodone products and any oral solid hydrocodone IR products (includes oral solid hydrocodone IR acetaminophen products and oral solid hydrocodone IR SE products) and oral solid hydrocodone IR SE products, (2) any oral solid codeine products and oral solid codeine acetaminophen products, (3) any oral solid oxycodone products and any oral solid oxycodone IR products (includes oral solid oxycodone IR acetaminophen products and oral solid oxycodone IR SE products) and oral solid oxycodone IR acetaminophen products, and (4) any oral solid morphine products and oral solid morphine ER/LA products. A: Number of oral solid prescriptions dispensed (in millions) by quarter. B: Number of oral solid dosage units dispensed (in millions) by quarter. C: Number of oral solid dosage units per prescription dispensed by quarter.

Figure 2.

Interrupted Time-Series Analyses of the Estimated Number of Hydrocodone and Codeine Prescriptions and Dosage Units Dispensed from U.S. Retail Pharmacies by Quarter Prior to and Following the Rescheduling of Hydrocodone Combination Products Source: IQVIA National Prescription Audit^™, 2012–2016. Data extracted November 2019. Period prior to rescheduling: July 1, 2012 through September 30, 2014. Period after rescheduling: October 1, 2014 through December 31, 2016. A: Number of any oral solid hydrocodone prescriptions dispensed (in millions) by quarter. B: Number of any oral solid hydrocodone dosage units dispensed (in millions) by quarter. C: Number of any oral solid hydrocodone dosage units per prescription dispensed by quarter. D: Number of any oral solid codeine prescriptions dispensed (in millions) by quarter. E: Number of any oral solid codeine dosage units dispensed (in millions) by quarter. F: Number of any oral solid codeine dosage units per prescription dispensed by quarter.

Figure 3.

Quarterly Abuse, Misuse/Abuse, and Overdose Death Rates Involving Hydrocodone Products, Select Opioid Analgesics, and Heroin Prior to and Following the Rescheduling of Hydrocodone Combination Products Abbreviations: ER/LA- extended release/long acting; IR- immediate-release; PC- poison center; SE- single-entity. Sources: Researched abuse, Diversion, and Addiction-related Surveillance System (RADARS^®) Treatment Center Program (TCP) surveys patients seeking treatment for opioid use disorder; America’s Poison Centers - National Poison Data System (NPDS); Drug- Involved Mortality (DIM): 2012–2016. RADARS^® TCP surveys patients seeking treatment for opioid use disorder. America’s Poison Centers - NPDS is a near real-time surveillance database that captures PC exposure information from callers. DIM data enriches the National Vital Statistics System, Mortality (NVSS-M) data with information on substances mentioned on death certificates as having been involved in deaths. Information regarding product formulation cannot be determined using DIM data. Period prior to rescheduling: July 1, 2012 through September 30, 2014. Period after rescheduling: October 1, 2014 through December 31, 2016. Quarterly trends and patterns are displayed for select formulations where applicable given that similar trends and patterns were observed between: (1) any hydrocodone products and any hydrocodone IR products (includes hydrocodone IR acetaminophen products and hydrocodone IR SE products) and hydrocodone IR SE products, (2) any codeine products and codeine acetaminophen products, (3) any oxycodone products and any oxycodone IR products (includes oxycodone IR acetaminophen products and oxycodone IR SE products) and oxycodone IR acetaminophen products, and (4) any morphine products and morphine ER products. A: RADARS^® TCP population adjusted abuse rates per 100,000 population by quarter. B: NPDS PC misuse/abuse case rates per 1,000,000 population by quarter. C: DIM overdose death rates per 1,000,000 population by quarter.

Figure 4.

Interrupted Time-Series Analyses of Quarterly Abuse, Misuse/Abuse, and/or Overdose Death Rates Involving Hydrocodone and Codeine Products Prior to and Following the Rescheduling of Hydrocodone Combination Products Abbreviations: PC- poison center. Sources: Researched Abuse, Diversion, and Addiction-related Surveillance System (RADARS^®) Treatment Center Program (TCP) surveys patients seeking treatment for opioid use disorder; America’s Poison Centers-National Poison Data System (NPDS); Drug-Involved Mortality (DIM): 2012–2016. RADARS^® TCP surveys patients seeking treatment for opioid use disorder. America’s Poison Centers - NPDS is a near real-time surveillance database that captures PC exposure information from callers. DIM data enriches the National Vital Statistics System, Mortality (NVSS-M) data with information on substances mentioned on death certificates as having been involved in deaths. Period prior to rescheduling: July 1, 2012 through September 30, 2014. Period after rescheduling: October 1, 2014 through December 31, 2016. Note: Trend After Rescheduling = Trend Before Rescheduling + Trend Change. An estimate >0 indicates an increasing trend, while <0 indicates a decreasing trend. A: RADARS^® TCP population adjusted any hydrocodone abuse rates per 100,000 population by quarter. B: NPDS PC any hydrocodone misuse/abuse case rates per 1,000,000 population by quarter. C: DIM any hydrocodone overdose death rates per 1,000,000 population by quarter. D: NPDS PC any codeine misuse/abuse case rates per 1,000,000 population by quarter. E: DIM any codeine overdose death rates per 1,000,000 population by quarter.