Table 5:

Evidence for and against effective opioid abuse deterrence from use of available abuse deterrent formulations (ADFs). Drug liking is scaled from 0 to 100. Doctor shopping is defined as the practice of engaging multiple prescribers and/or pharmacies to obtain excess drugs that can be diverted for non-medical use. Diversion is defined as any intentional act that results in transferring a prescription medication from lawful to unlawful distribution or possession.

Outcome	Findings
Overall Drug Liking	8 RCT found significantly lower levels of oral abuse potentials such as drug liking for intact or crushed ADF-opioids vs. non-ADF opioids. (Xtampza ER intact (68.8) vs. xtampza ER crushed (73.4) vs. oxycodone IR crushed (81.8); Troxyca ER intact (59.3) vs. Troxyca ER crushed (74.5) vs. oxycodone IR crushed (89.8); Targiniq ER intact (54.7) vs. Targiniq ER crushed (54.6), vs. oxycodone IR solution (77.9); Hysingla ER intact (63.3) vs. Hysingla ER crushed (69) vs. hydrocodone IR crushed (94), Vantrela ER intact (53.9) vs. Vantrela ER crushed (66.9) vs. Hydrocodone IR (85.2); Embeda crushed (65.2) vs. Morphine ER crushed (80.8); Embeda intact (67.6) vs. Embeda crushed (68.1) vs. Morphine ER crushed (89.5); Arymo ER intact (62) vs. Arymo ER crushed (67) vs. Morphine ER crushed (74)) [1–8] 7 RCT found significantly less likely to re-take for intact or crushed ADF-opioids vs. non-ADF opioids of the same class. (Xtampza ER intact (70.2) vs. xtampza ER crushed (73.7) vs. oxycodone IR crushed (76.2); Troxyca ER intact (48.7) vs. Troxyca ER crushed (72.5) vs. oxycodone IR crushed (81.5); Targiniq ER intact (38.5) vs. Targiniq ER crushed (32.6), vs. oxycodone IR solution (61.4); Hysingla ER intact (32.6) vs. Hysingla ER crushed (43) vs. hydrocodone IR solution (86.7), Vantrela ER intact (46.4) vs. Vantrela ER crushed (58.7) vs. Hydrocodone IR (75.2); Embeda crushed (57.7) vs. Morphine ER crushed (70.7); Arymo ER intact (56) vs. Arymo ER crushed (61.5) vs. Morphine ER crushed (67.5)) [1–8]
	7 RCT found significantly lower levels of oral abuse potentials such as drug liking for intact or crushed ADF-opioids vs. non-ADF opioids. (Troxyca ER (60.5) vs. oxycodone IR (92.8); Targiniq ER (59.1) vs. oxycodone IR (94.8); Hysingla ER (66.8) vs. Hydrocodone (90.4); Vantrela ER (72.8) vs. Hydrocodone (90.4); Embeda (69.6) vs. Morphine ER (87.6); Morphabond ER (71.1) vs. Morphine ER (84.8); Arymo ER (52.5) vs. Morphine ER (77.5)) [9–17] 8 RCT found significantly less likely to re-take for intact or crushed ADF-opioids vs. non-ADF opioids of the same class. (Oxycontin crushed (64) vs. original Oxycontin crushed (89.6) vs. Oxycodone IR powder (86.6); Xtampza ER (47.8) vs. oxycodone IR (71.3); Troxyca ER (58.9) vs. oxycodone IR (88.4); Targiniq ER (42.6) vs. oxycodone IR (93.6); Hysingla ER (34.6) vs. Hydrocodone (83.9); Embeda (60.6) vs. Morphine ER (84.9); Arymo ER (50) vs. Morphine ER (73)) [9–17]
Tampering	1 prospective cohort study found less tampering potential with the reformatted Oxycontin compared to original Oxycontin. (easy to cut-up: 21% vs. 79%, p<0.05; easy to dissolve (14% vs. 74%, p<0.01; unpleasant to tamper and inject: 5% vs. 50%, p<0.01) [18]
Real World Evidence of Abuse	16 studies found reduced rate of abusing reformulated OxyContin (−38%, −75%, −55%, −42%, −30%, −37%, −41%, −22%, −48%, −28%, −28%, −36%, −35%, −55%, −12%, −57%). 13 studies found overall increased rate of abusing other prescription opioids (oxymorphone ER: +38%, +246%, +191%, +236%; morphine ER: +44%, non-significant in three other studies; oxycodone IR: +20%, +36%, +23%, all other opioids: −33%, −7%, +16%, +5%, −3%, non-significant in one other study). 4 studies found increased rate of abusing heroin (+100%, +78%, −11%, +42%). [19–30]
	3 studies found reduced non-oral reformulated Oxycontin abuse rate (snort: −28%, −51%; inject: −20%, −22%; smoke: −2%, −10%) but mixed effect in oral reformulated Oxycontin abuse rate (−71%, +21%, +26%). 2 studies found different abuse patterns with other opioid products. No change in route of administration was noted with ER morphine. ER oxymorphone showed significantly increased snorting (+7%) and injection (+7%) and significantly decreased oral route abuse (−8%). [20, 23, 25]
Overdose and Fatality	5 studies suggested a decline in overdose rate (−34%, −20%, −85%, −87%), 2-year overdose fatality rate (−56%, −65%), and 3-year overdose fatality rate (−85%, −87%) after OxyContin reformulation. However, heroin overdose rate and overdose fatality increased (23% and 310% respectively), while other opioids (morphine ER, oxymorphone ER, oxycodone IR, hydromorphone IR, ilicit drugs) showed no statistically significant changes in overdose and overdose fatality rate. [21, 31, 32, 33, 34]
Doctor shopping	2 studies reported a 50% reduction in doctor-shopping after OxyContin reformulation, but an increase in doctor-shopping for oxycodone IR (5%), hydromorphone IR (25), and oxymorphone ER (66%). [35, 36]
Diversion rate	3 studies suggested a decrease in population adjusted change in diversion (−53%, −89%, −66%, all statistically significant), sale (−24%), and dispensing rate (−39%) of OxyContin after OxyContin reformulation. During the same study periods, other opioids had inconsistent change in diversion rates (−6%, −27%, +6%, all not statistically significant), but increased sales (11%). [19, 20, 21]
Conclusion: Overall, despite a decrease in abuse potential for all abuse deterrent formulations, there is only mixed real-world evidence to suggest that ADFs reduce overall abuse and overdose fatality. Thus, there is not sufficient evidence to conclusively determine the superiority of their health benefit.