Results
Ninety-three patients received naloxone in the VASDHCS ED. Thirty-five met inclusion criteria and were included in the primary analysis. All subjects received IV naloxone with a mean 0.8 mg IV boluses (range, 0.1-4.4 mg).
Most patients were male with a mean age of 59.8 years (Table 1). Almost all overdoses were nonintentional except for 3 suicide attempts that were reviewed by the Suicide Prevention Committee. Three patients had previously been treated for opioid overdose at the VA with a documented positive clinical response to naloxone administration.
At the time of overdose, 29 patients (82.9%) had an active opioid prescription. Of these, the majority were issued through the VA with a mean 117 mg morphine equivalent daily dose (MEDD). Interestingly, only 24 of the 28 patients with a UDS collected at time of overdose tested positive for opioids, which may be attributable to the use of synthetic opioids, which are not reliably detected by traditional UDS. Concomitant BZD use was involved in 13 of the 35 index overdoses (37.1%), although only 6 patients (17.1%) had an active BZD prescription at time of overdose. Seven patients (20.0%) were prescribed medication-assisted treatment (MAT) for opioid use disorder (OUD), with all 7 using methadone. According to VA records, only 1 patient had previously been dispensed a naloxone kit at any point prior to overdosing. Mental health and SUD diagnoses frequently co-occurred, with 20 patients (57.1%) having at least 1 mental health condition and at least 1 SUD.
Rates of follow-up varied by clinician type in the 6 months after NFO (Figure). Of those with mental health disorders, 15 patients (45.5%) received mental health services before and after overdose, while 8 (40.0%) and 10 (50.0%) of those with SUDs received addiction treatment services before and after overdose, respectively. Seven patients presented to the psychiatric emergency clinic within 6 months prior to overdose and 5 patients within the 6 months following overdose.
Of patients with VA opioid prescriptions, within 2 years of NFO, 9 (42.9%) had their opioids discontinued, and 18 (85.7%) had MEDD reductions ranging from 10 mg to 150 mg (12.5-71.4% reduction) with a mean of 63 mg. Two of the 4 patients with active BZD prescriptions at the time of the overdose event had their prescriptions continued. Seven patients (20.0%) were dispensed naloxone kits following overdose (Table 2).
Rates of ORAEs ranged from 0% to 17% with no documented overdose fatalities. Examples of AEs observed in this study included ED visits or hospitalizations involving opioid withdrawal, opioid-related personality changes, and opioid overdose. Five patients died during the study period, yielding an all-cause mortality rate of 14.3% with a mean time to death of 10.8 months. The causes of death were largely unknown except for 1 patient, whose death was reportedly investigated as an accidental medication overdose without additional information.
Repeat overdose verified by hospital records occurred in 4 patients (11.4%) within 2 years. Patients who experienced a subsequent overdose were prescribed higher doses of opioids with a mean MEDD among VA prescriptions of 130 mg vs 114 mg for those without repeat overdose. In this group, 3 patients (75.0%) also had concomitant BZD use, which was proportionally higher than the 10 patients (32.3%) without a subsequent overdose. Of note, 2 of the 4 patients with a repeat overdose had their opioid doses increased above the MEDD prescribed at the time of index overdose. None of the 4 subjects who experienced a repeat overdose were initiated on MAT within 2 years according to VA records.
Discussions
This retrospective study is representative of many veterans receiving VA care, despite the small sample size. Clinical characteristics observed in the study population were generally consistent with those published by Clement and Stock, including high rates of medical and psychiatric comorbidities.12 Subjects in both studies were prescribed comparable dosages of opioids; among those prescribed opioids but not BZDs through the VA, the mean MEDD was 117 mg in our study compared with 126 mg in the Clement and Stock study. Since implementation of the Opioid Safety Initiative (OSI) in 2013, opioid prescribing practices have improved nationwide across VA facilities, including successful reduction in the numbers of patients prescribed high-dose opioids and concurrent BZDs.13
Despite the tools and resources available to clinicians, discontinuing opioid therapy remains a difficult process. Concerns related to mental health and/or substance-use related decompensations often exist in the setting of rapid dose reductions or abrupt discontinuation of opioids.6 Although less than half of patients in the present study with an active opioid prescription at time of index overdose had their opioids discontinued within 2 years, it is reassuring to note the much higher rate of those with subsequent decreases in their prescribed doses, as well as the 50% reduction in BZD coprescribing. Ultimately, these findings remain consistent with the VA goals of mitigating harm, improving opioid prescribing, and ensuring the safe use of opioid medications when clinically appropriate.
Moreover, recent evidence suggests that interventions focused solely on opioid prescribing practices are becoming increasingly limited in their impact on reducing opioid-related deaths and will likely be insufficient for addressing the opioid epidemic as it continues to evolve. According to Chen and colleagues, opioid overdose deaths are projected to increase over the next several years, while further reduction in the incidence of prescription opioid misuse is estimated to decrease overdose deaths by only 3% to 5.3%. In the context of recent surges in synthetic opioid use, it is projected that 80% of overdose deaths between 2016 and 2025 will be attributable to illicit opioids.3 Such predictions underscore the urgent need to adopt alternative approaches to risk-reducing measures and policy change.
The increased risk of mortality associated with opioid misuse and overdose is well established in the current literature. However, less is known regarding the rate of ORAEs after survival of an NFO. Olfson and colleagues sought to address this knowledge gap by characterizing mortality risks in 76,325 US adults within 1 year following NFO.14 Among their studied population, all-cause mortality occurred at a rate of 778.3 per 10,000 person-years, which was 24 times greater than that of the general population. This emphasizes the need for the optimization of mental health services, addiction treatment, and medical care for these individuals at higher risk.