Introduction

The United States is experiencing an ongoing nationwide opioid epidemic which has been exacerbated by the COVID-19 pandemic. Several abrupt social changes, dictated by the pandemic, along with the increased introduction of synthetic opioids (e.g., fentanyl) into the domestic illicit drug supply, have resulted in a dramatic increase in opioid overdoses and overdose deaths since 20191. Per the CDC, the rate of drug overdose deaths has increased by 279% over a 5-year span for drug overdoses involving fentanyl; specifically, the rate increased from 5.7 per 100,000 standard population in 2016 to 21.6 per 100,000 in 20212. Further, the impact of synthetic opioids, which may be 50 times more potent than heroin3, are not limited to persons who misuse opioids. Fentanyl, inexpensive to produce, has permeated and contaminated the illicit domestic drug supply, resulting in accidental use, overdose, and death, by persons with no intent to use fentanyl or opioids4. Although illicit fentanyl use is not equivalent to opioid use disorder (OUD), many patients with OUD are using illicit fentanyl, which significantly increases their overdose risk and even death5,6.

Studies have also shown that numerous people with substance use disorders have concurrent psychiatric disorders7,8. Studies showed that, in the outpatient setting, patients with mood and anxiety disorders, rather than attention disorders and post-traumatic stress disorders, are more likely to be prescribed opioids which results in a greater likelihood of developing OUD7,9. In contrast, patients with psychotic disorders are markedly less likely to be prescribed opioids7,9. Other studies reported that patients with psychiatric disorders may use opioids to self-medicate for their disease which can increase the risk for developing OUD10,11. One study indicated that mood disorders were the most common psychiatric disorder in patients with OUD12, and those with mood disorders showed a high rate of self-medication using nonmedical opioids13. Furthermore, the number of psychiatric disorders a patient is diagnosed with largely increases the presence of concurrent OUD14. For example, patients diagnosed with 3 or 4 psychiatric disorders exhibit a 9-fold increase in developing OUD14. Although the relationship of OUD and psychiatric disorders has been investigated, studies on illicit fentanyl use and psychiatric disorders are limited, especially in Emergency Department (ED) patients. Illicit fentanyl use has been a major reason for historically high records of opioid-related overdose; thus, it is important to understand their relationship15.

The Emergency Department represents a unique medical setting which has been particularly impacted by the opioid epidemic. The number of opioid-related ED visits have increased, despite the pandemic, even when general ED patient volumes decreased16,17. Further, the proportion of ED visits for mental health complaints has also been on the rise18. As ED clinicians are increasingly tasked with the acute management of psychiatric illness as well as patients with opioid exposure or misuse, understanding how these patient presentations and pathology might overlap is increasingly important. To our knowledge, there are no prior studies which specifically consider illicit fentanyl use and its association with psychiatric disorders and other patient characteristics in the ED. This study seeks to better understand the attributes of ED patients with co-occurring illicit fentanyl use and psychiatric disorders, as well as the associated impact on healthcare recidivism and utilization in the Southeastern region.

Methods

This was a retrospective, cross-sectional review that received full approval by the Institutional Review Board at the University of Alabama at Birmingham (UAB) (IRB-300002304) on 4/30/2022. All methods were performed in accordance with relevant guidelines and regulations. Due to the retrospective nature of the study using electronic medical records (EMR), the IRB at the UAB waived the need of obtaining informed consent. Patients presenting to the ED at UAB Hospital with a urine drug screen positive for illicit fentanyl from June 1, 2021 until November 31, 2021 were identified from the EMR and included in the analysis. The use of other illicit substances, identified in the urine drug screen results, was obtained as well. The Fentanyl Enzyme Immunoassay in urine drug screening is a qualitative assay that screens for the presence of norfentanyl, the major metabolite of fentanyl, in human urine. Samples that contain greater than 5 ng/mL of norfentanyl are reported as positive for fentanyl at UAB ED. Samples that are below the 5 ng/mL cutoff are reported as negative. Ordering for urine drug screens was at clinicians’ own discretion if it contributed to medical decision making and/or differential diagnosis at UAB ED. Trauma patients were excluded because they may have been exposed to fentanyl in the pre-hospital setting per Emergency Medical Service pain control protocols. Patients with prescribed fentanyl (either while in the ED or as an outpatient) were also excluded during the study period. Both EMR and the prescription drug monitoring program were used to identify patients with prescribed fentanyl in the outpatient setting.

Demographic characteristics, including sex, age, race/ethnicity, and registration-verified insurance status were also obtained from the EMR. Additional characteristics from the EMR included initial visit disposition, discharge (from ED or hospital) with buprenorphine and/or naloxone, and repeat ED or hospital admission within 30 days and six months after the initial visit. We queried provider documentation in the patient’s problem list and past medical history. The problem list in the EMR allowed documentation of all pre-existing medical and psychiatric diagnoses, such as non-substance-induced psychiatric disorders, which are electronically linked to International Classification of Diseases-10 codes, including F01.xx-F99.xx. Nasal spray naloxone prescription or kit provision in the ED and buprenorphine prescriptions among ED patients during the study period were also considered. Descriptive statistical and Chi-square analyses were performed using SPSS version 27 (IBM).

Results

Patient characteristics

During the study period, a total of 2,158 patients tested positive for illicit fentanyl by urine drug screen when they presented to the ED. Among them, 408 unique patients were identified with 67.2% white, 30.1% Black, 63.5% men (Table 1). A majority of patients (67.4%) were between 25 and 44 years of age: 25–34 years (32.1%) and 35–44 years (35.3%) (Table 1). Approximately half of patients were insured. Public insurance was the most prevalent (33.5%) followed by commercial insurance (16.7%). 49.8% of patients were uninsured (Table 1).

Table 1 Patients’ characteristics (N = 408).
Full size table

Co-occurring psychiatric disorders and concurrent substance use disorders

Approximately 36.0% of patients had co-occurring psychiatric disorders with mood disorders as the most prevalent (47.6%) followed by psychotic disorders (19.1%) and anxiety disorders (8.8%) (Table 2). Approximately 21.8% of patients had more than one psychiatric disorder (Table 2).

Table 2 Co-occurring psychiatric disorders (N = 408).
Full size table

Compared to patients without co-occurring psychiatric disorders, patients with concurrent psychiatric disorders had significantly higher rates of marijuana use (53.8% vs. 38.0%, p < 0.05) (Table 3). The concurrent use of other substances, including heroin and self-reported nonmedical opioid use, cocaine, and methamphetamine, did not differ between the two groups (Table 3). Additionally, more patients with psychiatric disorders were using polysubstance (≥ 3) than patients without psychiatric disorders, but not significantly so (51.0% vs. 41.1%, p = 0.06) (Table 3).

Table 3 Comparisons between patients with and without psychiatric disorders.
Full size table

Healthcare utilization

When comparing healthcare utilization between patients with and without psychiatric disorders, patients with psychiatric disorders had a higher rate of repeat ED visit and/or hospital admission at six months (57.2% vs. 43.0%, p < 0.05), but not within 30 days after ED discharge (Table 3). Additionally, a higher rate of patients with concurrent psychiatric disorders were admitted to psychiatry inpatient settings during the study period (p = 0.002). Rates of naloxone provision (8.3% vs. 16.3%, p < 0.05), but not buprenorphine prescribing, at discharge were different between the two groups (Table 3).

Discussion

In this study, a substantial proportion of ED patients using illicit fentanyl were found to have co-occurring psychiatric disorders. They had higher rates of lack of naloxone provision at ED discharge, concurrent other substance use, and inpatient admission. They also had higher rates of repeat ED use and hospital admission at six months after initial ED visit, indicative of a lower proportion seeking and retaining definitive treatment after discharge. Lower provision of naloxone to patients with psychiatric disorders could be due to the idea that patients with psychiatric disorders may not present to the ED even though they have overdose risks, so naloxone is not prescribed. Additionally, some patients with a documented diagnosis of OUD and psychiatric disorders may not actively need naloxone, if they are in successful recovery for example, thereby contributing to the low naloxone prescription. Other barriers reported by other health systems include time, stigma or lack of knowledge surrounding naloxone, medication cost for patients and the hospital, and administrative logistics when attempting to prescribe naloxone to patients19,20. Our findings indicate that patients with co-occurring illicit fentanyl use and psychiatric disorders represent a highly disadvantaged group as the majority are uninsured, at increased risk for adverse outcomes, and facing challenging barriers to treatment6.

Although patients with concurrent OUD and psychiatric disorders may represent a challenging population, studies reported that patients with OUD and at least one psychiatric disorder had higher retention rate in an integrated, interdisciplinary model21. Furthermore, receiving treatment, including antidepressants, is also associated with higher odds of retention in addiction care, including buprenorphine treatment22,23. However, one study showed that addiction treatment facility might be a barrier for continuing buprenorphine treatment24. Another study identified several risk factors for discontinuing buprenorphine, including low initial buprenorphine dosage (i.e., ≤4 mg), male sex, comorbid substance use disorders, opioid overdose history, and inpatient care25. Thus, findings from our study and these studies indicate that more strategic and supportive treatment options should be available to engage this disadvantaged and vulnerable patient population. The critical importance of screening for and treating psychiatric disorders concomitantly with illicit fentanyl use or potentially opioid use disorder should be noted.

Currently, emergency departments, such as the UAB ED, have established Screening, Brief Intervention, and Referral to Treatment (SBRIT) protocols to screen for substance use disorders and refer patients. However, there are no standardized and broadly implemented ED-based screening, intervention, and referral protocols for patients with illicit fentanyl use and co-occurring psychiatric disorders. Although point-of-care toxicology tests for fentanyl in human urine are available, they are not routinely used in many EDs, and detailed guidance on how to use and interpret such test results in the ED setting is not available. Most likely, routine fentanyl testing would introduce additional workload on patient evaluation in the ED and add economic costs, but they could be warranted if needed for aiding clinical decisions. Furthermore, routine collection of self-reported opioid misuse data and urine toxicology tests, including illicit fentanyl detection, could help guide ED treatment and referral for ongoing care. For example, FDA approved medications for treatment of opioid use disorders and harm reduction approaches (i.e., naloxone and fentanyl test strips) are available if illicit fentanyl use is identified and diagnosis of opioid use disorder is accurately made26. Identification, evaluation, treatment, and referral of individuals with illicit fentanyl use should be considered as part of strategic plans to prevent nonfatal and fatal opioid overdose. Further rigorous research and intervention development is needed to address these challenges.

Our findings are consistent with the existing literature in many areas. Specifically, our results show that a great number of patients who engage in illicit fentanyl use and may concomitantly be impacted by opioid use disorder also suffer from at least one psychiatric illness. Additionally, we found that mood disorders are the most common among ED patients with illicit fentanyl use (Table 2). Regarding treatment and healthcare utilization, we found that patients with co-occurring illicit fentanyl use and psychiatric disorders presented to the ED more often in a six-month period than those without (Table 3), which is also consistent with previous studies of patients with substance use disorders and concurrent psychiatric disorders27,28. There are multiple reasons why patients may return to the ED. One reason is that patients have not received the help and treatment they need in the interim. This cohort is likely further impacted by under-insured status or lack of insurance, as evidenced by this study (Table 1). They may have limited options for definitive outpatient addiction and/or psychiatric follow-up, particularly in a non-Medicaid expansion state such as Alabama. The ED may be a patient’s only recourse for social support and medical care.

Studies have shown that individuals who use illicit opioids also use other substances29,30. Consistently, our study observed the concurrent use of illicit fentanyl and other substances in patients (Table 3), indicating the need to evaluate other substance use among individuals presenting with illicit fentanyl use and/or psychiatric disorders. Despite significant barriers to providing effective interventions for illicit fentanyl use and other substance use, medications and behavioral or psychosocial interventions that could be potentially effective for treatment have been identified31. Effective ED treatment approaches in the subset of individuals with illicit fentanyl use and concurrent other substance use will need to be augmented by additional medical or behavioral interventions and enhanced social support efforts. For example, peer support specialists and addiction counselors could be helpful to engage and link patients with community programs for definitive addiction care. Additionally, diagnosing patients with illicit fentanyl use for opioid use disorder and then providing medications for opioid use disorder with referral for ongoing treatment may be essential for patients with concurrent opioid use disorder and other substance use.

Limitations

The data in this study comes from a large, urban, tertiary hospital ED over a limited time during the COVID-19 pandemic. Therefore, results may not be generalizable to other settings or regions. Second, because our designation of co-occurring psychiatric disorders resulted from patients’ problem lists in the EMR and not from a diagnostic interview, it is likely that the prevalence of co-occurring psychiatric disorders is underestimated in this study. Third, due to the limited information in the EMR, specific diagnosis and disease severity for psychiatric disorders are not available. Fourth, our ED has over 75,000 visits annually, and urine drug screening tests are conducted in selected patients, not universally, resulting in potential selection bias. We did not confirm illicit fentanyl results in urine drug screening because the confirmatory tests are not available in the ED setting at UAB Hospital. Lastly, this current study did not include alcohol use disorder because we realize that alcohol use is significantly under reported or not reported.

Conclusion

The opioid overdose epidemic, which has been markedly exacerbated by illicit fentanyl, highlights the urgency for ED providers to be well versed on the proper screening for it and management of potential opioid use disorder. Co-occurring psychiatric disorders among patients presenting to the ED with illicit fentanyl use is associated with distinct sociodemographic characteristics and increased healthcare utilization. Improved identification, treatment, and referral for individuals with illicit fentanyl use (potentially opioid use disorder) and psychiatric disorders are needed to engage them in effective interventions, decrease ED use, and improve patient treatment outcomes.