The United States continues to face an opioid crisis; from 2000 to 2014, the prevalence of opioid use disorders increased 125%, and opioid-related overdose deaths increased 200% (
1,
2), even when levels of prescribing did not increase (
3). Treatment for opioid use disorder in general medical settings may be more convenient and less stigmatizing for patients than in settings for specialized treatment for substance use and allows for interventions in the context of other health needs (
4). At the same time, the burden on primary care continues to expand, straining resources (
5). As primary care–based opioid use disorder treatment proliferates, understanding the landscape of disorder complexity among patients is important, as is identifying effective means of triage and resource allocation, including what is needed to successfully and comprehensively treat patients with opioid use disorder (
6).
Mental disorders and other substance use disorders are common among patients with opioid use disorder (
7–
10) and may require protocols and clinical pathways that differ from standard treatment. Diagnoses of comorbid mental and substance use disorders are also associated with higher risk for relapse, nonadherence to medication treatment for opioid use disorder (
11,
12), and lower likelihood of completing treatment (
13). Current estimates of these diagnoses among individuals with opioid use disorder range widely, however—from 25% to 90% for mental disorders (
7,
8,
10,
14–
17) and from 16% to 75% (
7–
9,
14,
15) for nonnicotine substance use disorders. Nearly all of these estimates come from studies of patients seeking opioid use disorder treatment and may not provide an accurate picture of primary care populations. Given the potential impact of these diagnoses on opioid use disorder treatment protocols, resource allocation, and patient outcomes, it is important to estimate their prevalence in the general population.
It is essential, however, to consider sex when examining the prevalence of mental health and substance use comorbidity among patients with opioid use disorder (
18). Findings from national data of individuals with opioid use disorder indicate that females are twice as likely as males to have a mood or an anxiety disorder (
19). Results of a pretreatment assessment of individuals with opioid use disorder indicated that females were more likely to test positive for amphetamines, methamphetamine, and phencyclidine, whereas males more commonly tested positive for alcohol, methadone, and cannabis use (
20). In studies of opioid use disorder (
21,
22) or general substance use disorders (
20,
23), females reported current and past psychiatric problems more often than did males. Finally, females have reported greater functional impairment due to a substance use disorder or psychiatric symptoms (
20,
23,
24).
Discussion
In this large multisite observational study, diagnoses of mental and nonnicotine substance use disorders were common among both female and male primary care patients with a documented opioid use disorder. Females with opioid use disorder had a higher prevalence of mental health conditions than males, and males with opioid use disorder had a higher prevalence of other substance use disorders than females. This sex-stratified pattern was also present among patients receiving medication treatment for opioid use disorder. Very few individuals receiving such medications were without a diagnosis of a comorbid mental or substance use disorder. Females in our sample with comorbid mental disorder only were less likely to receive medication treatment for opioid use disorder than were males with comorbid mental disorder only.
According to data from EHRs (
16,
17), intake interviews (
10), and chart reviews (
7), rates of comorbid mental and opioid use disorders range from 66% to 79%, similar to the range in our sample (71%–83%). Rates of comorbid nonnicotine substance use disorders with opioid use disorder range from 16% to 75% (
7–
9,
14,
15), with higher rates among patients receiving office-based medication treatment and lower rates among individuals in mental health (
15) or chronic pain treatment (
9). The prevalence of nonnicotine substance use disorder comorbid with opioid use disorder was lower when a structured clinical interview, rather than health record data, was used (
9,
14). We note that our estimates are based on a 3-year period, and opioid use disorder treatment was not restricted to primary care, whereas samples described in the literature consist almost exclusively of individuals seeking opioid use disorder treatment (vs. the general primary care population). Regardless, our estimates suggest that significant resources are needed for treating individuals with opioid use disorder in primary care. Collaborative care models may be useful, given the spread of responsibility across multiple providers and previous successes in primary care (
36). Recent expansion of telemedicine services due to the COVID-19 pandemic (
37) may improve primary care capacity to treat this population.
Consistent with studies reporting differences in mental health conditions and substance use disorder among sexes (
38), females with opioid use disorder were more likely than males to have comorbid psychiatric diagnoses, whereas males with opioid use disorder were more likely to have comorbid substance use disorders (both for individuals with or without treatment for opioid use disorder). It is possible that the clinical setting in which individuals presented may have played a role in these sex differences. Females are more likely to present in primary care (
39,
40), where providers may be more comfortable addressing mental disorders (
41) rather than substance use disorders (
42,
43). It was beyond the scope of this study to determine where diagnoses were originally documented, precluding conjecture about these sex-specific patterns aside from their similarity to general population trends.
Males and females appeared similarly likely to receive medication treatment for opioid use disorder regardless of a diagnosis of a comorbid mental or substance use disorder, a finding that conflicts with results from research indicating that females are less likely to receive substance use disorder treatment of all types (
38). Females who had an additional diagnosis of a comorbid mental disorder only were the sole subgroup to be less likely to receive medication treatment for opioid use disorder. Given that females are more likely to visit primary care (
39,
40), it is possible that, without primary care–based opioid use disorder treatment, this subgroup may have experienced service disparities. In contrast, females with an additional substance use disorder may seek specialty care that subsequently identifies and manages their opioid use disorder with medications. As noted, our study could not assess where diagnoses were made within the health system or via contact in the community or whether patients received mental health treatment. In general, however, levels of medication treatment for opioid use disorder were low, consistent with previous studies (
44–
47) and likely a result of numerous barriers to care (
48,
49).
We note several limitations of this study. The use of EHRs and claims as the data source, rather than standardized assessments, had the potential for diagnosis misclassification. Misclassification can occur in either direction (e.g., a missed diagnosis because of underdiagnosis or undercoding or overdiagnosis because of incorrect coding of, for example, physical dependence on prescribed opioids coded as opioid use disorder). Moreover, some patients may have been using buprenorphine for symptom management during an opioid taper rather than for opioid use disorder treatment. External medication orders were not captured in the EHRs (which was relevant to one study site with such orders), and medications dispensed from pharmacies not owned by the health plan were not captured if no insurance claim was submitted (e.g., self-pay, which was relevant to five sites with dispensings). In general, however, capture of health care utilization was almost complete at the five sites that received claims for outside services, and the community health system site reported providing comprehensive care to most of its patients.
Our treatment estimates were focused on opioid use disorder treatments that can be provided in primary care; therefore, data from methadone maintenance treatment were absent in our analysis, likely underestimating the true prevalence of treatment for opioid use disorder in our sample. We did not have data on the number of patients offered medications to manage opioid use disorder. Prevalence of posttraumatic stress disorder among our population was very low (0.3%; data not shown), which may reflect some underdiagnosis of this disorder. Identification of trauma exposure is important for accurate analysis (
50), given both sex differences in trauma diagnoses (
51) and impact of trauma on treatment outcomes (
52). Our data were solely descriptive and did not offer explanations for the observed differences in prevalence of disease and treatment, and we cannot make conclusions about whether any comorbid conditions preceded or followed opioid use disorder. Our sample was predominantly White and therefore may not be generalizable to patients of other races or ethnicities who may be more or less likely to receive care in other settings (
53,
54). Finally, the generalizability of our findings may have been limited by the fact that the sample included only patients regularly interacting with the health care systems whose data were used in this study.