Primary care and medication management characteristics among patients receiving office-based opioid treatment with buprenorphine

Abstract

Background

Office-based opioid treatment (OBOT) is an evidence-based treatment model for opioid use disorder (OUD) offered by both addiction and general primary care providers (PCPs). Calls exist for more PCPs to offer OBOT. Few studies have been conducted on the primary care characteristics of OBOT patients.

Objective

To characterize medical conditions, medications, and treatment outcomes among patients receiving OBOT with buprenorphine for OUD, and to describe differences among patients by age and by time in care.

Methods

This study is a retrospective review of medical records on or before 4/29/2019 at an outpatient primary care clinic within a nonprofit addiction treatment setting. Inclusion criterion was all clinic patients actively enrolled in the OBOT program. Patients not prescribed buprenorphine or with no OBOT visits were excluded.

Results

Of 355 patients, 42.0% had another PCP. Common comorbid conditions included chronic pain and psychiatric diagnosis. Few patients had chronic viral hepatitis or HIV. Patients reported a median of 4 medications. Common medications were cardiovascular, antidepressant, and nonopioid pain agents. Older patients had a higher median number of medications. There was no significant difference in positive opioid urine toxicology (UT) based on age, chronic pain status, or psychoactive medications. Patients retained >1 year were less likely to have positive opioid UT.

Conclusion

Clinical needs of many patients receiving OBOT are similar to those of the general population, supporting calls for PCPs to provide OBOT.

Key messages.

• Office-based opioid treatment (OBOT) is a model of opioid use disorder treatment.

• Primary care needs of many OBOT patients are in generalist scope.

• At a primary care/addiction clinic: 42% second PCP, median of 4 other medications.

• Top med classes: cardiovascular, antidepressants, and nonopioid pain.

Background

Untreated opioid use disorder (OUD) is cause of significant morbidity and mortality in the United States and internationally.^1,2 In the United States, office-based opioid treatment (OBOT) typically entails a DEA-waivered medical provider prescribing buprenorphine/naloxone to be dispensed at a local pharmacy and access to counselling. OBOT has been shown in randomized trials to be effective at both reducing illicit opioid use and overdose mortality.^1–3 As many patients diagnosed with OUD currently do not receive evidence-based treatment and specialized facilities are often over capacity, primary care providers (PCPs) are increasingly encouraged to provide OBOT, a methodology which has been implemented and studied in many countries.^1,4 Although previous research shows that PCPs view buprenorphine treatment as effective,^5–7 recent studies also reported that a minority of PCPs in the United States were interested in providing OBOT.⁷ PCPs report barriers such as lack of institutional support⁵ and discomfort managing conditions they associate with OUD, such as infectious diseases.⁶ Additional knowledge about the primary care aspects of patients with OUD receiving OBOT may help address such barriers.

While there is an increasing body of research on substance use disorder (SUD) treatment integration into primary care, few studies have examined the primary health care needs and outcomes of patients treated for OUD. A systematic review of primary care models with medications for OUD in several countries² found less than half of the reviewed studies measured common primary care comorbidities: one study measured medical comorbidities,⁸ one measured primary care screenings,⁹ while the others measured HIV/HBV/HCV or psychological outcomes,¹⁰ but not other medical comorbidities.²

Chronic medical conditions among patients receiving OBOT are a potential clinical concern for the scale up of OBOT because patients with OUD often have gaps in primary care coverage.¹¹ Several studies have noted that patients with OUD have higher mortality rates than expected for their age and sex in the general population.^12,13 Furthermore, a large proportion of mortality in patients with OUD has been found to be due to nonsubstance related, nonpsychiatric conditions (46% in 1 international study,¹³ 41%–75% a US study,¹⁴ and 46% in a Norwegian study¹⁵). These studies suggest the need to better characterize the primary care health conditions and characteristics among patients receiving OBOT, and underscore the importance of cotreatment of OUD and medical conditions in the primary care setting.

Ageing, retention in treatment, and medication management are important concerns in the management of chronic diseases in primary care, but are not well characterized among patients receiving OBOT. Currently, the clinical needs of older patients with OUD, defined in several studies as patients aged 50 years and older, have not been systematically investigated.¹⁶ Long-term retention, often defined as remaining in treatment greater than 1 year, is associated with long-term recovery from OUD and provides opportunities for routine health maintenance.^2,17 However, studies have found that only approximately 60% of patients are retained at 3 months of initiation of OBOT in primary care.^2,18 An increased understanding of the characteristics of long term retained patients in primary care OBOT may suggest strategies for promoting retention. While some studies have documented that a large proportion of patients receiving medication for OUD are also receiving psychoactive medications (PAMs),^13,19 the management of medications in addition to medication for OUD is not well studied. The aims of the present study were to characterize the primary care conditions and medications among patients receiving OBOT, and to compare primary care conditions, medications, and SUD treatment outcomes in older (age ≥50 years) vs younger patients and patients retained ≥1 year in treatment vs those retained <1 year.

Methods

Study setting and design

The APT Foundation (APT) is a not-for-profit addiction treatment program in the northeastern United States which provides psychiatric and medical care to patients with SUDs. APT provides outpatient primary medical care in a central medical unit (CMU). All patients presenting to APT undergo medical and psychiatric evaluation, including HCV and HIV antibody screening in an opt-out fashion.

The study is a retrospective chart review of patients receiving OBOT at CMU. Inclusion criteria were all patients marked as actively enrolled the OBOT program in the APT electronic health record (EHR) system on or before 4/29/2019, with no stipulation of length of enrolment. Patients enrolled in the OBOT program were treated with buprenorphine/naloxone or buprenorphine. Exclusion criteria were patients with no visits to the CMU or who upon chart review, were found not to be treated with buprenorphine.

Data collection

Patient data at their most recent CMU visit on or before 4/19/2019 were extracted through EHR review. Demographic information included age at reviewed visit, sex, race, and ethnicity. Similar to other studies of OUD, older age was defined as age 50 years and older.¹⁶ Clinical information directly extracted were problem list ICD-10 codes and medication lists, however problem list ICD-10 codes were only used for analysis of chronic viral disease (codes B18—viral hepatitis, Z21—HIV, and other related codes) due to inconsistent utilization of the problem list feature for general medical and psychiatric conditions, for example, cardiovascular disease or depression. Chronic pain status (i.e. pain lasting at least 3 months) and other primary care practitioner status were coded from the reviewed visit’s progress note by a single author (C.X.D.) with review of any coding concerns by the physician authors jointly (J.M.T. and J.S.).

Urine toxicology panel (UT) results for 3 months prior to the reviewed visit were extracted from a laboratory services’ electronic results portal. UT samples were collected unobserved in clinic with frequency dependent on clinical status of the patient. The UT panel included testing for benzodiazepines, buprenorphine, cocaine, nonbuprenorphine opioids, and oxycodone. Analysis of UT results only includes the patients who did have UT results in the 3 months prior to the reviewed visit (N = 333). Buprenorphine adherence as well as the use of other substances was calculated as percentage of patients who had 1 or more positive UT results.

Medication class analysis

CMU providers perform medicine reconciliation of all prescription (both prescribed by CMU or outside) and over the counter (OTC) medications. Therefore, extracted medication list reflects all sources. Medication class was analysed from the medications list in the visit note using a rubric designed by physician authors (J.T. and J.S.) (Supplementary Fig. 1). Separate analyses of prescription or OTC medications were not performed as many medications are available both OTC and by prescription. The proportion of patients using ≥5 medications (including OTC) was calculated, as ≥5 is a common definition for polypharmacy.²⁰

Data analysis

Statistics were calculated using R version 3.6.1 (2019).²¹ Analyses of differences in number of medications between subgroups were calculated using independent two-group Mann–Whitney Wilcoxon rank-sum test since the data were not distributed normally. Analysis of proportion of ever-positive UT between subgroups was calculated with Fischer’s exact test. Exploratory analyses were performed, stratifying patients by older age (≥50 years), retained >1 year in treatment, and chronic pain status. Further post hoc exploratory multivariable logistic analyses were performed to identify predictors of polypharmacy and ever-positive opioid UT (ever positive for nonbuprenorphine opioids or oxycodone). Patients prescribed nonbuprenorphine opioids were excluded from ever-positive opioid UT analysis. Potential predictors in both models were age, chronic pain status, and long-term retention status, and prescription of any PAMs was a potential predictor for ever-positive opioid UT analysis only. Final models were built with a stepwise algorithm, “stepAIC,” from the package MASS.²² Final predictors in the model for polypharmacy were age and chronic pain status, and the final predictor in the model for ever-positive UT was long-term retention status.

Ethics

This medical record review involving a waiver of signed consent and HIPAA authorization was approved by the APT Foundation Board of Directors and the Human Investigations Committee at the Yale University School of Medicine per 100 FR 7 (2014-1).

Results

Demographics

Three hundred and fifty-five patients were included in the final study sample (Fig. 1). One hundred and twenty (33.7%) patients were age 50 or older. Two hundred and thirty-five (66.1%) patients had been retained in treatment for over 1 year. The median length retained in treatment was 2.0 years (interquartile range [IQR]: 277–2,494 days), with a range of 0 days to 10.8 years (Table 1).

Fig. 1.

Flow diagram of inclusion criteria for chart review. Of 361 patients marked as enrolled in our study center’s OBOT program (with no additional criteria for length of time enrolled), 6 were excluded, 2 for not having had a medical record indicating a CMU visit and 4 for not receiving OBOT with buprenorphine.

Table 1.

Demographics of patients enrolled in OBOT with buprenorphine in 2019 at a US clinic.

Demographics of study sample	N = 355
Age (mean) (range)	44.38 (21–79)
Gender (%)
Female	100 (28.2)
Male	254 (71.5)
Other	<5 (<1.4%)
Race (%)
African American	15 (4.2)
Asian	0 (0.0)
White/Caucasian	316 (89.0)
Other	24 (6.8)
Ethnicity (%)
Latino/Hispanic	26 (7.3)
Not Latino/Hispanic	329 (92.7)

Primary care characteristics

One hundred and seven patients (42.0%) had another primary care practitioner mentioned in their most recent visit note. Eighty-seven patients (24.5%) had management of chronic pain of various aetiologies mentioned in their most recent visit note. One hundred and thirty-seven (38.5%) patients had 1 or more non-SUD psychiatric diagnoses, 195 (54.8%) had other SUDs (including alcohol, cannabis, cocaine, methamphetamine, nicotine, sedative hypnotic, multiple, and other stimulant use disorders). While chronic viral disease is a known concern for patients with SUD, few patients in this cohort had conditions on their problem list, with 0 patients with HIV on their problem list and 25 (7.04%) with viral hepatitis (including both active and treated).

Medication management

Two hundred and ninety-three (82.3%) patients had 1 or more medications in addition to buprenorphine on their medications list, with a median of 4.0 medications (IQR: 2–6). Two hundred and thirty-seven (59.6%) patients were prescribed 1 or more PAMs. The most common classes of medications were cardiovascular (n = 130, 36.6%), antidepressants (n = 130, 36.6%), other psychoactive (n = 85, 23.9%), and nonopioid pain medications (n = 80, 22.5%). Older patients (age 50 or older) had a higher median number of total medications, with a median of 5 (IQR: 3–7.25) compared with a median of 3 (IQR: 2–5) for patients younger than 50 (P < 0.001). One hundred and forty-three patients (40.3%) were taking 5 or more medications, a common threshold for polypharmacy. In multivariate analysis, polypharmacy was associated with age and chronic pain status (Table 2).

Table 2.

Medications by drug class taken by patients enrolled in OBOT with buprenorphine in 2019 at a US clinic.

Drug class	N (N = 355)	Percentage
Cardiovascular	130	36.6
Antidepressants	130	36.6
Other PAMs	85	23.9
Nonopioid pain	80	22.5
Benzodiazepines	52	14.7
Mood stabilizers/antipsychotics	32	9.0
Pulmonary	30	8.5
Gabapentin	27	7.6
Other sleep	26	7.3
Other SUD	21	5.9
Diabetes	20	5.6
Sedative hypnotics	18	5.1
Hepatitis C	<5	<1.4
Naloxone	<5	<1.4
HIV	<5	<1.4
Nonbuprenorphine opioids	<5	<1.4
Other prescriptiona	132	37.1
Other over the counterb	56	15.8

“Other prescription” captures any medications available only by prescription that did not fall into any of the above categories, e.g. nondiabetes endocrine medications, contraceptive medications.

“Other over the counter” captures any medications marked as OTC or not available by prescription, e.g. commercial herbal supplements.

Substance use outcomes

Three hundred and thirty-three patients were included in the analysis of UT results; the remaining 22 patients did not have a UT result within 3 months prior to the reviewed visit. Positive buprenorphine adherence and other substance use were calculated as percentage of patients who had 1 or more positive UT results. Overall, UT results showed good adherence to buprenorphine and low use of opioids, with 99.4% of patients with UT positive for buprenorphine, and 7.8% of patients positive for opioids (other than buprenorphine). Also included on the panel were cocaine, benzodiazepines, and oxycodone. Patients with chronic pain, and patients prescribed PAMs were not more likely than their counterparts to have a positive opioid UT by univariate analysis (odds ratio [OR] 0.93, OR 1.3, P value = 0.83, P value=0.68, respectively). In multivariate analysis, ever-positive opioid UT was associated only with being retained in treatment less than 1 year (Table 3).

Table 3.

UT results within 3 months of most recent visit from patients enrolled in OBOT with buprenorphine in 2019 at a US clinic.

Substance [N (%)]	Ever positive total (N = 333)	Ever positive in older patients (N = 110)	Ever positive in patients with chronic pain (N = 82)	Ever positive in patients retained over 1 year (N = 235)
Buprenorphine	331 (99.4%)	109 (99.1%)	82 (100%)	220 (93.6%)
Benzodiazepines	54 (16.2%)	20 (18.2%)	11 (13.4%)	30 (12.8%)
Cocaine	28 (8.4%)	9 (8.1%)	6 (7.3%)	12 (5.1%)
Opiates	26 (7.8%)	9 (8.1%)	7 (8.5%)	12 (5.1%)
Oxycodone	12 (3.6%)	6 (5.4%)	<5 (<6%)	<5 (<2%)

Analysis of UT results within 3 months of their most recent visit from patients enrolled in OBOT with buprenorphine in 2019 at a US clinic. Patients who did not have a UT result within 3 months of the reviewed visit were excluded from UT analysis. Three hundred and thirty-three total patients had a UT result and were included in this analysis. Ever positive was defined as having 1 or more positive UT results within 3 months of the reviewed visit.

Older patients

One hundred and twenty (33.7%) patients in our study population were age 50 or older. Older patients did not have a significant difference in positive opioid UT results compared with younger patients (OR 0.93, P value = 0.83). Older patients (age 50 or older) had a higher median number of total medications, with a median of 5 (IQR: 3–7.25) compared with a median of 3 (IQR: 2–5) for patients younger than 50 (P < 0.001). Polypharmacy is a noted concern in primary care for older patients, and is shown here to be relevant also in the OBOT population. The most common medications in older patients were similar to those for younger patients, with the most common categories of medications being cardiovascular, antidepressants, and nonopioid pain medications (Supplementary Table 1).

Patients retained long term in treatment

Two hundred and thirty-five (66.1%) patients in our cohort were retained in treatment long term, defined as longer than 1 year. The mean age of the long-term patients was 45.4 years, with a range of 23–79 years. The average duration of the long term retained group was 4.67 years (range: 1.08–10.8 years; IQR: 2.02–7.2 years). One hundred and seventy-seven (75.3%) long-term patients identified as male, 209 (88.9%) identified as White/Caucasian, and 16 (6.8%) identified as Latino/Hispanic. Long-term patients were less likely to have positive opioid UT, with 5.1% of those retained over 1 year ever positive compared with 11.7% of those retained less than 1 year (OR 0.408, P value = 0.03). There was no difference in median number of total medications between patients retained long term and not, with a median of 4 medications (IQR: 2–6) in both groups. The most common medications in patients retained or not retained long term did not differ significantly, with the most frequently occurring categories being cardiovascular, antidepressants, and nonopioid pain medications (Supplementary Table 2). There was no difference in median number of PAMs medications between patients retained long term and not, with a median of 1 psychoactive PAMs (IQR: 0–2) in both groups.

Discussion

Primary care conditions and medications among patients receiving OBOT

In this retrospective chart review of 355 patients receiving OBOT, common comorbid conditions included chronic pain, psychiatric diagnosis, and other SUDs. Notably, few patients had infectious diseases often associated with OUD such as chronic viral hepatitis or HIV. Patients were taking a median of 4 medications, with common classes of medications being cardiovascular, antidepressants, and nonopioid pain relievers. Regarding UT results, patients with chronic pain, and patients prescribed PAMs were not more likely than their counterparts to have a UT result positive for nonprescribed opioids.

One unexpected finding in our study was that 107 patients (42.0%) had another PCP mentioned in their most recent visit note. Lack of connection to primary care is a known problem among people with SUD,² but having multiple PCPs has also been noted in prior work.²³ Our study site offers traditional primary care for all patients, including preventative medicine, urgent care, and medication reconciliation. This approach is not intended to promote multiple PCPs, but to ensure patients do not have gaps in care. Data were not available to systematically analyse conditions managed by CMU vs an outside PCP, nor ascertain whether patients initiated care seeking primarily primary care vs expanded access to buprenorphine treatment.

Primary care concerns prevalent in our study included chronic pain, psychiatric diagnosis, and other SUDs. Chronic pain is a very common condition in primary care, and the intersection of chronic pain and OUD is well studied.²⁴ Notably, the patients with chronic pain in our sample did not have significantly different positive opioid UT results than patients without chronic pain. While chronic infectious diseases commonly occur among patients with OUD and screening and prevention efforts are important,¹ HIV and HCV were uncommon in our sample. This contrasts with findings from a prior study that HCV is common among primary care patients in OBOT.⁸ Given recent improvements in HCV testing and treatment, HCV may not be reflected in the problem list as a current active medical problem.

Common concerns of patients receiving OBOT in our study, as reflected in their medications, included musculoskeletal pain, cardiovascular conditions, and depression. This is similar to previous studies which have found cardiovascular conditions⁸ and depression^8,25 to be common in patients receiving OBOT. Cardiovascular disease is one of the leading causes of mortality worldwide, and opioid use and OUD are increasingly recognized as risk factors for cardiovascular disease.²⁶

Polypharmacy, often defined as 5 or more medications, can compound adverse effects of medications and burden patients.²⁰ The percentage of patients receiving OBOT in our study with polypharmacy (40.3%) was numerically greater than in US adults (15%).²⁷ With our study design, it was not possible to assess potential for deprescribing. The most common classes of medications in our sample, antidepressants and cardiovascular medications, are most common among all US adults.²⁷ While the medical complexity of patients receiving OBOT has been suggested as a barrier to PCPs providing OBOT,⁶ our study patients had primary care health and medication management concerns that are common in the generalist scope of practice.

Older patients receiving OBOT

Older patients had a higher median number of medications than younger patients, but the most common classes of medications were similar. Older and younger patients did not differ significantly in UT result positive for opioids. One hundred and twenty participants (33.7) were age 50 years or older, compared with 38.8% of the population of Connecticut.²⁸ Unlike in prior studies,^29,30 where older patients had fewer positive UTs for opioids, no significant differences emerged in opioid UT results between older and younger study patients. However, several other studies underscore a significant burden of continued substance use in older patients.^31,32 Older patients had a higher median number of total medications, which highlights polypharmacy, already a concern among all older adults,²⁷ as a special concern in this population.

Patients receiving OBOT long term

More than half of patients in our study were retained over 1 year, similar to the proportion found in a prior study.¹⁸ Long-term patients were less likely to have positive opioid UT and had no difference in median number of PAMs than non-long-term patients. Although psychiatric conditions have historically been viewed as a concern for OUD treatment retention and outcome,³³ studies have found patients diagnosed with psychiatric conditions actually have improved retention and that patients transferred from specialists to PCP OBOT had continued improvement of psychiatric outcomes.^10,18,33 Our findings that PAMs were not associated with lower treatment retention are congruent with previous research that patients also treated for psychiatric conditions were successfully retained in OBOT,^10,18 which may be encouraging to PCPs concerned about negative effect of psychiatric comorbidities.

Limitations

Self-reported data about other PCPs were not corroborated independently. UT results positive for benzodiazepines, opioids, and oxycodone could potentially reflect nonmedical use or prescription medications not included on the medication list; however, the likelihood of the latter is minimized by careful medicine reconciliation by clinic providers and regular queries of the state prescription monitoring program. We only used data from our EHR, which did not have systematic information on prior medications for OUD treatment, nor systematic data on the origins of patients’ OUD (iatrogenic vs illicit use).

Conclusion

The clinical needs of patients receiving OBOT found in this study are similar to those reported in studies of the general population. Possible provider concerns about the negative impact of chronic pain and psychiatric conditions on buprenorphine adherence and drug use were not borne out in this study. Our findings suggest that medical conditions seen in patients receiving OBOT are within generalist scope of practice, and therefore support calls for PCPs to provide OBOT. Future studies should investigate how medical resources could be used most parsimoniously to avoid some of the apparent duplicate care found in this study.

Funding

This research was partially funded by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number T35AA023760 granted to Dr. John Krystal and Dr. John Forrest of Yale University in New Haven CT, which supported Ms. Du, and NIH/NHLBI/NIDA to Dr. Barry (MPI; U01 HL150596-01, RM1 DA055310).

Ethical approval

This retrospective medical record review was approved by the APT Foundation Board of Directors and the Human Investigations Committee at the Yale University School of Medicine, as “APT Medical Record Review” ID: 1512016867.

Conflict of interest

None declared.

Data availability

The datasets generated during and/or analysed during the current study are not publicly available due to containing protected health information.