Opioid treatment program and community pharmacy collaboration for methadone maintenance treatment: Results from a feasibility clinical trial

Abstract

Background and Aims:

Pharmacy administration and dispensing of methadone for methadone maintenance treatment (MMT) can expand treatment access for opioid use disorder (OUD). This study investigated the feasibility and acceptability of a novel model permitting an opioid treatment program (OTP) physician to prescribe methadone for OUD treatment through collaboration with a partnered pharmacy.

Design:

Nonrandomized, single-arm, open-label feasibility trial.

Setting:

One OTP and one community pharmacy in the US.

Participants:

One OTP physician, two pharmacists, and 20 MMT patients receiving between 6 and 13 take-home methadone doses at 5–160 mg/day.

Intervention:

Patients’ methadone administration and dispensing of take-home doses was transferred from the OTP to the pharmacy for 3 months.

Measurements:

Primary outcome was medication adherence. Secondary outcomes were recruitment, treatment retention, substance use, counseling attendance at the OTP, pharmacist prescription drug monitoring program (PDMP) use, safety, and satisfaction.

Findings:

Of 29 patients eligible at prescreen, 20 patients (69%) enrolled into the study. Recruitment occurred from August 6, 2020 to October 7, 2020. Treatment retention rate at Month 3 was 80% (16/20). Two participants returned early to the OTP because of a work/schedule change, one due to pregnancy, and one following a non-study related hospitalization. Medication adherence among 16 patients who were retained was 100%. Intervention fidelity was 100%. All participants attended random call-back visits. None showed evidence of tampering/diversion of methadone. Pharmacists checked the PDMP at all visits. All participants attended psychosocial counseling as planned. There were no positive urine screens for illicit opioid use and no study-related adverse events. All participants endorsed “pharmacy is the right location for receiving methadone for MMT,” 88% endorsed “convenient or very convenient to receive methadone at the pharmacy, and 88% were satisfied or very satisfied with the quality of treatment offered.

Conclusions:

This feasibility trial has found pharmacy administration and dispensing of physician-prescribed methadone for methadone maintenance treatment to be feasible and acceptable.

INTRODUCTION

The opioid overdose death epidemic in the US has continued for over 20 years [1–3]. There has been a shortage of providers of methadone and buprenorphine treatment for opioid use disorder (OUD) that limits access to treatment [4]. Approximately 81% of Americans with OUD have not received OUD treatment [5]. The interpretation of the Harrison Narcotic Act of 1914 prohibited physicians to provide opioids to treat OUD [6]. This Act essentially limited the medical profession for providing such treatment (outside of FDA Investigational New Drug permits) for six decades until federal methadone treatment regulations were finalized in around 1974 [6], which permitted methadone maintenance treatment (MMT) of OUD in licensed opioid treatment programs (OTPs). These regulations permitted the establishment of medication units to administer/dispense methadone under a physician order (not by prescription) as part of the OTP license and direction [7]. However, medication units in pharmacies and elsewhere have not been widely utilized. The US Drug Addiction Treatment Act of 2000 permits certain practitioners to obtain a waiver of the Controlled Substances Act to prescribe buprenorphine to increase OUD treatment [8]. However, less than 10% of US providers are buprenorphine-waivered [9], and 56.3% of all US rural counties lack a buprenorphine practitioner [10]. There is a need to identify strategies to increase access to OUD treatment.

There are approximately 1,800 OTPs across the US [11], which limits geographic access to MMT. In contrast, there are approximately 65,000 community pharmacies in the US [12]. One solution is to leverage community pharmacies to expand the number of methadone dispensing sites. Community pharmacists are well-suited for this role because of their expertise in medication therapy management and high accessibility, even in rural areas [13]. Many countries have implemented community pharmacy-based administration/dispensing of methadone for MMT (e.g., Australia, Canada, New Zealand, United Kingdom). In Australia, MMT has been provided through community pharmacies since 1985 [14,15]. In Scotland, the number of methadone patients treated through pharmacies increased from 3,387 in 1995 to 12,400 in 2006 [16]. In the UK, the proportion of pharmacies dispensing methadone for OUD increased from 51% in 1995 to 63% in 2005 [17]. The introduction of supervised methadone dosing in pharmacies was associated with declines in deaths related to overdose of methadone in Scotland and England [18]. In Canada, methadone patients stabilized at an OTP are able to receive supervised methadone administration at local pharmacies [19,20]. Thus, pharmacy administration/dispensing of methadone abroad has increased the access to MMT for OUD [19,20].

Pharmacy-based methadone treatment in the US has been vastly understudied. Harris et al. [21] reported on a 5-year follow-up of 127 stable patients enrolled in an office-based methadone program. The physician met monthly with patients and prescribed methadone which dispensed monthly in a pharmacy. A chart review showed that treatment retention rate was high (98%) [21]. The second such report was of a pilot trial exploring a model in which office-based physicians prescribed methadone with pharmacy administration and dispensing [22]. Twenty-six stable female patients were randomized to either methadone maintenance at physician office, pharmacy dispensing, and social work counseling (n=14) or routine care in an MMT program (n=12). None of the 14 patients in the pharmacy group left treatment compared with one patient in the MMT group. While this early study [22] and a recent study of community pharmacist-provided buprenorphine treatment care for OUD [23] provide support for community pharmacist-provided services for OUD treatment, the US federal regulations currently prohibit physicians from prescribing methadone to treat OUD. Hence, there is a need for pilot research to explore the feasibility of pharmacy administration and dispensing of methadone via prescription.

We conducted a pilot study to determine the feasibility and acceptability of an OTP-community pharmacy collaboration to permit the OTP physician to prescribe methadone outside of the federal OTP regulations for medication units. This study will provide timely data to inform efforts aimed at expanding access to MMT in nonmetropolitan areas via methadone prescriptions written by OTP prescribers and electronically submitted to community pharmacies in nonmetropolitan areas where individuals with OUD reside [24].

METHODS

Setting

This study was conducted within an OTP and one independent community pharmacy located 5.4 miles from the OTP in Raleigh, North Carolina, US. Methadone prescriptions were written by one physician in the OTP, and administration/dispensing was done by two licensed pharmacists in the pharmacy. Study activities were conducted within a private space at the pharmacy used for private consultations and immunizations. This study obtained the necessary approvals from the Drug Enforcement Administration (DEA), Substance Abuse and Mental Health Services Administration, NC State Opioid Treatment Authority, and Duke University Health System’s Institutional Review Board (IRB) for research with human subjects.

Study Design (Figure 1)

Figure 1.

Study diagram

Pharmacists completed four one-hour training modules from the Providers’ Clinical Support System for Medication Assisted Treatment on epidemiology of OUD/substance use disorders, medication treatment for OUD, methadone safety, and motivational enhancement techniques [25]. Pharmacists and the prescribing OTP physician also completed human subjects’ protection training, Good Clinical Practice training, three group meetings involving review and discussion of MMT materials, protocol-specific training, and a mock study visit. After completing study training, research staff pre-screened MMT patients who were eligible to receive between 6- and 13-days of take-home methadone doses from the OTP. Next, research staff conducted the informed consent process with patients who expressed some interest in participating in the study. Patients who provided consent to participate in the study then completed baseline assessments to confirm study eligibility. Each participant was compensated for their time for completing baseline and three followup assessments ($50/each). Pharmacists and the OTP physician were compensated for their time as members of the research team.

The OTP physician prescribed methadone electronically for participants to have their methadone administration/dispensing of take-home doses transferred to the pharmacy for 3 months. Methadone was provided in tablet formulation that was matched to their dosage from the OTP for the study using 40-mg dispersible tablets for oral suspension and/or 5-mg non-dispersible tablets. Participants picked up their methadone take-home doses from the pharmacy regularly based on their allowed take-home schedule. Prior to dispensing take-home doses at each pharmacy visit, the study pharmacist observed ingestion of one dose at the pharmacy. During the course of study, participants continued to receive drug testing and counseling as usual at the OTP. At the end of the study, participants returned to the OTP for routine methadone administration/dispensing.

Participant Eligibility

Patients were eligible for the study if they were aged ≥18 years, were receiving a methadone dose between 5 mg and 160 mg, met federal/state regulations for eligibility to receive between 6- and 13-days of take-home methadone doses, and had no missed methadone recalls or positive UDS tests (except for prescribed methadone or ethanol) at the OTP in the past 12 months (Supplement Table S1). Patients with a serious medical/psychiatric condition that would increase safety concerns were excluded.

Study Intervention

An operational care agreement (OCA) was used to establish collaboration for the partnered OTP and pharmacy and specify pharmacist’s and physician’s roles and responsibilities during pharmacy visits [23,26]. The OCA specified that the OTP physician was responsible for the treatment plan, prescribing methadone and dose adjustment, keeping records for federal/state regulations, and providing clinical guidance/coaching and supervision to the pharmacist, who will in turn administer and dispense methadone to the patient according to the physician’s prescription. Clinical activities performed by the pharmacist at each pharmacy visit were recorded on a Methadone Visit Checklist (MVC), such as performing methadone reconciliation; conducting safety assessments by asking participants’ use of new medications, side effects of methadone, drug overdoses, emergency department (ED) visits, and hospitalizations; checking the patient’s controlled medications prescription status using the prescription drug monitoring program (PDMP) before dispending methadone [27]; providing patient education/counseling; communicating with the OTP physician regarding any concern; and administering one methadone dose at the pharmacy and dispensing methadone according to the prescription) (Table 1).

Table 1.

Summary of tasks for the opioid treatment program/physician and community pharmacists during the study

Tasks/Items	OTP/Physician	Community Pharmacist
Methadone prescription and dose adjustment	X
Methadone call-back	X
Urine drug screen	X
Psychosocial counseling	X
Physician consult, as needed	X	X
Medication reconciliation		X
Safety event assessment (e.g., participant receipt of new medications, side effects of methadone, overdose, emergency department admission, hospitalization)		X
Check state prescription drug monitoring program		X
Patient education (e.g., overdose prevention, other drug use, compliance with psychosocial treatment and medications, safe storage of medications)		X
Dispensing of take-home methadone doses		X
Methadone dose preparation and administration		X

OTP: Opioid Treatment Program.

Outcome Assessments

Primary outcome measure was medication adherence (i.e., the proportion of participants receiving their scheduled methadone dose administration and methadone dispensed at the pharmacy pickup out of the methadone prescribed). Treatment adherence was also checked randomly by a methadone dose call-back at the OTP. One methadone call-back was randomly scheduled for each participant during the 3-month study period. Failure to attend the random methadone dose call-back visit was an indicator of non-adherence.

Secondary outcomes included recruitment, treatment retention (i.e., the proportion of participants retained in the study), substance use, psychosocial counseling attendance, pharmacists’ PDMP use, participant safety, and treatment satisfaction. Substance use were measured by monthly UDS results collected at the OTP (i.e., methadone/methadone metabolites, buprenorphine, opiates, oxycodone, heroin, ethanol, amphetamine, barbiturates, benzodiazepines, cocaine, marijuana [THC]). During the study period, participants continued to receive their usual psychosocial counseling at the OTP. Compliance with the OTP’s psychosocial counseling attendance was measured by a chart review to assess whether participants attended the scheduled psychosocial counseling session at the OTP. Pharmacists’ PDMP use included monitoring for multiple buprenorphine prescriptions and other class II and III medication prescriptions with a potential for misuse [28]. Participant, pharmacist, and physician satisfaction with treatment delivery was assessed using a self-administered, web-based satisfaction survey [23]. Participant safety measures included substance-related overdoses and substance-related ED visits or hospitalizations, which was assessed at each pharmacy visit.

Intervention fidelity (protocol adherence by pharmacists) was monitored by assessing adherence to MVCs (one for each pharmacy visit attended), which was determined by reviewing the number of items (tasks) completed on 35% of randomly sampled MVCs [23]. Intervention adherence was defined by the proportion of MVCs with ≥80% tasks completed [23,29].

Statistical Analyses

Descriptive analyses were conducted to characterize distributions of outcome measures. Analyses were conducted in SAS 9.4 [30]. The primary research question and analysis plan were not pre-registered on a publicly available platform. The results should be considered exploratory.

RESULTS

Recruitment

Recruitment occurred from August 6, 2020 to October 7, 2020. Of the 35 patients pre-screened, 6 patients (17%, 6/35) were not eligible due to positive UDS in the past 12 months. Among 29 patients eligible at pre-screen, 20 patients (69%, 20/29) enrolled into the study (Figure 2). Reasons for declining participation included “work schedule issue” (n=3) and “not interested in participating in the study” (n=6). Of the 6 patients “not interested,” two indicated “don’t want to change routine at clinic” and one indicated “don’t want to take tablet methadone.”

Figure 2.

CONSORT flow diagram

Baseline Demographics

The mean age of 20 participants at baseline was 37.2 years (SD=8.3 years). The majority of participants were female (70%) or white (90%), had some college or higher education (55%), and were employed (75%). All participants were non-Hispanic (Table 2).

Table 2.

Participant characteristics at baseline (n=20)

Characteristic	n (%)
Sex
Male	6 (30%)
Female	14 (70%)
Age in years (Mean [SD])	37.2 (8.3)
18–35	10 (50%)
36–55	10 (50%)
Range	24–55 years
Ethnicity
Not Hispanic or Latino	20 (100%)
Hispanic or Latino	0 (0%)
Race
White	18 (90%)
Black/African American	1 (5%)
Other	1 (5%)
Education completed
High school graduate/GED or less	9 (45%)
Some college or more	11 (55%)
Marital status
Married/Living with partner	9 (45%)
Divorced	4 (20%)
Never married	7 (35%)
Employment
Working now	15 (75%)
Not working/other	5 (25%)
Health Insurance
None	9 (45%)
Medicaid	1 (5%)
Private	9 (45%)
Champus, Champ VA, VA, or Military health insurance	1 (5%)

SD: Standard Deviation

Treatment retention and medication adherence

Treatment retention rate at Month 3 was 80% (16/20) (Figure 3). Reasons for early study termination included job change/work schedule (n=2), pregnancy (n=1), and hospitalization that was unrelated to the study (n=1). Medication adherence was 100% (Table 3): retained participants attended each expected pharmacy visit in Month 1 (77/77 visits), Month 2 (66/66 visits), and Month 3 (64/64 visits). All participants (100%) who retained in the study completed their random methadone dose call-back and had no signs of diversion/tampering of methadone (Supplement Table S3).

Figure 3.

Treatment retention

Table 3.

Medication adherence: Pharmacy visit adherence among participants who retained in the study

Month 1a	Month 2	Month 3	Overall
n=19	n=17	n=16	n=19
77/77 (100%)	66/66 (100%)	64/64 (100%)	207/207 (100%)

All participants were on a once a week methadone pick-up schedule. Each participant was expected to go to the pharmacy weekly (i.e., 4 visits/month).

^aOne participant had an extra pharmacy visit during Month 1 due to a medication schedule change, and another participant withdrew from the study prior to the first pharmacy visit and hence, did not have any scheduled pharmacy visits. Thus, there were a total of 77 expected pharmacy visits in Month 1.

Opioid/other substance use

Except for methadone, there was no positive opioid UDS (Table 4). During the study period, there was one participant with a positive THC UDS due to use of THC-containing cannabidiol oil. There was another participant with a positive amphetamine UDS due to use of a prescription stimulant medication. There was no other drug use from UDS.

Table 4.

Urine drug screen (UDS) results

	Study completer analysis (n=20)a	Intent-to-treat analysis (n=20)
n (%)	Months 1–3	Months 1–3
Methadone	20 (100%)	20 (100%)
Methadone metabolites	20 (100%)	20 (100%)
Buprenorphine	0 (0%)	0 (0%)
Opiates	0 (0%)	0 (0%)
Oxycodone	0 (0%)	0 (0%)
Heroin	0 (0%)	0 (0%)
Ethanol	0 (0%)	0 (0%)
Marijuana (THC)	1 (5.0%)b	1 (5.0%)b
Benzodiazepines	0 (0%)	0 (0%)
Cocaine	0 (0%)	0 (0%)
Amphetamine	1 (5.0%)c	1 (5.0%)c
Barbiturates	0 (0%)	0 (0%)

^aStudy completer analysis was based on UDSs during each month participants received pharmacy-based methadone administration/dispensing; a total of 52 UDSs were analyzed from all 20 enrolled participants during the 3-month study period. Each participant who completed the study (n=16) had 3 UDS’s each (1 UDS/month), except one participant who had 2 UDS results during the study (no UDS scheduled during Month 1). Among participants who discontinued study early (n=4), three participants who discontinued prior to Month 2 had 1 UDS each, and one participant who discontinued prior to Month 3 had 2 UDS results.

^bPositive Tetrahydrocannabinol (THC) result due to one participant’s use of a THC-containing cannabidiol (CBD) oil product.

^cPositive amphetamine result due to one participant’s use of prescribed stimulant medication (i.e., not illicit use).

Psychosocial counseling attendance

All participants continued to attend their scheduled (usual) psychosocial counseling sessions at the OTP.

Pharmacists’ use of the PDMP

Pharmacists used the PDMP in all pharmacy visits (207/207 visits) (Supplement Table S3). There were no issues of other opioid prescriptions, unauthorized benzodiazepine prescriptions, or other controlled medication use reported for all visits where the PDMP was consulted.

Safety

There were no substance-related overdoses and hospitalizations. There was only one participant hospitalized for abdominal pain (unrelated to the study) who was removed from the study.

Treatment delivery satisfaction in participants

All sixteen participants who remained in the study for 3 months completed the self-administered satisfaction survey at Month 3 (Table 5). Among them, 87.5% were very satisfied with their overall experience in this study; 87.6% were either satisfied (6.3%) or very satisfied (81.3%) with the quality of treatment offered in this study; 93.8% reported that methadone administration/dispensing transfer from the OTP to the pharmacy was not difficult at all; 87.5% reported that receiving methadone doses at the pharmacy was either extremely useful/convenient (62.5%) or very useful/convenient (25.0%); 100% endorsed that they would choose to participate in the study again if given the opportunity. Reasons for influencing their decision to participate in a future study were: “My participation may help to improve and expand treatment delivery/options” (100%); “Pharmacy is the right location for this type of treatment” (100%); “The treatment offered at the pharmacy was of better quality than the usual treatment (i.e., at the OTP)” (86.7%); and “It was easy to understand/distinguish patient, physician, and pharmacist roles” (93.8%).

Table 5.

Treatment satisfaction among study completers at Month 3 (n=16)

Questions	n (%)
Overall, how satisfied are you with your experience in this study?
Very satisfied	14 (87.5%)
Satisfied	0 (0%)
Neither satisfied nor dissatisfied	1 (6.3%)
Dissatisfied	0 (0%)
Very dissatisfied	1 (6.3%)
Overall, how satisfied are you with the quality of treatment offered in this study?
Very satisfied	13 (81.3%)
Satisfied	1 (6.3%)
Neither satisfied nor dissatisfied	1 (6.3%)
Dissatisfied	0 (0%)
Very dissatisfied	1 (6.3%)
How difficult do you think it made it for the treatment to be transferred from the clinic to the pharmacy?
Not difficult at all	15 (93.8%)
Somewhat difficult	1 (6.3%)
Very difficult	0 (0%)
Extremely difficult	0 (0%)
How useful/convenient do you think it is to receive take-home methadone doses at the pharmacy?
Not at all useful/convenient	1 (6.3%)
Somewhat useful/convenient	1 (6.3%)
Moderately useful/convenient	0 (0%)
Very useful/convenient	4 (25.0%)
Extremely useful/convenient	10 (62.5%)
How effective did you find the following aspects of the study?
Having more than one health professional figure involved
Less effective	1 (6.3%)
No difference in effectiveness	8 (50.0%)
More effective	7 (43.8%)
Time spent in each pharmacy visit
Less effective	0 (0%)
No difference in effectiveness	5 (31.3%)
More effective	11 (68.8%)
Time to receive methadone
Less effective	0 (0%)
No difference in effectiveness	5 (31.3%)
More effective	11 (68.8%)
Efficiency of treatment delivery
Less effective	2 (12.5%)
No difference in effectiveness	4 (25.0%)
More effective	10 (62.5%)
If you had to do it all over again, would you still choose to participate in the study?
Definitely participate	16 (100.0%)
Probably participate	0 (0%)
Probably not participate	0 (0%)
Definitely not participate	0 (0%)
Indicate whether each of the following would influence your decision to participate again
My participation may help to improve and expand treatment delivery/options
No	0 (0%)
Yes	16 (100.0%)
Pharmacy is the right location for this type of treatment
No	0 (0%)
Yes	16 (100.0%)
The treatment offered was of better quality than the usual treatment
No	2 (13.3%)
Yes	13 (86.7%)
It was easy to understand/distinguish patient, physician, and pharmacist roles
No	1 (6.3%)
Yes	15 (93.8%)

The survey also asked participants to assess effectiveness of this model that permitted pharmacy dispensing of methadone compared to the usual care (i.e., at OTP) they had. The majority reported pharmacy administration/dispensing of methadone to be “more effective” regarding “time spent in each pharmacy visit” (68.8%), “time to receive methadone” (68.8%), and “efficiency of treatment delivery” (62.5%). About 44% reported more effectiveness regarding “having more than one health professional figure (i.e., pharmacist) involved.”

Treatment delivery satisfaction in physicians and pharmacists

All study physician and pharmacists (n=3) completed the self-administered satisfaction survey at Month 3 (Table 6). All reported being very satisfied with their overall experience and the quality of treatment offered in this study; that methadone administration/dispensing transfer from the OTP to the pharmacy was not difficult at all, and that receiving methadone doses at the pharmacy was either extremely useful/convenient (66.7%) or very useful/convenient (33.3%); and, that they would choose to participate in the study again if given the opportunity. Reasons for influencing their decision to participate in a future study were: “My participation may help to improve and expand treatment delivery/options” (100%); “Pharmacy is the right location for this type of treatment” (100%); “The treatment offered was of better quality than the usual treatment” (100%); and “It was easy to understand/distinguish patient, physician, and pharmacist roles” (100%). Regarding effectiveness of this model, 100% reported being more effective regarding “having more than one health professional figure (i.e., pharmacist) involved,” 66.7% reported being more effective with regard to “time spent in each pharmacy visit,” and 33.3% reported being more effective regarding “time to receive methadone” and “efficiency of treatment delivery.”

Table 6.

Treatment satisfaction among study physician and pharmacists at Month 3 (n=3)

Questions	n (%)
Overall, how satisfied are you with your experience in this study?
Very satisfied	3 (100%)
Satisfied	0 (0%)
Neither satisfied nor dissatisfied	0 (0%)
Dissatisfied	0 (0%)
Very dissatisfied	0 (0%)
Overall, how satisfied are you with the quality of treatment offered in this study?
Very satisfied	3 (100%)
Satisfied	0 (0%)
Neither satisfied nor dissatisfied	0 (0%)
Dissatisfied	0 (0%)
Very dissatisfied	0 (0%)
How difficult do you think it made it for the treatment to be transferred from the clinic to the pharmacy?
Not difficult at all	3 (100%)
Somewhat difficult	0 (0%)
Very difficult	0 (0%)
Extremely difficult	0 (0%)
How useful/convenient do you think it is to receive take-home methadone doses at the pharmacy?
Not at all useful/convenient	0 (0%)
Somewhat useful/convenient	0 (0%)
Moderately useful/convenient	0 (0%)
Very useful/convenient	1 (33.3%)
Extremely useful/convenient	2 (66.7%)
How effective did you find the following aspects of the study?
Having more than one health professional figure involved
Less effective	0 (0%)
No difference in effectiveness	0 (0%)
More effective	3 (100%)
Time spent in each pharmacy visit
Less effective	0 (0%)
No difference in effectiveness	1 (33.3%)
More effective	2 (66.7%)
Time to receive methadone
Less effective	1 (33.3%)
No difference in effectiveness	1 (33.3%)
More effective	1 (33.3%)
Efficiency of treatment delivery
Less effective	0 (0%)
No difference in effectiveness	2 (66.7%)
More effective	1 (33.3%)
If you had to do it all over again, would you still choose to participate in the study?
Definitely participate	3 (100%)
Probably participate	0 (0%)
Probably not participate	0 (0%)
Definitely not participate	0 (0%)
Indicate whether each of the following would influence your decision to participate again
My participation may help to improve and expand treatment delivery/options
No	0 (0%)
Yes	3 (100%)
Pharmacy is the right location for this type of treatment
No	0 (0%)
Yes	3 (100%)
The treatment offered was of better quality than the usual treatment
No	0 (0%)
Yes	3 (100%)
It was easy to understand/distinguish patient, physician, and pharmacist roles
No	0 (0%)
Yes	3 (100%)

Intervention fidelity

A total of 207 MVCs were completed by two pharmacists. We randomly evaluated 72 MVCs (35%), assessing a total of 2,880 items. All 2,880 items were completed. Intervention fidelity was 100% (Supplement Table S4).

DISCUSSION

We present promising findings from a novel pilot trial studying feasibility and acceptability of permitting an OTP physician to prescribe methadone through community pharmacies for their stable patients. These results show support for feasibility and acceptability regarding recruitment, treatment retention and adherence, intervention fidelity, substance use, pharmacists’ use of the PDMP, participant safety, and satisfaction with treatment delivery. The findings have timely implications for clinical practice of MMT, future research with regard to leveraging pharmacists’ medication therapy management expertise to expand OUD treatment, and potentially for policy changes regarding methadone prescribing [23].

Increasing access to buprenorphine and methadone treatment is a key priority to address the US opioid overdose death crisis [31]. However, one of the most difficult challenges in expanding OUD treatment is the shortage of OUD treatment providers and limited numbers of OTPs [4]. Despite the serious increase in opioid-related overdoses in the past decades, annual rates of buprenorphine prescriptions filled for OUD in the US only increased slightly from 1.97 per 1000 population in 2009 to 4.43 per 1000 population in 2018 [32]. Results of this study and two other studies of medication treatment for OUD conducted among US pharmacists provide a compelling rationale for developing partnerships between OUD providers ad community pharmacists to increase the workforce (i.e., pharmacists) for OUD treatment delivery [22,23]. Community pharmacy-based MMT allows individuals with OUD living in a nonmetropolitan areas to receive MMT at pharmacies closer to their home, thereby reducing transportation-related burdens. Research data from US studies indicate that long drive times to an OTP is a major barrier to MMT, as transportation burdens affect treatment retention and the opportunity to maintain employment [33–35]. Kleinman [36] analyzed the US data from 1,682 OTPs and 69,475 pharmacies, and found that the mean population-weighted driving time from census tract mean center of population was 20.4 minutes to OTPs and 4.5 minutes to pharmacies, and that differences in driving time and distance between 1-way trips ending at OTPs and pharmacies were largest in nonmetropolitan counties. Thus, this study produces relevant data to support pharmacy administration and dispensing of methadone for MMT. Our findings suggest that e-prescription of methadone by a supervising OTP physician and use of methadone tablets are feasible for supporting pharmacy administration/dispensing of methadone for OUD treatment. While pharmacy administration/dispensing of methadone could have been accomplished under a physician order as part of an OTP medication unit, the purpose of this study was a proof of concept to permit prescribing of methadone under a research permit, which otherwise would not have been permitted under US regulations. Future research involving prescribing of methadone opens up alternatives to the current US OTP model. Additional research is needed to understand barriers to establishing alternative models of care from perspectives of pharmacists/pharmacy staff, OTP providers/staff, and patients with OUD (e.g., perceived stigma/attitudes towards pharmacy administration/dispensing, training for pharmacists, reimbursement) [37–39].

The US federal regulations allow OTPs to develop partnerships with community pharmacies to establish methadone medication units to enable pharmacy administration and dispensing of methadone for MMT [7]. Currently, we are not aware of methadone medication units at pharmacies in the US. There are approximately 65,000 community pharmacies in the US [12]. About 300,000 pharmacists were active in the US workforce in 2016; by 2030, the supply of pharmacists is expected to increase 36% to 410,490 pharmacists [40]. Thus, research is needed to identify facilitators of and barriers to establishing methadone medication units at pharmacies in the US (e.g., pharmacist competence, communication between pharmacists and OTP providers, MMT procedures, reimbursement) [7,37–39], which would help expand the OUD treatment capability.

Limitations

Because of a lack of research on pharmacy administration/dispensing of MMT in the US, we used a non-randomized design to explore its feasibility and acceptability. Given the constraint of limited resources of a pilot study, the non-randomized design allows us to explore feasibility of this new MMT model in a lager sample of patients with OUD than a randomized trial. This study was also restricted to one OTP and one pharmacy in North Carolina, and participants were from a small sample of stable patients, mostly white and female. Results may not be generalizable to patients newer in treatment or in more diverse samples of men or and non-whites. Additional studies are needed to test the model in pharmacies at different locations (e.g., rural areas) that include patients newer in treatment and those with diverse backgrounds (e.g., men, nonwhites). Additionally, patients receive doses of liquid methadone at the OTP (usual care). Study participants were asked to take methadone tablets at the pharmacy. We specified the tablet methadone requirement in the informed consent, and only one participant cited the tablet formulation as a reason for not participating in the study. There were no study withdrawals as a result of taking tablet methadone. Further, it was unclear whether the location or type of pharmacy (e.g., independent, chain) influenced participant recruitment. This study was conducted at an independent community pharmacy that is not part of a large pharmacy chain. The distance between the OTP and the pharmacy was 5.4 miles. A potential advantage of pharmacy administration/dispensing of methadone is the possibility of reducing long travel distances to the OTP [36], which cannot be determined by this pilot study. Due to the US federal regulations [7], participants continued to receive their usual counseling and drug testing at the OTP during the study period. Thus, this pharmacy model with close ties to the OTP differs from the model in other countries in which the provider can be located in primary care settings rather than an OTP [14–20].

Conclusions

This pilot study was conducted in the “real-world” setting of a community pharmacy partnered with a non-academic OTP. Participant recruitment was completed efficiently. Indicators of medication adherence and intervention fidelity were successful. The results show support for OTP-pharmacy collaboration to establish electronic prescribing of methadone from an OTP physician to a pharmacy to improve MMT access. Further research on the OTP providers, pharmacists, and patients with OUD are needed to identify potential barriers to and workable strategies of implementing and testing such a model [24]. Future clinical trials could test effects of different combinations of services (e.g., medication unit, methadone prescribing, counseling), provider (OTP vs. non-OTP prescriber), and patient type (e.g., new, stable, highly stable) on patient outcomes.