Treatment retention in opioid agonist therapy: comparison of methadone versus buprenorphine/naloxone through analysis of daily observed drug dispenses in a Canadian province – BMC Psychiatry

Our data further provide insight into the relationship between opioid use disorder medication and treatment maintenance for the subset of patients receiving predominantly daily observed medications. These patients are typically those who are less stable and clinically represent the most common patients receiving long-term medications for opioid use disorders.

In line with the 2014 Cochrane meta-analysis [10]we found that patients treated with buprenorphine/naloxone were less likely to remain on treatment at some point after induction than patients started with methadone. In the meta-analysis, this finding related to the “flexible dosing” of buprenorphine, which is typical clinical practice – continued titration until adequate protection against withdrawal symptoms is provided.

We also found that initial retention in the first few weeks of therapy was quite similar between the drugs, with an insignificant difference between methadone and buprenorphine/naloxone groups at discontinuation in the first 14 days. In our sample, we report fewer dropouts in the first 2 weeks than is typically the case in other epidemiological samples of OAT retention [13, 14],

Many strategies have been described to improve treatment retention in OAT patients, including alternative forms of care, integration of multiple medical/psychiatric/social services, emergency management/reward systems, and long-acting OAT drug formulations [15]. While many of these strategies did not differ significantly from treatment retention as an outcome, a recent study from Ontario, Canada, described greater patient retention when care was provided in a telemedicine/virtual care model [16].

The study period included treatment initiated between 2014 and 2018 and follow-up through September 2020. The treatment landscape has changed significantly in terms of prescribing practice in Nova Scotia and this is reflected in our data for this specific population. In 2014, only 3% of OATs consisted of buprenorphine, while in 2018 it made up 50% of all OAT drug prescriptions in our population. This shift likely represents a provider preference to initiate patients on buprenorphine/naloxone due to its lower risk of crushing and injecting buprenorphine and a more tolerable safety profile, particularly in the context of the trend toward more permissive and expeditious access for “take home” dosing of OAT drugs [17].

Another emerging technique to improve treatment retention, which could contribute to a further shift in prescribing toward buprenorphine/naloxone, is the practice of microinduction dosing of this drug so that patients can be started on buprenorphine/naloxone at the same time as full-opioid agonists are administered and titrated to a treatment dose before stopping full agonist medication so that opioid withdrawal is avoided [17, 18].

A secondary finding of interest is the potential association between prescription psychostimulant use and treatment retention in this population. We used this indicator as a proxy for previous diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD), although we had no information on current psychostimulant use or adherence to this category of drugs. We found that a positive history of this indicator at any time point was associated with decreased treatment maintenance after accounting for the opioid agonist medications the patient was prescribed. ADHD is a well-documented risk factor that predisposes to substance use disorders [19]and it has previously been described that ADHD may be a factor leading to reduced retention in treatment for use with drugs for opioid use disorders [20, 21].

A further subgroup analysis was performed in patients less than 25 years of age as this is a particularly vulnerable population in terms of morbidity and mortality associated with opioid use disorders [22]. A position statement was recently released by the American Academy of Pediatrics indicating that it is of paramount importance to engage this population and offer the best evidence-based MOUD treatment options as a first choice [23]. Our analysis suggests that despite a changing treatment landscape in this age group in recent years, methadone continues to offer a superior treatment retention profile compared to buprenorphine/naloxone.

Interestingly, the association between a history of psychostimulant prescription and reduced treatment retention was not maintained in the subgroup analysis of patients younger than 25 years of age, such that there was no difference in treatment retention by a positive history of psychostimulant prescription. This may reflect a previously proposed theory of early onset ADHD medication prescribing acting as a protective factor against ADHD-related difficulty in adhering to treatment, although more research is needed [24].

There are several clear limitations of the current study. We used data collected for prescription monitoring purposes and not specifically for epidemiological research purposes. There were several difficulties in translating this data to draw clinically relevant conclusions, including a limited number of cases where pharmacies reported that patients had been dosed when in fact they had not, as they occasionally used OAT drugs charge for a full day in advance regardless of when a patient picks up their dose. There was a possibility that several patients were incorrectly excluded because they might have been flagged as take-home doses (>3 days of consecutive medication), when in fact it was a pharmacy transcription error. History of psychostimulant use as a proxy for ADHD is an imperfect measure and does not provide us with information on the validity of the diagnosis or ongoing medical management thereof. Finally, the COVID-19 pandemic began during the follow-up window for treatment monitoring, and thus some patients may have received take-home doses of medication while otherwise falling within the population we were attempting to characterize, potentially leading to early discontinuation dates of treatment episodes.

The choice of OAT medication for each treatment episode was a prescriber-specific decision. It was created in discussion with the patient, based on past experiences of both the prescribing physician and the patient, as well as the patient’s individual clinical profile.

Data are collected from community pharmacies and do not represent hospital or facility prescribing patterns. Data for this study period are intended to represent the maintenance dose of each opioid agonist. It is forbidden to send patients to certain pharmacies in NS, so numerous pharmacies have been used to dispense OAT. However, evaluating site differences was beyond the scope of this analysis of secondary data.

This could be useful research in the future.

In the last 18 months, the COVID-19 pandemic has drastically changed the practices of prescribers worldwide regarding OAT. Rapid roll-out of telehealth services and easing restrictions on take-away cans have been adopted in many countries [25, 26]. While this is still a very active area of ​​research, these changes were seen as a public health imperative to both reduce transmission of COVID-19 and attempt to alleviate the social and environmental pressures of the pandemic on already vulnerable populations [27]. This shift in OAT practice will undoubtedly impact expected treatment retention rates, and there will be a great need for follow-up studies on these trends.

There are many variables that contribute to initiation and discontinuation of treatment with any of the drugs studied, or indeed any drug, for opioid use disorders. The aim of our present study was to assess the rather narrow view of the current treatment climate in Nova Scotia only in relation to the few data points available to us in this secondary analysis. It is possible that buprenorphine/naloxone may be prescribed off-label for chronic pain in some cases, but this treatment has not been approved by guidelines.

It is unlikely to provide adequate pain relief for patients without opioid dependence or addiction.