Our data continue to provide insight into the relationship between medication for opioid use disorders and retention in treatment for the subset of patients who receive predominantly daily witnessed medications. These patients are typically those who are less stable, and clinically represent most patients on long term medications for opioid use disorder.
In agreement with the Cochrane meta-analysis from 2014 [10], we found that patients maintained on buprenorphine/naloxone were less likely to be retained in treatment at a given time after induction than those started on methadone. In the meta-analysis, this finding was for “flexible dosing” of buprenorphine, which is the typical clinical practice – continued titration until enough protection is offered from withdrawal symptoms.
We also found that the initial retention in the first several weeks of therapy was quite similar between the medications, with an insignificant difference between methadone and buprenorphine/naloxone groups on dropout in the first 14 days. In our sample we report fewer drop-outs in the first 2 weeks than is typically shown in other epidemiological samples of OAT retention [13, 14],
Many strategies have been described to improve treatment retention amongst patients enrolled in OAT, including alternative means of care delivery, integration of multiple medical/psychiatric/social services, contingency management/reward systems, and long acting formulations of OAT medications [15]. While treatment retention as an outcome was not significantly different between many of these strategies, a recent study from Ontario, Canada described greater retention when care was offered in a telehealth/virtual care model [16].
The study period covered treatment initiated between 2014 and 2018 and follow up continued through September 2020. The treatment landscape changed significantly with respect to prescribing practices in Nova Scotia, and this is reflected in our data for this specific population. In 2014, only 3% of OAT consisted of buprenorphine, while in 2018 it comprised 50% of total OAT medication prescriptions in our population. This shift likely represents a provider preference toward initiating patients on buprenorphine/naloxone as it has less risk crushing and injecting buprenorphine and a more tolerable safety profile, particularly in the context of the trend toward more permissive and rapid access to “take home” dosing of OAT medications [17].
Yet another emerging technique to improve treatment retention, and which may be contributing to the shift of prescribing further towards buprenorphine/naloxone, is the practice of micro-induction dosing of this medication, such that patients can be initiated on buprenorphine/naloxone concurrently with ongoing full opioid agonists and titrated to a treatment dose prior to cessation of full agonist medication such that opioid withdrawal is avoided [17, 18].
A secondary outcome of interest is the potential association of prescription psychostimulant use history on treatment retention in this population. We used this indicator as a proxy for past diagnosis and treatment of Attention Deficit Hyperactivity Disorder (ADHD), although we did not have information on current psychostimulant use or compliance with this medication category. We found that a positive history of this indicator was associated with decreased treatment retention at any given time, after accounting for the opioid agonist medication that the patient was prescribed. ADHD is a well documented risk factor predisposing to substance use disorders [19], and it has previously been described that ADHD may be a factor leading to decreased retention in treatment for use with medications for opioid use disorder [20, 21].
Further subgroup analysis on patients under age 25 was conducted as this is a particularly vulnerable population in terms of morbidity and mortality associated with opioid use disorder [22]. A position statement by the American Academy of Pediatrics has been published recently which suggests the paramount importance of engaging this population and offering the most evidence based MOUD treatment options as first line [23]. Our analysis suggests that methadone continues to offer a superior profile of treatment retention as compared to buprenorphine/naloxone in this age group, despite a changing landscape of treatment in recent years.
Interestingly, the association between history of psychostimulant prescription and decreased treatment retention was not maintained in the subgroup analysis of patients younger than 25, such that there was no difference in treatment retention by positive history of psychostimulant prescription. This may be reflective of a previously proposed theory of early onset prescribing of ADHD medication acting as a protective factor against ADHD related difficulties with complying with treatment, though more research will be needed [24].
There are several clear limitations to the current study. We were using data collected for the purpose of prescription monitoring and not specifically for epidemiological research. There were several difficulties in translating this data to make clinically relevant conclusions, including a limited number of instances where pharmacies reported that patients had received doses when in fact they had not, as they may occasionally bill ahead for OAT medications for an entire day regardless of when a patient picks up their dose. There was the potential that several patients may have been inappropriately excluded because they may have been marked as having take home doses (dispensed > 3 days sequential medication) when it was in fact a pharmacy transcription error. Previous history of psychostimulant use as a proxy for ADHD is an imperfect measure and does not give us any information about the validity of the diagnosis or the ongoing medical treatment of it. Finally, the COVID-19 pandemic began during the follow up window for treatment monitoring, and as such some patients may have received take home doses of medication while otherwise falling into the population we were trying to characterize, potentially leading to premature stop dates of treatment episodes.
Choice of OAT medication for each treatment episode was a prescriber-specific decision. It was made in discussion with the patient based on previous experiences of both the prescriber and patient, as well as the individual clinical profile of the patient.
The data are collected from community pharmacies, and they do not represent any prescribing patterns in hospital or institutional settings. The data for this study period is intended to represent maintenance dosage of each opioid agonist. It is prohibited to send patients to specific pharmacy in NS therefore numerous pharmacies were used to dispense OAT. Evaluation of site differences was beyond the scope of this analysis of secondary data, but.
this could be useful research In the future.
Over the last 18 months, the COVID-19 pandemic has drastically shifted the practices of prescribers worldwide with respect to OAT. Rapid adoption of tele-health services and loosening of restrictions on “take home” doses were 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 both to decrease transmission of COVID-19 and to attempt to mitigate the social and environmental pressures of the pandemic on already vulnerable populations [27]. This shift in OAT practice will undoubtedly have an impact on prospective rates of treatment retention, and there will be ample need for follow up study of these trends.
There are many variables which contribute to treatment initiation and dropout with either of the studied medications, or in fact any medication for opioid use disorder. The aim of our present study was to assess the rather narrow view of this in looking at the current treatment climate in Nova Scotia with respect only to the few data points we had available in this secondary analysis. It is possible that in few cases, buprenorphine/naloxone is prescribed off-label for chronic pain, but this treatment has not been approved by guidelines and.
is unlikely to provide adequate pain relief for patients without opioid dependence or addiction.
