Patient perspectives of methadone formulation change in British Columbia, Canada: outcomes of a provincial survey

The goal of this study was to explore the perceptions of how persons enrolled in MMT in BC were affected by the transition to Methadose™. Our findings revealed large proportions of participants reported worse taste, the need to increase methadone dose, and increased withdrawal and pain symptoms. Worse taste was significantly correlated with reported lack of effectiveness and deterioration of symptoms across multiple parameters, as demonstrated by more withdrawal symptoms, pain and need to increase dose. These associations were not significantly related to how patients heard about the formulation change, geographic region, or other sociodemographic factors. Overall, our findings of increased pain, withdrawal symptoms, and need to increase methadone dose following the formulation change to Methadose™ have implications for the wellbeing of MMT patients in BC that must be considered.

Previous studies support our findings that medication transition periods can have pronounced bio-psychosocial impacts on patients. In the United Kingdom, change in methadone formulation in 1992 was correlated with an increase use of non-prescription opioids, decline in social stability, and an increase in pharmacy break-ins [20]. A clinical study conducted by Soyka and Zingg in 2009 found the transfer from racemic methadone to (R)-methadone decreased withdrawal symptoms, cravings, and supplementing with additional drugs [21]. In our study, over half of participants reported supplementing with other drugs following the transition to Methadose™. Methadone diversion and its illicit use are not uncommon; the 2014 survey of clients at harm reduction supply distribution sites in BC found that 8 % of respondents accessed methadone without a prescription (unpublished BCCDC data). Diversion in medication compliance has been critical in subsequent injection drug use, crime, and morbidity and mortality rates [22, 23]; hence, any instability in MMT leading to a rebound in illicit drug use may result in possible decline in social function and worse health outcomes in BC.

Silver and Shaffer (1997) found patients could be more intolerant to methadone formulation changes than others (coined ‘change intolerance’) [24]. In their study of 177 MMT patients, researchers found gender, treatment history, and previous methadone abuse predicted change intolerance. Gourevitch et al. provides further evidence demonstrating that change intolerance to different methadone formulations is related to psychosocial stressors rather than having a pharmacodynamic basis [17]. In a small double-blind crossover trial of three methadone formulations they demonstrated self-reported withdrawal symptoms did not correlate with plasma methadone levels [17]. The effect of taste on patients’ perception of pharmacological efficacy and side effects is not well studied. A randomized control trial conducted by Farr (1986) showed that medication taste affected participants’ perceptions [25]. In this study, bitter tasting zinc gluconate lozenges were perceived to have more negative side effects than the tasteless placebo tablets. This effect diminished when taste-matching placebos were used [25]. In France, where the capsule formulation of MMT recently became available in addition to the syrup formulation, two recent studies showed the potential superiority of the dry (capsule) MMT formulation [18, 26]. Boucherie et al. (2015) demonstrated that there was a rise in capsule MMT users in a five year period with a corresponding drop in prevalence of individuals using the syrup formulation [26], and Eiden et al. (2013) described 80 % of patients experienced negative side effects from use of the syrup MMT formulation [18]. In light of the large proportion of MMT patients in our study who reported worse taste and its relation to negative outcomes, consideration of other formulations of methadone including the capsule form, may be warranted. However, some literature has highlighted that non-syrup forms of MMT may increase diversion and misuse liability [18].

These findings are corroborated by a recent qualitative study conducted by McNeil et al. (2015) who interviewed 34 MMT patients in the Vancouver region; 31 who had transitioned to Methadose^TM at the time of interview [16]. This study supports the notion that the methadone formulation transition in BC produced considerable negative health and social impacts on patients and demonstrated that these effects were exacerbated by the structural vulnerability that patients on MMT are subjected to [16]. They also suggest real or perceived withdrawal symptoms might have a psychological component, as in our study, which strongly suggests perceptions of changes in taste contribute to withdrawal symptoms, pain, and need to increase dose. Although we anticipated similar findings, our study had a number of strengths and adds to the literature. We had quantitative responses from over 400 people throughout the province and, thus, our results were not limited to the Vancouver area. While methadone formulation changes have occurred in other provinces in Canada (i.e. Alberta, Ontario), there remains a lack of evaluation data of the impact and differences of the implementation of these policies.

These studies and ours underscore the importance of recognizing that many persons participating in MMT belong to a particularly vulnerable population who are often victim to structural discrimination, which may make them less able to cope with imposed medication changes and loss of autonomy [25]. Trujols et al. (2011) argue much of the satisfaction with MMT comes from patients who perceive themselves as participating to some extent in treatment decisions [27]. The impact of the transition to Methadose™ in BC among MMT patients may be further exacerbated by the change in home delivery policy further adding to the instability and dissatisfaction to the program. The capacity for agency and a flexible interim period appear to be important factors in the stability of medication transitions. There is evidence that patients are more satisfied with their MMT programs when they perceive themselves as participating in treatment decision-making [27]. Another study suggested that although there may be some transitional instabilities encountered after methadone formulation changes, they could be further mitigated by providing patients with a longer transition period as well as a choice of the transitional process [28].

One strategy to mitigate this impact that could be incorporated during medication formulation changes, is involving and consulting the community affected in the development and implementation of new regulatory policies. El Ansari and Phillips (2004) found that a low amount of involvement with the community is associated with decreased costs and increased satisfaction with policies [29]. In BC, the College of Pharmacists, College of Physicians and Surgeons and Ministry of Health met with representatives from the Vancouver Area Network of Drug Users and BC Association of People on Methadone on three occasions over ten months prior to the change to Methadose™ (Personal communication Solven S., 2015). During this time patient groups provided feedback regarding the dispensing standards for MMT that resulted in several changes and helped to produce communication materials (i.e. “Think before you drink” campaign) [30].

Despite a concerted effort by the College of Pharmacists of BC to engage with people on methadone, our study found significant negative perceptions of the methadone formulation change in the province. It is interesting to note that our results showed nearly three-quarters heard about the methadone formulation transition from their methadone-prescribing physician or pharmacist, who could be a useful avenue for the dissemination of educational resources. However, the remaining one-quarter of participants could have benefited from greater awareness and public education campaigns during the transition period. Patients may benefit from longer and more flexible transitional timeline of several months, rather than weeks, when the old formulation may be accessible during the introduction of the new formulation. During this time, patients could be monitored closely for changes in pain and dope sickness. Although patients may be more accepting with a longer and more flexible transition period, the College of Pharmacists of BC believed a shorter transition period would minimize the chance of error with the two different strengths, and therefore decided against an increased transition period(Personal communication Solven S., 2015). Lastly, it may have been helpful to introduce different formulation options for patients; similar to Alberta and Ontario, Methadose™ may be better tolerated (particularly taste) if MMT patients were given the option to have unflavored Methadose™ or be able to dilute in a Tang™-flavored drink which would maintain consistency with previous volume and flavor [31, 32].

While our study highlights some important findings that may have policy implications, several limitations must be considered. First, we recruited and sampled people who access harm reduction sites for supplies across BC, signifying that many of our survey participants may use illicit drugs in addition to their MMT. These patients may represent a structurally vulnerable population [16]; as such, these findings may not be generalizable to all MMT patients. However, it is important to understand the challenges of MMT for these individuals and reduce their heightened barriers for access [33]. Although our study was administered in all five regional health authorities at 50 harm reduction sites across BC, access to MMT varies across regions. Regions where patients have one source of MMT may be more accepting of changes as they are not accustomed to having a choice of MMT; however, our findings were not significantly different across regions. As this study was a cross-sectional design after the change occurred, satisfaction with MMT was not assessed prior to the change. Future research may benefit from measuring dose and satisfaction with MMT longitudinally, capturing both before and after measures. This study did not examine whether negative experiences following the formulation change impacted continuation on MMT, which could be an area for future research. Finally, multiple bivariate analyses were conducted with many variables serving as both explanatory and outcome variables. With multiple analyses, we acknowledge the consequent risk of Type I error that may be inflated with this type of analysis.

In conclusion, we characterized several negative perceptions and outcomes among a sample of MMT patients following a province-wide methadone formulation change to Methadose™ in BC, Canada. These findings highlight the structural vulnerability PWUD and MMT patients face, and point to the importance of involving all stakeholders policy decision-making. We urge policy makers to consider a more engaging and transparent approach when working with structurally vulnerable populations, including people with a history of substance misuse, incarceration and mental health illness, and homelessness.

This study was approved by the University of British Columbia Research Ethics Board prior to collecting data, and for the duration of this research. Informed consent was obtained from all participants, including consent to publish.