Risk of Relapse Following Discharge from Non-Hospital Residential Opioid Use Disorder Treatment: A Systematic Review of Studies Published from 2018 to 2022

Introduction

Substance use disorder (SUD) treatment has varying levels of care, such as outpatient and residential treatment. Ideally, a multidimensional assessment^1–4 specifies an individual’s biomedical, psychological, and social needs to select the appropriate setting focusing on personalized treatment.^5–9 Residential treatment is a higher level of care recommended for those with significant social or treatment needs.^8,10 The importance of residential treatment is signified by the often complex clinical and environmental needs of individuals for whom residential treatment is recommended.

Residential SUD treatment is categorized by services provided in a 24-hour setting that is substance-free.^11–13 Compared to those who receive outpatient treatment, individuals who receive residential treatment are more likely to complete treatment.¹⁰ Also, relative to outpatient treatment, the protective environment of residential treatment is especially beneficial to individuals with environmental concerns or living arrangements that may hinder their treatment goals. Residential treatment, by providing a stable environment in which substances cannot be easily accessed, serves as a wedge between an individual and their typical living arrangements. This allows individuals receiving care to focus on treatment without being impacted by their typical environmental factors.

Discharging from the protective environment of residential treatment may pose a risk of relapsing on substance(s).¹⁴ Relapse can be described as returning to previous patterns of substance use, although varying definitions for the word relapse exist in the literature.^15,16 Reasons for relapse can be multifactorial, extending across biological, psychological, or social domains. For example, having poorer physical health, co-occurring mental health disorders, greater SUD severity, greater stress, being of younger age, and having poorer social support systems are associated with a greater risk of relapse.^17–19 A systematic review on the effectiveness of residential treatment suggested that best practice should include aftercare/continuing care after discharge.¹¹ This aftercare/continuing care can further support individuals after treatment to sustain potential improvements obtained during residential treatment, such as reaching their recovery goals, and limit the potential of relapsing. It is, therefore, essential to consider the risk of relapse after discharge from residential treatment.

The risk of overdose makes relapsing on opioids after leaving residential treatment particularly problematic. After treatment, an individual’s tolerance of opioids may be lower. Factoring in a lower tolerance to opioids, ingesting a posttreatment dose of opioids equivalent to a pretreatment quantity may increase the risk of an overdose or hospitalization.^20–22 The prominence of fentanyl,²³ a more potent opioid than heroin, in the illicit drug market is also a primary overdose concern. Specifically, fentanyl and its analogues have caused numerous overdoses worldwide.^24–27 Moreover, relapsing on opioids after treatment can be demoralizing to many individuals in recovery,²⁸ and impact the improvements that were acquired from treatment. Reviewing the literature concerning relapse following residential treatment for opioid use disorder (OUD) is essential, considering we are currently in the fentanyl era, where fentanyl and its analogues are implicated in numerous overdoses and have prominence in the illicit drug market.^29–34

The Substance Abuse and Mental Health Service (SAMHSA) differentiates hospital-based inpatient treatment as facilities connected to hospitals from non-hospital residential treatment.³⁵ Non-hospital residential treatment facilities usually include treatment that lasts from one month to a year and may assist those with a more severe SUD such as a severe OUD diagnosis.³⁵ Other review articles have examined recovery outcomes among residential treatment facilities,¹¹ including those focusing on residential treatment in therapeutic communities, which tend to have a longer duration of treatment.^36,37 However, a gap in the research literature exists regarding a review paper on relapse with a focus on individuals with OUD in non-hospital residential treatment settings during the fentanyl era. This review paper examined the literature related to adults relapsing after receiving residential treatment for an OUD. Studies of interest were published during the years 2018 to 2022 with a focus on free standing non-hospital residential treatment facilities.

Materials and Methods

A research librarian at the University of North Carolina at Chapel Hill was consulted to refine the search strategy by identifying the appropriate databases and key terms. The reporting of this protocol is guided by the standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for protocols (PRISMA-P).³⁸

Eligibility Criteria

This review included published studies that report on relapse among adults following discharge from non-hospital residential treatment for OUD. Articles were considered eligible if they met the following criteria: [1] adult sample (≥18 years old), [2] written in English, [3] published from 2018 to 2022, [4] includes data about relapse, returning to patterns of previous use, abstinence, using a substance after a period of abstinence or reduced substance use after discharge, [5] includes information about discharging from the facility, [6] includes a sample with OUD, and [7] did not describe their treatment setting as hospital-based. Due to the variability in how relapse is defined,^15,16 for the purpose of this paper, we operationalized relapse as using a substance after treatment or a period of abstinence reported in the studies included in this review. No restrictions were placed on the geographic area where the study was conducted. Included articles could be quantitative or qualitative. During the planning stages in September 2023, we limited eligible studies to those recently published in the last five years, between 2018 and 2022 to focus on papers published during the fentanyl era. Excluded studies were those that included only minors (≤17 years old), were not written in English, did not include individuals with an OUD, had hospital-based inpatient treatment as the setting, had outpatient treatment as the setting, did not include post-treatment data, did not include a description about post-treatment relapse/returning to patterns of previous use, were review articles, were meta-analyses, or focused on residential mental health disorder treatment instead of residential SUD treatment. Non-hospital residential treatment (inclusion criterion) was differentiated from hospital inpatient (exclusion criterion) using SAMHSA’s definitions, which identify non-hospital residential treatment as typically longer and not connected to a hospital or clinic.³⁵

Search Strategy

Eligible studies were identified through database searches. Databases used for this review include CINAHL, PsychINFO, PubMed, and Scopus. When searching the databases, the following key terms were used: “opioid use disorder” OR “heroin use disorder” OR “opiate use disorder” OR “opioid related disorders” and “residential treatment” OR “residential rehabilitation” OR “residential therapy” OR “residential care” OR “institutional care” OR “group care” OR “therapeutic community” OR “therapeutic communities” OR “inpatient” and “Discharge” OR “post treatment” OR “post residential treatment” OR “release” OR “post care” OR “post rehabilitation” OR “relapse” OR “outcomes”. The search was conducted between September 14, 2023 and March 6, 2024. The authors also checked for additional relevant cited and citing articles using included studies.

Study Records

Search results were pooled in Endnote and de-duplicated [www.endnote.com]. This set was uploaded to Covidence [www.covidence.org] for screening.

Selection Process

Using Covidence [www.covidence.org], two screeners independently reviewed the titles and abstracts for eligibility criteria and made a yes, no, or maybe decision. The full texts were downloaded for studies coded as yes or maybe to be further reviewed for eligibility. At each stage of review, any conflicts were resolved through consensus with a third reviewer. The study team held regular meetings throughout the selection process to discuss article eligibility.

Data Collection Process

Once the studies were identified for inclusion, the authors extracted data from each study to complete Table 1. For each study, there was a primary reviewer who extracted the data and a secondary reviewer to confirm the accuracy of the extracted data. Specifically, for each study, we reported [1] the lead author, [2] article title, [3] aim of the study, [4] total number of participants, [5] sample description, [6] inclusion criteria, [7] exclusion criteria, [8] country in which the study was conducted, [9] study design, [10] OUD treatment description, [11] post-discharge main outcomes, [12] post-discharge secondary outcomes, and [13] main findings related to outcomes of interest.

Table 1 Included Studies of Residential Treatment for OUD

Risk of Bias

To reduce the risk of bias, we assessed sources of funding, disclosure of conflicts of interests, the reliability and validity of the measures used for the outcome, collection of longitudinal data, and the inclusion of a comparison group.

Results

The selection process for the articles included in this study may be found in Figure 1. A total of ten articles were retained for inclusion in this review.^39–48 Descriptions of the ten articles may be found in Table 1. Regarding the risk of bias assessment (Table 2), six studies^40,42–46 cited funding from the National Institutes of Health (NIH), two^41,48 studies specified other fundings sources, and one study⁴⁷ did not disclose their funding sources. The authors from four studies^42,44,46,47 declared no conflicts of interest and the authors of three studies.^41,43,48

Table 2 Risk of Bias Assessment

Figure 1 PRISMA flowchart of included studies. Adapted from Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. Creative Commons.

Samples

When the average age of participants was included in the study, five studies described a sample with an average age of 30 to 39.^{39,40,43,44,46} Exceptions included studies that focused specifically on younger samples, such as young adults,⁴¹ and the Hartung et al, 2022 study, which presented age as categorical.⁴² Another exception is the Uğurlu et al, 2020 study, which had a sample with an average age of 22.5 among a case group and 22.2 among a control group.⁴⁷ The study by Mukherjee et al, in 2021 identified the average age of a subsample that relapsed as being 31.9 years old and the subsample that remained abstinent as being 28.0 years old.⁴⁵ Regarding reported sex, females were in the minority across all studies,^39–46,48 including the Uğurlu et al, 2020 study in which 100% of the sample participants were male among the case group.⁴⁷ Not all studies included the race and ethnicity of the participants. Among the six studies^{39,41–43,46,48} that did include this information, the majority of participants were non-Hispanic White in all six studies. Nine of the ten studies were conducted in the United States, one study⁴⁷ was conducted in Turkey. Five studies used a cohort design, two were randomized controlled trials, two were case–control design, and one was a retrospective chart review, which analyzed notes made by the study team regarding communications with the participant or their significant other.

Defining Treatment

The details regarding treatment received greatly varied across studies. All studies included in the final synthesis (Table 1) presented data from participants who had attended or completed residential treatment, but the specifics of what was included in that treatment were not always provided. Five studies^{39,41,43,46,48} specifically mentioned MOUD with either naltrexone, methadone, or buprenorphine. Six studies^{40,41,43,44,46,47} mentioned some form of individual or group therapy or psychoeducation.

Defining Relapse

Variability in the time that participants were followed after discharge for data collection purposes and how substance use was identified after discharge among these different studies exists. The follow-up periods ranged from 1 month³⁹ to 6 months.^43,46,47 Three studies captured follow-up substance use data using self-report only.^39,43,46 One study analyzed patient chart notes for mentions of lapse or relapse.⁴⁸ Other ways that follow-up substance use data were captured included hair samples,^40,44,45 urine drug screening,^{40,41,44,45,47} overdose data,⁴² and opioid-related emergency department engagement.⁴²

Relapse

There was a broad range across the studies regarding the reported percentage of individuals who relapsed. These ranges include 0% (n = 0 / 6) from the Uğurlu et al, 2020⁴⁷ study to 95% (n = 19 / 20) opioid relapse among the treatment as usual group in the Fishman et al, 2021 study.⁴¹ Regarding percentages of the individuals relapsing, findings include: 24% (n = 5 / 21) relapsing onto opioids after receiving all doses of the study drug, extended-release naltrexone,⁴⁸ 38% (n = 21 / 55) relapsing onto any substance,⁴⁵ 51% (n = 36 / 70) relapsing onto any substance at follow-up,⁴⁴ 57% using a non-prescribed opioid,³⁹ and 61% (n = 11 / 18) opioid relapse of a study’s intervention arm (intervention: youth opioid recovery support) relapsing.⁴¹

Percentages of other reported substances in the Baxley et al, 2019 study include cannabis at 29%, alcohol at 20%, benzodiazepines at 16%, and cocaine at 10%.³⁹ The Mukherjee et al, 2021 study identified three individuals using alcohol and 18 individuals using opioids at follow-up.⁴⁵ Cleveland et al, found that greater variability among within-person assessments of craving was associated with a lower likelihood of relapse when compared to participants with lower within-person variability of craving.⁴⁰ In the Hartung et al, 2022 study, 2.5% (n = 24 / 957) had an opioid overdose, and 15.4% (n = 147 / 957) had an opioid-related engagement with emergency department services.⁴² Hayaki et al, found that lower self-efficacy in being able to withstand opioid use during negative states as measured at baseline was associated with using an illicit opioid at follow-up.⁴³ The study by Stein et al, found the buprenorphine induction group had lower illicit opioid use at follow-up days 12, 35, 95, and 185 than the treatment as usual group that received withdrawal management.⁴⁶ Wenzel et al, found that relapse occurred among 24% (n = 5 / 21) relapsing onto opioids after receiving all doses of the study drug, extended-release naltrexone.⁴⁸ In three descriptive patient vignettes, Wenzel et al, described one individual having a non-fatal opioid overdose and two individuals relapsing on opioids.⁴⁸

Discussion

After discharging from residential treatment, some individuals may decide to return to substance use,¹⁴ which is concerning for those with an OUD, as fentanyl and its analogues are potent and largely dominate the illicit opioid market.^23–26,49 With fentanyl’s potency, relapse onto opioids after residential treatment presents the possibility for an overdose due to a lower tolerance to opioids.^50,51 Therefore, this review paper focused on the risk of relapse following residential treatment.

Across the studies included in this review, returning to substance use after residential treatment was captured differently. However, this variability can be explained by the different definitions of relapse identified in the research literature^15,16,52 and the availability of time and resources needed to capture follow-up data. Different time periods in which the relapse data were collected ranged from 1 month³⁹ to 6 months.^43,46,47 Perspectives of individuals experiencing relapse while in recovery highlight a more substantial risk of relapse in the long-term compared to the earlier stages of recovery.²⁸ Further, some individuals may discharge from treatment initially confident that they will abstain from returning to substance use.⁵³ Regardless of when the relapse occurs, some individuals may feel a sense of powerlessness after relapsing.²⁸

Even with the range in the time to follow-up across studies, the percentage of reported relapse across studies was high. Except for one study included in this review which reported 0% relapse among cases and controls at follow-up timepoints,⁴⁷ the percentages of individuals who relapsed ranged from a quarter to 95%.^{39,41,44,45,48} The wide variation in the types of treatments delivered makes it difficult to assess differences in relapse rates between treatment modalities. Other studies in the literature have identified this broad range of the percentage of individuals relapsing.^52,54–58 Across studies included in this review, how substance use was captured after discharge included the number of times data was collected from participants during the follow-up period and how substance use data were collected, including hair samples^40,44,45 and urine drug screening.^{40,41,44,45,47} Utilizing biospecimens such as hair and urine samples may provide more accurate data than self-report.^59–62 However, factors such as the frequency that a substance was used, the window of time that biospecimen tests will identify substance use, and the cost of collecting biospecimen after residential treatment must be considered.^59–62

Collecting biospecimen after a patient’s discharge may be logistically challenging for treatment providers that provide follow-up outpatient telehealth services. Regardless of whether self-report and/or biospecimen collection are used to determine substance use, these strategies should be tools to support the individual after their recovery and not as a tool for punishment if substance use is detected. Post-treatment contingency management interventions could support individuals in continuing to reach recovery goals and remaining abstinent from opioids and other substances.^63–65 Contingency management is effective for increasing abstinence among individuals in recovery from opioids and other substances after treatment.^64,65 A common barrier that prevents clinical implementation of known effective treatments is the lack of funding to support efficacious programs. There is a need for policy changes to financially support these treatment options for individuals with and without private insurance. Future research is needed to conduct cost-effectiveness systematic reviews of interventions which can inform policies based on the interventions that show the highest return on investment (ROI). This area of study can bridge the gap between community dissemination/implementation and policy-level translational science.

Participants using other substances, such as alcohol and cannabis, were also identified in studies included in this review.^39,45 Some individuals with an OUD may engage in polysubstance use and use other non-opioid substances,^29,66–71 highlighting the importance of screening for and treating other potential SUD during treatment. This is especially important for some individuals receiving treatment who may have a treatment goal of not using any substances regardless of the drug class (ie, stimulants, opioids) after treatment.

Negative emotional states may be encountered after discharge which makes the findings by the Hayaki et al, 2021 study important since lower self-efficacy during these negative states was associated with a greater risk of relapse.⁴³ Self-efficacy interventions in treatment are needed to support recovery goals, such as not leaving treatment prematurely and reducing substance use after discharge.^43,72,73 One such intervention includes brief values clarification during treatment to improve self-efficacy towards reaching recovery goals.⁷⁴ Relapse prevention strategies that address and prepare individuals for the potential for negative states after treatment may improve self-efficacy.⁷⁵ Being able to cope with negative emotional states by using avoidance, cognitive, or distraction strategies may assist individuals with avoiding returning to substance use as a potential coping mechanism.⁷⁶

Considering the risk of relapse after treatment, other proactive models of engaging people after treatment often provide extra support to help individuals continue to achieve their recovery goals even after treatment.⁷⁷ These continuing care and support services after treatment can assist individuals as they are discharged from the safe environment of residential treatment in which substances cannot be easily accessed.^77,78 A meta-analysis suggested that long-term treatment and support after discharge, compared to shorter treatment was associated with greater chances of remaining abstinent.⁷⁷ Other individuals may opt to receive outpatient services after discharging from residential treatment to continue engaging with treatment services.⁷⁹ Whether aftercare/continuing care or outpatient services are provided, individuals discharging from residential treatment must have the appropriate resources to support them as they achieve their recovery goals.¹¹

Overall, the risk of relapse after residential treatment for OUD is a prominent concern, considering the potential for overdose. The rates of overdose and opioid-related emergency department encounters after residential treatment presented by Hartung et al, 2022 are indicative of the inherent risk of biomedical harm after relapsing.⁴² There is a risk of death due to opioids after discharging from treatment,^50,80 such as one study in New York identifying crude overdose death rates as 71.6 per 1000 person-years in a 14-day period after discharging from treatment.⁵¹ It is imperative to reduce these risks by including relapse prevention techniques during residential treatment that may assist individuals after discharge. Even when aftercare/continuing care services¹¹ are not available for the individual after treatment, providers must ensure that individuals leaving residential treatment have appropriate resources to support them in their recovery. Doing so may be the difference between someone achieving their recovery goals after treatment or risking potentially harmful outcomes of returning to previous patterns of substance use.

Limitations

Although this study focused on non-hospital residential treatment and studies specifically mentioning the study site as being hospital-based were excluded, some included studies may have occurred in a hospital setting, which may not have been explicitly described in their text. Studies included in this review were limited by the databases used: CINAHL, PsychINFO, PubMed, and Scopus, which may not include the full research literature. While this review focused on works published starting in 2018 to capture potential findings from the fentanyl era of OUD, other studies prior to 2017 were excluded as a result. Another limitation is this review included studies that were naturalistic and experimental, representing two different research approaches. This is further highlighted by differences in relapse that were identified in some of the experimental studies such the Fishman et al, 2021 study identifying relapse occurring among 61% of the experimental group and among 95% of the treatment as usual group.⁴¹ While we examined funding and conflicts of interest for potential risk of bias assessment, other standardized Risk of Bias tools were not included in this current paper. Considering the importance of aftercare/continuing care, these factors not being examined in the current review is also a limitation. All the included studies except for one (Uğurlu et al, 2020) were based in the United States. Our a priori inclusion and exclusion criteria did not allow for excluding this study based on location. The Uğurlu et al, 2020 study also had the smallest sample size and was the only study to report a 0% relapse rate. This may reflect the greater focus on opioid-related treatments within the United States, which is likely based on need and severity of OUD. Another study limitation is some included studies were both the parent and secondary studies using different pools of the sample participants. Lastly, studies included in this review had both short-term and long-term residential treatment settings, which have varied lengths of stay.

Conclusion

This review paper focused on the risk of relapse following non-hospital residential treatment for OUD. Pertinent clinical considerations are presented by merging findings from the papers included in this review. There was a broad range across the included studies regarding the percentage of individuals who relapsed from 0% to 95%. Differences in the time in which relapse data were collected across included studies ranged from 1 month to 6 months. Craving and negative emotional states were associated with relapse, pointing to the importance of interventions to address these factors during and after treatment. Considering the potential for a fatal overdose in the current fentanyl era, it is imperative to provide resources during residential treatment that can reduce the risk of relapse after discharge.