Opioid Use Disorder Medications: What We (Don’t) Know About Day-to-Day Functioning

Methadone, suboxone, and naltrexone are lifesaving treatments that help individuals recover from opioid use disorder. We know that they help to reduce opioid use, but what do we know about their effects on other aspects of life and everyday functions?

WHAT PROBLEM DOES THIS STUDY ADDRESS?

Opioid use disorder has become a major public health problem and is now the leading reason for addiction treatment, second to alcohol. Fortunately, medications (i.e. pharmacotherapies) are available to aid recovery from opioid use disorder and are becoming more widely available. In the United States, federally approved pharmacotherapies include methadone, buprenorphine (e.g., suboxone), and naltrexone. While evidence supports their ability to help individuals recover from opioid use disorder (i.e. reduce opioid use), anecdotally a common concern is whether medications improve other areas of function too.

While important in their own right, improvements in these non-substance use domains of psychosocial functioning and resources, often called recovery capital, may help sustain recovery over the long-term. Thus, there is a need to better understand how these lifesaving treatments affect everyday functions like social relationships and cognitive skills, that might play an important role in longterm recovery. This review evaluates the research conducted to-date that examines the effects of opioid use disorder pharmacotherapies on functioning in various aspects of one’s life, including physical, social, occupational (i.e. work-related functioning), and neurocognitive outcomes.

HOW WAS THIS STUDY CONDUCTED?

The authors performed an extensive review on 40 english-language studies, conducted between the years 1969 and 2017, that assessed the effects of methadone, buprenorphine, and/or naltrexone treatment on functional outcomes.

READ MORE ON STUDY METHODS

All studies evaluated adults diagnosed with opioid use disorder who were receiving one of the three pharmacotherapies. The authors entered specific search terms into databases containing hundreds of thousands of scientific articles to find the studies that met their specific criteria for this review.

Studies meeting their criteria investigated one of four functional outcomes, including 1) physical functioning (e.g., physical health), 2) social functioning (e.g., criminal behaviors, family relationships), 3)occupational function (e.g., obtaining work, ability to perform job-related duties), and 4) neurocognitive abilities (e.g., attention, memory). This review was limited to controlled trials and observational studies comparing two or more groups at baseline and follow-up. Only investigations of individuals receiving outpatient treatment in a methadone clinic or doctor’s office were included. Reports compared opioid use disorder patients to 1) each other (e.g., buprenorphine treated patients vs. methadone treated patients), 2) healthy community controls without a history of substance use disorder, or 3) individuals with opioid use disorder who were not receiving pharmacotherapy. Studies were excluded if they assessed pregnant women or individuals who were only receiving brief opioid pharmacotherapy for detoxification purposes.

The quality of each study was assessed by evaluating selection bias (e.g., methods for randomly assigning groups), performance and detection bias (e.g., blinding of participants and staff to group assignment), attrition bias (e.g., data on study completion), and reporting bias (e.g., reporting on selective outcomes measures). Quality was also assessed by evaluating participant representativeness of the general patient population, how well groups were matched, how outcomes were assessed, and whether potential confounds were controlled for.

WHAT DID THIS STUDY FIND?

The current review highlights the limited number of studies that have examined functional outcomes in opioid use disorder patients. Within each of the four major functional outcome domains, this review revealed several specific topics of study for which conclusions are limited to one or two investigations.

Findings are as follows:

Cognition (2 studies):

• When compared to healthy controls, methadone and buprenorphine patients do not appear to have difficulty in verbal memory or attention, but do show impairments in working memory and cognitive speed.
• Comparison of pharmacotherapy patients was uncommon. When assessed, significant differences between buprenorphine and methadone patients were not observed.

Driving Safety (1 study):

Use of buprenorphine or methadone are associated with increased risk of injurious road traffic accidents.

Occupational Function (5 studies):

• Whether patients received psychosocial treatment without medication, buprenorphine, methadone, or naltrexone treatment, employment rates did not significantly differ.

Physical Function (11 studies):

• Buprenorphine patients generally exhibit less fatigue than methadone patients and untreated individuals with opioid use disorder.
• Buprenorphine, naltrexone, and methadone patients do not report higher levels of insomnia than untreated individuals (placebo or no treatment) with opioid use disorder.

Social Function (25+ studies):

• Changes in family functioning (1 study) are similar between methadone patients and individuals enrolled in an enriched detoxification program.
• Methadone and buprenorphine patients have similar psychological (i.e. mental health) function (3 studies) to individuals enrolled in a detoxification or needle-exchange program.
• Buprenorphine and methadone patients show a tendency to respond more aggressively and violent/harmful behaviors are similar among buprenorphine and naltrexone patients (2 studies).
• Methadone patients may spend less time engaging in criminal activity than opioid use disorder patients not actively receiving pharmacotherapy. However, findings are not entirely consistent and higher doses might yield greater benefit. In general, criminal activity during naltrexone treatment is comparable to other pharmacotherapies or standard treatment (7 studies).
• Prevalence of arrest or incarceration (10 studies) does not differ between pharmacotherapy patients and medication-free patients. Although extended duration of treatment in the general population has shown to have no significant effect on illegal engagement, studies have suggested lower risk of reincarceration among methadone treated prisoners who continue treatment relative to those who terminate it post release.
• Buprenorphine and methadone treatment are associated with fewer legal problems than needle-exchange or detoxification programs (2 studies).

Quality of Studies:

• Studies revealing a difference in functional outcomes between any two groups were generally found to be of low quality. The low quality evidence was due to a combination of the limited number of studies within each functional domain and low quality ratings among individual publications (i.e. rated as having a high risk of bias)

WHAT ARE THE IMPLICATIONS OF THE STUDY FINDINGS?

Given the personal and societal impact of opioid use disorder and the growing number of individuals seeking opioid pharamacotherapy in the United States, this review reveals the desperate need for high quality controlled investigations of functional outcomes in pharmacotherapy patients. By understanding cognitive, psychosocial, and physical functioning in individuals receiving these treatments, we may find ways to further aid long-term recovery and combat the opioid epidemic. Studies conducted to-date generally suggest that opioid use disorder patients exhibit functional difficulties relative to healthy controls, but pharmacotherapy might help to alleviate functional impairment. However, the quality of this evidence is questionable and conclusions can not be formed for specific functional domains with so few studies.

Despite the lack of literature addressing functional outcomes, this review is important because it helps guide the next step in research. It suggests a need for high quality controlled investigations that further explore the cognitive deficits seen in patients, assess the potential benefits of pharmacotherapy on criminal activity and legal problems, and address occupational function in more detail. As this area of research develops, it will provide an essential compliment to our knowledge of substance use outcomes in patients treated with pharmacotherapies for opioid use disorder.

LIMITATIONS

1. The outcomes of this review are limited to the inclusion criteria. Therefore, they do not extend to pregnant women, inpatient treatment populations, or adolescents. Further study is needed to determine whether these functional outcomes extend to broader patient populations. This review was also limited by the investigations and dependent measures that the authors chose to report. For example, cognitive findings are limited to two investigations, specific cognitive functions and select task measures, as chosen by the authors of this review. Within the two investigations meeting their criteria, impairment among and differences between pharmacotherapy patient groups are demonstrated in different cognitive domains (e.g., decision making skills) and for cognitive task measures not addressed in this review (e.g., reaction time vs. accuracy). Therefore, it is important to take these nuances into consideration and not generalize the findings here to all cognitive abilities. Further investigation is imperative to develop a clear and reliable interpretation.
2. In general, functional outcomes were not the primary measures of interest in these studies. Although functioning was assessed as a secondary measure in several studies, most of them were designed to assess treatment and drug-use outcomes. Of the studies included in this review, only six randomized controlled trials focused investigation on functional outcomes. Furthermore, sample size among many of these studies was relatively small and power to detect differences between groups may have been limited.
3. Among the prospective studies included in this review, baseline measures were not discussed in detail. Thus, conclusions regarding functional improvement and decline over time can not be made.

BOTTOM LINE

CITATIONS

Maglione, M. A., Raaen, L., Chen, C., Azhar, G., Shahidinia, N., Shen, M., … & Hempel, S. (2018). Effects of medication assisted treatment (MAT) for opioid use disorder on functional outcomes: A systematic review. Journal of substance abuse treatment, 89, 28-51.