Can Buprenorphine Treatment for Opioid Addiction Aid Cognitive Recovery?

Rates of opioid use disorder are on the rise and opioid agonist medications are evidence-based first-line options for treating opioid addiction. This study examined the neurocognitive changes associated with one of these medications, as well as the impact of medication adherence and depression on the rate of cognitive change.

WHAT PROBLEM DOES THIS STUDY ADDRESS?

The prevalence of opioid use disorder in the U.S. is on the rise. Opioid agonist therapies (medications that reduce withdrawal and craving but do not produce the euphoric feelings caused by the original opioid of misuse), including buprenorphine, are evidence-based medications and the most widely available treatments for opioid use disorder. Yet, there is still much to be learned about opioid agonist therapy and its impact on recovery. Research is particularly needed to better understand buprenorphine’s role in cognitive improvement among patients in recovery from opioid use disorder.

Only a handful of studies have looked at longitudinal cognitive changes during opioid addiction recovery. Among them, cognition is suggested to improve with abstinence and reduced substance misuse, but the impact of buprenorphine on these neuropsychological trajectories is unclear. Additional research is also needed to identify factors with the potential to influence cognitive change, including treatment regiments, and comorbid psychiatric and medical disorders. Given the growing number of opioid use disorder patients receiving buprenorphine treatment and the potential for cognitive function to impact recovery outcomes, characterizing various aspects of cognitive change during the course of recovery is essential is essential in this population.

To begin addressing some of these issues, this preliminary study assessed cognitive changes in patients diagnosed with opioid use disorder across the first 6 months of buprenorphine treatment and explored the impact of medication adherence and depressive symptoms on the rate of neuropsychological change.

HOW WAS THIS STUDY CONDUCTED?

Twenty individuals (75% male) with current opioid use disorder who were seeking buprenorphine treatment were recruited and followed over 6-months as part of a larger investigation.

MORE ON STUDY METHODS

Upon enrolling in the study, participants began buprenorphine (i.e. buprenorphine/naloxone commonly known as ”Suboxone”) treatment. Medication was dispensed at a community-based clinic providing integrated substance use disorder and standard medical care. Stable buprenorphine doses ranged from 4-16 mg.

Substance use disorders were diagnosed with the Diagnostic and Statistical Manual of Mental Disorders (DSM, 4^th edition) and substance use severity was assessed with the Addiction Severity Index.

Within 14 days of receiving their first dose (baseline), participants completed a number of neuropsychological tests assessing a variety of cognitive domains, including:

Verbal fluency: the ability to mentally retrieve and produce words based on the way they sound (lexical fluency; e.g., naming words that begin with the letter ‘S’) or their conceptual meaning (semantic fluency; e.g., naming words that can be categorized as ‘animals’)
Processing speed: ability to understand and appropriately respond to incoming information in a timely manner
Attention/Working memory: ability to focus on incoming information, hold onto that information and manipulate it in short-term memory
Learning: the process of gaining knowledge, verbal or visual, through exposure, studying, or teaching
Memory: the ability to recognize or recall newly presented information after a short delay
Fine motor skills: coordination of small motor movements for example with your hands and fingers
Executive functioning (set-shifting): ability to adjust tactics for handling new situations or cues in the environment and implement purposeful behaviors to achieve an ultimate goal.

Participants completed the same set of neuropsychological tests approximately 6-months after baseline testing (ranging from 5.5 to 7.5 months after baseline). Authors undertook several procedures to try and ensure that any observed improvements were not simply due to getting better at taking the test over time (i.e., “practice effects”). To limit the impact of practice effects on certain cognitive functions, learning and memory were tested with alternate task versions at follow-up. Statistical methods also accounted for potential practice effects. Scores on tasks administered within each cognitive domain were converted to z scores (conversions made to compare scores based on population norms), averaged, and assessed for rate of change relative to their expected values. A summary score was also calculated (average of all cognitive change scores) to examine overall neuropsychological improvement (participants whose scores were in the top 5%) and decline (participants in the bottom 5%). Those falling in-between these scores were defined as showing no significant overall cognitive change (cognitive stability).

Self-report questionnaires were administered to assess depressive symptoms (Beck Depression Inventory) and medication adherence (Visual Analogue Scale where participants indicated the percentage of days they took the medication during the past month) averaged across the 6-month study period; depression questionnaires were completed at baseline and 6-months, while medication adherence was assessed halfway through the study (3 months) and at 6-months.

On average, participants had 12 years of education, were 45 years old and primarily identified as Hispanic/Latino (55%) or African American (25%). Twenty-eight percent of the sample tested positive for HIV. Chronicity of opioid use averaged 16 years for heroin, 4 years for methadone, and 4 years for opioid analgesics. On average, buprenorphine adherence across the 6-month study was 91%; 30% of participants exhibited moderate depressive symptoms. All participants had a lifetime diagnosis of at least one other (non-opioid) substance use disorder (majority: alcohol, cocaine, and/or cannabis) whereas 20% had a coexisting current substance use disorder. At baseline, urine toxicology screens indicated recent use of opioids (35%), cocaine (35%), Methadone (20%), benzodiazepines (10%), and Oxycodone (10%). Overall, participants used heroin on 9 of the 30 days prior to baseline (all other substances used <4 days) and on 2 of the 30 days preceding follow-up (all other substances used <2 days).

WHAT DID THIS STUDY FIND?

After approximately 6 months of buprenorphine treatment, 15% of participants showed overall improvement in neuropsychological functioning and 80% remained stable. Interestingly, 5% of the sample showed overall neurocognitive decline. Although global neuropsychological function was relatively unchanged in most participants, at least some improvement was seen in the domain of executive functioning when average scores were assessed for rate of change.

Medication adherence was significantly and positively related to the rate of cognitive change, both overall and in particular neuropsychological domains. More specifically, better adherence to buprenorphine was associated with improvements in learning and memory. Depressive symptoms, on the other hand, were not related to overall cognitive change or changes in any particular neuropsychological domain.

WHY IS THIS STUDY IMPORTANT?

Observation of neurocognitive improvement as a function of medication adherence suggests that buprenorphine might aid the recovery of cognitive function among individuals with opioid use disorder – that is, if it is taken as prescribed. Although it is unclear from these data whether buprenorphine adherence directly or indirectly (via reducing substance use) benefits cognition, this study points to recovery of cognitive ability in individuals suffering from opioid addiction and suggests that proper adherence to buprenorphine can facilitate this recovery.

More specifically, buprenorphine was shown to positively influence improvement in learning and memory, functions that are essential for the acquisition and retention of newly learned skills that facilitate continued recovery from substance use disorders. Given the lack of research on buprenorphine and cognition, these preliminary findings call for additional investigation of neuropsychological functioning and its recovery during opioid use disorder treatment.

Although opinions are beginning to change, opioid agonist therapies are sometimes misunderstood and negatively perceived. However, they are effective evidence based treatments for opioid use disorder, a disorder for which long-term recovery is particularly difficult. Studies like these are an important reminder that opioid agonist therapies are not a means of trading one addiction for another. Buprenorphine has different mechanism of action on the brain than heroin and commonly misused opioid painkillers (e.g., oxycodone). Through its actions on various types of opioid receptors in the brain, buprenorphine can block the effects of misusing other opioids (e.g., heroin) and alleviate craving, when taken properly. Thus, opioid agonist treatments for opioid addiction, like buprenorphine, have the potential to facilitate recovery, not only from opioid use disorders but also from the neurocognitive deficits associated with them.

LIMITATIONS

Multiple tasks were used to test each cognitive domain. Different tasks that are meant to test the same domain can require the use of slightly different skills that still fall within a broader cognitive category. Performance was averaged across these tasks and tasks were not assessed independently. This approach could potentially mask a more specific and pronounced change on one of the task. Therefore, it is not entirely clear if particular aspects of cognitive function within a domain are differentially influenced by buprenorphine adherence.
Factors independently associated with cognitive deficits could have influenced study outcomes. Specifically, comorbid HIV was present in the sample and is known to have specific effects on cognition. Furthermore, prescribed medication-use other than buprenorphine was not reported and the dose of buprenorphine was not assessed as a potential correlate of cognitive change. It is unclear if these factors influenced neuropsychological performance in the current report.
The sample size in this preliminary study was small and the majority of participants were Hispanic/Latino. Additional research is needed to replicate these findings and generalize them to other racial or ethnic groups.
Demographic and substance use data were not assessed by medication adherence rate. Therefore, it is unknown if individuals with less adherence misused substances more frequently across the 6-month period. More frequent substance use during treatment could certainly hinder cognitive improvement. Therefore, it is not clear if buprenorphine shares a direct relationship with cognitive change or if buprenorphine adherence resulted in reduced substance misuse which, in turn, resulted in improved cognitive function (i.e. indirect relationship).

NEXT STEPS

Given the small sample size, these preliminary data need to be replicated. Additional investigations with larger samples with more diverse backgrounds are needed to truly understand buprenorphine’s role in cognitive change. Investigations that examine task-specific performance and other cognitive domains will provide additional insight.

Further investigation is also needed to identify the factors that influence cognitive change during buprenorphine treatment, including sex, race/ethnicity, and other comorbid psychiatric/medical disorders that are common among treatment seeking populations. The impact of dose and history of opioid use also requires additional study.

Research addressing pharmacotherapies for opioid use disorder and their effects on cognitive change is just beginning to gain momentum. At present, there are more questions than there are answers. As additional research continues to emerge, so will our understanding of opioid use disorder treatments, recovery, and associated cognitive change.

BOTTOM LINE

For individuals & families seeking recovery: This study provides information about cognitive change during recovery from opioid use disorder and its relationship to buprenorphine, a medication commonly used to treat opioid addiction. Although this research needs to be repeated, it suggests that cognitive functions important for recovery can improve in individuals with opioid use disorder and that taking buprenorphine as prescribed may facilitate these changes. Cognitive functions like learning and memory play an important role in the recovery process when individuals are learning how to change harmful behaviors and implement appropriate coping skills. This preliminary study suggests that, if taken properly, buprenorphine could potentially help improve learning and memory skills that may have declined after prolonged opioid misuse. Additional research that examines larger samples and incorporates comparison groups is needed to make stronger conclusions.
For scientists: This longitudinal investigation yields preliminary evidence that, among individuals with opioid use disorder, adherence to pharmacotherapy with buprenorphine is associated with improved cognitive function over 6-months of treatment. Findings suggest that learning and memory, in particular, can improve with buprenorphine but medication adherence plays a significant role in neuropsychological change. However, it is unclear if the relationship between buprenorphine and cognition is direct, or if buprenorphine adherence indirectly benefits cognitive change via its effects on substance use patterns during treatment. Methods also limit interpretation of function elicited by specific task demands. Given the preliminary nature of this investigation, further study is needed with larger samples, additional comparison to healthy controls and medication-free patients with opioid use disorder, and control for or evaluation of potentially confounding factors. Nonetheless, this study lays the foundation for future investigations in a vastly understudied and relevant area of research.
For policy makers: Research studies like this one provide important information about cognitive change during recovery from substance use disorders and the factors that influence change. In the context of this study, cognitive abilities (specifically learning and memory) that play an important role in recovery from substance use disorders have the potential to improve in opioid use disorder patients receiving buprenorphine treatment. Importantly, these improvements are dependent upon proper adherence to buprenorphine. Buprenorphine is one of the most widely prescribed evidence-based pharmacotherapies for opioid use disorder and cognitive ability is an important factor in recovery outcomes. However, the relationship between cognitive functioning and pharmacotherapies for opioid use disorder are vastly understudied. Given the current opioid crisis and the rising rates of opioid use disorder, allocating funding to better understand the effects and correlates of pharmacotherapies for opioid addiction will certainly improve our ability to more effectively treat opioid use disorders, promote recovery, and important components of the ongoing opioid crisis.
For treatment professionals and treatment systems: This longitudinal investigation provides preliminary data suggesting that cognitive function in individuals with opioid use disorder may benefit from buprenorphine pharmacotherapy. More specifically, buprenorphine might aid the recovery of learning and memory, which are cognitive functions essential for changing addictive behaviors. However, it appears that medication adherence plays a key role in whether or not these neuropsychological benefits are realized. Medication adherence is a significant problem among patients with opioid use disorder. If adherence can be improved, cognition and recovery outcomes may also benefit. Strict regulation or assessment of patients’ medication adherence might help to identify reasons underlying poor adherence or signify when greater intervention is needed to promote adherence and thereby benefit multiple facets of recovery.