Elsevier

Drug and Alcohol Dependence

Volume 126, Issue 3, 1 December 2012, Pages 309-315
Drug and Alcohol Dependence

Comparative patterns of cognitive performance amongst opioid maintenance patients, abstinent opioid users and non-opioid users

https://doi.org/10.1016/j.drugalcdep.2012.05.032Get rights and content

Abstract

Background

To compare the cognitive performances of maintenance patients (MAIN), abstinent ex-users (ABST) and healthy non-heroin using controls (CON).

Methods

Case control study of 125 MAIN (94 subjects maintained on methadone, 31 on buprenorphine), 50 ABST and 50 CON. Neuropsychological tests measuring executive function, working memory, information processing speed, verbal learning and non-verbal learning were administered.

Results

There were no differences between the cognitive profiles of those maintained on methadone or buprenorphine on any administered test. After controlling for confounders, the MAIN group had poorer performance than controls in six of the 13 administered tests, and were poorer than the ABST group in five. The MAIN group exhibited poorer performance in the Haylings Sentence Completion, Matrix Reasoning, Digit Symbol, Logical Memory (immediate and delayed recall), and the Complex Figure Test (immediate recall). There were no differences between the ABST and CON groups on any of the administered tests.

Conclusions

Poorer cognitive performance, across a range of test and domains, was seen amongst maintenance patients, regardless of their maintenance drug. This is a group that is likely might benefit from approaches for managing individuals with cognitive and behavioural difficulties arising from brain dysfunction.

Introduction

Recent years have seen growing interest in cognitive impairment amongst opiate users. Whilst opioids are not neurotoxic (Karch, 2009), heroin users face a number of risks that might expose them to acquired brain injury, including overdose, traumatic head injury and heavy alcohol intake (Darke, 2011). Consistent with these risks, a number of studies have reported poorer cognitive functioning amongst opioid users compared to controls (Brand et al., 2008, Darke et al., 2000, Davis et al., 2002, Ersche et al., 2005, Ersche et al., 2006, Fishbein et al., 2007, Lyvers and Yakimoff, 2003, Mintzer et al., 2004, Mintzer et al., 2005, Mintzer and Stitzer, 2002, Ornstein et al., 2000, Pau et al., 2002, Prosser et al., 2006, Wang et al., 2007).

Evidence of the extent and nature of these deficits remains unclear, with some studies showing performance deficits across a wide range of cognitive domains (Darke et al., 2000, Davis et al., 2002, Mintzer and Stitzer, 2002, Verdejo et al., 2005), whilst others report focal deficits (Darke et al., 2000, Lyvers and Yakimoff, 2003, Pau et al., 2002). Furthermore, the evidence on abstinent ex-users is ambiguous. The abstinent show poorer performance than controls on some tasks, but are comparable in the overwhelming majority (Mintzer et al., 2005, Prosser et al., 2006, Wang et al., 2007). To add to the ambiguity, they have shown both superior (Mintzer et al., 2005, Loeber et al., 2008), and inferior (Prosser et al., 2006), performance to methadone patients. Importantly, these findings do not appear to be artefacts of the acute effects of opioids (Friswell et al., 2008, Loeber et al., 2008). There is also some neurological evidence that appears to support the evidence of pathology suggested by neuropsychological testing, including evidence of axonal damage, hyperphosphorylated tau deposition and neuroinflammation (Anthony et al., 2010, Buttner et al., 2006). The emerging pattern is of poorer executive functioning, the cognitive domain associated with decision making and impulse control. Executive dysfunction has been attributed to impaired function of frontal cerebral systems and is vulnerable to a range of conditions including traumatic brain injury (Tate et al., 1991), cerebral anoxia (Caine and Watson, 2000) and chronic alcoholism (Glass et al., 2009). Executive function is a multi-faceted domain that, in general, is attributed to successful goal directed behaviour. Deficits may arise at various stages in this process including the initiation and flexible use of strategies, the inhibition of inappropriate responses, and response planning. Such dysfunction has clinical implications for risk taking and treatment compliance, and opiate users have been shown to engage in higher risks in decision-making tasks (Brand et al., 2008, Ornstein et al., 2000, Loeber et al., 2008, Mintzer et al., 2004). Slowed information processing is a major feature of the cognitive sequelae of traumatic brain injury, possibly reflecting the impact of diffuse axonal injury (Felmingham et al., 2004). Impaired new learning of either verbal or non-verbal information is prevalent across many conditions impacting cerebral function including, once again, head injury, anoxia and alcoholism (Bowden, 1992, Caine and Watson, 2000, Tate et al., 1991). Slowed processing and poor learning will make it difficult for opiate users to adjust to new situations or learn new ways of behaving.

The current study aimed to extend our knowledge of cognitive performance amongst opioid users by examining three groups: maintenance patients (methadone, buprenorphine), abstinent ex-users enrolled in drug free therapeutic communities, and a matched comparison group of healthy adults with no history of opioid dependence. The recruitment of those patients maintained on methadone and buprenorphine enabled examination of the role of the maintenance drug upon performance, as buprenorphine has less of a sedative effect than methadone and, unlike methadone, has antagonist properties (Mattick et al., 2009). All analyses controlled for factors associated with opioid use, such as psychological distress, that might independently affect cognitive performance. Specifically, the study aimed to:

(1) compare the cognitive performance of methadone and buprenorphine maintenance patients; and (2) compare cognitive performance across maintenance patients, abstinent ex-users and healthy non-heroin using controls.

Section snippets

Procedure

Three groups were recruited: 125 opioid maintenance (MAIN) outpatients, 50 abstinent ex-users (ABST) living in therapeutic communities for the treatment of their heroin dependence, and a control (CON) group of 50 healthy controls with no history of opioid use. The MAIN group consisted of 94 subjects maintained on methadone, and 31 maintained on buprenorphine. MAIN subjects were recruited by advertisements placed in the waiting areas of maintenance units, and ABST clients by advertisements in

Sample characteristics

A sample of 225 participants was recruited (Table 1). There were no differences in gender (p = .81). Despite attempts to match participants on major demographic variables, there were group differences in age, years of schooling, estimated premorbid IQ and DASS scores (Table 1). In all subsequent multivariate analyses, these variables were controlled.

Consistent with drug use patterns seen amongst opioid users (Darke, 2011), the mean age at first intoxication varied across groups, as did the number

Discussion

A number of major findings emerged from this study. Firstly, there were no substantive differences between methadone and buprenorphine maintenance patients, despite the different pharmacological profiles of these drugs. Secondly, there were significant differences in group cognitive performance, with the MAIN group exhibiting the poorest profile. Importantly, these were not artefacts of factors associated with opioid use, such as psychological distress. Finally, the performance of the ABST

Role of funding source

This research was funded by the National Health and Medical Research Council. The NHMRC had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Contributors

Professors Darke and McDonald designed the study, and conducted the statistical analyses and write-up of the paper. Dr. Kaye and Ms. Torok participated in data collection, data entry, analysis and review of the manuscript. All authors contributed to and have approved the final manuscript.

Conflict of interest

None to declare.

Acknowledgement

We wish to thank staff at all participating treatment agencies.

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