Neuropsychological functioning in methadone maintenance patients versus abstinent heroin abusers

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Abstract

Several studies have reported on neuropsychological status as an important contributing variable in drug abuse rehabilitation outcomes. However, few studies have dealt with cognitive impairment in methadone maintenance patients (MMP), despite the fact that methadone is the most frequently used opioid substitution treatment in European countries. The objective of the present study is to contrast the neuropsychological performance of MMP with that of abstinent heroin abusers (AHA). Participants were matched with respect to age, education, pre-morbid IQ, employment status and lifetime drug abuse, and they underwent a set of tests aimed at assessing visuo-spatial attention, processing speed and executive functions. Although processing speed and attention deficits have previously been the focus of studies with MMP, executive functions have not received a similar degree of attention. The purpose of comparing matched MMP and AHA is two-fold: firstly, to test the differential effects of current opioid consumption and past opioid abuse on cognitive–executive performance and secondly, to assess the potential consequences of opioid-related neuropsychological deficits. Results showed a significantly slower performance by MMP on processing speed, visuo-spatial attention, and cognitive flexibility tests (Five Digit Test (FDT) parts 1 and 3; Oral Trails (OT) parts 1, 2; Interference 2–1), and less accuracy in working memory and analogical reasoning tests extracted from the Wechsler Adult Intelligence Scale (WAIS III). Effect sizes for significant comparisons ranged from 0.67 to 1. These results seem to suggest that methadone consumption by itself induces significant cognitive impairments that could compromise drug-treatment outcomes in MMP.

Introduction

Methadone treatment is the most frequently used opioid substitution treatment in European countries, and the number of opioid-dependent individuals enrolled in methadone maintenance treatment has steadily grown over the last few years (European Monitoring Centre for Drugs and Drug Addiction, 2003). Furthermore, several studies have emphasized the influence of neuropsychological status on the results of different substance abuse treatment approaches (Aharonovic et al., 2003, Teichner et al., 2002). Nevertheless, the possible cognitive impairments associated with methadone consumption have not received as much attention as those related to cannabis, cocaine or methamphetamine use (Rogers and Robbins, 2001, Verdejo-García et al., 2004).

Recent studies have addressed the issue of methadone-related cognitive impairments from a double perspective: firstly, by examining the effects of methadone dosing on the neuropsychological functioning of current methadone users and secondly, by comparing the neuropsychological performance of groups of methadone patients with that of healthy subjects. Using the first approach, Curran et al. (2001) implemented a double-blind experimental design in which the methadone dose given to the methadone maintenance patients (MMP) was manipulated across two different conditions. Users in the first group were administered 100% of the normal daily dose, whereas those in the second group were administered only 50% of the normal daily dose. Memory and psychomotor skills were assessed subsequently, and results showed that episodic memory was significantly impaired after the full dose of methadone, but not after the half-dose. In a similar fashion, Lyvers and Yakimoff (2003) manipulated methadone dose in current users, and compared performance on the Wisconsin Card Sorting Test (WCST) shortly after dosing with that of early abstinent MMP (24 h after last dose). Their results showed that previous lifetime drug use having been controlled, early abstinent MMP made more perseverative responses and errors on the WCST.

Using the second approach described above, Darke et al. (2000) compared the neuropsychological performance of 30 MMP and 30 control subjects (matched for gender, age and education) on a series of tests aimed at assessing information processing, attention, short- and long-term memory and problem solving skills. MMPs were significantly more impaired than controls on all the measures used. However, the most striking finding was that the poorer performance of the MMP group was predicted by concomitant alcohol dependence and greater exposure to heroin overdose.

In order to address the main methodological problems of prior methadone studies, Specka et al. (2000) increased the sample size, calculated effect sizes and controlled several potentially confounding variables. They examined the performance of 54 MMP and 54 healthy comparison subjects on an extensive battery assessing cognitive domains related to driving skills. The most robust finding was a significantly poorer performance of MMP on tests of attention and visual orientation.

The most recent study using this second approach was carried out by Mintzer and Stitzer (2002), who examined the performances of 18 MMP and 21 healthy comparison subjects on an extensive battery that included measures of psychomotor speed, selective attention, working memory, long-term episodic memory, meta-memory, time estimation and decision-making. Although lifetime drug use was not considered, both groups were matched for several possible confounding variables (demographics, employment status and pre-morbid IQ). Recent abstinence from all drugs except methadone was verified by urine screening. The authors reported that MMP performed significantly worse than healthy comparison subjects on psychomotor speed, working memory, selective attention and decision-making measures.

Viewed together, these results suggest the presence of a wide range of cognitive deficits related to psychomotor speed, attention, memory and executive functions in MMP. However, few studies have carried out an extensive assessment of executive functions in this population. The aim of this study is to compare the neuropsychological performance of a group of MMP to the performance of a group of currently abstinent, former opioid abusers (both groups being matched for sex, age, education, estimated pre-morbid IQ, employment status and lifetime drug use). Recent reports have emphasized impairments of executive function associated with opioid abuse (Ornstein et al., 2000), and executive dysfunction has been proposed as negatively affecting drug rehabilitation (Rogers and Robbins, 2001, Verdejo-García et al., 2004). Our assessment focused on different aspects of executive functions, along with attention and processing speed. By comparing the two groups, we attempt to discriminate the differential effects of current methadone prescription on cognitive–executive functioning from the effects of former opioid abuse, and to assess the potential consequences of these deficits over the course of drug abuse treatment for both groups.

Section snippets

Participants

Twenty-three abstinent heroin abusers (AHA) were recruited as they joined inpatient rehabilitation programs in the “Proyecto Hombre” and “Cortijo Buenos Aires” centers in Granada, Spain. Eighteen methadone maintenance patients were recruited as they joined outpatient programs in the “Proyecto Hombre” center in Granada, and the “Centro Comarcal de Drogodependencias” in Andújar, Spain. Participants were informed about the aims of the study, and they gave their written consent before the study

Results

As shown in Table 2, MMP had significantly higher scores on duration of abuse of cannabis and heroin than AHA.

To subtract the effects of duration of heroin and cannabis abuse from the different test scores, we used a series of multiple regression analyses. We also kept the standardized residuals of the regression analyses for each dependent variable for use as dependent measures in subsequent analyses. We included duration of cannabis and heroin use as predictor variables, and the scores on the

Discussion

Compared to AHA, MMP showed slower performance on tests of processing speed, visuo-spatial attention and cognitive flexibility; and impaired performance on tests of working memory and analogical reasoning. These results are consistent with recent well-controlled studies showing a higher incidence of cognitive impairment in MMP when compared to AHA (Davis et al., 2002); impaired performance on a wide range of functions when compared to healthy comparison subjects (Darke et al., 2000, Mintzer and

Acknowledgements

This study has been supported by Research Grants BSO2003-07169 from the Spanish “Ministerio de Ciencia y Tecnología”; and INT/2012/2002, from the Spanish “Ministerio del Interior”, whose principal researcher is Dr. Miguel Pérez García.

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    In particular, cognitive impairment has also been documented among opioid use patients receiving methadone maintenance treatment (MMT). Impairment in attention, working memory, cognitive flexibility, and problem solving have been found across studies comparing MMT patients to non-opioid-using controls and abstinent opioid abusers (Darke, Sims, McDonald & Wickes, 2000; Mintzer & Stitzer, 2002; Pirastu et al., 2006; Rapeli et al., 2007; Verdejo et al., 2005; Prosser et al., 2006). Evaluating cognitive function in MMT patients is necessary because it has a direct impact on the rehabilitation process.

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