Cognitive impairment in methadone maintenance patients

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Abstract

Few well-controlled studies have examined psychomotor and cognitive performance in methadone maintenance patients (MMP). In the present study, performance of 18 opioid-dependent MMP was evaluated relative to that of 21 control participants without substance abuse histories. The MMP and control groups were balanced with respect to gender, race, age, years of education, current employment status, current reading level, and estimated IQ score. Recent drug abstinence was verified by urine testing. Participants with a urine screen positive for benzodiazepines or a breathalyzer test positive for alcohol prior to performance testing were excluded. To avoid testing under conditions of acute heroin or cocaine intoxication, but without testing under conditions of acute withdrawal, participants with current use of heroin or cocaine were only required to abstain for 24 h prior to performance testing. MMP exhibited impairment relative to controls in psychomotor speed (digit symbol substitution and trail-making tests), working memory (two-back task), decision making (gambling task), and metamemory (confidence ratings on a recognition memory test); results also suggested possible impairment in inhibitory mechanisms (Stroop color-word paradigm). MMP did not exhibit impairment in time estimation, conceptual flexibility or long-term memory. The wide range of impaired functions is striking, and may have important implications for daily functioning in MMP. Further research is necessary to determine the clinical significance of the impairments in laboratory-based tests for daily performance in the natural environment, as well as to differentiate impairments due to acute methadone dosing, chronic methadone maintenance, chronic poly-drug abuse, and other factors.

Introduction

An estimated 179 000 opioid-dependent individuals were enrolled in United States methadone maintenance treatment (MMT) programs in 1998 (American Methadone Treatment Association, 1998). For many patients, an important benefit of MMT is that it provides the stability necessary to initiate lifestyle changes, obtain steady employment and function in society. Thus, a critical question is the extent to which chronic MMT is associated with impairments in psychomotor and cognitive performance which might affect daily functioning. Over the past decade, a considerable amount of research has focused on characterizing the pattern of impairment associated with chronic cocaine abuse (e.g. Bolla et al., 1999, Gillen et al., 1998, Hoff et al., 1996, O'Malley et al., 1992, Strickland et al., 1993), sometimes using sophisticated performance measures and state-of the art functional neuroimaging techniques. In contrast, few studies have examined impairment associated with chronic MMT, and these studies often suffer from methodological problems.

Several early studies examined performance in methadone maintenance patients (MMP) (Gordon, 1970, Gritz et al., 1975, Appel and Gordon, 1976, Lombardo et al., 1976, Rothernberg et al., 1977, Appel, 1982). Lombardo et al. (1976) found no significant difference in performance on the Wechsler adult intelligence scale between MMP being maintained on 50 versus 80 mg daily methadone; however, the absence of a non-MMP control group makes these results difficult to interpret. Results of studies which included a control group of non-drug abusers suggest that simple reaction time (RT) (Gordon, 1970, Rothernberg et al., 1977) and vigilance performance (Appel, 1982, Rothernberg et al., 1977) are unimpaired in MMP. Results of another study suggest that performance on the digit symbol substitution test (DSST; a measure of psychomotor performance and speed) is impaired in MMP relative to controls, although the effect was restricted to unemployed MMP (Appel and Gordon, 1976). While these results suggest minimal impairment for MMP relative to controls, it is important to note that these studies included a limited range of measures (cf. Zacny, 1995 for a similar criticism in a review of effects of opioids on psychomotor and cognitive functioning). Using a broader range of measures, Gritz et al. (1975) observed a selective pattern of impairment in which MMP were impaired relative to a control group of former heroin abusers on measures of perception, memory for a story (when assessed via recall), and memory for difficult pairs of words, but unimpaired on measures of immediate digit span, memory for a story (when assessed via recognition), object recognition memory, memory for easy pairs of words, and the DSST.

Two recent studies examined performance in MMP relative to non-drug abusing controls (Darke et al., 2000, Specka et al., 2000). Darke et al. (2000) compared performance of MMP relative to controls matched with respect to age, gender, and years of education, on a standardized neuropsychological battery. The battery included measures of premorbid intelligence, psychomotor performance, information processing, attention, short term memory, long term memory, and problem solving. While the groups did not differ with respect to premorbid intelligence, the MMP group performed significantly worse than controls on all other measures. The wide range of impaired functions is striking; however, conclusions based on this study are limited for the following reasons. First, a urine drug screen was not performed prior to neuropsychological testing. A larger proportion of MMP than controls in the study reported current use of a variety of drugs, including benzodiazepines which have well-documented performance-impairing effects (see Curran, 1991, Curran, 2000 for reviews); thus, it is difficult to differentiate effects of chronic MMT from acute drug effects. Second, there was an exceptionally high prevalence of reported head injury in the MMP group (67% compared to only 20% for controls), which may also have contributed to impaired performance in MMP. Third, the MMP and control groups were not matched with respect to current employment status, a factor which may be related to cognitive performance; in the MMP group, 90% were unemployed and none were working full-time, whereas in the control group, only 53% were unemployed and 33% were working full-time.

Specka et al. (2000) compared performance of MMP relative to controls matched with respect to age, gender, and years of education, on several measures of psychomotor performance and attention relevant to driving fitness. MMP were impaired relative to controls on measures of attention and tachistoscopic perception. On a choice RT task, MMP were faster but produced more errors. On two tasks requiring visual tracking, results suggested that MMP were more accurate but slower. These results suggest that MMP are particularly impaired when performing at high speeds; however, it should be noted that, while a urine drug screen was performed prior to performance testing in this study, participants with a positive drug screen were not excluded, again making it difficult to differentiate effects of chronic MMT from acute drug effects.

The present study was designed to evaluate performance of MMP on a broad range of psychomotor and cognitive measures relative to that of control participants without histories of drug abuse. The MMP and control groups were balanced with respect to several important factors including gender, race, age, years of education, current employment status, current reading level, and estimated IQ score. Recent drug abstinence was verified by urine testing. The testing battery included measures of psychomotor speed, time estimation, working memory, and long-term memory, as well as measures of higher order processes (i.e. conceptual flexibility, metamemory, decision-making, and inhibitory mechanisms). Many of these measures have not been examined previously in MMP.

Section snippets

Participants

Participants consisted of 18 opioid-dependent MMP recruited from outpatient methadone maintenance programs on the campus of the Johns Hopkins Bayview Medical Center, and 21 matched controls without histories of substance abuse recruited from the local community.1

Results

As shown in Table 3, MMP performed significantly worse than controls on the DSST (psychomotor/cognitive speed) and the two-back task (d′; working memory), and took significantly longer to complete both trail-making A and B tasks (psychomotor speed) (see also Fig. 1); however, they were not impaired relative to controls on the trail-making measure of conceptual flexibility (i.e. trail-making B−A). MMP did not differ from controls in recognition memory or free recall performance (long-term

Discussion

The present findings of slowed psychomotor performance (i.e. DSST, trail-making A and B; Table 3, Fig. 1) and impaired working memory performance (i.e. two-back task; Table 3) in MMP relative to controls are consistent with results of recent studies (Darke et al., 2000, Specka et al., 2000). The highly reliable impairment in psychomotor speed is particularly striking. Normative data are not available on the computerized tasks used in the present study. However, the computerized version of the

Acknowledgements

This project was supported by National Institute on Drug Abuse Research Grant DA-O5273. The authors thank Ryan Vandrey and Felicia Vlcek for technical assistance, John Yingling for computer programming assistance and technical support, and Tim Mudric and Paul Nuzzo for assistance with data analysis. The authors also thank Steve Grant for providing the computer software for the gambling task, and Liz Katz for initial discussions regarding the study.

References (53)

  • American Methadone Treatment Association, 1998. Methadone maintenance provider survey, American Methadone Treatment...
  • P.W. Appel

    Sustained attention in methadone patients

    Int. J. Addict.

    (1982)
  • P.W. Appel et al.

    Digit-symbol performance in methadone-treated ex-heroin addicts

    Am. J. Psychiatr.

    (1976)
  • A. Baddeley

    Exploring the central executive

    Q. J. Exp. Psychol.

    (1996)
  • A.D. Baddeley

    Working Memory

    (1986)
  • A.D. Baddeley

    Working memory: the interface between memory and cognition

    J. Cogn. Neurosci.

    (1992)
  • W.W. Beatty et al.

    Metamemory in multiple sclerosis

    J. Clin. Exp. Neuropsychol.

    (1991)
  • A. Bechara et al.

    Dissociation of working memory from decision making within the human prefrontal cortex

    J. Neurosci.

    (1998)
  • A. Bechara et al.

    Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions

    Brain

    (2000)
  • K.I. Bolla et al.

    Dose-related neurobehavioral effects of chronic cocaine use

    J. Neuropsychiat. Clin. Neurosci.

    (1999)
  • J.D. Cohen et al.

    Activation of the prefrontal cortex in a nonspatial working memory task with functional MRI

    Hum. Brain Mapp.

    (1994)
  • H.V. Curran

    Benzodiazepines, memory, and mood: a review

    Psychopharmacology

    (1991)
  • H.V. Curran

    Psychopharmacological approaches to human memory

  • S. Darke et al.

    Cognitive impairment among methadone maintenance patients

    Addiction

    (2000)
  • M.T. Fillmore et al.

    Alcohol affects processing of ignored stimuli in a negative priming paradigm

    J. Stud. Alcohol.

    (2000)
  • J.H. Flavell

    What is memory development the development of?

    Hum. Dev.

    (1971)
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