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Neuropsychological performance in opiate addicts after rapid detoxification
Drag and Alcohol Dependence, Elsevier Scientific Publishers
20 (19871261Ireland Ltd.
270
261
NEUROPSYCHOLOGICAL PERFORMANCE AFTER RAPID DETOXIFICATION*
DIANA GUERRA’, aDepartment bDepartment (Spainl
ANGELS
IN OPIATE
ADDICTS
SOL&. JORDI CAMf’~” and ADOLF TOBEfiAb
of Pharmacology, Hospital de1 Mar and Institut Municipal d’lnvestigacid M2dica of Psychiatry and Psychology, Autonomous University of Barcelona Bellaterra
(Received July 28th, 19871
SUMMARY
Neuropsychological performance before and after a rapid (1 week) detoxification treatment, was studied in heroin addicts.‘Ninety-three opioid dependents (DSM-III) were evaluated with a brief test battery assessing attention, memory and verbal fluency performance prior to their admission to a Detoxification Unit. Significant differences were noted between the addicts’ performance and a group of 30 comparable normals, whose intellectual ability was similar. At re-evaluation addicts showed improvement in most measures, including general clinical status. Moreover, no differences between the sample of detoxificated addicts and controls on measures of neuropsychological performance were then detected. No relationship was found between psychopathological symptoms and neuropsychological functioning after the pharmacological detoxification of addicts. The length of addiction or drug consumption were not predictive of neuropsychological impairment in the present sample of heroin addicts. Key words: Heroin addiction
-
Attention
-
Memory
-
Cognitive impairment
INTRODUCTION
Several studies on neuropsychological functions in opiate addicts have produced contradictory findings. Some studies [l - 31 reported neuropsychological deficits in polydrug users, not confirmed by other authors [4] Rounsaville et al. found neuropsychological impairment in opiate addicts in their first study [5], but failed to replicate these results later [6]. These contradictions might he due to several factors: different populations, tests selected, evaluation time and other methodological issues. For example, *Supported in part by a Grant from CAICYT No. 1391182. **To whom reprint requests should be sent at: Instituto Municipal de Investigation Maritimo, 25 - 29,08003 Barcelona, Spain. 0376.8716/87/$3.50 0 1987 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland
Mkdica, P”
262
the subjects studied by Adams [2] were polydrug users, but not opiate addicts. Bruhn and Maage [7] evaluated prisoners, while Rounsaville assessed primarily opiate addicts. Control groups have also been very different in each study, (i.e. epileptics, inpatients, outpatients, healthy subjects). In addition, the history of the addicts varied regarding years of dependence and drug of abuse. Another factor which could influence the contradictory results obtained until now is the time of evaluation. In some works the evaluation was done while the subjects were under the drug’s effects and then retested 3 to 5 months later. Others evaluated their samples after applying for treatment, while either on methadone maintenance, on outpatient narcotic antagonist treatment or drug-free. Although there are several opinions about the causes, the majority of authors agree that on re-testing an improvement in neuropsychological functioning was observed [3,5,6]. Grant and Judd [3] reported that even though the addicts showed an improvement in performance they were still neuropsychologically impaired. On the other hand, Rounsaville [6] failed to detect differences between a sample of treated addicts and demographically matched controls on individual or composite measures of neuropsychological functioning. The present study was carried out to evaluate some measures of neuropsychological performance of inpatient opiate addicts after rapid pharmacological detoxification in a Drug Addiction Unit. We selected an abbreviated battery similar to that used by Rounsaville et al. [6] in order to compare the performance on attention, verbal fluency and memory measures with pre-detoxification results. We expected that our homogeneous sample, the controlled treatment and the fixed time of evaluation could contribute to clarify previous contradictory results. SUBJECTS
AND METHODS
Subjects Sixty-five male and twenty-eight female heroin addicts whose ages ranged from 18 to 35 (mean 25 f 4 years), were screened before entering a Detoxification Unit in the Hospital de1 Mar, for a short detoxification treatment prior to their admission to a drug-free Therapeutic Community or other programs. Most of them belonged to the lower classes from inner city areas in Barcelona. All gave informed written consent regarding voluntary stay in the Unit and compliance with a series of inpatient regulations, including random supervision of urine specimens and answering psychological tests. They had the right to leave the Unit at any time without prejudice to future treatments. The Detoxification Unit The Detoxification Unit is a voluntary admission center that accepts individuals under controlled inpatient conditions, provided that they agree to
263
participate in a Therapeutic Program after discharge from the Unit. The Detoxification Unit consists of six beds in a General Hospital where patients are treated for physical dependence and associated organic complications.
Procedure
Addicts requesting treatment were evaluated with the abbreviated battery of neuropsychological tests described below. This testing session occurred between 2 and 3 weeks before their admittance to the Detoxification Unit. At this time some of the patients reported current opiate effects, while others reported being on abstinence for hours only. The veracity of this report was not corroborated by urinealysis. To be included in the study patients had to accomplish DSM-III diagnostic criteria for actual opioid dependence, not having any other psychiatric diagnosis on Axis I. Once admitted the patients underwent detoxification by short treatment: 1 week as a general rule (no more than 10 days) with either oral clonidine or methadone in progressively decreasing dosages down to drug free state [8]. Doses were calculated in accordance with body weight and the amount of heroin consumed during the last month. During hospitalization patients were carefully evaluated to achieve a diagnostic on Axis II, personality disorders according DSM-III and received daily psychotherapeutic support from a team of two psychologists and a psychiatrist as reported elsewhere [8]. Between 7 and 14 days after admission the patients were tested with the initial neuropsychological battery. A minimum of 2 weeks lasted between both tests. In addition they were administered the Raven’s Progressive Matrices to assess their level of intellectual ability for comparison with control subjects. In the same period, subjects completed other clinical and personality scales.
The Battery
The following tests were used because they were considered to be brief and relatively free from cultural bias and effects of administration: Toulouse-Pieron (TP) a cancellation test as a measure of perception and attention [9]; F factor of PMA (PMA-F) as a measure of verbal fluency [lo]; Immediate Auditory Memory (MA11as a measure of immediate recall (Digit Span), Memory of words - short-term memory task - and long term memory - evocation of events - [ll]; and Raven’s Progressive Matrices as a measure of intelligence [12]. Normative scores for all these tests in a comparable Spanish population were available. To evaluate psychopathological symptoms that might be associated with their performance the addicts were administered the MMPI [13], the SCL-90R [14]; the Manifest Anxiety Scale [15]; and the State Scale of the STAI [16], the latter one repeatedly through the detoxification period to monitor variations in state anxiety.
264 Comparison
group
A control sample was formed by 31 volunteers (18 males and 13 females1 with a mean age of 19 f 2 years, recruited from a Technical Secondary School with similar demographic, educational and cultural characteristics as the clinical sample and coming from the same inner city areas as the patients in the study. RESULTS Clinical characteristics
of the sample
Although all the patients were opiate dependents (DSM-III Diagnostic criteria), they occasionally used barbiturates, other sedatives and alcohol, and could be also called polydrug abusers. The mean years of street-heroin consumption was 4.9 f 2.1, and the amount consumed before seeking treatment was 485 f 336 mg daily. These data characterize the sample as ‘heavy users’, using criteria of inpatient detoxification. Intelligence mean score (Raven Test) of the sample was comparable to the mean of the control group as well as the normative scores. The results of the clinical diagnostic evaluation showed that 68O,b of the addicts had a Personality Disorder, mainly Antisocial Personality Disorder (44.8%). These results were confirmed by the MMPI since the most frequent profiles were Neurotic (36.6%) and Personality Disorder (28.1%~). Neuropsychological
performance
at pre-detoxification
There were no significant differences between genders in the neuropsychological measures, except that men scored higher than women on the Raven’s Progressive Matrices b! = - 2.93, P < 0.0051. There were also significant differences between subjects with a higher educational background and those with a lower educational level in the same test (t = 2.49, P < 0.005) (Table 11when comparing those who had college level to those with elementary school. No relationship was noted between any of the measures of the test battery and current drug status when a t-test was performed comparing those under the effects of a recent dose of opiates and those who declared being abstinent during the hours prior to the assessment. In the pre-detoxification tests the addict sample obtained neuropsychological performance scores below those of the control group in all measures (Table II), indicating that addicts had poorer performance in attention, verbal fluency and memory than controls (healthy non-abuser students of the control group had scores perfectly comparable with normative scores in the tests used). The addicts were divided according to the amount of street-heroin consumed during the last week before screening for treatment. Results comparing heavy (> 500 mgl with mild addicts (< 500 mgl showed no differences between them on neuropsychological measures at the predetoxification time.
265 TABLE I COMPARISON OF LOW ELEMENTARY ADDICTS ON NEUROPSYCHOLOGICAL lP
WITH COLLEGE BATTERY
EDUCATIONAL
LEVEL
OPIATE
< 0.005; +*p < 0.025; +**p< 0.01. Elementary
PMA-F (pre) PMA-F (day 11) TP (pre) TP (day 9) Digit span (pre) Digit span (day 10) Short term memory (pre) Short term memory (day 10) Long term memory (pre) Long term memory (day 10) Raven (pre)
TABLE
College
t-test
Mean
(S.D.)
n
Mean
(S.D.)
n
27.2 40.2 129.4 196.6 8.8 10 21
(9.8) (14.7) (49.4) (64.8) (3.2) (4.8) (6.9)
54 40 59 49 59 49 58
39.3 52.4 159.7 258.3 10.4 11.2 23.6
(11.6) (10.7) (42.2) (83.6) (2.7) (3.4) (10.5)
19 16 19 18 19 18 19
4.4. 2.67* 2.61* 3.39* 1.88** NS NS
28.2
(9)
50
30.8
(10.6)
18
1.03*+
4.7
(1.2)
59
5.5
(5.3)
19
2.729
5.2
(0.8)
49
5.7
(0.4)
17
2.12**
42.1
(7.7)
56
47.5
(6.8)
20
2.49***
II
COMPARISON OF OPIATE ADDICTS PERFORMANCE AT PRE-DETOXIFICATION WITH CONTROLS AND WITH OPIATE ADDICTS AT POST-DETOXIFICATION (MEAN (S.D.1)
*P < 0.01; l*P < 0.005. All results are expressed as mean (S.D.). Controls
Predetoxification
PMA-F TP Digit span Short term memory Long term memory
t-test
Opiate addicts
46.1 195.7 10.3 28.8
(11.9) (40.5) (2) (9.3)
5.3 (0.8)
30.7 137.8 8.9 21.9
Opiate
Re-test
VS.
controls
(11.5) (50.9) (2.6) (8.1)
5.3 (2.8)
44.7 213.6 10.4 29.3
(16) (77) (5) (10)
5.8 (4)
Matched t-test opiate addicts at predetoxification vs. re-test
5.89* 5.26* 2.53. 3.14**
6.79** 9.94** 2.51** 9.03**
NS
3.74**
266
Neuropsychological
performance
at re-evaluation
When subjects were re-evaluated after detoxification an improvement in their neuropsychological performance was observed. Statistically significant differences with t-test for repeated measures were seen regarding verbal fluency, attention, immediate recall, short and long-term memory (Table II). All measures increased up to a level similar or slightly superior to the controls’ performance, with the exception of verbal fluency which remained lower (but non-significantly) than in controls. There were no significant differences when the addicts’ re-evaluation results were compared with the scores obtained from the control group. In order to avoid confounding results due to differences in educational level, an additional comparison at re-evaluation was performed on only those
TABLE
III
COMPARISON
OF LOW ELEMENTARY
OPIATE ADDICTS
WITH CONTROLS
(MEAN 6.D.))
*P < 0.005; **P < 0.05; ***P < 0.025. Controls
Mean
Opiate addicts (S.D.)
n
(11.91
27
PMA-F (pre) PMA-F
46.18
(day 11) TP (pre) 195.7 TP (day 9) Digit span (pre) Digit span (day 10) Short term memory (pre) Short term memory (day 10) Long term memory (pre)
10.3
28.8
5.3 Long term memory (day 10) Raven (pre)
46.2
(40.5)
(2.4)
(9.3)
(0.7)
(6.3)
Mean
t-test
(S.D.)
n
27.27
(9.8)
54
7.07*
39.53
(15.9)
41
1.96**
129.5
(49.47)
59
6.46*
192.6 8.45
(69.9) (2.7)
50 59
0.24 2.86*
9.7
(4.9)
50
N.S.
21.03
(6.9)
58
3.17*
27.6
(9.8)
51
N.S.
4.79
(1.2)
59
2.26***
5.1
(1.1)
50
NS
42.1
(7.7)
56
2.39*
26
18
17
18
21
267
subjects whose education ended at the elementary level (n = 56) against control scores. As in the previous comparison no significant differences in neuropsychological performance were found between the two groups (Table III). As Pearson correlation coefficients between clinical measures of psychopathology and neuropsychological tests were not significant, they are not included. DISCUSSION
Sociodemographic
and clinical characteristics
Regarding demographic and clinical characteristics in the present sample, our results could be compared to findings reported by others [17,18], especially with respect to the high percentages of personality disorders and psychopathic profiles. Nevertheless, there are shortcomings that could limit the generalization of the present findings: the characteristics of the hospital (inner city location, suburban and low economic class people), and the exclusion criteria used. The high percentage of personality disorders (68%) is in agreement with the elevated psychopathy reported in the literature [19]. Our sample of heroin addicts scored high in the Psychopathy (Pdl, Depression (Dl and Mania (Ma) scales of the MMPI, resulting in psychopathic profiles as expected [20], since it has been reported that drug abusers manifest constant elevations in these MMPI scales independent of their state in the addiction cycle [21]. Neuropsychological
performance
The differences between addicts at pre-detoxification and the control sample indicate that the drug abusers were impaired. Controls were individuals with a comparable intellectual ability as demonstrated by their Raven scores. All the measures used in the current study were sensitive to the neuropsychological impairment, except for the long-term memory test which rarely appears impaired in toxic encephalopathies. Our results agree with those of Grant et al. [l?] even though we used a different battery to evaluate neuropsychological performance. Although self-reports can not always be considered reliable, there were no differences between neuropsychological performance of those who were under the effect of heroin during the pre-detoxification testing and those who reported themselves to be undergoing the withdrawal symptoms. This suggests that neuropsychological test results were not significantly altered at predetoxification by recent drug ingestion in our subjects. Nevertheless, we agree with Grant et al. [17] that the central depressant effects of acute or chronic heroin are enough to explain the decrement in the performance which could be due to a diminished arousal level and attentional capability. The group of addicts as a whole experienced a neuropsychological improvement in all the measures when retested after detoxification. Similar
268
changes have been shown in other studies of polydrug abusers such as alcoholics [22], and heroin addicts [17]. It is likely that the change observed in the addict sample was due to heroin detoxification with a normalization of previously depressed cognitive function following the controlled withdrawal of the drug. Probably, the drugs used during detoxification did not help to improve cognitive functions since elonidine and methadone also tend to diminish performance. Therefore we might have observed more improvement if no drug had been interfering. Any significant difference in neuropsychological performance was not found between subjects treated with clonidine and those receiving methadone in the present sample, as was reported previously [8]. A practice effect might have accounted for the significant results obtained, as observed in other studies using repeated measures designs [23]. Because of the high attrition rate of polydrug dependents we decided to retest them while still in the Unit. It is unlikely that the neuropsychological performance improvement was only due to a practice effect, considering the impairment in learning ability and memory at initial testing and the depressing effect of substitute drugs. On the other hand, the time elapsed between the two assessments was enough for forgetting effects to emerge and interfere with previous learning. Nevertheless, without a re-assessment in the control group it is impossible to discern to what extent neuropsychological recovery was due to practice effects or to the controlled withdrawal of the drug or to both factors acting together. Another factor that may explain the change in the selected tests is the generally improved clinical status. One of the goals of this study was to evaluate the relationship between neuropsychological performance and the psychopathological symptoms. However no significant correlation was detected between these and neuropsychological measures.
Other correlates Male addicts showed better pre- and post-treatment performance on the Raven test than did female addicts, and higher educational levels gave better performances in neuropsychological measures. The drug use history (mean years of consumption) of our subjects was shorter than that reported by others [18]. This is probably due to the relatively recent appearance of heroin addiction in our environment in comparison to other countries [24]. Other investigators reported findings that suggested a relationship between the degree of impairment and the amount of drug consumed [25]. In our study measures of opiate use and length of abuse were unrelated to any of the neuropsychological tests. There were no differences in neuropsychological performance between subjects who were consuming above and below 500 mg street-heroin at the time of screening for treatment. Similarly, Rounsaville and associates found no correlation between the length of drug consumption and the degree of impairment (except in the case of cocaine) [6].
269
It cannot be concluded that the chronic use of heroin caused the neuropsychological impairment of the subjects, since it is possible that they were neuropsychologically impaired before initiation to drugs. It could be alternatively hypothesized that moderate neuropsychological impairment drives individuals to self-medication with heroin. One of the problems facing clinical neuropsychology is the assessment of previous intellectual functioning. The premorbid IQ could have been estimated retrospectively but this clinical measure is not considered to be very sensitive in research. Moreover, Grant reported that the analysis of the medical records and the effects of the covariates of the educational level were not indicative of previously impaired subjects [17]. Since no changes were found in the neuropsychological impairment of the subjects at a 3-month follow-up he concluded that the CNS depressants induced irreversible changes. It cannot be stated from the present study that the length of addiction-or drug consumption is predictive of neuropsychological impairment in heroin addicts. To conclude, in common with most previous investigators we have failed to detect a difference between a sample of detoxificated addicts and demographically matched controls on several measures of neuropsychological functioning. To our knowledge this is the first study re-testing subjects after such a short time of detoxification. Our results suggest that heroin addiction does not result in a long-term neuropsychological impairment of performance in the specific cognitive functions we have explored. More research is clearly needed in order to know whether chronic heroin consumption leads to lasting deficits in cognitive functions. ACKNOWLEDGEMENTS
We thank the team of the Detoxification Unit, J. Vilaseca for statistical T. Torrubia and R. Junque for methodological suggestions.
help,
REFERENCES
2 3 4 5 6 7 8 9 10 11 12 13
H.J. Korin, Abnorm. Psychol.. 83 (1974) 208. K. Adams et al., J. Psychol. Drugs, 7 (1975) 151. I. Grant and L. Judd, Am. J. Psychol.. 133 (1976) 1039. J. Fields and J.J. Fullerton, Consult. Clin. Psychol.. 43 (1975) 114. B.J. Rounsaville et al., Ann. N.Y. Acad. Sci.. 362 (1981) 79. B.J. Rounsaville et al.. J. Nerv. Ment. Dis.. 4 (1982) 209. P. Bruhn and N. Maage, Am. J. Psychol., 132 (1975) 397. J. Cami et al.. Clin. Pharmacol. Ther., 38 (1985) 336. E. Toulouse and H. Pieron (Spanish adaptation of), M. Yela et al., TEA S.A., Madrid, 1978. L.L. Thurstone and T.G. Thurstone (Spanish adaptation of), A. Cordero, M. Seisdedos and M. Gonzalez, TEA S.A., Madrid, 1979. A. Corder0 Pando, TEA S.A., Madrid, 1978. J.C. Raven (Spanish adaptation of), A. Murga, TEA S.A., Madrid, 1970. S.R. Hethaway and J.C. McKinley (Spanish adaptation), TEA S.A., Madrid, 1981.
270 14 15 16 17 18 19 20 21 22 23 24 25
L.R. Derogatis (Personal Spanish adaptation), Barcelona, 1985. J.A. Taylor, Psyehol. Bull., 53 (1956) 303. C.D. Spielberger, TEA S.A., Madrid, 1983. I. Grant et al., Arch. Gen. Psychiatry, 35 (1978) 1063. B.J. Rounsavilie, et al., Arch. Gen. Psychiatry, 39 (1982) 151. M.R. Gossop and S.B.G. Eysenck, Person. Indiv. Diff., 4 (1983) 207. A. Sole et al., Abstract presented at Congress International Society for the Study of Individual Differences, St. Feliu de Guixols, Spain, June 1985. P.B. Sutker et al., Psychol., Rep., 34 (1974) 495. J. Brandt et al., Arch. Gen. Psychiatry, 40 (1983) 435. C.A. Haertzen and N.T. Hooks, Am. J. Psychol., 130 (1973) 1031. J. Cami et al., Med. Clin. (Barcelona) 82 (1984) 1. J. Spotts and F. Shoritz, Int. J. Addict., 18 (1983) 633.
20 (19871261Ireland Ltd.
270
261
NEUROPSYCHOLOGICAL PERFORMANCE AFTER RAPID DETOXIFICATION*
DIANA GUERRA’, aDepartment bDepartment (Spainl
ANGELS
IN OPIATE
ADDICTS
SOL&. JORDI CAMf’~” and ADOLF TOBEfiAb
of Pharmacology, Hospital de1 Mar and Institut Municipal d’lnvestigacid M2dica of Psychiatry and Psychology, Autonomous University of Barcelona Bellaterra
(Received July 28th, 19871
SUMMARY
Neuropsychological performance before and after a rapid (1 week) detoxification treatment, was studied in heroin addicts.‘Ninety-three opioid dependents (DSM-III) were evaluated with a brief test battery assessing attention, memory and verbal fluency performance prior to their admission to a Detoxification Unit. Significant differences were noted between the addicts’ performance and a group of 30 comparable normals, whose intellectual ability was similar. At re-evaluation addicts showed improvement in most measures, including general clinical status. Moreover, no differences between the sample of detoxificated addicts and controls on measures of neuropsychological performance were then detected. No relationship was found between psychopathological symptoms and neuropsychological functioning after the pharmacological detoxification of addicts. The length of addiction or drug consumption were not predictive of neuropsychological impairment in the present sample of heroin addicts. Key words: Heroin addiction
-
Attention
-
Memory
-
Cognitive impairment
INTRODUCTION
Several studies on neuropsychological functions in opiate addicts have produced contradictory findings. Some studies [l - 31 reported neuropsychological deficits in polydrug users, not confirmed by other authors [4] Rounsaville et al. found neuropsychological impairment in opiate addicts in their first study [5], but failed to replicate these results later [6]. These contradictions might he due to several factors: different populations, tests selected, evaluation time and other methodological issues. For example, *Supported in part by a Grant from CAICYT No. 1391182. **To whom reprint requests should be sent at: Instituto Municipal de Investigation Maritimo, 25 - 29,08003 Barcelona, Spain. 0376.8716/87/$3.50 0 1987 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland
Mkdica, P”
262
the subjects studied by Adams [2] were polydrug users, but not opiate addicts. Bruhn and Maage [7] evaluated prisoners, while Rounsaville assessed primarily opiate addicts. Control groups have also been very different in each study, (i.e. epileptics, inpatients, outpatients, healthy subjects). In addition, the history of the addicts varied regarding years of dependence and drug of abuse. Another factor which could influence the contradictory results obtained until now is the time of evaluation. In some works the evaluation was done while the subjects were under the drug’s effects and then retested 3 to 5 months later. Others evaluated their samples after applying for treatment, while either on methadone maintenance, on outpatient narcotic antagonist treatment or drug-free. Although there are several opinions about the causes, the majority of authors agree that on re-testing an improvement in neuropsychological functioning was observed [3,5,6]. Grant and Judd [3] reported that even though the addicts showed an improvement in performance they were still neuropsychologically impaired. On the other hand, Rounsaville [6] failed to detect differences between a sample of treated addicts and demographically matched controls on individual or composite measures of neuropsychological functioning. The present study was carried out to evaluate some measures of neuropsychological performance of inpatient opiate addicts after rapid pharmacological detoxification in a Drug Addiction Unit. We selected an abbreviated battery similar to that used by Rounsaville et al. [6] in order to compare the performance on attention, verbal fluency and memory measures with pre-detoxification results. We expected that our homogeneous sample, the controlled treatment and the fixed time of evaluation could contribute to clarify previous contradictory results. SUBJECTS
AND METHODS
Subjects Sixty-five male and twenty-eight female heroin addicts whose ages ranged from 18 to 35 (mean 25 f 4 years), were screened before entering a Detoxification Unit in the Hospital de1 Mar, for a short detoxification treatment prior to their admission to a drug-free Therapeutic Community or other programs. Most of them belonged to the lower classes from inner city areas in Barcelona. All gave informed written consent regarding voluntary stay in the Unit and compliance with a series of inpatient regulations, including random supervision of urine specimens and answering psychological tests. They had the right to leave the Unit at any time without prejudice to future treatments. The Detoxification Unit The Detoxification Unit is a voluntary admission center that accepts individuals under controlled inpatient conditions, provided that they agree to
263
participate in a Therapeutic Program after discharge from the Unit. The Detoxification Unit consists of six beds in a General Hospital where patients are treated for physical dependence and associated organic complications.
Procedure
Addicts requesting treatment were evaluated with the abbreviated battery of neuropsychological tests described below. This testing session occurred between 2 and 3 weeks before their admittance to the Detoxification Unit. At this time some of the patients reported current opiate effects, while others reported being on abstinence for hours only. The veracity of this report was not corroborated by urinealysis. To be included in the study patients had to accomplish DSM-III diagnostic criteria for actual opioid dependence, not having any other psychiatric diagnosis on Axis I. Once admitted the patients underwent detoxification by short treatment: 1 week as a general rule (no more than 10 days) with either oral clonidine or methadone in progressively decreasing dosages down to drug free state [8]. Doses were calculated in accordance with body weight and the amount of heroin consumed during the last month. During hospitalization patients were carefully evaluated to achieve a diagnostic on Axis II, personality disorders according DSM-III and received daily psychotherapeutic support from a team of two psychologists and a psychiatrist as reported elsewhere [8]. Between 7 and 14 days after admission the patients were tested with the initial neuropsychological battery. A minimum of 2 weeks lasted between both tests. In addition they were administered the Raven’s Progressive Matrices to assess their level of intellectual ability for comparison with control subjects. In the same period, subjects completed other clinical and personality scales.
The Battery
The following tests were used because they were considered to be brief and relatively free from cultural bias and effects of administration: Toulouse-Pieron (TP) a cancellation test as a measure of perception and attention [9]; F factor of PMA (PMA-F) as a measure of verbal fluency [lo]; Immediate Auditory Memory (MA11as a measure of immediate recall (Digit Span), Memory of words - short-term memory task - and long term memory - evocation of events - [ll]; and Raven’s Progressive Matrices as a measure of intelligence [12]. Normative scores for all these tests in a comparable Spanish population were available. To evaluate psychopathological symptoms that might be associated with their performance the addicts were administered the MMPI [13], the SCL-90R [14]; the Manifest Anxiety Scale [15]; and the State Scale of the STAI [16], the latter one repeatedly through the detoxification period to monitor variations in state anxiety.
264 Comparison
group
A control sample was formed by 31 volunteers (18 males and 13 females1 with a mean age of 19 f 2 years, recruited from a Technical Secondary School with similar demographic, educational and cultural characteristics as the clinical sample and coming from the same inner city areas as the patients in the study. RESULTS Clinical characteristics
of the sample
Although all the patients were opiate dependents (DSM-III Diagnostic criteria), they occasionally used barbiturates, other sedatives and alcohol, and could be also called polydrug abusers. The mean years of street-heroin consumption was 4.9 f 2.1, and the amount consumed before seeking treatment was 485 f 336 mg daily. These data characterize the sample as ‘heavy users’, using criteria of inpatient detoxification. Intelligence mean score (Raven Test) of the sample was comparable to the mean of the control group as well as the normative scores. The results of the clinical diagnostic evaluation showed that 68O,b of the addicts had a Personality Disorder, mainly Antisocial Personality Disorder (44.8%). These results were confirmed by the MMPI since the most frequent profiles were Neurotic (36.6%) and Personality Disorder (28.1%~). Neuropsychological
performance
at pre-detoxification
There were no significant differences between genders in the neuropsychological measures, except that men scored higher than women on the Raven’s Progressive Matrices b! = - 2.93, P < 0.0051. There were also significant differences between subjects with a higher educational background and those with a lower educational level in the same test (t = 2.49, P < 0.005) (Table 11when comparing those who had college level to those with elementary school. No relationship was noted between any of the measures of the test battery and current drug status when a t-test was performed comparing those under the effects of a recent dose of opiates and those who declared being abstinent during the hours prior to the assessment. In the pre-detoxification tests the addict sample obtained neuropsychological performance scores below those of the control group in all measures (Table II), indicating that addicts had poorer performance in attention, verbal fluency and memory than controls (healthy non-abuser students of the control group had scores perfectly comparable with normative scores in the tests used). The addicts were divided according to the amount of street-heroin consumed during the last week before screening for treatment. Results comparing heavy (> 500 mgl with mild addicts (< 500 mgl showed no differences between them on neuropsychological measures at the predetoxification time.
265 TABLE I COMPARISON OF LOW ELEMENTARY ADDICTS ON NEUROPSYCHOLOGICAL lP
WITH COLLEGE BATTERY
EDUCATIONAL
LEVEL
OPIATE
< 0.005; +*p < 0.025; +**p< 0.01. Elementary
PMA-F (pre) PMA-F (day 11) TP (pre) TP (day 9) Digit span (pre) Digit span (day 10) Short term memory (pre) Short term memory (day 10) Long term memory (pre) Long term memory (day 10) Raven (pre)
TABLE
College
t-test
Mean
(S.D.)
n
Mean
(S.D.)
n
27.2 40.2 129.4 196.6 8.8 10 21
(9.8) (14.7) (49.4) (64.8) (3.2) (4.8) (6.9)
54 40 59 49 59 49 58
39.3 52.4 159.7 258.3 10.4 11.2 23.6
(11.6) (10.7) (42.2) (83.6) (2.7) (3.4) (10.5)
19 16 19 18 19 18 19
4.4. 2.67* 2.61* 3.39* 1.88** NS NS
28.2
(9)
50
30.8
(10.6)
18
1.03*+
4.7
(1.2)
59
5.5
(5.3)
19
2.729
5.2
(0.8)
49
5.7
(0.4)
17
2.12**
42.1
(7.7)
56
47.5
(6.8)
20
2.49***
II
COMPARISON OF OPIATE ADDICTS PERFORMANCE AT PRE-DETOXIFICATION WITH CONTROLS AND WITH OPIATE ADDICTS AT POST-DETOXIFICATION (MEAN (S.D.1)
*P < 0.01; l*P < 0.005. All results are expressed as mean (S.D.). Controls
Predetoxification
PMA-F TP Digit span Short term memory Long term memory
t-test
Opiate addicts
46.1 195.7 10.3 28.8
(11.9) (40.5) (2) (9.3)
5.3 (0.8)
30.7 137.8 8.9 21.9
Opiate
Re-test
VS.
controls
(11.5) (50.9) (2.6) (8.1)
5.3 (2.8)
44.7 213.6 10.4 29.3
(16) (77) (5) (10)
5.8 (4)
Matched t-test opiate addicts at predetoxification vs. re-test
5.89* 5.26* 2.53. 3.14**
6.79** 9.94** 2.51** 9.03**
NS
3.74**
266
Neuropsychological
performance
at re-evaluation
When subjects were re-evaluated after detoxification an improvement in their neuropsychological performance was observed. Statistically significant differences with t-test for repeated measures were seen regarding verbal fluency, attention, immediate recall, short and long-term memory (Table II). All measures increased up to a level similar or slightly superior to the controls’ performance, with the exception of verbal fluency which remained lower (but non-significantly) than in controls. There were no significant differences when the addicts’ re-evaluation results were compared with the scores obtained from the control group. In order to avoid confounding results due to differences in educational level, an additional comparison at re-evaluation was performed on only those
TABLE
III
COMPARISON
OF LOW ELEMENTARY
OPIATE ADDICTS
WITH CONTROLS
(MEAN 6.D.))
*P < 0.005; **P < 0.05; ***P < 0.025. Controls
Mean
Opiate addicts (S.D.)
n
(11.91
27
PMA-F (pre) PMA-F
46.18
(day 11) TP (pre) 195.7 TP (day 9) Digit span (pre) Digit span (day 10) Short term memory (pre) Short term memory (day 10) Long term memory (pre)
10.3
28.8
5.3 Long term memory (day 10) Raven (pre)
46.2
(40.5)
(2.4)
(9.3)
(0.7)
(6.3)
Mean
t-test
(S.D.)
n
27.27
(9.8)
54
7.07*
39.53
(15.9)
41
1.96**
129.5
(49.47)
59
6.46*
192.6 8.45
(69.9) (2.7)
50 59
0.24 2.86*
9.7
(4.9)
50
N.S.
21.03
(6.9)
58
3.17*
27.6
(9.8)
51
N.S.
4.79
(1.2)
59
2.26***
5.1
(1.1)
50
NS
42.1
(7.7)
56
2.39*
26
18
17
18
21
267
subjects whose education ended at the elementary level (n = 56) against control scores. As in the previous comparison no significant differences in neuropsychological performance were found between the two groups (Table III). As Pearson correlation coefficients between clinical measures of psychopathology and neuropsychological tests were not significant, they are not included. DISCUSSION
Sociodemographic
and clinical characteristics
Regarding demographic and clinical characteristics in the present sample, our results could be compared to findings reported by others [17,18], especially with respect to the high percentages of personality disorders and psychopathic profiles. Nevertheless, there are shortcomings that could limit the generalization of the present findings: the characteristics of the hospital (inner city location, suburban and low economic class people), and the exclusion criteria used. The high percentage of personality disorders (68%) is in agreement with the elevated psychopathy reported in the literature [19]. Our sample of heroin addicts scored high in the Psychopathy (Pdl, Depression (Dl and Mania (Ma) scales of the MMPI, resulting in psychopathic profiles as expected [20], since it has been reported that drug abusers manifest constant elevations in these MMPI scales independent of their state in the addiction cycle [21]. Neuropsychological
performance
The differences between addicts at pre-detoxification and the control sample indicate that the drug abusers were impaired. Controls were individuals with a comparable intellectual ability as demonstrated by their Raven scores. All the measures used in the current study were sensitive to the neuropsychological impairment, except for the long-term memory test which rarely appears impaired in toxic encephalopathies. Our results agree with those of Grant et al. [l?] even though we used a different battery to evaluate neuropsychological performance. Although self-reports can not always be considered reliable, there were no differences between neuropsychological performance of those who were under the effect of heroin during the pre-detoxification testing and those who reported themselves to be undergoing the withdrawal symptoms. This suggests that neuropsychological test results were not significantly altered at predetoxification by recent drug ingestion in our subjects. Nevertheless, we agree with Grant et al. [17] that the central depressant effects of acute or chronic heroin are enough to explain the decrement in the performance which could be due to a diminished arousal level and attentional capability. The group of addicts as a whole experienced a neuropsychological improvement in all the measures when retested after detoxification. Similar
268
changes have been shown in other studies of polydrug abusers such as alcoholics [22], and heroin addicts [17]. It is likely that the change observed in the addict sample was due to heroin detoxification with a normalization of previously depressed cognitive function following the controlled withdrawal of the drug. Probably, the drugs used during detoxification did not help to improve cognitive functions since elonidine and methadone also tend to diminish performance. Therefore we might have observed more improvement if no drug had been interfering. Any significant difference in neuropsychological performance was not found between subjects treated with clonidine and those receiving methadone in the present sample, as was reported previously [8]. A practice effect might have accounted for the significant results obtained, as observed in other studies using repeated measures designs [23]. Because of the high attrition rate of polydrug dependents we decided to retest them while still in the Unit. It is unlikely that the neuropsychological performance improvement was only due to a practice effect, considering the impairment in learning ability and memory at initial testing and the depressing effect of substitute drugs. On the other hand, the time elapsed between the two assessments was enough for forgetting effects to emerge and interfere with previous learning. Nevertheless, without a re-assessment in the control group it is impossible to discern to what extent neuropsychological recovery was due to practice effects or to the controlled withdrawal of the drug or to both factors acting together. Another factor that may explain the change in the selected tests is the generally improved clinical status. One of the goals of this study was to evaluate the relationship between neuropsychological performance and the psychopathological symptoms. However no significant correlation was detected between these and neuropsychological measures.
Other correlates Male addicts showed better pre- and post-treatment performance on the Raven test than did female addicts, and higher educational levels gave better performances in neuropsychological measures. The drug use history (mean years of consumption) of our subjects was shorter than that reported by others [18]. This is probably due to the relatively recent appearance of heroin addiction in our environment in comparison to other countries [24]. Other investigators reported findings that suggested a relationship between the degree of impairment and the amount of drug consumed [25]. In our study measures of opiate use and length of abuse were unrelated to any of the neuropsychological tests. There were no differences in neuropsychological performance between subjects who were consuming above and below 500 mg street-heroin at the time of screening for treatment. Similarly, Rounsaville and associates found no correlation between the length of drug consumption and the degree of impairment (except in the case of cocaine) [6].
269
It cannot be concluded that the chronic use of heroin caused the neuropsychological impairment of the subjects, since it is possible that they were neuropsychologically impaired before initiation to drugs. It could be alternatively hypothesized that moderate neuropsychological impairment drives individuals to self-medication with heroin. One of the problems facing clinical neuropsychology is the assessment of previous intellectual functioning. The premorbid IQ could have been estimated retrospectively but this clinical measure is not considered to be very sensitive in research. Moreover, Grant reported that the analysis of the medical records and the effects of the covariates of the educational level were not indicative of previously impaired subjects [17]. Since no changes were found in the neuropsychological impairment of the subjects at a 3-month follow-up he concluded that the CNS depressants induced irreversible changes. It cannot be stated from the present study that the length of addiction-or drug consumption is predictive of neuropsychological impairment in heroin addicts. To conclude, in common with most previous investigators we have failed to detect a difference between a sample of detoxificated addicts and demographically matched controls on several measures of neuropsychological functioning. To our knowledge this is the first study re-testing subjects after such a short time of detoxification. Our results suggest that heroin addiction does not result in a long-term neuropsychological impairment of performance in the specific cognitive functions we have explored. More research is clearly needed in order to know whether chronic heroin consumption leads to lasting deficits in cognitive functions. ACKNOWLEDGEMENTS
We thank the team of the Detoxification Unit, J. Vilaseca for statistical T. Torrubia and R. Junque for methodological suggestions.
help,
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