1 Center of Psychiatry and Psychological Medicine, Gilead Hospital, Bethel, Bielefeld, Germany, 2 Department of Psychiatry, Luebeck School of Medicine, Luebeck, Germany and 3 Department of Psychiatry I, Johann Wolfgang Goethe University, Frankfurt, Germany
* Author to whom correspondence should be addressed at: Martin Driessen, Center of Psychiatry and Psychological Medicine, Gilead Hospital, Bethel, Remterweg 69/71, D-33617 Bielefeld, Germany. Tel.: +49 521 144-2031; Fax: +49 521 144-3841; E-mail: martin.driessen{at}evkb.de
Received 25 January 2005; first review notified 15 March 2005; in revised form 11 April 2005; accepted 12 April 2005
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ABSTRACT |
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INTRODUCTION |
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The aim of the present study is to characterize different courses of alcohol withdrawal by observable symptoms and to propose a comprehensive clinical typology of alcohol withdrawal syndromes that would ideally fulfil the following clinical and methodological criteria: (i) All types should be in agreement with general clinical experience. (ii) These types should be clearly defined. (iii) Vegetative and psychopathological symptoms should be considered as well. (iv) The different types should be related to severity and duration of alcohol withdrawal. (v) Patients without relevant symptoms should be clearly identified. (vi) One type should represent the full delirium syndrome. (vii) All types should be predicted by data available at the start of assessment. (viii) The types should be associated with therapeutic consequences.
In order to characterize the different aspects of alcohol withdrawal, including its dynamic course, operational criteria are needed for the valid and reliable assessment of symptoms and severity. Thus, several scales were developed for monitoring the clinical course and the treatment (Shaw et al., 1981; Kristensen et al., 1986
; Banger et al., 1992
; Metcalfe et al., 1995
). The CIWA-A-Scale is a widespread scale, revised and shortened versions were published by Sullivan et al. (1989)
. Our work group developed the Alcohol Withdrawal Scale (AWS), which was previously reported by Wetterling et al. (1997)
. Therefore, the AWS is based on a factor-analysed version of the CIWA-A-Scale and consists of six vegetative (pulse rate, diastolic blood pressure, body temperature, breathing rate, sweating, and tremor) and five mental or psychopathological symptom items (agitation, anxiety, tactile disturbances, disorientation, and hallucinations) each of which are exactly operationalized. These two subscales lead to a maximum score of 17 points each. All items and the scoring system are clearly operationalized. The interrater reliability (based on scoring by the same team as in the present study) was good to excellent for single items, subscales, and the total scale with
-values ranging from 0.64 to 1.0 (Wetterling et al., 1997
). In addition, the AWS covers the whole spectrum of withdrawal syndromes including delirium.
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METHOD |
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Of the 217 patients, 27.2% were female (age 43.4 ± 8.1 years), 72.8% were male (age 41.3 ± 9.4 years), and 84 still had detectable alcohol in the blood at the time of admission
Medication
A study of the natural course of alcohol withdrawal was not accepted for ethical reasons. So patients were medicated as follows: carbamazepine (600 mg/day) as a standard medication was given, when the AWS vegetative subscore (VS) was between 7 and 10 and the psychopathological subscore (PS) was <6. In case of reported previous withdrawal seizures carbamazepine was prescribed independent of AWS scores. On the appearance of a VS 10 and/or a PS
6, 384 mg clomethiazole was given every 2 to 4 h depending on severity of withdrawal symptoms. Patients additionally received haloperidol when the PS was
10.
Statistics
All AWS score sheets were transferred into a data matrix and descriptive analyses were performed. For each subject the maximum VS, the maximum PS, and the maximum AWS-score were identified. The statistical analyses included mean, crosstabs, 2-test (two-tailed), analysis of variance (ANOVA), and a hierarchical cluster analysis procedure using SPSS, Windows version 10.0.7. The cluster analysis was performed by using standarized clustering variables (Z-scores). The Squared Euclidian Distance and the Ward's method for linking were applied. In order to predict these clusters the maximum VSs and PSs as well as specified items of the AWSobtained within the first 24 h after admissionwere analysed by a post hoc stepwise discriminant analysis. In a second step, demographic data and characteristics of the alcohol-related history were added to the analysis.
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RESULTS |
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Duration of withdrawal
The average duration of withdrawal of all subjects was 3.0 ± 2.0 days. In 24.0% of all patients withdrawal symptoms did not appear (AWS-Score 3) at all, or finished within 24 h after admission. In 33.2% withdrawal symptoms finished during the second day, in 13.8% during the third day, in 10.6% during the fourth day, and in 7.8% during the fifth day. In only 10.8% the withdrawal period lasted >5 days (up to 10 days).
Cluster analysis
Cluster analysis yielded five clusters representing an increasing severity of alcohol withdrawal. Each cluster is characterized by a combination of the maximum VS, of the maximum PS, and of the presence or absence of anxiety, disorientation, and hallucination.
Of all 217 patients, 18.4% did not develop any clinically relevant symptoms (cluster 1). All of these subjects reached a maximum AWS-score 5, a maximum VS
4, and a maximum PS
2 at each of the first five assessments (first day). Apart from one convulsive event, none of these patients developed any psychiatric or medical complication during the entire period of observation until discharge, and Anxiety, disorientation, or hallucination were not present. Cluster 2 was nearly as frequent as cluster 1 (18.9%). These patients suffered from vegetative symptoms like increased heart rates (87.8%), increased systolic blood pressure (95.1%), increased temperature (63.4%), sweating (90.2%), and/or tremor (97.6%). Psychopathological symptoms were not prominent in this cluster. Subjects belonging to cluster 3 (40.6%) presented vegetative as well as mild or moderate psychopathological symptoms. Anxiety was the most prominent symptom (100%), whereas disorientation and hallucinations were absent. In cluster 4 (11.1%) the most frequent psychopathological symptoms were disorientation (100%) and anxiety (75.0%). Cluster 5 patients (11.1%) suffered from vegetative as well as severe psychopathological symptoms. High rates of anxiety (70.8%) and disorientation (83.3%) were observed in this cluster as well asin contrast to clusters 3 and 4hallucinations in all cases (100%). All these cases fulfilled the diagnosis of delirium tremens.
The mean maximum AWS total scores significantly increased from cluster 1 to cluster 5 (Table 1). Convulsions were observed in all clusters but they occurred most frequently in cluster 4 (12.5%) and cluster 5 (20.8%). Within the first 24 h after admission 81.3% of the convulsions occurred. This was also true for one patient of cluster 1 (case No. 452) who had a convulsion during the admission procedure. Convulsions occurred only in three cases on the second, third, and fourth day. In 50% of the cluster 4, patients disorientation was found only once or twice at the time of assessment (i.e. within a period of 48 h) and frequently was not noted by the other members of the staff. Disorientation began with equal frequency by day and by night.
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While significant gender differences could not be found between the five clusters of alcohol withdrawal, patients in cluster 2 and 5 were slightly older than those in other clusters (Table 2). Neither the years of alcohol abuse nor the quantity of daily alcohol consumption in the last 30 days prior to admission differed between the clusters.
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Medication
Medication was prescribed to 79.3% of patients, carbamazepine to 62.7%, clomethiazole to 37.3%, and haloperidol to 5.5%.
Predicting the five clusters of alcohol withdrawal
In order to predict the five clusters of alcohol withdrawal a discriminant analysis was performed using variables obtained within the first 24 h after admission as independent variables the maximum VS, the maximum PS, and the presence or absence of anxiety, disorientation, and hallucinations (Tables 3 and 4).
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A more detailed analysis of cluster 5 patients comparing correctly and falsely classified subjects has been done. Within the first 24 h we found significantly higher maximum scores, only 58.3% were on the scales tactile disturbances (correct: 1.50; false: 0.20; T = 3.675, df = 22, P = 0.001) and hallucinations (correct: 2.36; false: 0.40; T = 4.769, df = 22, P < 0.001) leading to a significant higher maximum PS (correct: 7.21; false: 2.70; T = 3.752, df = 22, P = 0.001) and maximum AWS score (correct: 12.29; false: 8.00; T = 3.014, df = 22, P = 0.013) in correctly classified patients. No other differences could be found with regard to vegetative symptoms and other psychopathological symptoms like disorientation, agitation, and anxiety.
In a second step, demographic data (gender, age, and family status) and alcohol-related data (duration of alcohol abuse, grams of pure alcohol per day in the 30 days prior to admission, positive history of convulsions, previous delirium states, withdrawal syndromes, and inpatient detoxifications) were added into discriminant analysis. They did not improve but worsened the results of discriminant analysis (data available on request).
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DISCUSSION |
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Clusters of alcohol withdrawal |
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It may be discussed, if cluster 4 represents a subgroup of cluster 5 (delirium tremens) under the early beginning of neuroleptic therapy, because the absence/presence of hallucinations seem to be the main difference between both clusters. However, previously published prevalence rates of alcohol withdrawal delirium in detoxification samples (Wetterling et al., 1994; Palmstierna, 2001
) are in agreement with the rate of cluster 5 in this study (11.1%) while the prevalence of cluster 4 and 5 together (22.2%) substantially exceeds this rate.
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Convulsions |
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Implications for treatment |
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Limitations |
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Surprisingly, we did not find an association between lifetime or one month alcohol use (grams of pure alcohol per day) on the one hand and the severity of the withdrawal syndrome on the other hand. This finding differ from previous studies that reported such a relationship supporting the kindling hypothesis of alcohol withdrawal (Ballenger and Post, 1978; Carrington et al., 1984
; Brown et al., 1988
; Becker and Hale, 1993
). This discrepancy may be owing to the consequent and differentiated drug regime leading to a milder course of alcohol withdrawal in general.
The most striking limitation of our findings is the medication we gave for ethical reasons. In addition, medication was not in all cases strictly prescribed according to rules, a default owing to the clinical environment (e.g. doctors on duty who were not dircectly involved in the study). Thus we cannot refer to the natural course of alcohol withdrawal. In addition, it cannot completely be excluded that treatment itself was associated with the subtypes identified. This limitation, however, may be reduced by two factors: (i) The medication was not the cause but a consequence of the appearance of symptoms. (ii) Discriminant analysis on the basis of data obtained at the first five times of assessment, i.e. when only a minor influence of treatment can be expectedcorrectly predicted a high percentage of clusters. This finding supports predictive validity of the proposed typology. Further studies using different medical treatment schemes, e.g. benzodiazepines only, are needed to definitely clarify the impact of pharmacological treatment on withdrawal clusters.
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CONCLUSION |
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