Vrije Universiteit, Department of Psychiatry and Institute for Extramural Medicine, Lassusstraat 2, 1075 GV Amsterdam,
1 Leiden University Medical Centre and
2 Amsterdam Medical Centre, University of Amsterdam, Amsterdam Institute for Addiction Research, Amsterdam, The Netherlands
Received 17 July 2002; in revised form 2 December 2002; accepted 19 December 2002
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ABSTRACT |
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INTRODUCTION |
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Clinical and epidemiological studies have shown substantial co-occurrence of anxiety disorders with alcohol use disorders. A large community-based study of psychiatric disorders, such as the Epidemiological Catchment Area (ECA) study (Regier et al., 1990), reported that 12.2% of the population with an alcohol dependence had a comorbid anxiety disorder (OR = 1.8). A higher OR was found in the National Comorbidity Study (NCS) (Kessler et al., 1997
). The NCS found that 35.8% (odds ratio, OR = 2.22) of the males diagnosed with an alcohol dependence also met criteria for a comorbid anxiety disorder, vs 60.7% (OR = 3.08) of the females. For the comorbidity of the specific anxiety disorders with alcohol dependence, the following lifetime prevalence rates and ORs were found in the NCS. Males: panic disorder 3.6% (OR = 2.27); agoraphobia 6.5% (OR = 1.82); social phobia 19.3% (OR = 2.41). Females: panic disorder 12% (OR = 2.98); agoraphobia 18.5% (OR = 2.53); social phobia 30.3% (OR = 2.62) (Kessler et al., 1997
). In clinical studies, high comorbidity rates were also found. Schneider et al. (2001)
diagnosed in alcohol-dependent patients an overall comorbidity rate of 42.3% for any anxiety disorder, and for panic disorder 5.2%, agoraphobia 13.1% and social phobia 13.7%.
A possible explanation for the high comorbidity rates is the self-medication hypothesis. Although at first the use of alcohol may decrease anxiety symptoms, later on it promotes persistent and excessive use via negative reinforcement (Kushner et al., 2000). Data suggest that in patients with dual diagnosis, agoraphobia and social phobia precede the development of alcohol use disorders (Kushner et al., 1990
; Brady and Lydiard, 1993
), whereas generalized anxiety disorder and panic disorder are more frequently diagnosed after the onset of the drinking problem (Brady and Lydiard, 1993
; Romach and Doumani, 1997
).
Based on the frequent co-occurrence of anxiety disorders with alcohol use disorders and the negative influence of other comorbid psychiatric disorders on the outcome of treatment of alcohol dependence, it has been stated that comorbid anxiety disorders predict poor outcome of alcoholism treatment (Chambless et al., 1987; Oei and Loveday, 1997
; Kushner et al., 2000
). In this report, we critically investigated this claim by reviewing all outcome studies in patients with alcohol use disorders and comorbid anxiety disorders or comorbid anxiety symptoms. First, we report the results of studies on the predictive value of comorbid anxiety disorders in alcoholism treatment. Subsequently, we try to answer the question of whether pharmacological and/or psychotherapeutic treatment of the comorbid anxiety disorder can improve treatment outcome in alcohol-dependent patients. We distinguished improvement on alcoholism treatment outcome and/or improvement on the comorbid anxiety disorder or symptoms.
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METHODS |
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A search in the databases of Pubmed, Psychinfo and Cochrane was conducted until 2002 using a combination of the key words anxiety disorder or anxiety, alcohol or alcohol dependence, and medication or treatment. This search yielded 355 articles in Pubmed, 297 in Psychinfo and 358 in the Cochrane database. The search was extended by a manual search of cross-references from the papers included. After screening the abstracts and if necessary the full text, we found 12 articles relevant for this review. We included four papers on the predictive value of comorbid anxiety disorders on alcoholism treatment outcome (LaBounty et al., 1992; Tomasson and Vaglum, 1997
, 1998
; Driessen et al., 2001
), five on the efficacy of pharmacological treatment of comorbid anxiety disorders in alcohol-dependent patients (Bruno, 1989
; Tollefson et al., 1991
; Malcolm et al., 1992
; Kranzler et al., 1994
; Randall et al., 2001a
), and three on the efficacy of psychotherapeutic treatment of comorbid anxiety disorders (Fals-Stewart and Schafer, 1992
; Bowen et al., 2000
; Randall et al., 2001b
).
Assessments and evaluation
Two of the authors (A.S. and L.A.M.) independently reviewed the studies selected, using a standardized coding form. Discrepancies in the coding were resolved by consensus. The coding form consisted of the following items: year of publication, setting, number of patients, type of anxiety disorder, type of diagnostic interview, type of study, duration of the interval between the assessment of the comorbid anxiety disorder and withdrawal from alcohol, duration of the follow-up period, and outcome rate at follow-up. We originally intended to use one common alcohol outcome measure. However, as the studies used different outcome ratings, we decided to present the results as defined in the original studies. The intervention studies were coded for the following items as well: type of intervention for the anxiety disorder and for the alcohol dependence, results at follow-up concerning the severity of the anxiety symptoms and the proportion of abstinent patients. Given the small number and the heterogeneity of the studies included, the results are not pooled but presented descriptively.
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RESULTS |
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In the papers by Tomasson and Vaglum (1997, 1998)
, patients were assessed between 1 and 4 days after alcohol withdrawal. The authors stated that the time of this assessment might have affected the results. Panic attacks are often confused with alcohol withdrawal symptoms (Kushner et al., 1990
). It is therefore possible that the frequency of the panic disorder diagnosis was overestimated. However, the authors feared that, if the assessment were to take place later on, a substantial part of the population would already have left the clinic, which might bias the composition of the sample included in the analysis. A second problem was the use of lifetime DSM-III diagnoses. This means that it is not clear whether patients still met the criteria for the anxiety disorder at the time of the interview. A third problem with the interpretation of these results is that the main outcome variable was not the abstinence rate, but re-admission for alcoholism treatment. Patients with lifetime agoraphobia or panic disorder admitted for the first or second time, had a 5-fold increased risk for re-admission within the 28-month follow-up period (OR = 5.8). Among patients with more than two re-admissions, this increased risk was not present. In addition, the authors (Tomasson and Vaglum, 1997
) found that, in contrast to the other anxiety disorders, comorbid general anxiety disorder and social phobia were associated with better outcome in abstinence (OR = 0.25). However, this finding only held for the subgroup with an onset of alcohol-related problems before the age of 25 years.
Driessen et al.(2001) compared abstinence rates within three diagnostic groups: (1) alcohol dependence without comorbidity (n = 62); (2) alcohol dependence with comorbid depressive disorder and various types of anxiety disorders (n = 15); (3) alcohol dependence with these comorbid anxiety disorders alone (n = 23). These disorders were diagnosed with the Composite International Diagnostic Interview (CIDI) (Robins et al., 1988b
) at least 3 weeks after withdrawal, thus ensuring a reliable DSM-III-R diagnosis. At 6-month follow-up, 60.5% of the non-comorbid patients had remained abstinent, as opposed to 30.8% of the group with depression and anxiety and 23.5% of the group with comorbid anxiety alone.
Two of the three studies (Tomasson and Vaglum, 1998; Driessen et al., 2001
) found a higher relapse rate for comorbid anxious patients. One study (LaBounty et al., 1992
) did not find significant differences in outcome between comorbid patients with panic and agoraphobic symptoms and patients with alcohol dependence alone. In contrast, one study (Tomasson and Vaglum, 1997
) appeared to show that comorbid social phobia and general anxiety disorder were associated with better outcome. As indicated above, the studies by LaBounty et al.(1992)
and Tomasson and Vaglum (1997
, 1998)
suffered from serious methodological limitations. However, the Driessen et al.(2001)
study used valid assessment procedures, ensuring a reliable diagnosis of the comorbid disorders. This study showed that a comorbid anxiety disorder leads to a lower abstinence rate at follow-up.
Pharmacological treatment of anxiety disorders in comorbid alcohol-dependent patients
The pharmacological treatment of alcohol-dependent patients with a comorbid anxiety disorder has not often been the subject of research. We found four double-blind randomized controlled trials (RCTs) comparing the 5-HT agonist, buspirone, with placebo in comorbid patients suffering from general anxiety disorder or anxiety symptoms (Bruno, 1989; Tollefson et al., 1991
; Malcolm et al., 1992
; Kranzler et al., 1994
). In addition, one RCT compared the efficacy of the SSRI, paroxetine, with placebo in patients with comorbid social phobia (Randall et al., 2001a
). In these five studies, no additional psychotherapy was offered for the treatment of the comorbid anxiety disorders. The results are listed in Table 2
.
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The 8-week RCT of Randall et al. (2001a) was a pilot study with only 16 patients. The study compared the efficacy and tolerability of paroxetine and placebo in a double-blind fashion in patients with social anxiety disorder and alcohol use disorder. Since the patients were drinking at the time of assessment, it is remarkable that none of their conditions was diagnosed as substance-induced anxiety disorder. In cases when subjects are still drinking during the assessment, this diagnosis usually precedes the diagnosis social anxiety disorder. Social anxiety symptoms improved in both groups, but significantly more in the paroxetine-treated group. However, there was no effect of paroxetine on drinking outcome.
Psychotherapeutic treatment of anxiety disorders in comorbid alcohol-dependent patients
Three RCTs were found with comorbid obsessive compulsive disorder (OCD) (Fals-Stewart and Schafer, 1992), panic disorder (Bowen et al., 2000
) and social phobia (Randall et al., 2001b
) (Table 3
). The results of the three studies are not consistent.
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In the study by Bowen et al.(2000), 146 patients with an alcohol problem and comorbid panic disorder with or without agoraphobia were treated for both disorders and compared with patients treated for their alcohol problem alone (n = 85). At follow-up, the anxiety symptoms had improved significantly in both conditions. However, there was no significant difference between the two groups with respect to the amount of alcohol consumed, frequency and severity of panic attacks and severity of agoraphobic avoidance. A problem with this study is that the patients were diagnosed only 1 week after detoxification, as a result of which alcohol withdrawal might have been confused with panic symptoms.
Randall et al. (2001b) included 93 alcohol-dependent patients with a comorbid diagnosis of social phobia. One group received cognitive behavioural therapy (CBT) for the alcohol dependence alone. The other group received CBT for both alcohol dependence and anxiety disorder at the same time. Both groups improved significantly on alcohol use and social anxiety symptoms. It should be noted that at follow-up, the group which received concurrent treatment for alcohol dependence and social anxiety disorder used alcohol more frequently, consumed significantly more drinks per day and experienced significantly more frequent heavy-drinking days, compared with the group which received treatment for their alcohol dependence alone. As an explanation for this unexpected finding, the authors suggested that patients in the combination group were more exposed to social situations, which could possibly have resulted in drinking as a coping strategy. This study included out-patients who were not necessarily abstinent at the assessment. As drinking alcohol can influence the presence of anxiety symptoms, the same mechanism as in the study of Bowen et al.(2000)
might have occurred.
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DISCUSSION |
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We also tried to find indirect evidence for the negative predictive value of comorbid anxiety disorders on the outcome of alcoholism treatment. We reviewed eight studies. Our hypothesis was that, in the case of a negative effect of comorbid anxiety disorders, successful pharmacological or psychotherapeutic treatment of anxiety would increase abstinence rates. We found five outcome studies for pharmacological treatment and three for psychotherapeutic treatment.
The pharmacological studies with buspirone measuring abstinence did not find a positive effect of the drug on alcohol dependence. There was an effect on craving, and, in one study, on drinks per day and slower return to heavy drinking. However, in these studies, buspirone appeared to be superior to placebo in reducing the severity of comorbid anxiety symptoms. These results suggest that reduction of anxiety symptoms with buspirone does not critically influence abstinence rates, but has some influence on craving and drinks per day in dually diagnosed patients.
The three psychotherapeutic studies did not show a consistent pattern. One study with comorbid OCD suggested a positive influence of psychotherapy on obsessivecompulsive symptoms but it was performed with a sample of mixed alcohol and drug misusers (Fals-Stewart and Schafer, 1992). Only 28% of the patients were dependent on alcohol and no separate data on this group were provided. Therefore, this study cannot be used to prove the positive effect of psychotherapy for anxiety disorders in comorbid alcohol-dependent patients. A study with comorbid panic disorder did not yield significant differences in abstinence rates between the group treated with CBT and the control condition (Bowen et al., 2000
), as the anxiety symptoms improved equally in both groups. The third study with comorbid social phobia showed a negative effect of CBT on abstinence rates (Randall et al., 2001b
). In this study, anxiety symptoms improved equally in CBT and in the control condition. We conclude that, due to the heterogeneous results of the pharmacological and psychotherapeutic treatment of comorbid anxiety disorders, these studies do not unambiguously support the observation that comorbid anxiety disorders have a negative influence on abstinence rates after alcoholism treatment.
It is interesting to note that, in two of the three psychotherapeutic studies, therapy for the anxiety disorders did not seem to contribute to improvement in anxiety symptoms. This suggests a rather non-specific influence of the alcoholism treatment provided on comorbid anxiety. RCTs have recently been published showing a superior effect of CBT and medication over placebo in the treatment of anxiety disorders (Van Balkom et al., 1997; Stein and Berk, 2000
). These studies used clean populations. Patients with alcohol or drug dependence were excluded. As a substantial proportion of patients with an anxiety disorder also suffer from a comorbid alcohol dependence (Noyes et al., 1986
), we can conclude that these positive results have been biased by the exclusion of an important segment of the patient population. If comorbid alcohol-dependent patients had also been included, perhaps the results would have been less convincing.
We found some important methodological problems in the assessments used for the diagnosis of the comorbid disorders. This raises the question of which procedures should be followed in order to diagnose comorbid patients in a valid way. Since excessive use of alcohol and the subsequent withdrawal influence the presence and severity of anxiety symptoms, there must be sufficient time between detoxification and the diagnosis of comorbid anxiety disorders (Driessen et al., 2001; Schneider et al., 2001
). Schuckit and Monteiro (1988)
suggested a period of 48 weeks of abstinence before Axis I disorders can be diagnosed validly. Only Driessen et al.(2001)
observed this minimum period. They found that 6 weeks after cessation of drinking, anxiety and depression scores stabilized. Patients who scored high on anxiety and depression measurements at this point, appeared to suffer from anxiety or affective disorders. After this period, the clinician can reasonably assume that existing psychiatric symptoms are part of a separate syndrome, which can be diagnosed validly in order to identify patients with dual diagnoses.
In this review, we have tried to answer the question of whether comorbid anxiety disorders predict poor outcome in the treatment of alcohol dependence and if treatment of the comorbid anxiety disorder reduces relapse into use of alcohol. It appears that the negative effect of comorbid anxiety disorders on treatment outcome in dually diagnosed patients is not an established fact, as we found only one high quality study with this result (Driessen et al., 2001). Therefore, statements in the literature to the effect that comorbid anxiety disorders influence outcome of alcoholism treatment in a negative way (Chambless et al., 1987
; Oei and Loveday, 1997
; Kushner et al., 2000
) seem premature. In future, prospective studies with adequate assessment methods should confirm whether anxiety disorders have a negative influence on abstinence rates in comorbid alcohol-dependent patients. For the moment, we cannot conclude that comorbid anxiety disorders in alcohol-dependent patients need a specific treatment to prevent relapse into drinking. However, medication and perhaps CBT can be useful in alcohol-dependent patients with a comorbid anxiety disorder to reduce anxiety symptoms. Further research is necessary to develop treatment programmes to reduce the high relapse rates and to treat anxiety disorders among alcohol-dependent patients.
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ACKNOWLEDGEMENTS |
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FOOTNOTES |
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