Alcohol and Alcoholism Advance Access originally published online on December 13, 2005
Alcohol and Alcoholism 2006 41(2):168-173; doi:10.1093/alcalc/agh252
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COMORBID PHOBIC DISORDERS DO NOT INFLUENCE OUTCOME OF ALCOHOL DEPENDENCE TREATMENT. RESULTS OF A NATURALISTIC FOLLOW-UP STUDY
1 Department of Psychiatry and Institute for Research in Extramural Medicine, VU—University Medical Centre, GGZ Buitenamstel and 2 Academic Medical Centre, University of Amsterdam, Amsterdam Institute for Addiction Research, Amsterdam, The Netherlands
* Author to whom correspondence should be addressed at: Tel: +31 65 5197 293; Fax: +31 20 5736 524; E-mail: LMarquenie{at}ggzba.nl
(Received 29 September 2005; first review notified 31 October 2005; in revised form 9 November 2005; accepted 10 November 2005)
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSUBJECTSRESULTSDISCUSSIONREFERENCES |
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Aims: Despite claims that comorbid anxiety disorders tend to lead to a poor outcome in the treatment of alcohol dependence, the few studies on this topic show conflicting results. Objective: To test whether the outcome of treatment-seeking alcohol-dependent patients with a comorbid phobic disorder is worse than that of similar patients without a comorbid phobic disorder. Methods: The probabilities of starting to drink again and of relapsing into regular heavy drinking in (i) a group of 81 alcohol-dependent patients with comorbid social phobia or agoraphobia were compared with those in (ii) a group of 88 alcohol-dependent patients without anxiety disorders in a naturalistic follow-up using Cox regression analysis. Results: Adjusted for initial group differences, the hazard ratio for the association of phobic disorders with resumption of drinking was 1.05 (95% CI, 0.85–1.30, P = 0.66) and the adjusted hazard ratio for the association of phobic disorders with a relapse into regular heavy drinking was 1.02 (95% CI, 0.78–1.33, P = 0.89). Conclusion: The findings of this study do not confirm the idea that alcohol-dependent patients who have undergone alcohol-dependence treatment are at greater risk of a relapse if they have a comorbid anxiety disorder. No differences were found in abstinence duration or time to relapse into regular heavy drinking between patients with and without comorbid phobic disorders.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSUBJECTSRESULTSDISCUSSIONREFERENCES |
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Treatment of alcohol dependence generally aims for stable abstinence or in some cases for controlled drinking without days of heavy or riskful drinking. Using these outcome parameters, treatment is successful in 40–60% of patients seeking treatment (Nathan, 1997
; Bowen et al., 2000; Moyer and Finney, 2002). The frequent co-occurrence of psychiatric disorders (e.g. anxiety disorders) has been suggested as an explanation for these rather disappointing results (McLellan et al., 1983; Rounsaville et al., 1987; Van den Brink, 1995; Tómasson and Vaglum, 1998). As patients with alcohol dependence frequently suffer from comorbid anxiety disorders (Schneider et al., 2001), it has been claimed that comorbid anxiety disorders predict poor outcome of alcohol treatment (Chambless et al., 1987; Oei and Loveday, 1997; Kushner et al., 2000). A recent review (Schadé et al., 2003) concluded, however, that the empirical basis for this claim is rather weak, and rests on only four small sample studies (LaBounty et al., 1992; Tómasson and Vaglum, 1997; Tómasson and Vaglum, 1998; Driessen et al., 2001). No specific anxiety treatment was provided in these studies.
Methodologically, the study by Driessen et al. (2001) is probably the best currently available. It showed a significantly higher relapse rate in alcohol-dependent patients with a comorbid anxiety disorder. However, even this study has some serious limitations: (i) it was based on 68 patients only; (ii) the abstinence rate in the group without comorbid anxiety disorder was unusually high (60.5% as compared with 26.7% in the comorbid group) and (iii) the difference found between the groups without and with comorbid anxiety disorder could be explained by this high abstinence rate. Unfortunately, no alcohol relapse data were provided for different groups of comorbid patients (e.g. alcohol-dependent patients with generalized anxiety disorder, panic disorder, agoraphobia, or social phobia). This is important because different authors have mentioned the possibility that certain anxiety disorders are more likely to precede the onset of alcohol dependence and comorbidity of these disorders is likely to have a negative effect on the treatment outcome of alcohol dependence, whereas other anxiety disorders are more likely to occur in the course of an alcohol use disorder and are less likely to influence the course of alcohol dependence (e.g. Kushner et al., 2000).
The objective of the present study was to test the specific claim that comorbid phobic disorders predict a poor outcome in alcohol-dependence treatment on a larger sample of patients. We concentrated on comorbid social phobia and agoraphobia because these anxiety disorders are known to tend to precede alcohol dependence, whereas panic disorder and generalized anxiety disorder more often develop in the course of alcohol dependence (Kushner et al., 1990; Brady and Lydiard, 1993; Romach and Doumani, 1997). Patients with a comorbid social phobia or agoraphobia seem to use alcohol as ‘self-medication’. Hence these anxiety disorders are likely to constitute a specific risk of relapse into alcohol use after treatment. A naturalistic follow-up study was used to compare abstinence duration and time to relapse into regular heavy drinking in a group of treated alcohol-dependent patients with comorbid social phobia or agoraphobia with those in patients without any anxiety disorder.
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METHOD |
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TOPABSTRACTINTRODUCTIONMETHODSUBJECTSRESULTSDISCUSSIONREFERENCES |
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Procedure
All patients diagnosed with alcohol dependence and detoxified at the outpatient or inpatient clinics of the Jellinek Addiction Treatment Centre Amsterdam during the period from November 1998 to February 2001 who remained abstinent for at least 4 weeks were asked by their therapist to participate in the study. Since excessive use of alcohol and subsequent withdrawal are likely to influence the presence and severity of anxiety symptoms, sufficient time needs to elapse between detoxification and the diagnosis of comorbid anxiety disorders (Driessen et al., 2001
). Schuckit and Monteiro (1988) suggest a period of 4–8 weeks of abstinence before a valid diagnosis of comorbid Axis I disorders can be reached. After detoxification, patients participated in an alcohol-dependency treatment programme that generally did not include a specific treatment of anxiety (In fact, 26 patients in the PHOBIA+ group received additional treatment for their anxiety disorder as part of a randomized controlled trial.). The patients gave their informed consent after the study procedures had been fully explained to them. They were then diagnosed using the Structured Clinical Interview for DSM-IV (SCID, First et al., 1996) and were assigned to the group with a comorbid phobic disorder (PHOBIA+: social phobia and/or agoraphobia), the group without a comorbid anxiety disorder (ANX–: no anxiety disorder), or excluded from further participation in case of a non-phobic anxiety disorder (Fig. 1). Those included were required to fill out several questionnaires.
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All patients were followed-up by means of a telephone interview in March and April 2002. The time to follow-up for inpatients was the time between discharge and follow-up; in the case of outpatients it was the time between baseline assessment and follow-up. This distinction was made because inpatients are at lower risk of relapse as long as they are hospitalized. The mean time to follow-up was 20.3 months (SD 10.8, range 5–42) in the PHOBIA+ group and 23.5 months (SD 7.5, range 3–38) in the ANX– group, which was significantly different between groups (P = 0.03). If patients could not be contacted by phone after four attempts, they were asked to contact our research team by mail. If that failed, we tried to obtain information on relapse from parents (in 4.9% of the responders) or others (e.g. general practitioner in 5.6%).
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SUBJECTS |
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TOPABSTRACTINTRODUCTIONMETHODSUBJECTSRESULTSDISCUSSIONREFERENCES |
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Patients were included in the study if they met the DSM-IV criteria for alcohol dependence as diagnosed using the SCID and scored at least 5 on the alcohol severity scale of the EuropASI (range 0–9) (Kokkevi and Hartgers, 1995
), indicating that their alcohol use was a problem of at least moderate severity for which treatment was necessary.
Based on the presence (PHOBIA+) or absence (ANX–) of comorbid phobic disorders, patients were allocated to the two groups under study: (i) if they met the criteria for a comorbid social phobia, panic disorder with agoraphobia, or agoraphobia without a history of panic attacks (PHOBIA+) and (ii) if they did not meet the criteria for a comorbid anxiety disorder (ANX–) (Fig. 1). Patients with non-phobic anxiety disorders (panic disorder without agoraphobia, generalized anxiety disorder, obsessive compulsive disorder, and post-traumatic stress disorder) were excluded from further study. Patients with other comorbid mental disorders, including other substance use disorders, were not excluded. Although simple phobia is a phobic anxiety disorder, the presence of a simple phobia was not taken into account when allocating subjects to the two groups (PHOBIA+ and ANX–). The focus on social phobia and agoraphobia was based on the suggestion in the literature (Kushner et al., 1990) that patients with comorbid phobic disorders seem to use alcohol as ‘self-medication’ and would thus run a higher risk of relapse.
Instruments
SCID-IV
Psychiatric disorders with age at onset were assessed using the Structured Clinical Interview for DSM IV (SCID, First et al., 1996).
EuropASI
At baseline demographic characteristics were obtained using the European version (Kokkevi and Hartgers, 1995) of the fifth edition of the Addiction Severity Index (McLellan et al., 1992). Clinical aspects of alcohol dependence were also assessed using the EuropASI.
Evaluation at follow-up
A semi-structured interview based on the ‘life chart interview’ model (Lyketsos et al., 1994) was used to establish (i) abstinence duration and (ii) time to relapse into regular heavy drinking. The interview used calendar-linked landmarks and life-change anchors to prime recall where necessary. The patients were asked if/when they started to use alcohol again after baseline assessment (in the case of outpatients) or after discharge from the alcohol treatment centre (in the case of inpatients). In addition, they were asked if/when they started with regular heavy drinking again. The criterion used was five or more standard drinks of alcohol three or more days a week. A standard drink in The Netherlands contains 
10 g of alcohol.
The interview was administered by telephone. It has been concluded on the basis of a large survey of over 8000 male Vietnam veterans that the reliability and validity of telephone interview assessments of alcoholism are as good as those of an in-person interview (Slutske et al., 1998).
Statistical analyses
The baseline characteristics of the two groups under study were analysed using t-tests for continuous variables and 
2 tests for categorical variables. Proportional hazards survival analysis (Cox and Oakes, 1984) was used to test whether the presence of a phobic disorder (PHOBIA+/ANX–) predicted the first drink or relapse into regular heavy drinking. The analyses were adjusted for initial group differences (P < 0.05) in baseline characteristics.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSUBJECTSRESULTSDISCUSSIONREFERENCES |
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Recruitment, participation, refusals, and dropouts
Figure 1 shows that 860 patients were considered for participation. Of these, 232 (27%) were suitable and willing to participate (103 PHOBIA+, 129 ANX–), and 169 (73%: 81 PHOBIA+, 88 ANX–) of these completed the follow-up procedure (The main analyses were repeated after excluding the 26 patients from the PHOBIA+ group who had received additional treatment for their anxiety disorder as part of a randomized controlled trial. The results did not differ from the present findings.).
Reasons for not participating differed between outpatients and inpatients. All inpatients started the study abstinent and were checked for alcohol use at regular intervals until discharge; participation in the research procedure was easy to incorporate in the treatment programme. More outpatients failed to remain abstinent for at least 4 weeks and more outpatients dropped out of treatment; participation required a greater effort for them, increasing the number of refusals. Moreover, the objective of many outpatients was to become moderate drinkers rather than abstinent.
The proportion of patients who were successfully followed-up (responders) did not differ significantly between the PHOBIA+ group and the ANX– group (78.6 vs 68.2%; 2 = 3.15, P = 0.08). Patients who could not be followed-up (non-responders) did not differ significantly from responders on most baseline characteristics, apart from sex, ASI alcohol score, employment status, and treatment setting (Table 1). Non-responders were significantly more often male, had a significantly higher ASI alcohol score, were less frequently employed, and more frequently treated in an inpatient setting.
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No differences in baseline characteristics of the non-responders were found between the PHOBIA+ and ANX– groups, with the exception of lifetime and current comorbid depressive disorders, which were more prevalent in PHOBIA+ non-responders than among ANX– non-responders (lifetime 46 vs 17%, P = 0.02; current 32 vs 2%, P = 0.001).
Baseline characteristics
Patients with complete follow-up data (n = 169) were predominantly male (73%), single (61%), unemployed (63%), and in their mid-forties (Table 1). Most patients had received inpatient treatment (68%). Alcohol-dependent patients with and without phobic anxiety disorders were comparable as regards most demographic and clinical status variables. Alcohol-dependent patients with a comorbid anxiety disorder, however, had significantly more additional comorbid diagnoses (1.9 vs 1.0, P < 0.001), were more likely to have a lifetime or current depressive disorder (54 vs 24%, P < 0.001; 21 vs 5%, P < 0.001), and had been drinking for significantly fewer years (20.1 vs 23.1, P = 0.05) (Table 1).
Abstinence and relapse into regular heavy drinking
Descriptive analyses showed that 25.9% of the PHOBIA+ group and 20.5% of the ANX– group were abstinent after a mean period of almost 2 years follow-up. The proportion of patients relapsing into regular heavy drinking was 44.3 and 50.6% in the PHOBIA+ and ANX– group, respectively. These results do not take into account the fact that the time to follow-up was significantly longer in the ANX– group than in the PHOBIA+ group (23.5 vs 20.3 months, P = 0.03). Therefore, Cox regression was applied.
Cox regression was used to determine whether the presence of a comorbid phobic anxiety disorder (PHOBIA+ vs ANX–) was associated with breaking of the abstinence (taking the first drink) or with resumption of regular heavy drinking. The Cox regression analysis revealed a non-significant hazard ratio of 1.05 (95% CI, 0.74–1.48, P = 0.78) for starting to drink again (Fig. 2). Adjustment for initial group differences (i.e. number of additional diagnoses, comorbid lifetime or current depressive disorder, and years of drinking; P < 0.05) did not change this finding substantially: the effect of the group remained insignificant (adjusted hazard ratio 1.06, 95% CI, 0.72–1.57, P = 0.77). The presence of a comorbid phobic anxiety disorder (PHOBIA+ vs ANX–) was also not significantly associated with relapse into regular heavy drinking (hazard ratio: 0.95, 95% CI, 0.63–1.45, P = 0.83). Adjustment for initial group differences did not change this finding substantially either (adjusted hazard ratio: 0.96, 95% CI, 0.59–1.54; P = 0.86).
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We repeated these analyses first for men and women separately, then for inpatients and outpatients, but no significant association of comorbid phobic disorders with resumption of drinking (abstinence violation) or relapse into heavy drinking was found.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSUBJECTSRESULTSDISCUSSIONREFERENCES |
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This study of the influence of comorbid social phobia or agoraphobia on relapse after alcohol-dependence treatment revealed no significant effects of phobic disorders. It had been expected that alcohol-dependent patients with these specific comorbid anxiety disorders would respond less well to treatment and would relapse more quickly afterwards. It has been found that social phobia and agoraphobia tend to precede alcohol dependence (Kushner et al., 1990
; Brady and Lydiard, 1993; Romach and Doumani, 1997), suggesting that these comorbid patients use alcohol as ‘self-medication’. This expectation was not corroborated by the present study.
This finding is in line with the results of LaBounty et al. (1992), who reported similar relapse rates in alcoholics with and without symptoms of phobia, panic, or both.
By contrast, Tómasson and Vaglum (1997, 1998) found on the one hand that comorbid social phobia and generalized anxiety were significantly associated with better post-treatment abstinence [odds ratio (OR) = 0.25] (Tómasson and Vaglum, 1997), but on the other hand that patients with lifetime agoraphobia or panic disorder admitted to alcohol-dependence treatment programmes for the first or second time had a 5-fold increased risk of re-admission (OR = 5.8) (Tómasson and Vaglum, 1998). Similarly, Driessen et al. (2001) studied the response to treatment among alcohol-dependent patients with and without comorbid anxiety disorders (where the PHOBIA+ group included all types of anxiety disorders but predominantly phobias) and found a poorer outcome after 6 months in patients with comorbid anxiety (26.7% of 30 patients in the PHOBIA+ group as compared with 60.5% of 38 patients in the ANX– group).
The conclusions of the first-mentioned studies (LaBounty et al., 1992; Tómasson and Vaglum, 1997; Tómasson and Vaglum, 1998) are difficult to interpret, however, as the diagnoses of comorbid anxiety disorder may not have been valid. Tómasson and Vaglum (1997) made their baseline assessments after too short a period of abstinence, whereas the patients studied by LaBounty et al. (1992) were not abstinent at all. Diagnosis within less than 4 weeks of the start of abstinence may lead to anxiety symptoms caused by alcohol use being misdiagnosed as independent comorbid anxiety disorders (Schneider et al., 2001). In the Driessen study, on the other hand, the diagnosis of comorbid anxiety disorder was potentially valid: patients were abstinent for at least 3 weeks before they were diagnosed using the CIDI (Robins et al., 1988).
In the present study, the abstinence rates after a 6 month follow-up period were 35.8% of 81 patients in the PHOBIA+ group and 36.4% of 88 patients in the ANX– group. The frequency for alcohol-dependent patients with a comorbid anxiety disorder is similar to that found by Driessen et al. (2001), while these authors found a much higher abstinence level in patients without anxiety disorders. A recent systematic review (Moyer and Finney, 2002) reported abstinence rates of 35% in 232 randomized trials and 39% in 92 non-randomized trials, suggesting that the high abstinence rate of 60.5% found by Driessen might be due to some (unknown) population characteristics peculiar to their study.
LaBounty et al. (1992) found no significant influence of comorbid anxiety disorders on outcome, but did conclude that a phobic disorder was a significant predictor of relapse associated with drinking to cope with anxiety. This finding suggests that anxiety disorders may be a cause of relapse, even if alcoholics without anxiety disorders relapse for other reasons at the same rate. Hence, additional treatment of phobic disorders in alcohol-dependent patients might improve the prognosis after alcohol-dependence treatment. However, a randomized controlled trial among phobic alcohol-dependent patients showed that a significant reduction of anxiety symptoms after a specific anxiety treatment is not associated with better outcome of simultaneous alcohol-dependence treatment (Schadé et al., 2005).
The most important strength of the present study is that the sample is a good representation of the clinical reality of treatment seeking alcohol-dependent patients with a comorbid phobic disorder, since patients with psychotropic medication or other substance use disorders were not excluded. Consideration of baseline characteristics suggests that the prognosis for responders was probably slightly better than that for non-responders. Non-responders were more frequently male, unemployed, treated in an inpatient setting, and had a higher ASI alcohol score. The second strength of this study lies in the response rate of 73% after an average period of 2 years, which can be regarded as high.
The study is also subject to some limitations. First, the sample size is small, although the largest so far. Therefore, it cannot be excluded that an existing difference in outcome between alcohol-dependent patients with and without a comorbid phobic disorder was not detected in the current study. It should be noted, however, that the hazard ratios did indicate very small absolute effect sizes, which are hardly clinically relevant.
Second, there was a differential non-response between the ANX– and the PHOBIA+ groups with higher depression comorbidity in the PHOBIA+ non-response compared with the ANX– non-responders. With regard to the possible consequence of the reported differential non-response, it seems reasonable to assume that this may have resulted in relative low rates of depression in the PHOBIA+ and as a consequence an underestimation of the effect of comorbid phobic disorders on outcome. However, depression co-morbidity among patients with a phobic disorder is more likely to be an epiphenomenon of the phobic disorder than an independent predictor of relapse.
Third, the time to follow-up was significantly longer in the ANX– group than in the PHOBIA+ group (23.5 vs 20.3 months). This implies that patients in the PHOBIA+ group had less time to relapse, so the relapse rate could have been higher if the time to follow-up had been equal to that for the ANX– group. However, the chance that this would have biased the results is small, because the time to follow-up in the PHOBIA+ group was at least 5 months. Figure 2 shows that most relapses took place in the first 5 months. Furthermore, Cox regression analysis accounts for the time to follow-up.
The fourth and final limitation is the inclusion of patients who received additional specific treatment for their phobic disorders as part of their participation in the above-mentioned randomized controlled trial on the effect of treatment of phobic disorders in alcohol-dependent patients (Schadé et al., 2005). In fact this intervention was meant to reduce the difference in outcome of alcohol treatment between the PHOBIA+ and the ANX– group. However, there are no indications that this intervention in this subgroup of PHOBIA+ patients was responsible for the null finding in our study. First, analysis of the data of the current study after exclusion of these treated patients gave very similar results with no indication of an effect of phobic co-morbidity on alcohol-dependence treatment outcome. Second, the conclusion of the randomized clinical trial (Schadé et al., 2005) was that additional specific treatment of phobic disorders did not improve the effect of alcohol-dependence treatment.
The conclusion of this study is that comorbid phobic disorders are not predictive of a negative outcome in the treatment of alcohol-dependent patients.
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ACKNOWLEDGEMENTS |
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This research was supported by the Dutch Organization for Scientific Research (NWO), and the Dutch Fund for Mental Public Health (NFGV).
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