Research Report
Anxiety Disorders: Treatable regardless
of the Severity of Comorbid Alcohol

Annemiek Schadé a Loes A. Marquenie a Anton J.L.M. van Balkom a Maarten W.J. Koeter b Edwin de Beurs c Richard van Dyck a Wim van den Brink b a Department of Psychiatry and Institute for Extramural Medicine, VU University Medical Centre, GGZ-Buitenamstel, Amsterdam , b Academic Medical Centre, University of Amsterdam, Amsterdam Institute for Addiction Research, Amsterdam , and c Leiden University Medical Centre, Leiden , The Netherlands Key Words
comorbid alcohol dependence did not influence the benefi- Anxiety disorder, treatment ؒ Alcohol dependence ؒ cial effect of CBT on the anxiety disorder. Psychological dis- tress (SCL-90), neuroticism (NEO N), conscientiousness (NEO
C), gender, employment and age of onset of alcohol depen-
dence showed some predictive value. Conclusions: Alco-
hol-dependent males with a comorbid anxiety disorder Aims: Clinical and epidemiological research has shown that
seem to benefit most from CBT if their alcohol dependence comorbidity is the rule rather than exception in the case of started after age 25, if they are employed and if their gen- psychiatric disorders. Cognitive behavioral therapy (CBT) eral psychopathology is less severe. The most important has been clearly demonstrated to be effective in treating conclusion, however, is that even severely alcohol-depen- anxiety and avoidance symptoms in patient samples of so- dent patients with an anxiety disorder can benefit from psy- cial phobia and agoraphobia without comorbid alcohol use disorders. It has recently been shown that treatment of co- morbid anxiety disorders in alcohol-dependent patients can also be very successful. The purpose of the present study was to find predictors of treatment success for comorbid Introduction
anxiety disorders in alcohol-dependent patients. Methods:
The study was conducted in a sample of 34 completers with
Until recently it was common practice to select only a double diagnosis of alcohol dependence and agoraphobia ‘pure’ patient samples for randomized controlled trials or social phobia who received CBT for their comorbid anxi- (RCTs) to measure the efficacy of a certain treatment. ety disorder in a 32-week randomized controlled trial com- However, the selection of pure patient samples has been paring alcohol and CBT anxiety disorder treatment with al- criticized on account of their limited generalizability. cohol treatment alone. In the current report, treatment Clinical and epidemiological research has shown that co-success was defined as a clinically significant change (recov- morbidity with psychiatric disorders is the rule rather ery) on the anxiety discomfort scale. Results: The severity of
than the exception [1–3] . Anxiety disorders have fre- Department of Psychiatry and Institute for Extramural Medicine VU University Medical Centre, Oldenaller 1 Tel. +31 20 7884 666, E-Mail [email protected] quently been shown to be comorbid with alcohol use dis- In addition to variables often found to be related to treat- orders [4] , but such ‘dual-diagnosed’ patients are usually ment success in phobic anxiety disorders – e.g. severity not included in RCTs on the treatment outcome of anxi- of psychopathology and neuroticism – we were especial- ety disorders. Given the high comorbidity rates, it is im- ly interested in the question whether alcohol dependence portant that the large group of double-diagnosed patients severity would critically influence outcome.
Studies of social phobia and agoraphobia (no alcohol use disorders allowed) using pure patient samples have clearly demonstrated that cognitive behavioral therapy (CBT) is effective in treating anxiety and avoidance symptoms [5–9] . Few studies have been published on the In the original RCT, 49 patients were randomized to alcohol treatment of anxiety symptoms in comorbid alcohol-de- treatment alone and 47 patients were randomized to the com-bined treatment for their alcohol use disorder and their phobic pendent patients, though in a recent study we showed that disorder. The current article focuses on the prediction of anxiety this can be very successful [10] . In an RCT of 96 such pa- reduction in the combined treatment group. A full set of predictor tients we investigated whether anxiety symptoms could data was available for 34 of the 47 patients in the combined treat-be reduced by the addition of optimal treatment for the ment group. They were diagnosed with a co-occurring diagnosis comorbid anxiety disorder, and whether such treatment of alcohol dependence and agoraphobia or social phobia and re- ceived CBT for their anxiety disorder and alcohol treatment as could reduce the alcohol relapse rates after an alcohol usual at the same time. The study received ethical approval from treatment program. In the group which was treated for the VU Medical Centre and took place from 1997 to 2001. All pa- both disorders at the same time (n = 47), abstinence, re- tients gave written informed consent.
lapse rates and heavy drinking days were the same as in the group treated only for the alcohol problem (n = 49). Subjects and Design The sample consisted of 23 men and 11 women with a mean However, additional CBT did significantly reduce the age of 42 (SD 8.6) years. Fourteen patients had a partner and 16 patients were employed. Only detoxified patients were included A remaining question is what factors contribute to a with a primary DSM-IV diagnosis of alcohol dependence and a better anxiety treatment outcome. A fair amount of re- comorbid diagnosis of panic disorder with agoraphobia, agora- search has been done on the prediction of treatment fail- phobia without a history of panic attacks or social phobia. The essential feature of the agoraphobic patients was anxiety about ures and successes in samples of patients with an anxiety being in places or situations from which escape might be difficult disorder but no comorbid alcohol use disorder. The find- or in which help may not be available in the event of having a ings do not always converge owing to methodological is- panic attack. The patients with the diagnosis of social phobia were sues (variability of diagnostic criteria, measurements, characterized by the persistent fear of social or performance situ-criteria for improvement, statistical analysis, selection of ations. Most patients avoided the fearful situations.
Since excessive use of alcohol and subsequent withdrawal is predictors) [11] . In general, though, it appears that the likely to influence the presence and severity of anxiety symptoms, severity of phobic symptoms, longer duration and pres- sufficient time needs to elapse between detoxification and the di- ence, and the severity of comorbid psychopathology, ben- agnosis of a comorbid anxiety disorder [19] . A 4- to 8-week pe- zodiazepine use, depressive symptoms and personality riod of abstinence is required before a valid diagnosis of comorbid disorders are frequently associated with poorer outcome Axis I disorders can be reached [20] . To ensure a valid diagnosis, the patients were assessed using the clinician administered Struc- [6, 12–17] . In all these studies, patients with comorbid tured Clinical Interview for DSM IV (SCID) [21] at least 6 weeks alcohol use disorders were excluded, thus limiting the after detoxification. Patients were assessed at baseline (intake) generalizability of the findings. Only the non-controlled and 16, 24 and 32 (follow-up) weeks after intake. The assessments moclobemide study by Versiani et al. [18] , which de- at baseline and 16 and 24 weeks were carried out by a trained psy- scribed long-term treatment outcome and prediction of chiatrist. An independent assessor conducted the follow-up as- response to treatment for social phobia, did not exclude Twenty-two patients met the criteria for social phobia, 2 for patients with comorbid alcohol use disorders and showed agoraphobia and 10 for both phobic disorders. When patients that alcohol abuse was by far the strongest predictor of a were diagnosed with both phobic disorders, the psychotherapist negative outcome.
chose together with the patient one of the phobic disorders as a The purpose of the present study was to find predic- primary treatment goal. As a result of this 31 patients received CBT for their social phobia and 3 patients received CBT for their tors of anxiety treatment success in dual diagnosed pa- agoraphobia. The severity of alcohol problems (Addiction Sever- tients with alcohol dependence and a comorbid anxiety ity Index score) before detoxification was assessed using the clini-disorder. No study of this kind has been published to date. cian-administered European version of the ASI (EuropASI) [22] . The ASI score (range 0–9) includes such things as the number of tient center offered a weekly treatment program on an individual drinking days and amounts of alcohol consumed, duration of the or group basis during 10 weeks. After this period, aftercare ses- alcohol problem, and alcohol treatment history. The patients in- sions were offered when necessary and wanted. The content of the cluded in the study had an ASI score of 1 4, indicating that alcohol therapy was similar to the treatment package described under the use forms a problem of at least moderate severity for which treat- ment is necessary. Heavy drinking days were defined as the num- The conclusion of the RCT was that anxiety treatment for al- ber of days with 5 or more alcoholic beverages per day in the 30 cohol-dependent patients with a comorbid anxiety disorder can days prior to the baseline assessment.
alleviate anxiety symptoms, but it has no significant effect on the The anxiety treatment took place in an outpatient treatment outcome of alcohol treatment programs [10] .
center (the Anxiety Clinic). The patients received 12 individual weekly 60-min therapy sessions by experienced trained thera- pists. The CBT was based on Beck and Emery [23] . The major Criterion Measure. Treatment success in the study was defined treatment component was cognitive restructuring. In the first as a clinically significant change [24] on the anxiety discomfort session, the cognitive model of panic attacks, agoraphobia and scale (ADS) [25] . The clinician administering the ADS rates anx- social phobia was explained. The patients subsequently learned to iety and avoidance on five personally identified social phobia or identify dysfunctional automatic thoughts with the aid of a diary. agoraphobia targets (0 = no anxiety or avoidance, 8 = extreme These automatic thoughts were challenged in the sessions using a anxiety or complete avoidance). At baseline the patients and the Socratic Dialogue and changed into non-distressing thoughts. therapist formulated these five relevant social phobia or agora-Patients were instructed to monitor and challenge their automat- phobia situations. Cronbach’s ␣ of ADS Avoidance was 0.60 and ic thoughts in diaries for 30–60 min/day as homework. In later of ADS Anxiety 0.77. The scales are sensitive to clinical change sessions behavioral experiments were conducted to test the em- [26] . To meet the criterion of a clinically significant change on the pirical basis of dysfunctional thoughts. During the first six CBT ADS (‘recovery’), patients must (a) be reliably changed and (b) fall sessions all patients continued to receive treatment for their alco- outside the range of two standard deviations (SD) of the mean of hol problem. The therapy sessions were standardized using a de- the baseline ADS score [24] (SD ADS Avoidance 5.2 and ADS tailed treatment manual. Weekly supervision sessions were held Anxiety 6.1). Of the 34 patients completing the follow-up, 27 and all sessions were audiotaped. During the weekly supervision (79%) patients recovered on ADS Avoidance, and 22 (65%) on sessions, some of the audiotapes were discussed. Additional treat- ADS Anxiety. There were no significant differences in demo- ment with fluvoxamine was offered in a target dose of 150 mg/day. graphic and psychopathology measures between patients with a Seventeen of the 34 patients (50%) started with fluvoxamine. follow-up score on the ADS (n = 34) and those with no follow-up Eight patients stopped within 1 month, mainly because of side ef- fects. Nine patients used 100–150 mg fluvoxamine for at least 6 months. CBT was regarded as the main anxiety therapy, and when patients refused medication they were not regarded as having Since this is the first study of predictors of treatment success dropped out of treatment. We determined that patients were ‘anx- in dual-diagnosed patients, we used a broad set of predictive vari- iety treatment completers’ when they followed 8 or more CBT ses- ables despite the limited number of patients.
sions. Twenty-four patients were treatment completers (70%). Treatment: Use of fluvoxamine, amount of attended CBT ses- There were no significant differences in demographic and psy- chopathology measures either between patients who were treat- Demographic variables: Age, sex, partner and current employ- ment completers and those who followed less than 8 sessions CBT. Of the 10 non-completers, 7 followed 5 or 6 sessions. The average Severity of comorbid psychopathology: number of sessions attended was 9 of the possible 12 (75%).
(SCL-90) [27] Cronbach’s ␣ = 0.98, Fear Questionnaire [28] Cron- The alcohol treatment offered, inpatient and outpatient, was bach’s ␣ = 0.79, Beck Depression Inventory [29] Cronbach’s ␣ = ‘as usual’ and not according to protocol. The goal of alcohol treat- ments was stable abstinence. Various strategies were used to max- Personality Factors: The NEO Five-Factor Inventory [30] – imize motivation and relapse prevention. The inpatient centers Neuroticism scale (NEO N) Cronbach’s ␣ = 0.81, Extraversion offered the following treatment package, mainly in group format scale (NEO E) Cronbach’s ␣ = 0.80, Openness to experience scale for 25 h/week during 12–16 weeks: psycho-education, self-control (NEO O) Cronbach’s ␣ = 0.79, Agreeableness (NEO A) Cron- training, social skills training, covert sensitization, and use of di- bach’s ␣ = 0.81, and Conscientiousness (NEO C) Cronbach’s ␣ = sulfiram. Self-control training teaches patients a set of self-man- 0.77 (all self-administered measurements).
agement skills such as making a functional analysis, alternative Severity and characteristics of alcohol dependence: Alcohol Se- coping skills and self-monitoring. Social skills training teaches verity Index (ASI), number of heavy drinking days, number of patients to communicate and listen to other people and they are alcohol dependence criteria met (SCID) and age at onset of alco- trained in problem solving and assertiveness. Covert sensitization is a form of aversion therapy that uses the patient’s own imagina-tion to develop a conditioned avoidance of alcohol. When neces- sary, there was help with job functioning, financial management, The influence of separate predictors of success was evaluated housing and marital or family therapy. After discharge the pa- using a two-stage procedure. First each potential predictor’s rela- tients were offered weekly follow-up sessions on an outpatient ba- tionship to outcome was assessed separately using univariate lo- sis. This treatment was tailored to the individual needs and wish- gistic regression analysis, with a clinically significant change on es of the patient. Duration varied from 0 to 32 weeks. The outpa- ADS Anxiety and ADS Avoidance as the dependent variable (n = Table 1. Demographic and psychopathology predictors (univariately tested): mean baseline and follow-up ADS
scores and proportion of clinically significant change stratified on significant predictors
Corrected for ADS Avoidance baseline scores.
* p ! 0.05; ** p ! 0.10. 1 Median = 195. 2 Median = 32.8. 3 Median = 42.5.
34). At baseline there were significant differences between males score on the Fear Questionnaire, total score on the Beck and females on ADS Avoidance. As different baseline scores for Depression Inventory and the personality traits ‘Extra- ADS Avoidance could have been a confounder in the relationship version’ (NEO E), ‘Openness to experience’ (NEO O) and between sex and treatment outcome, the relationship between ‘sex’ and clinically significant change in ADS Avoidance was cor- rected for the baseline scores. Second, to assess the minimum set of predictors required, all significant predictors were entered in a Severity of Psychopathology and Demographic multiple logistic stepwise forward procedure.
The mean baseline and follow-up ADS scores, and proportion Table 1 shows the potential psychopathology and de- clinical change stratified on significant predictors were added to tables 1 and 2 .
mographic predictors which were univariately signifi-cantly related to clinically significant change on either Avoidance or Anxiety. The 95% confidence interval of the OR of sex for ADS Avoidance is fairly wide because almost all males recovered in terms of clinically signifi- cant change (95.2%, n = 20) and the small number of pa- The following potential predictors were not related to tients in the non-recovered cell provided a wide confi- clinically significant change: use of fluvoxamine, num- ber of CBT sessions attended, age, having a partner, total Table 2. Alcohol predictors (univariately tested): mean baseline and follow-up ADS scores and proportion of clinically significant
change stratified on significant predictors
Age at onset of alcohol dependence – SCID Age at onset of alcohol dependence – SCID Entering all the univariately significant predictors in treatment success of CBT for comorbid anxiety symp- a multiple logistic stepwise forward procedure, we deter- toms. Among treatment-seeking alcoholics, even the sub- mined the minimum set of predictors required related to group of severely addicted patients can benefit from CBT clinically significant change on ADS Avoidance and for their comorbid anxiety disorder. Another interesting Anxiety. ‘Sex’ (OR 14.4, 95% CI 1.91–108.36, p = 0.030) finding was the influence of the age at onset of alcohol and the SCL-90 total score (OR 0.92, 95% CI 0.85–0.98, dependence on treatment outcome: a higher age at onset p = 0.056) remained the independent significant predic- predicted a positive treatment outcome. Different ages at tors of ADS Avoidance, and NEO Neuroticism (OR 0.78, onset of alcohol dependence are associated with particu-95% CI 0.67–0.92, p = 0.0015) of ADS Anxiety ( table 1 ).
lar types of alcoholic [31–34] . A late age at onset (after age 25) is found in both males and females: these alcoholics are influenced by paternal drinking patterns and usually None of the three alcohol severity measures was re- not associated with a pattern of criminality; they are low lated to clinically significant change on either ADS Avoid- in novelty seeking and high in harm avoidance and re- ance or ADS Anxiety ( table 2 ). Age at onset of alcohol ward dependence. The patients in our study with a high-dependence was a predictor of treatment outcome; how- er age at onset of alcohol dependence were able to derive ever, late age at onset predicted better treatment results more benefit from the anxiety treatment offered.
( table 2 ).
Higher general psychopathology measured in terms of the SCL-90 total or NEO N (anxiety, angry hostility, de-pression, self-consciousness, impulsiveness and vulner- Discussion
ability) is a predictor of a less successful CBT treatment outcome for anxiety and avoidance symptoms in alcohol- This study has a small sample size (n = 34) and should dependent patients with a comorbid anxiety disorder. therefore be regarded as exploratory in nature and more This finding is in line with CBT studies where patients research is necessary before firm conclusions can be diagnosed with only an anxiety disorder were treated for drawn. However, it is an important that the severity of their anxiety symptoms [6, 17] .
alcohol dependence does not negatively influence the In the present study males derived more benefit from remained abstinent for the duration of at least part of the CBT than females. From anecdotal evidence it seems CBT. Also, the CBT was given by experienced psycho-plausible that these positive outcomes in males could be therapists. Despite the fact that alcohol-dependent pa-related to more active exposure in males than in females: tients with a comorbid anxiety disorder make up a sig-sex differences in the response to psychotherapy for de- nificant part of the population of alcohol clinics and gen- pressive symptoms are frequently reported [35–37] . No eral psychiatric hospitals, they are often not treated for studies have been published on different responses among their anxiety disorder. Alcohol clinics do not usually males and females to CBT for anxiety symptoms.
reach a valid diagnosis of the anxiety disorder nor do they The major limitation of the study is the small sample have the facilities to provide psychotherapy for it. Psychi- size (n = 34). The fact that significant predictors were atric hospitals, on the other hand, often refuse to treat found, however, suggests that it was possible to detect patients for psychiatric disorders if they have a comorbid clinically relevant predictors.
substance abuse disorder. It is important for this large group of double-diagnosed patients to receive optimal treatment. Given the success of CBT, alcohol clinics and Conclusion
psychiatric hospitals should provide facilities for simul-taneous treatment of comorbid anxiety disorders in alco- Alcohol-dependent males with a comorbid anxiety hol-dependent patients.
disorder and late age at onset of alcohol dependence, who are in employment and have low levels of general psycho-pathology, seem to benefit most from CBT for phobic Acknowledgements
avoidance. This appears to hold true regardless of the se-verity of their alcohol problem. It should be noted that This research was supported by the Dutch Organization for Scientific Research (NWO), and the Dutch Fund for Mental Pub- this effect was obtained in a population with adequate lic Health (NFGV).
treatment for alcohol dependence and that the patients References
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