درمان افراد مبتلا به اختلال اضطراب اجتماعی و در معرض خطر مصرف الکل: توقف تدریجی در یک مداخله مختصر الکل پاروکستین

Abstract Paroxetine alone is not sufficient to decrease alcohol use in socially anxious alcoholics seeking anxiety treatment. We tested the hypothesis that adding a brief-alcohol-intervention (BI) to paroxetine would decrease alcohol use. All subjects (N = 83) had a diagnosis of social anxiety disorder, endorsed drinking to cope with anxiety, were NIAAA-defined at-risk drinkers, and were randomized to either paroxetine alone, or paroxetine plus BI. Both groups showed significant improvement in both social anxiety severity (F(5,83) = 61.5, p < 0.0001) and drinking to cope (e.g. F(4,79) = 23, p < 0.0001) and these two constructs correlated with each other (B = 3.39, SE = 0.696, t(71) = 4.88, p < 0.001). BI was not effective at decreasing alcohol use (e.g. no main effect of group, all p values >0.3). Paroxetine decreased social anxiety severity in the face of heavy drinking and decreasing the anxiety was related to a concurrent decrease in coping related drinking. BI was not effective at decreasing drinking or drinking to cope.

Introduction Social anxiety disorder (SAD) has a well-documented relationship with problematic alcohol use. SAD often begins in early adolescence and predicts the development of an alcohol use disorder (AUD) in adulthood (Buckner, Timpano, Zvolensky, Sachs-Ericsson, & Schmidt, 2008). In fact, about 1 in 5 people who present for treatment for social anxiety disorder also have an AUD (Book & Randall, 2002). One explanation of this co-occurrence is that people with high social anxiety endorse drinking alcohol to cope with their anxiety (Buckner and Heimberg, 2010 and Thomas et al., 2003) and expect alcohol to be anxiolytic (Carrigan & Randall, 2003). Drinking to cope (DTC) in and of itself has been shown to be associated with alcohol related problems including the development of alcohol dependence (Buckner & Heimberg, 2010). In a previous study, our research group previously showed that successfully reducing social anxiety through pharmacologic treatment with paroxetine does not translate into changes in drinking in individuals with co-occurring SAD and AUD who drink to cope (Book et al., 2008 and Thomas et al., 2008). At that time, we conducted a double-blind, placebo-controlled trial of the efficacy of paroxetine in decreasing both anxiety and alcohol use in 42 social anxiety treatment seeking subjects over 16 weeks. Although the medication group experienced a robust amelioration of anxiety, comparable in magnitude to the effects of paroxetine in socially anxious subjects without an alcohol use disorder, there were no differences between the paroxetine and placebo group in traditional measures of alcohol use (i.e., quantity or frequency). Although paroxetine did not change the overall amounts of alcohol consumed, it did decrease drinking specifically for the purpose of coping. Additionally, it uncoupled the relationship between anxiety and alcohol use. That is, in the group receiving paroxetine, there was no longer a significant positive relationship between quantity nor frequency of alcohol use and severity of social anxiety (Thomas et al., 2008). These data implied that although drinking did not automatically change, there may have been less reliance on alcohol for coping with social anxiety, and paroxetine-treated individuals might be receptive to targeted alcohol interventions once they no longer needed alcohol to cope. These findings from our previous study were relevant in guiding the current randomized clinical trial, which examines whether the addition of an alcohol intervention (BI), delivered when social anxiety symptoms have been successfully reduced by paroxetine, results in reduced alcohol use in participants who engage in risky drinking as defined by NIAAA (National Institute on Alcohol Abuse and Alcoholism, 2009). We hypothesized that participants who received paroxetine and BI vs. paroxetine only would have lower quantity and frequency of drinking. Because the study participants are seeking treatment for their anxiety, the alcohol intervention (BI) would need to have applicability in a mental health setting and be appropriate for individuals who are not motivated to change their drinking behaviors and do not view their alcohol use as a problem. To be adaptable for regular mental health practice, the alcohol intervention would need to be brief (without extended assessment, scoring, and feedback booklets) and unintimidating for a psychiatrist without experience in treating hazardous drinking in his/her practice. Additionally, it would have to be amenable to seamless integration into the treatment of a psychiatric disorder like social anxiety disorder in the sense that it could tie together for the study participant the relationship between drinking and relief from social anxiety with the risks involved in continued use of alcohol at risky levels. Brief interventions meet all these criteria. They are effective (Moyer, Finney, Swearingen, & Vergun, 2002) and are recommended for individuals who are heavy drinkers with mild or moderate problems associated with alcohol. The brief intervention chosen for this study, Helping Patients Who Drink Too Much- A Clinician's Guide ( National Institute on Alcohol Abuse and Alcoholism, 2007) is recommended for use in mental health settings and is used to link the severity of the social anxiety disorder being treated with the effect of continued drinking.

. Results 3.1. Demographic and baseline data Of 1676 potential participants who went through an initial telephone screening process, 160 qualified, 123 received paroxetine at baseline and 83 were randomized at week 6. Progress of recruitment and randomization is summarized in Fig. 1. There were no significant baseline differences between the group randomized to BI (n = 44) and the group randomized to the control condition (n = 39) on gender (about 55% male), race (about 75% Caucasian), or age (early 1930s), nor did groups differ on baseline social anxiety severity and alcohol use severity. Social anxiety disorder was relatively severe with a mean LSAS of 93, and many participants (43%) received a CGI severity rating by the study physician of at least “markedly ill.” Mean (±SD) age of onset of social anxiety was 13 (±5.7). As an inclusion criterion, all participants endorsed using alcohol to cope with their social anxiety, and all participants drank at levels considered “at-risk” ( National Institute on Alcohol Abuse and Alcoholism, 2007). For men, the mean (±SD) number of drinks per drinking day was 6.3 (±2.7) and drinks per week was 19.0(±12.4). Baseline mean (±SD) drinks per drinking day for women was 4.2(±1.6) and drinks per week was 11.8 (±10.5). The mean age of onset of at-risk drinking was 23.9 (±8.4). These and other baseline characteristics are detailed in Table 1. Table 1. Comparison of baseline characteristics of participants. BI group (n = 44) Control group (n = 39) p Value Male (%) 52 59 0.35 Caucasian (%) 77 74 0.95 Age, mean (SD) 31 (10.6) 31 (10.4) 0.97 Never married (%) 68 72 0.75 College grad (%) 30 28 0.82 Working full-time (%) 27 36 0.80 Non-smokers (%) 57 72 0.09 Age of social phobia onset 14.3 12.3 0.12 Comorbid mood or anxiety disorder (%) 64 59 0.42 ADS score (scale 0–47), mean (SD) 8 (5.3) 9.3 (6.4) 0.30 LSAS score, mean (SD) 94.2 (18.9) 91.4 (13.9) 0.46 At least “markedly severe”(CGI-S) (%) 43 41 0.76 Drinks per week, mean (SD) Men 18.0 (8.6) 19.3 (14.9) 0.68 Women 12.5 (12.4) 9.8 (6.2) 0.44 Drinks per drinking day, mean (SD) Men 6.9 (2.4) 5.9 (2.9) 0.14 Women 4.3 (1.6) 3.9 (1.5) 0.46 Alcohol dependent (%) 34 51 0.11 Alcohol abuse (%) 16 15 0.95 All statistical comparisons by simple ANOVA or Chi square as appropriate. Table options 3.2. Treatment adherence In general, participants adhered to the intervention and attended the treatment sessions. Those randomized to BI were more likely to attend all sessions as compared to those randomized to control (91% vs 72%) (Fisher's exact test p = 0.043). A majority of the participants in the BI group (n = 39, 89%) agreed to set a “drinks per week” and/or “drinks per drinking day” goal in the context of the intervention. Of the 83 randomized subjects, final visit data were collected on all but 12 (3 BI, 9 control), for an 86% research data completion rate. 3.3. Social anxiety and drinking to cope outcomes Social anxiety severity decreased significantly over time during the course of the study. As shown in Fig. 2, LSAS total scores decreased over time, with the most significant reduction occurring, as expected, in the first 6 weeks of treatment. The overall analysis revealed a significant effect of time on LSAS scores (F(5,83) = 61.5, p < 0.0001). Similarly, CGI-Severity for social anxiety also improved significantly over time (F(9,83) = 29, p < 0.0001). Neither of these measures showed a time × treatment group effect (all F values <1.7, all p values >10) Social anxiety severity scores over time and by treatment group as measured by ... Fig. 2. Social anxiety severity scores over time and by treatment group as measured by the LSAS. There is a significant decrease from baseline to week 6 for both groups. There is no effect of treatment group. Figure options In addition to reporting decreases in social anxiety severity over time, participants also reported a significant decrease in drinking to cope (DTC) with anxiety. Specifically, participants reported less percent time DTC before social situations over time (F(4,79) = 14, p = 0.0001) and less percent time DTC during social situations (F(4,79) = 23, p < 0.0001) as measured by SADS-B and SADS-D, respectively. However, there were no group x time differences on these measures (SADS-B: F < 1, p = 0.43; SADS-D: F < 1, p = 0.63). Similarly, Fig. 3 shows the significant decrease over time without a treatment × time effect of the percent DTC as measured on the TLFB (and described in Section 2). Drinking to cope over time and by treatment group as measured by the modified ... Fig. 3. Drinking to cope over time and by treatment group as measured by the modified TLFB. This is a measure of the percent of days participants engaged in social situations (denominator) that were also days they endorsed drinking to cope (numerator). There is a significant decrease in both groups over time. There is no effect of treatment group. Figure options There was a strong relationship between the improvement in LSAS total scores and the improvement in DTC (B = 3.39, SE = 0.696, t(71) = 4.88, p < 0.001). Fig. 4 shows a partial regression plot of SADS-D scores (percent of time drinking during a social engagement corrected for baseline) on improvement in LSAS (slope of baseline to week 6 from the piecewise regression). LSAS improvement accounted for 65% of the reduction in SADS-D scores. Partial regression plot of DTC (as measured by SADS-D scores) on changes in ... Fig. 4. Partial regression plot of DTC (as measured by SADS-D scores) on changes in social anxiety severity (as measured by the slope of LSAS scores from baseline to week 6). Social anxiety improvement accounted for 65% of the reduction in coping related drinking. Figure options 3.4. Drinking outcomes Contrary to our hypothesis, quantity and frequency of drinking did not differ between the two groups, nor did drinking decrease over the course of time. Drinks per week and drinks per drinking day outcomes are shown in Fig. 5. The mixed model analysis revealed no systematic differences between the two groups in the trajectories of either of these drinking variables. Analyses reported all use baseline values of the dependent variable as a covariate. There were no overall group mean differences on either measure (i.e., no main effect of group, all p values >0.3), no change over time (i.e., no main effect of time, all p values >0.45), nor any interaction of group with time (all p values >0.7) for either of the drinking variables. All possible covariates in Table 1 were examined and none altered these main findings. Drinking outcomes by treatment group. There was no effect of time or treatment ... Fig. 5. Drinking outcomes by treatment group. There was no effect of time or treatment group in drinks per drinking day or drinks per week.