Use of Alcohol and Drugs to Self-Medicate Anxiety Disorders in a Nationally Representative Sample

ORIGINAL ARTICLES Use of Alcohol and Drugs to Self-Medicate Anxiety Disorders in a Nationally Representative Sample James Bolton, MD, Brian Cox, PhD, Ian Clara, MA, and Jitender Sareen, MD Abstract: This study examined the prevalence and correlates of self-medication of anxiety disorders with alcohol and drugs in a nationally representative sample (N 5877). A modified version of the Composite International Diagnostic Interview was used to make DSM-III-R mental disorder diagnoses. Frequencies of self-medication ranged from 7.9% (social phobia, speaking subtype) to 35.6% (generalized anxiety disorder). Among respondents with an anxiety disorder, self-medication was significantly associated with an increased likelihood of comorbid mood disorders, substance use disorders, distress, suicidal ideation, and suicide attempts. Self-medication behavior remained significantly associated with an increased likelihood of suicidal ideation (adjusted odds ratio 1.66; 1.17 2.36) as well as suicide attempts (adjusted odds ratio 2.23; 1.50 3.31), even after adjusting for a number of sociodemographic and psychiatric variables. These results suggest that individuals with anxiety disorders who self-medicate their symptoms with alcohol or drugs may be at increased risk for mood and substance use disorders and suicidal behavior. Key Words: Self-medication, anxiety, suicide, epidemiology. (J Nerv Ment Dis 2006;194: 818 825) The comorbidity of substance use disorders and anxiety disorders has been clearly established in several nationally representative studies (Himle and Hill, 1991; Kessler et al., 1997, 2005; Regier et al., 1990). In the Epidemiological Catchment Area study, people diagnosed with any anxiety disorder had an odds ratio of 1.7 of being diagnosed with a substance use disorder, as compared with individuals without an anxiety disorder. Analysis of each anxiety disorder revealed that panic disorder, agoraphobia, obsessive-compulsive disorder, and social phobia were all associated with Department of Psychiatry, University of Manitoba, Winnipeg, Manitoba, Canada. Preparation of this article was supported by a CIHR operating grant awarded to Dr. Cox, a Manitoba Research Council Establishment Grant awarded to Dr. Sareen, and a Health Sciences Centre Research Foundation grant awarded to Dr. Cox. The NCS was supported by grants from the National Institute of Mental Health, the National Institute of Drug and Alcohol Abuse, and the W. T. Grant Foundation. Send reprint requests to Jitender Sareen, MD, PZ-430 771 Bannatyne Ave., Winnipeg, MB, Canada R3E 3N4. Copyright 2006 by Lippincott Williams & Wilkins ISSN: 0022-3018/06/19411-0818 DOI: 10.1097/01.nmd.0000244481.63148.98 increased likelihood of being diagnosed with a substance use disorder (Himle and Hill, 1991; Regier et al., 1990). Similar results were demonstrated in the National Comorbidity Survey (NCS). Individuals with panic disorder, agoraphobia, simple phobia, social phobia, and generalized anxiety disorder all had elevated risk of being diagnosed with alcohol dependence (Kessler et al., 1997). In the NCS Replication, panic disorder, social phobia, generalized anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder were all significantly correlated with a diagnosis of alcohol abuse (Kessler et al., 2005). The mechanism that may underlie the co-occurrence of anxiety disorders with substance use disorders is more controversial and has been the focus of debate in several recent reviews (Kushner et al., 1990, 2000a; Schuckit and Hesselbrock, 1994). There are three principal mechanisms explaining why two disorders could co-occur in the same individual (Kraemer et al., 2001). The first is a causal relationship, in which the presence of one disorder leads to the development of the second disorder. The second is an indirect causal relationship; the presence of one disorder affects a third variable, which in turn increases the risk of developing the second disorder. The third mechanism is one in which no causal relationship exists. Instead, common or associated risk factors increase the likelihood of developing both disorders. There are two proposed theories specifically pertaining to the relationship of anxiety and substance use disorders, both within a direct causality model, that differ in terms of which disorder is primary (Kushner et al., 2000a). The first states that a primary anxiety disorder promotes the development of a substance use disorder (the self-medication hypothesis; Quitkin et al., 1972), whereas the second holds that a primary substance use disorder promotes the development of an anxiety disorder. At the current time, there is a lack of consensus regarding the understanding of the association between anxiety and substance use disorders (Kushner, 1996). Initially described as the tension reduction hypothesis (Conger, 1956), the self-medication hypothesis suggests that people with a primary anxiety disorder use alcohol to reduce symptoms of anxiety (Quitkin et al., 1972; for reviews, see Cox et al., 1990 and Kushner et al., 1990). However, evidence for self-medication is mixed. A community sample of individuals with panic disorder found low rates of selfmedication with alcohol (10%) and drugs (6%; Katerndahl and Realini, 1999). Evidence for self-medication is more robust in clinical studies of agoraphobia and social phobia. In 818 The Journal of Nervous and Mental Disease Volume 194, Number 11, November 2006

The Journal of Nervous and Mental Disease Volume 194, Number 11, November 2006 Self-Medication of Anxiety one study, individuals with comorbid agoraphobia and alcoholism had high rates of self-medication (91%), although the group with agoraphobia alone had a lower rate (43%) (Bibb and Chambless, 1986). In studies of social phobia, the percentage of individuals reporting use of alcohol to cope with feared social situations ranges from 50% (Turner et al., 1986) to 74% (Thomas et al., 2003). A clinical sample of individuals with comorbid alcoholism and phobias (agoraphobia and social phobia) endorsed self-medication rates of 97% (Smail et al., 1984). Inherent in this model is a subjectively perceived efficacy that promotes an individual to continue to use alcohol to reduce anxiety. Studies examining the efficacy of self-medication have mainly focused on experimental situations (Abrams et al., 2001; Himle et al., 1999; Naftolowitz et al., 1994) and have primarily employed self-report measures to assess anxiety (Naftolowitz et al., 1994; Thomas et al., 2003). Self-medication has been found to be efficacious in reducing anxiety in some studies (Abrams et al., 2001; Thomas et al., 2003) but not in others (Himle et al., 1999; Naftolowitz et al., 1994). A concept that has not been previously studied is the objective efficacy of self-medication behavior with regard to broader determinants of health such as psychiatric comorbidity and distress. Although self-medication is proposed to result in alcohol dependence in vulnerable individuals (Frances, 1997; Khantzian, 1997), is it possible that moderate use of alcohol or drugs could actually be an efficacious strategy to treat anxiety and as such result in less distress? If moderate alcohol use reduces anxiety without the negative consequences associated with excess alcohol, theoretically it may be superior to abstinence among anxious individuals. Two community studies reported this U-shaped relationship between alcohol, mood and anxiety symptoms, finding that moderate alcohol use was associated with less symptomatology compared with abstinence (Power et al., 1998; Rodgers et al., 2000). At this time, it remains unknown whether self-medication with alcohol or drugs to reduce anxiety symptoms is associated with higher or lower rates of comorbidity and distress. The current study used data from a large nationally representative sample that included standardized assessment of anxiety disorders, other psychiatric disorders, measures of distress, and specific assessment of the use of alcohol and drugs to self-medicate anxiety symptoms. This is an important addition to the understanding of substance use among people with anxiety, because for the first time, prevalence estimates can be generated for self-medication behavior among individuals with anxiety disorders in the general population. Furthermore, studying the correlates of self-medication provides an understanding of the consequences of using alcohol and drugs to decrease anxiety. The goals of this study were to (1) determine the prevalence of self-medication among each anxiety disorder; (2) determine whether selfmedication was associated with an increased likelihood of comorbidity with other mental disorders; and (3) determine the association between self-medication behavior and measures of distress, including suicidal behavior. METHODS Sample The NCS was a representative community survey administered from September 1990 to February 1992. The sample was selected from a noninstitutionalized household population of the coterminous United States. A supplemental equal-probability subsample of students in campus group housing was also taken. There were 8098 respondents with an age range of 15 to 54 years. The response rate was 82.4%. Informed consent was obtained before beginning the interviews from all respondents in accordance with federal legislative requirements. The data were weighted for differential probabilities of selection and nonresponse. The sample was adjusted to approximate the cross-classification of the population distribution on a range of sociodemographic characteristics. Part II of the survey (N 5877; 99% response rate from Part I) contained a detailed psychosocial assessment battery that included questions that directly asked about self-medication behavior as well as suicidal behavior. The details of the NCS design have been described previously (Kessler et al., 1994). Assessment of Self-Medication Respondents who endorsed phobic fears were asked the following question: Did you ever drink more than usual or use drugs not prescribed (or in greater amounts than prescribed) to help you reduce the fears? The question was asked separately for each of the following anxiety disorders: generalized anxiety disorder, panic disorder, agoraphobia, social phobia (speaking and complex subtypes), and simple phobia. Therefore, it was possible to determine the presence or absence of self-medicating behavior for each individual anxiety disorder. We examined respondents endorsing selfmedication (N 324) among those meeting criteria for any anxiety disorder (N 1477) at any time in their lives. Diagnostic Assessment The NCS diagnoses were generated from a modified version of the World Health Organization Composite International Diagnostic Interview, a fully structured diagnostic interview designed for trained nonclinicians (World Health Organization, 1990). DSM-III-R diagnoses assessed in this study include generalized anxiety disorder, panic disorder, agoraphobia, social phobia (speaking and complex subtypes), simple phobia, major depression, mania, dysthymia, alcohol abuse and dependence, drug abuse and dependence, and antisocial personality disorder. World Health Organization field trials (Wittchen, 1994) and NCS clinical reappraisal studies (Kessler et al., 1998b) both document acceptable reliability and validity of all the aforementioned diagnoses. Assessment of Suicidal Ideation and Suicide Attempts Assessment of suicidal ideation and attempts in the NCS occurred in the life-event history section of the interview. All respondents were asked the following questions: Have you ever seriously thought about committing suicide? and Have you ever attempted suicide? 2006 Lippincott Williams & Wilkins 819

Bolton et al. The Journal of Nervous and Mental Disease Volume 194, Number 11, November 2006 Assessment of Disability and Distress Past 30-day functioning in the respondent s usual activities was assessed in the following manner. Respondents were asked, because of problems with your emotions, nerves or mental health, or with your use of alcohol or drugs, (1) how many days in the prior 30 they were totally unable to do the things they normally did, (2) how many days in the prior 30 they had to cut down on what they did or accomplished less, and (3) how many days in the prior 30 it took an extreme effort to perform their usual level of work. A dichotomous variable was created based on all three questions on past 30-day functioning: (1) 0 days affected by mental illness for all three questions, versus (2) 1 or more days affected by mental illness for any of the three questions. A 14-item continuous measure of past 30-day emotional distress was collected in the NCS, which has been noted to possess good psychometric properties (McWilliams et al., 2003). For the current investigation, we dichotomized the sample into high distress if the individual rating was 1 or more SDs above the mean of the NCS sample (22.44; SD 8.09). Statistical Analysis In all analyses, the appropriate statistical weight was employed to ensure the data was representative of the national population. The SEs were calculated using the Taylor Series Linearization method in the SUDAAN program (Shah et al., 1995) based on NCS stratification information in the public use dataset that is available specifically for this purpose. The prevalence of missing information for the principle variables was low, with a range of 0% to 0.3%. First, we examined the prevalence of self-medication with alcohol and drugs among each of the DSM-III-R anxiety disorders (panic disorder; generalized anxiety disorder; social phobia, speaking and complex subtype; simple phobia; agoraphobia; and any anxiety disorder). Previous analysis has demonstrated that social phobia, as assessed in the National Comorbidity Survey, can be disaggregated into two subtypes: (1) a speaking subtype characterized by fears related to public speaking, and (2) a complex subtype characterized by a broader range of social fears (Kessler et al., 1998a). Second, individuals with the aforementioned anxiety disorders (N 1477) were divided into two mutually exclusive categories: (1) any anxiety disorder without self-medication (N 1153) versus (2) any anxiety disorder with self-medication (N 324). We used 2 analysis to determine significant differences between these two groups on sociodemographic variables (sex, education, marital status, race, and income), DSM-III-R diagnoses (major depression, dysthymia, bipolar I disorder, alcohol abuse with or without dependence, drug abuse with or without dependence, and antisocial personality disorder), and distress variables (high distress, past 30-day dysfunction, lifetime suicidal ideation, and lifetime suicide attempts). 2 Analysis was also employed to compare the aforementioned diagnostic and distress variables between the two groups (self-medication and nonself-medication) for each separate anxiety disorder. Third, we used multiple logistic regression to examine whether self-medication behavior was associated with increased levels of distress. The subsample of individuals with anxiety disorders endorsing self-medication (N 820 324) was compared with the remainder Part II sample (N 5553), which comprised all individuals (including those with anxiety disorders) who did not self-medicate. Odds ratios were adjusted for sociodemographic variables (sex, education, marital status, race, and income; AOR a ) and then adjusted for sociodemographic and diagnostic variables (major depression, dysthymia, bipolar I disorder, alcohol abuse with or without dependence, drug abuse with or without dependence, antisocial personality disorder, and any anxiety disorder; AOR b ). RESULTS The prevalence of self-medication among anxiety disorders is presented in Table 1. People with generalized anxiety disorder had the highest prevalence of self-medication at 35.6%. The presence of any anxiety disorder was associated with a 21.9% prevalence of self-medication. Table 2 shows the association between sociodemographic variables and self-medication among anxiety disorders. 2 Analysis revealed statistically significant differences for the associations of self-medication with sex, marital status, and race variables. In the absence of self-medicating behavior, 65.6% of people with an anxiety disorder were female; among the subset of people with an anxiety disorder who self-medicate, 55.4% were male. People who self-medicate were significantly more likely to be separated or divorced compared with individuals who did not self-medicate (18.7% vs. 11.8%). Regarding race, blacks were significantly less likely to self-medicate, while whites were significantly more likely to self-medicate. There were no significant differences between the self-medication and nonself-medication groups among levels of education or income. The associations of diagnostic and distress variables with self-medication among anxiety disorders are presented in Table 3. The subsample that endorsed self-medicating behavior had significantly higher rates of every DSM-III-R disorder. Of those endorsing self-medication, 56.8% also had major depression, compared with 30.7% of those that did not self-medicate. All distress variables were also significantly higher among individuals who endorsed self-medication. Of the self-medicating group, 44.1% experienced suicidal ide- TABLE 1. Disorders Prevalence of Self-Medication Among Anxiety Anxiety Disorder N Prevalence of Self-Medication, N (%) SE Panic disorder 200 46 (23.0) 2.80 Generalized anxiety disorder 295 105 (35.6) 2.67 Social phobia 795 130 (16.4) 1.51 (1) Speaking subtype a 284 22 (7.9) 1.27 (2) Complex subtype b 509 108 (21.2) 2.21 Simple phobia 654 79 (12.1) 1.56 Agoraphobia 386 61 (15.8) 2.03 Any anxiety disorder 1477 324 (21.9) 1.17 a Fears confined to public speaking. b Fears related to a broad range of social situations. 2006 Lippincott Williams & Wilkins

The Journal of Nervous and Mental Disease Volume 194, Number 11, November 2006 Self-Medication of Anxiety TABLE 2. Sociodemographic Correlates of Self-Medication With Alcohol and Drugs Among Anxiety Disorders a (Expressed in Percentages) b Demographic No Self-Medication (N 1153) Self-Medication (N 324) 2 p Value Sex 22.4 0.01 Male 34.4 55.4 Female 65.6 44.6 Education (y) 3.5 NS 0 11 26.0 22.0 12 38.9 41.6 13 15 21.6 23.6 16 13.5 12.8 Marital status 10.4 0.01 Married or cohabitating 59.3 59.2 Separated or divorced 11.8 18.7 Never married 28.9 22.0 Race 17.5 0.01 White 76.2 84.5 Black 11.2 4.1 Hispanic 9.0 8.4 Other 3.6 3.0 Income 4.3 NS $0 to $19,999 30.0 32.7 $20,000 to $34,999 24.4 25.2 $35,000 to $69,999 34.1 34.2 $70,000 11.5 8.0 a Anxiety disorders represents the group comprised of panic disorder, generalized anxiety disorder, social phobia, simple phobia, and agoraphobia. b Individuals with anxiety disorders (N 1477) are compared based on the absence (N 1153) or the presence (N 324) of self-medication with alcohol or drugs. TABLE 3. Associations of Diagnostic and Distress Variables With Self-Medication Among Anxiety Disorders a,b No Self-Medication (N 1153) Self-Medication (N 324) 2 p Value Diagnostic variables Major depression 354 (30.7%) 184 (56.8%) 47.2 0.01 Dysthymia 128 (11.1%) 93 (28.7%) 38.3 0.01 Bipolar I disorder 32 (2.8%) 41 (12.6%) 19.6 0.01 Alcohol abuse with or without dependence 242 (20.9%) 217 (66.9%) 232.2 0.01 Drug abuse with or without dependence 116 (10.0%) 146 (45.0%) 103.4 0.01 Antisocial personality disorder 31 (2.7%) 61 (18.7%) 63.6 0.01 Distress variables Past 30-day high distress 354 (30.7%) 150 (46.4%) 19.3 0.01 Past 30-day dysfunction 192 (16.7%) 97 (30.2%) 20.2 0.01 Suicidal ideation 209 (18.1%) 143 (44.1%) 55.0 0.01 Suicide attempt 72 (6.2%) 77 (23.7%) 41.4 0.01 a Anxiety disorders represents the group comprised of panic disorder, generalized anxiety disorder, social phobia, simple phobia, and agoraphobia. Associations of diagnostic and distress variables were determined for each anxiety disorder separately (results not presented) with the same pattern observed in each. b Individuals with anxiety disorders (N 1477) are compared based on the absence (N 1153) or the presence (N 324) of self-medication with alcohol or drugs. ation, compared with 18.1% of the nonself-medicating group. Similarly, self-medication was significantly associated with a higher likelihood of suicide attempts (23.7% vs. 6.24%) compared with those without self-medication. Analysis for each separate anxiety disorder revealed the same pattern of higher rates of comorbid mental disorders and distress among individuals endorsing self-medication compared with those who did not self-medicate (results not presented). 2006 Lippincott Williams & Wilkins 821

Bolton et al. The Journal of Nervous and Mental Disease Volume 194, Number 11, November 2006 TABLE 4. Distress, Disability, and Suicidal Behavior Among Subjects Who Self-Medicate Compared to Nonself-Medicators Self-Medication (N 324) vs. Nonself-Medication (N 5553) Characteristics AOR a (95% CI) AOR b (95% CI) Lifetime suicidal ideation 6.55* 1.66* (4.95 8.66) (1.17 2.36) Lifetime suicide attempts 8.92* 2.23* (6.68 11.90) (1.50 3.31) Past 30-day dysfunction 5.07* 1.33 (1 or more days vs. none) (3.86 6.68) (0.93 1.90) Past 30-day high distress 5.87* 1.18 (4.47 7.72) (0.85 1.63) *p 0.01. a Adjusted for sex, education, marital status, race, and income. b Adjusted for sex, education, marital status, race, income, major depression, dysthymia, bipolar disorder, antisocial personality disorder, alcohol abuse with or without dependence, drug abuse with or without dependence, and any anxiety disorder. These differences were statistically significant in most of categories. Table 4 presents the results of the multivariate logistic regression for lifetime suicidality and past 30-day distress. Both suicidal ideation and suicide attempts remained significantly associated with self-medication even after adjusting for all independent variables (AOR b suicidal ideation: 1.66, 95% CI, 1.17 2.36; AOR b suicide attempts: 2.23, 95% CI, 1.50 3.31). While past 30-day dysfunction and past 30-day high distress remained statistically significant after adjusting for sociodemographic variables (AOR a past 30-day dysfunction: 5.07, 95% CI, 3.86 6.68; AOR a past 30-day high distress: 5.87, 95% CI, 4.47 7.72), they lost significance when adjusting for all independent variables. DISCUSSION This study is the first to examine self-medication of anxiety disorders with alcohol or drugs in a nationally representative sample. Our findings indicate that self-medication is a common behavior in all the anxiety disorders. It is associated with significantly greater comorbidity and distress when compared with individuals with anxiety disorders who do not self-medicate. Multiple logistic regression analysis revealed that self-medicating behavior is significantly associated with an increased likelihood of suicidal ideation and suicide attempts, even after controlling for sociodemographic and diagnostic variables. This study extends the literature on self-medication in anxiety disorders by determining prevalence rates of the behavior in a nationally representative sample. Prevalence estimates to date have been primarily generated from clinical samples of either individuals with alcohol use disorders (Smail et al., 1984) or anxiety disorders (Bibb and Chambless, 1986; Thomas et al., 2003; Turner et al., 1986). One study determined the prevalence rate of self-medication among individuals with panic disorder in a community sample (Katerndahl and Realini, 1999). Rates of self-medication 822 in these studies have varied greatly; it is likely that sampling, as well as variance in the method of assessment of selfmedication, are contributing factors to the disparity among prevalence rates. The prevalence rates of self-medication among anxiety disorders in our study were significantly lower than in previous clinical study samples, underscoring the influence of selection bias and its propensity to inflate prevalence rates artificially. This study used a question that directly assessed self-medication behavior in anxiety disorders in a representative sample, and therefore our results likely demonstrate a valid reflection of self-medication in the population. An additional strength of the study is that self-medication was assessed separately for each anxiety disorder. The behavior was common in each anxiety disorder, with prevalence rates ranging from 7.9% to 35.6%. Interestingly, while literature reviews have focused on self-medication in panic disorder and social phobia (Carrigan and Randall, 2003; Cox et al., 1990), little research exists on self-medication in generalized anxiety disorder. Our study noted the highest reported prevalence of self-medication in generalized anxiety disorder (35.6%). Other studies have found higher rates of generalized anxiety disorder among individuals with alcohol dependence than would be expected in the general population (Bowen et al., 1984; Ross et al., 1988; Weiss and Rosenberg, 1985), but these studies did not specifically examine selfmedication behavior. One study found that the most common anxiety disorder among benzodiazepine-dependent outpatients was generalized anxiety disorder (33% of subjects; Romach et al., 1995). Furthermore, those subjects tended to shift their use of benzodiazepines from an as-prescribed to an as-needed pattern, perhaps indicative of self-medicating behavior. The high prevalence rate of self-medication among individuals with generalized anxiety disorder in our study may be explained by the pervasive worry pattern inherent in the disorder. An identifiable feared stimulus, such as in simple phobia, may be easier to avoid than generalized worries. Without the option of avoidance, substance use becomes the preferred coping mechanism. Further studies are needed to address a potentially underrecognized and significant mechanism underlying the comorbidity of substance use disorders and generalized anxiety disorder. A further contribution of this study is the examination of the associations between comorbidity, distress, and selfmedication among individuals with anxiety disorders. We hypothesized that the sample endorsing self-medicating behavior would have higher levels of comorbidity and distress compared with the sample that did not self-medicate, despite literature suggesting that moderate substance use is more beneficial than abstinence with respect to psychiatric morbidity (Power et al., 1998; Rodgers et al., 2000). Our findings demonstrate significant associations between self-medication and higher rates of major depression, dysthymia, bipolar I disorder, substance use disorders, and antisocial personality disorder when compared with individuals who do not selfmedicate. This is consistent with previous literature that has suggested that self-medication is associated with greater comorbidity (Cox et al., 1990). Particularly concerning were the 2006 Lippincott Williams & Wilkins

The Journal of Nervous and Mental Disease Volume 194, Number 11, November 2006 Self-Medication of Anxiety higher rates of suicidal ideation and suicide attempts among individuals with anxiety disorders who endorsed self-medication with alcohol and drugs compared with those who did not endorse self-medication. Previous studies have demonstrated that suicidality is associated with both anxiety disorders and substance use disorders (Kessler et al., 1999; Preuss et al., 2003). Multiple logistic regression analysis in this study suggests that self-medicating behavior is itself associated with higher rates of suicidal ideation and attempts. Adjusting for the effects of mental disorders reduced the association somewhat, suggesting that comorbid mental illness accounts for part of the association. This is an expected finding, considering previous findings suggesting that depressive illness is the strongest factor associated with suicidality (Beautrais et al., 1996; Kessler et al., 1999). However, controlling for these variables did not completely account for the association. This is especially interesting with respect to alcohol and drug use disorders. Self-medication in the absence of a substance use disorder implies that a person is using moderate, or subthreshold, amounts of alcohol or drugs to reduce anxiety. Our findings suggest that among those with an anxiety disorder, self-medication with moderate amounts of substances is associated with higher rates of lifetime suicidal ideation and suicide attempts when compared with people who do not self-medicate. This has potential importance in the clinical assessment of individuals with anxiety disorders who self-medicate with alcohol and drugs, in whom the clinician should rigorously screen for the presence of suicidal ideation and behavior. A trend toward an association of dysfunction and high distress was noted for individuals who self-medicate when compared with those who do not. However, this relationship did not maintain significance when comorbid mental disorders were controlled for. This may in part be due to the fact that the assessment of dysfunction and high distress was limited to the previous 30 days, whereas self-medication, suicidality, and all other mental disorder variables were lifetime figures. This temporal limitation in the dysfunction and distress measures resulted in an inability to capture previous episodes of significant distress possibly associated with self-medication behavior. There were also interesting gender differences among those who endorsed self-medication. Females were almost twice as likely as males to have an anxiety disorder among those who did not self-medicate (65.6% vs. 34.4%). However, among those who self-medicated, a greater proportion were male (55.4% vs. 44.6%). This may be related to tensionreduction alcohol outcome expectancies, which seem to mediate the relationship between negative life events and alcohol use for men but not for women (Cooper et al., 1992). High tension-reduction alcohol outcome expectancies have been positively correlated with anxiety and drinking behavior in men but not in women (Kushner et al., 1994). When specifically examining self-medication of panic disorder with alcohol, results are mixed: gender does not appear to be a significant predictive variable in some studies (Kushner et al., 2000b; Oswald et al., 1999), whereas in another study, males were more likely to self-medicate (Cox et al., 1993). Among individuals with agoraphobia or social phobia, men were more likely to self-medicate than women (Smail et al., 1984), although this trend failed to reach significance in another study (Bibb and Chambless, 1986). Further research needs to clarify gender differences in self-medication of anxiety disorders. There are limitations to this study that warrant attention. The first relates to the cross-sectional design of the NCS. By definition, the self-medication hypothesis implies a preexisting anxiety disorder that leads to substance use in an effort to reduce symptoms of anxiety. Cross-sectional design precludes the determination of the order of illness onset, and in that regard limits the inferences that can be made regarding the association between anxiety and substance use disorders in this study. However, the specificity of the question Did you ever drink more than usual or use drugs not prescribed (or in greater amounts than prescribed) to help you reduce the fears? directly assesses self-medication behavior. Therefore, while we cannot conclude which disorder is primary, we can conclude that self-medication with alcohol or drugs is common among individuals with anxiety disorders. Evidence to date suggests that social phobia and agoraphobia tend to occur prior to the development of substance use disorders (Chambless et al., 1987; Compton et al., 2000; Mullaney and Trippett, 1979; Stockwell et al., 1984; Stravynski et al., 1986), whereas generalized anxiety disorder often has its onset after the development of substance use disorders (Compton et al., 2000; Ross et al., 1988). Evidence for the order of onset of panic disorder with regard to substance use disorders is mixed (Chambless et al., 1987; Hesselbrock et al., 1985; Katerndahl and Realini, 1999; Powell et al., 1982). Complicating the issue is the fact that retrospective recall is often the method used to identify symptom onset, and as such, the validity of the results may be questionable (Schuckit and Hesselbrock, 1994). Therefore, significant controversy remains regarding the mechanism of the association, and at this time we can only conclude that both anxiety disorders and substance use disorders serve as primary disorders that lead to the development of the other (Kushner et al., 2000a). Prospective, longitudinal studies are required to clarify further whether self-medication behavior among those with an anxiety disorder is associated with incident comorbidity with mood disorders, substance use disorders, and suicidal behavior. The question assessing self-medication has important limitations that should be clarified. Although it asked about excessive use of both alcohol and drugs to reduce fears, the yes or no answers obtained preclude a more detailed analysis of the substance use. As a result, it was not possible to determine whether the person was using either alcohol or drugs, which type of drug or medication, or their amounts. Furthermore, self-medication was only examined in subjects who met criteria for an anxiety disorder. Therefore, the prevalence and correlates of self-medication in this study apply only to people with anxiety disorders. It is possible that subjects with subthreshold anxiety symptoms engage in selfmedicating behavior, which would in turn suggest that our results are an underestimate of the true prevalence of selfmedication. Furthermore, these may be subjects who in fact had threshold anxiety disorders but have successfully treated 2006 Lippincott Williams & Wilkins 823

Bolton et al. The Journal of Nervous and Mental Disease Volume 194, Number 11, November 2006 themselves with substances. In addition to altered prevalence rates, this would likely influence our results regarding comorbidity and distress. Theoretically they may represent a subsample with lower rates of comorbidity and distress given the resolution of their anxiety disorder. CONCLUSION In summary, self-medication is a common behavior among individuals with anxiety disorders in a nationally representative sample and is associated with greater psychiatric comorbidity and increased rates of suicidal ideation and suicide attempts when compared with individuals who do not self-medicate. 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The Journal of Nervous and Mental Disease Volume 194, Number 11, November 2006 Self-Medication of Anxiety Shah BV, Barnswell BG, Bieler GS (1995) SUDAAN User s Manual: Software for Analysis of Corrected Data. Research Triangle Park (NC): Research Triangle Institute. Smail P, Stockwell T, Canter S, Hodgson R (1984) Alcohol dependence and phobic anxiety states, I: A prevalence study. Br J Psychiatry. 144:53 57. Stockwell T, Smail P, Hodgson R, Canter S (1984) Alcohol dependence and phobic anxiety states, II: A retrospective study. Br J Psychiatry. 144:58 63. Stravynski A, Lamontagne Y, Lavallee YJ (1986) Clinical phobias and avoidant personality disorder among alcoholics admitted to an alcoholism rehabilitation setting. Can J Psychiatry. 31:714 719. Thomas SE, Randall CL, Carrigan MH (2003) Drinking to cope in socially anxious individuals: A controlled study. Alcohol Clin Exp Res. 27:1937 1943. Turner SM, Beidel DC, Dancu CV, Keys DJ (1986) Psychopathology of social phobia and comparison to avoidant personality disorder. J Abnorm Psychol. 95:389 394. Weiss KJ, Rosenberg DJ (1985) Prevalence of anxiety disorder among alcoholics. J Clin Psychiatry. 46:3 5. Wittchen HU (1994) Reliability and validity studies of the WHO Composite International Diagnostic Interview (CIDI): A critical review. J Psychiatr Res. 28:57 84. World Health Organization (1990) Composite International Diagnostic Interview (CIDI; Version 1.0). Geneva, Switzerland: World Health Organization. Correction to Table 2 in the article titled Symptom Improvement in Co-Occurring PTSD and Alcohol Dependence by Sudie E. Back et al, published in September 2006 (J Nerv Ment Dis 194:690 696): the last column heading should be Cramer s V and the first entry in that column should be 0.36. 2006 Lippincott Williams & Wilkins 825