By Lisa Simon Onken, Jack D. Blaine, Sander Genser, and Arthur MacNeill Horton, Jr.

Drug use disorders are frequently associated with mental disorders. Data from the Epidemiologic Catchment Area (ECA) study (Regier et al. 1990) showed that over half (53 percent) of individuals who have a lifetime diagnosis of a drug use disorder also have a lifetime diagnosis of a mental disorder.

Approximately two-thirds of individuals with a cocaine or opiate use disorder have, at some point in their lives, had a mental disorder. For those with a lifetime diagnosis, 15 percent have had a drug use disorder.

Twenty-eight percent of schizophrenics and 42 percent of those diagnosed with antisocial personality disorder have had a drug use disorder. Despite the common co-occurrence of drug use disorders and mental disorders, persons who have both of these problems tend to fall between the cracks of service delivery systems.

Individuals with mental disorders who seek treatment in the community may receive it within the mental health services system, and drug-addicted individuals may receive treatment within the drug abuse treatment system.

Those requiring treatment for both mental and drug use disorders may not be able to receive comprehensive treatment in one treatment program. In the worst case scenario, the clinicians responsible for the treatment of the mental disorder may not have any idea about what is going on with the addictive disorder (e.g., treatment or severity) and the clinicians responsible for the addiction treatment may not be aware of what is happening with the mental disorder.

Unfortunately, those persons who have concurrent mental and addictive disorders are not easily accommodated by the current treatment delivery system. Having separate service delivery systems and separate Federal institutes funding research on mental and addictive disorders has generally fostered the separation of mental health and addictive disorder research.

Typically, research on the treatment of mental disorders is addressed within the research programs of the National Institute of Mental Health, while research on the treatment of drug addiction is addressed within the research programs of the National Institute on Drug Abuse. Research on both drug use and mental disorders may, at times, be viewed with skepticism by reviewers who value the "homogeneous" samples needed to decrease "error variance."

It is entirely plausible, however, that there are circumstances in which different individuals with the same set of mental and drug use disorders are more alike than different individuals who have only one disorder.

Assume, for example, that there are many types of depression and many possible etiologies of depression. From this assumption, it is clear that a study of people with depression is a study of a very heterogeneous group of people.

Assume, also, that nicotine affects only people with a certain type of depression in a certain way, and that these are the people who become addicted to nicotine. In this scenario, those individuals who have a homogeneous type of depression coupled with nicotine addiction may be more like each other than a group of heterogeneously depressed people who are not addicted to nicotine.

This scenario seems quite possible in light of Glassman's work (this volume) on the relationship between depression and nicotine. Research on the treatment of individuals with comorbid mental and addictive disorders holds promise for a greater understanding of the relationship among these disorders and the potential for better treatments.

To date, however, research in this area has been limited. A meeting was held on September 27 and 28, 1994, to highlight some of the ongoing research in this area and to stimulate further research. Not only was research on the treatment of comorbid mental and addictive disorders addressed, but the additional problem of human immunodeficiency virus (HIV) in the context of these comorbid disorders was a topic of focus.

The findings presented at the meeting could not be viewed as a definitive statement on this complex subject. On the contrary, only a limited number of combinations of comorbid mental and addictive disorders have been researched, and no one type could be fully addressed within the confines of any one meeting.

The meeting was chaired by Lisa Simon Onken, Ph.D., Jack Blaine, M.D., Sander Genser, M.D., M.P.H., and Arthur MacNeill Horton, Jr., Ed.D. of the National Institute on Drug Abuse. Presentations were given by David Barlow, Ph.D., Robert Brooner, Ph.D., Kate Carey, Ph.D., Linda Cottler, Ph.D., Francine Cournos, M.D., John Docherty, M.D., Alexander Glassman, M.D., Bridget Grant, Ph.D., Edward V. Nunes, M.D., Kim Mueser, Ph.D., Bruce J. Rounsaville, M.D., Paul Satz, Ph.D., Andrew Shaner, M.D., and George Woody, M.D.

The presentations given by these scientists underscore the promise that research on comorbid mental and addictive disorders holds for future treatment advances and resultant public health benefits. Just as the meeting could not fully address the full range of comorbid mental and addictive disorders and associated HIV issues, neither can this monograph.

However, the chapters that follow, written by many of the participants of the meeting, are examples of exciting research being done in this important area, and they help to define the need for further research. It is the hope of all the editors of this monograph that the readers will be inspired by the contributions that follow.

REFERENCES

Regier, D.; Farmer, M.E.; Rae, D.S.; Locke, B.Z.; Keith, S.J.; Judd, L.L.; and Goodwin, F.K. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) study. JAMA 264:2511-2518, 1990.

AUTHORS

Lisa Simon Onken, Ph.D. Jack D. Blaine, M.D. Sander Genser, M.D., M.P.H. Arthur MacNeill Horton, Jr., Ed.D. Division of Clinical Research National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 

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NIDA Research Monograph, Number 172
  

The Influence of Comorbid Major Depression and Substance Use Disorders on Alcohol and Drug Treatment: Results of a National Survey

Bridget F. Grant

INTRODUCTION

The co-occurrence of alcohol use disorders, drug use disorders, and major depression has frequently been reported in alcoholic, drug abuse, and psychiatric patient samples (Allen and Francis 1986; Demilio 1989; El-Guebaly 1990; Ross et al. 1988; Rounsaville et al. 1982).

Significant associations between substance use disorders and major depression have also been found in general population surveys (Regier et al. 1990; Robins et al. 1988; Weissman and Meyers 1980), but the magnitude is much lower than that reported in clinical samples.

This suggests that people with comorbid substance use disorders and major depression may be more likely to seek alcohol or drug treatment than those without such comorbidities.

However, to date, no studies have examined the impact of comorbidity on alcohol or drug treatment in the population of greatest clinical and policy relevance, that is, among those persons with an alcohol use disorder or drug use disorder not found in the treated population.

The purpose of this study was to separately compare the comorbidity status of persons with alcohol and drug use disorders who did or did not seek alcohol or drug treatment, respectively.

Separate comparisons were also examined for major types of treatment facilities, including 12-step group programs and inpatient and outpatient facilities.

METHODS

Sample - The study was based on the 1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES), a nationwide household survey sponsored by the National Institute on Alcohol Abuse and Alcoholism (Grant et al. 1992). Field work for the study was conducted by the 5 Bureau of the Census. During the survey, direct face-to-face interviews were conducted with 42,862 respondents, 18 years of age and older, in the contiguous United States and the District of Columbia.

The household response rate for the NLAES was 91.9 percent, and the person response rate was 97.4 percent. The NLAES featured a complex multistage design (Massey et al. 1989). Primary sampling units (PSUs) were stratified according to sociodemographic criteria and were selected with probabilities proportional to size.

Approximately 2,000 PSUs comprised the 1992 NLAES sample, 52 of which were self-representing—that is, selected with certainty. Within PSUs, geographically defined secondary sampling units, referred to as segments, were selected systematically for each sample.

Oversampling of the black population was accomplished at this stage of sampling in order to have adequate numbers for analytic purposes. Segments were then divided into clusters of approximately four to eight housing units, and all occupied housing units were included in the NLAES.

Within each household, one randomly selected respondent, 18 years of age or older, was selected to participate in the survey. Oversampling of young adults, 18 to 29 years of age, was accomplished at this stage of the sample selection to include a greater representation of this heavier substance-abusing population subgroup. This subgroup of young adults was sampled at a ratio of 2.25 percent to 1.00.

Diagnostic Assessment

The survey questionnaire, the Alcohol Use Disorders and Associated Disabilities Interview Schedule (AUDADIS) (Grant and Hasin 1992), included an extensive list of symptom questions that operationalized the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) (American Psychiatric Association 1994) criteria for alcohol/drug use disorders and major depression.

These questions are described in detail elsewhere (Grant et al. 1994). Past year DSM-IV drug-specific diagnoses of abuse and dependence were first derived separately for alcohol, sedatives, tranquilizers, opioids (other than heroin), amphetamines, cocaine (and crack cocaine), cannabis (and THC and hashish), heroin, methadone, and hallucinogens.

A composite measure of any of these drug use disorders (except alcohol) was then constructed.

Consistent with the DSM-IV, an AUDADIS diagnosis of alcohol or drug abuse required that a person exhibit a maladaptive pattern of substance use leading to clinically significant impairment or distress, as demonstrated by at least one of the following in any 1 year: (1) continuing to use despite a social or interpersonal problem caused or exacerbated by the effects of use, (2) recurrent use in situations in which substance use is physically hazardous, (3) recurrent use resulting in a failure to fulfill major role obligations, or (4) recurrent substance-related legal problems.

An AUDADIS diagnosis of substance dependence required that a person meet at least three of seven criteria defined for dependence in any 1 year, including: (1) tolerance; (2) avoidance of withdrawal; (3) persistent desire or unsuccessful attempts to cut down or stop using; (4) spending much time obtaining a drug, using it, or recovering from its effects; (5) giving up or reducing occupational, social, or recreational activities in favor of use; (6) impaired control over use; and (7) continuing to use despite a physical or psychological problem caused or exacerbated by use.

Diagnoses of alcohol and drug abuse and dependence also satisfied the clustering or duration criteria of the DSM-IV. The duration criteria of the DSM-IV include the requirement for a clustering of symptoms within any 1-year period, in addition to associating duration qualifiers with certain abuse and dependence symptoms.

The duration qualifiers are defined as the repetitiveness with which symptoms must occur in order to be counted as positive towards a diagnosis. They are represented by the terms "recurrent," "often," and "persistent" appearing in the description of the diagnostic criteria.

Consistent with the DSM-IV, the AUDADIS diagnosis of major depression required the presence of at least five depressive symptoms (inclusive of depressed mood or loss of pleasure and interest) nearly every day for most of the day during any 2-week period.

Social and/or occupational dysfunction must also have been present during the disturbance, and episodes of major depression exclusively due to bereavement or physical illness were ruled out. The reliabilities of the diagnoses of DSM-IV alcohol and drug use disorders and major depression were 0.73, 0.80, and 0.65, as determined from an independent test-retest study conducted in a general population sample (Grant et al. 1995).

Alcohol and Drug Treatment Respondents in the survey were asked if, during the past year, they had gone anywhere or seen anyone for problems related to their drinking.

To more completely capture the entire alcohol help-seeking population, respondents were specifically instructed to indicate any help they had received for their drinking, including help for combined alcohol and drug use if alcohol was the major problem for which they sought help.

Alcohol treatment sources were defined broadly and respondents were asked to indicate separately whether they sought help from 23 different treatment sources: inpatient alcohol and/or rehabilitation programs and inpatient wards of general or psychiatric hospitals; outpatient clinics and alcohol and/or drug detoxification units; 12-step groups including Alcoholics Anonymous, Narcotics or Cocaine Anonymous, or Alanon; social services; and various health professionals such as psychiatrists, psychologists, social workers, and the clergy.

Respondents receiving help from any of these sources during the past year constituted the alcohol treatment group examined in this study. The drug treatment measure included the same range of treatment sources as described for alcohol, but information was solicited from respondents regarding help they had received for a drug problem, including help for combined drug and alcohol use if use of a drug or drugs was the major problem for which they sought help. 

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NIDA Research Monograph, Number 172
  

Challenges in Assessing Substance Use Patterns in Persons With Comorbid Mental and Addictive Disorders

Kate B. Carey

Assessment of substance use patterns can be distinguished from two related assessment goals. These consist of screening (i.e., identifying persons with addiction problems) and diagnosis (i.e., determining whether abuse or dependence criteria are met).

All three goals are important and relevant to persons with comorbid disorders. Nonetheless, this chapter focuses on substance use assessment for three reasons.

One, it is the least studied assessment goal in the comorbidity literature; very few published studies address this topic.

Two, substance use assessment is applicable to all persons in treatment for mental disorders. Use of illicit drugs or alcohol is more common than abuse, and information about use patterns may be desired to determine risk for medication-drug interactions and other health concerns.

Finally, substance use assessment should play a central role in the treatment of comorbid disorders. It serves as the basis for treatment planning and as a point of departure for outcome assessment.

It also constitutes the first step in conducting a functional analysis of drinking and/or drug use for an individual (Sobell et al. 1988).

Quantifying patterns of substance use allows for determination of increased versus decreased use, an outcome measure consistent with harm reduction approaches to treatment of substance misuse in the context of major mental disorders (Carey, in press).

In the addictions literature, a rich tradition of research exists on topics related to assessing alcohol and drug use patterns. Ample sets of instruments and guidelines for their use have been developed and standardized in substance abuse treatment settings.

However, importing such tools for use with persons with major mental disorders raises questions about their psychometric properties and other potential limitations.

This chapter briefly summarizes current approaches to, and problems with, substance use assessment. Because self-report measures continue to be widely used, emphasis is placed on factors generally considered to affect the accuracy of self-reported substance use. Next, concerns about the reliability and validity of self-reported substance use in persons with major mental disorders are discussed.

Finally, recommendations for enhancing the reliability and validity of assessment instruments are presented, highlighting areas in need of empirical research.

CURRENT APPROACHES TO SUBSTANCE USE ASSESSMENT

To borrow a scheme used by Skinner (1984), options available for sub- stance use assessment include (a) prospective methods, (b) retrospective methods, and (c) objective indicators.

Prospective methods consist of variants on self-monitoring. Self-monitoring reduces reliance on memory, and is generally regarded as the most accurate alternative to direct observation. Successful self-monitoring does, however, require a subject with the skills and motivation to complete the task.

Prospective information gathering also requires time. Retrospective methods involve asking the subject to report on past substance use over a designated time interval. Examples include the Addiction Severity Index (ASI) (McLellan et al. 1980), the Time Line Follow-back interview (TLFB) (Sobell and Sobell 1992), and various quantity-frequency methods (e.g., Cahalan and Room 1974; Polich et al. 1981).

Retrospective self-report is practical for most settings and is the most frequently used. However, its drawbacks include the potential for memory failure or other sources of distortion. Objective indicators include blood- or urine-based drug screens, breathalyzer tests, laboratory tests (e.g., gamma-glutamyl transpeptidadase, high density lipoproteins, mean corpuscular volume), collateral reports, and official records.

Each of these information sources has limitations. Breathalyzer tests and blood/urine screens yield information about recent use only (Schwartz 1988). Other laboratory tests identify medical consequences of substance use, but are generally sensitive only to prolonged high levels of use; furthermore, elevations are nonspecific to substance use.

None of these indices yields data on the pattern of substance use.

Collateral reports or other official records tend to be limited due to incomplete knowledge or representation of actual use history, and collaterals may be unavailable for some socially isolated subjects (Drake et al. 1993; O’Farrell et al. 1984). In the absence of a gold standard, confidence in the accuracy of assessment can be enhanced by adopting a convergent validity approach (Sobell and Sobell 1980).

This involves using multiple indicators that will tend to converge on a consistent picture of actuality. Significant discrepancies must be evaluated from a methodological perspective as well as allowing for subject-specific factors. In any given population, consideration must be given to 18 appropriate selection of measures as well as to ways in which their accuracy can be enhanced. Since retrospective self-reports continue to serve as the cornerstone of assessment, factors affecting the validity of self-reported substance use will be considered next.

Factors Affecting Validity of Self-Reported Substance Use

For substance use assessment to be useful in a treatment context, measures must be both accurate and sensitive to change. The literature on accuracy indicates that acceptable levels of reliability and validity are found for alcoholics' self-reports when recommended procedures are followed (e.g., O'Farrell and Maisto 1987; Sobell and Sobell 1980).

However, some samples and procedures have yielded less than impressive findings. Furthermore, the reliability and validity of self-reported drug use varies across both studies and types of drugs (Maisto et al. 1990). Test-retest reliability is infrequently reported and, when it is, shows only modest reliability coefficients.

Validity coefficients tend to be similarly moderate. A reasonable conclusion is that self-report data are "inherently neither valid nor invalid, but vary with the methodological sophistication of the data gatherer and the personal characteristics of the respondent" (Babor et al. 1990, p. 8). In the substance abuse field, questions have thus moved beyond "Are self-reports valid?" and are framed more as "When, and under what conditions, are self-reports valid?" (Brown et al. 1992).

It is this approach to evaluating the accuracy of self-reports that provides a framework for understanding the process of substance use assessment among persons with major mental disorders. In a discussion of the factors affecting the accuracy of self-reported substance use, Babor and colleagues (1990) highlighted four classes of variables. The first class yields characteristics of the respondent.

These include the respondent's state of sobriety at the time of assessment and the possible influence of a social desirability response set. The second class of variables includes aspects of the task that might enhance or detract from accurate responding. These include the degree of rapport between assessor and respondent, whether assurances of confidentiality can be made, the likelihood that selfreports will be verified, the criterion interval reported on, and the clarity of the questions.

Motivational factors constitute the third class of variables affecting accuracy of self-report. Obvious short-term goals (e.g., to obtain treatment or to avoid arrest) must be considered, as well as the fear of potentially judgmental attitudes or other threats to the respondent's self-esteem. Cognitive processes constitute the 19 fourth type of variables influencing self-report accuracy.

Impairment of attentional processes, verbal comprehension, or retrieval will interfere with the accuracy of an assessment. Cognitive processes may be impaired due to recent alcohol or drug use, to situational stress or anxiety, or to associated psychiatric syndromes such as depression.

In addition, recall of past behavior is subject to information-processing biases, so that recall is disproportionately influenced by salient and/or very recent events.

Application to Persons With Severe Mental Disorders

There are reasons for concern about the reliability and validity of substance use assessment in persons with severe mental disorders (e.g., schizophrenia, bipolar disorder, major depressive disorder).

Several studies suggest significant underreporting of substance abuse in this population (e.g., Safer 1987; Shaner et al. 1993; Test et al. 1989). No formal reliability or validity studies have been published on substance use assessment, but the accuracy of screening measures has been empirically addressed. For example, the criterion validity of screening measures (e.g., the Michigan Alcoholism Screening Test) has been evaluated in psychiatric settings.

Results indicate adequate sensitivity but low specificity (Drake et al. 1990; Teitelbaum and Carey, in press), suggesting that population differences may affect the psychometric properties of many of the standard industry tools.

A recently completed literature review (Teitelbaum and Carey, in press) found surprisingly few studies addressing the reliability of alcohol/drug screening or diagnostic measures used with psychiatric patients.

In this population, which is characterized by fluctuating mental status, the issue of test-retest stability is a fundamental psychometric concern. 

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NIDA Research Monograph, Number 172
 

Anxiety Disorders, Comorbid Substance Abuse, and Benzodiazepine Discontinuation: Implications for Treatment

David H. Barlow

INTRODUCTION

Comorbidity among various disorders complicates research and practice. Comorbidity among emotional disorders and substance use disorders is a particularly thorny problem due to the dearth of relevant clinical research.

This chapter reviews what is known about the comorbidity of substance use and anxiety disorders and presents recent data collected in the context of comorbid anxiety and mood disorders that may have implications for the relationship of anxiety and substance use disorders.

The specific case of the relationship of benzodiazepine use to successful outcome of psycho- social treatments and recent developments in successful psychosocial strategies for discontinuing benzodiazepines in anxious patients may provide important information for future studies. This chapter begins with a brief review of data on the co-occurrence of substance use and anxiety disorders.

COMORBIDITY AMONG SUBSTANCE USE AND ANXIETY DISORDERS

A number of studies have reported a high rate of comorbidity among anxiety and substance use disorders. Most of these studies have surveyed alcohol dependence and abuse.

Rates of comorbidity have typically been calculated in two different ways. First, the prevalence of anxiety disorders has been examined in alcohol dependence and abuse patient samples.

Second, rates of alcohol dependence and abuse have also been examined in samples of outpatients with anxiety disorders. The majority of surveys have followed the first approach and have found that the lifetime prevalence of clinically significant anxiety disorders in patients with alcohol abuse and dependence ranges from 25 percent to 45 percent for patients with clearly defined anxiety disorders, but may approach 60 percent if one includes identifiable anxiety disorders that are subthreshold in terms of severity (Bowen et  al. 1984; Chambless et al. 1987; Hesselbrock et al. 1985; Mullaney and Trippett 1979; Smail et al. 1984; Cox et al. 1989; Johannessen et al. 1989).

Surveys using the second approach and examining rates of alcohol dependence and abuse in anxiety disorder outpatient samples suggest that approximately 15 percent to 25 percent present with evidence of current or past alcohol abuse or dependence (Bibb and Chambless 1986; Thyer et al. 1986). Himle and Hill (1991) found that the frequency of alcohol abuse or dependence differed among persons with various anxiety disorders.

For example, the percentage of alcohol abuse or dependence among those individuals with a principal diagnosis of panic disorder (PD) with agoraphobia (who may also have presented with additional anxiety disorders) was 31.5 percent, as compared to 24.6 percent for obsessive-compulsive disorder and 14.4 percent for a specific phobia.

Thus, it would seem that some anxiety disorders confer a higher risk for substance abuse then others. In any case, there is evidence that patients presenting with these comorbid pictures have more clinically severe conditions than individuals with either condition alone.

Thus, there are reasons to examine factors contributing to comorbidity in this subgroup more closely. One method of examining the possible reasons for the acquisition of comorbid disorders is to ascertain a temporal sequence in their onset. Most studies indicate that anxiety precedes alcohol abuse and dependence.

This pattern would seem to confirm the frequent clinical observation that many individuals with anxiety disorders begin to abuse alcohol with the purpose of self-medicating their anxiety disorders. However, Kushner and colleagues (1990) noted that the pattern seems to hold true only for some disorders, such as PD with or without agora-phobia, social phobia, and specific phobia.

For some other disorders, particularly generalized anxiety disorder (GAD) and depression, the more prevalent pattern may be the reverse; that is, substance abuse seems to contribute to the onset of GAD and depression. One possible mechanism of action here is that the individual experiences a loss of control over the substance use subsequent to addiction and develops reactive anxiety or depression.

Illicit drug use has also been reported to precipitate anxiety disorders. For example, Aronson and Craig (1986), as well as Louie and colleagues (1989), reported a number of cases in which cocaine use and/or withdrawal from cocaine precipitated panic attacks.

In these  cases the resulting panic disorder continued well after the cessation of cocaine use. In fact, as many as 30 percent of patients presenting with PD have reported an onset associated with either licit or illicit drug use (Barlow 1988), with marijuana being one of the more common precipitants.

Hyperventilation and other symptoms associated with withdrawal from alcohol have also been reported to trigger longlasting PD (Weissman 1988). In cases where substance abuse seems to "trigger" anxiety disorders, clinical strategies might target the substance use first before addressing related anxiety on the chance that anxiety, to the extent that it might be related to the substance use, would concurrently remit.

These clinical speculations, however, are nothing more than assumptions since little is known about the effects of targeting one disorder when treating additional comorbid disorders in an individual.

COMORBIDITY AMONG ANXIETY AND MOOD DISORDERS: IMPLICATIONS FOR COMORBID SUBSTANCE USE DISORDERS
Research from the author’s anxiety disorders research clinic has produced some evidence on the effects of comorbidity among anxiety and mood disorders on treatment outcome, both short and long term. Since these results are somewhat surprising, it is possible that they may have some implications for similar comorbid patterns among anxiety disorders and substance use disorders.

One recently analyzed set of data examined the impact of treatment for panic disorder using an effective cognitive-behavioral treatment (Barlow et al. 1989) on the course and outcome of generalized anxiety disorder that was not directly treated (Brown and Barlow 1992). GAD was chosen because it is the most frequently co-occurring diagnosis in patients with a principal diagnosis of PD (Moras et al., submitted).

For purposes of this analysis, the comorbid presence of GAD was considered at both a clinical level of severity as well as a subclinical level of severity in which GAD was clearly identifiable but was not considered severe enough to interfere substantially with functioning. As noted in figure 1, of 68 panic disorder patients treated, 32 percent had a clinically significant GAD additional diagnosis at pretreatment, with an additional 9 percent evidencing subthreshold GAD.

At posttreatment the rate of GAD above threshold declined to 9 percent, whereas subthreshold GAD increased to 16 percent because several patients with a clinically significant GAD at pretreatment moved to the subclinical category at posttreatment. These results were relatively stable at a 3-month followup.

Thus, in this example, a comorbid disorder improved with successful treatment of the target disorder in spite of the fact that no attempts were made to treat it directly. Of course, one possible reason for these results is that GAD and PD share many symptoms, with GAD often considered to be the "basic" anxiety disorder (Brown et al. 1994).

Thus, the success-ful treatment of panic disorder may have "generalized" to symptoms comprising GAD such as anxious arousal and cognitions of future danger. 

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NIDA Research Monograph, Number 172
  

Alexander H. Glassman

Comorbidity is the existence of two conditions in the same individual at a greater frequency than would be expected by chance alone. The existence of such associations says nothing about the underlying cause of the comorbidity.

Cigarette smoking in the United States has long been associated with an increased level of psychiatric symptomatology, but until recently this was not thought of in terms of specific diagnostic entities. Cigarette smokers were simply thought more likely to be "nervous" people than nonsmokers (Glassman 1993).

However, it is important to realize that the appearance of comorbidity can be strongly influenced by social factors. If everybody smoked, there could be no association between smoking and any psychiatric condition.

In 1985, while testing a new drug for smoking cessation, Glassman and colleagues (1988) noted what they felt was an astounding lifetime rate of major depression among smokers coming to the clinic.

Forty two of 71 smokers (60 percent) had a history of major depression, while the best available data suggest lifetime rates for the general community of around 18 percent (Kessler et al. 1994).

This threefold increase in the observed rate of major depression was even more dramatic than it might first appear because smokers coming to the clinic were screened to exclude individuals who were presently ill.

Whereas community epidemiological data represent both individuals presently ill and those with only a past history of major depression, the clinic sample consisted only of smokers with a past history of depression. In retrospect, it is likely that the extraordinarily high rate of prior major depression observed by the researchers was an artifact of the particular academic population that they had happened to study.

The vast majority of the 71 smokers who participated in the study were either postdoctoral students or faculty at Columbia University, and most came from the medical school campus. This finding was undoubtedly related to the exceptionally high rate of major depression observed. Medical school faculty and their graduate students face considerably more social pressure to give up smoking than the general population.

It would seem reasonable to assume that in groups where awareness of the health risks increases and social pressure to stop smoking grows, those who can quit easily do so and those who remain smokers are individuals more vulnerable to nicotine.

Hughes and associates (1986) had earlier shown that patients coming to a medical center for treatment of a variety of psychiatric conditions, including depression, were more likely to be smokers than the general population.

That seemed intuitively reasonable. However, once the strength of the association with a specific history of depression became apparent, it seemed worthwhile to determine whether a history of major depression influenced smoking cessation—and it did.

Again, that patients presently depressed have more difficulty quitting than individuals not depressed seems obvious; however, the finding that a history of depression would still be associated with cessation failure, even when an individual had been euthymic for a considerable period of time, was not so obvious and required replication.

The first two replications both came from previously existing data sets. The St. Louis node of the Epidemiological Catchment Area (ECA) study contained both psychiatric diagnostic information and smoking history on over 3,200 randomly selected community residents (Glassman et al. 1990).

Among those individuals with either no psychiatric illness or any psychiatric illness except major depression, 47 percent of the women and 68 percent of the men had at some time in their lives been regular smokers.

By comparison, among those individuals with a history of major depression, 65 percent of the women and 80 percent of the men had been regular smokers. The increases among both men and women are highly significant, but the increased rate among the depressed women is particularly striking.

The data on cessation also very much paralleled the data for the original small clinical sample. Thirty-one percent of those smokers with no history of any psychiatric history were able to stop smoking for more than 1 year, and 28 percent of those individuals with either no psychiatric history or no psychiatric history except major depression were able to quit.

Among those with a lifetime history of major depression, less than 14 percent of smokers were able to stop and remain abstinent. Similarly, data on 3,023 individuals from the National Health and Nutrition Examination Survey (N-HANES) also demonstrated an increased rate of smoking and a decreased rate of quitting associated with increasing levels of depression (Anda et al. 1990).

The major difference between the ECA and the N-HANES data sets is that the ECA instruments classified individuals by diagnosis, while N-HANES obtained only symptomatic measures of depression. A subsequent community survey also produced by the Centers for Disease Control and

Prevention was the Hispanic NHANES, which studied 3,337 individuals of Mexican origin and obtained both symptomatic and diagnostic measures of depression on this sample (R.F. Anda, personal communication, January 11, 1995). It is important to understand that this is an epidemiology survey that records lifetime rates of illness, and lifetime major depression involves both cases that are presently ill and cases of past illness.

Presently ill cases will always show symptoms of depression as well as meeting diagnostic criteria. However, cases of past history may or may not presently have symptoms of depression.

Both those individuals with symptoms but no diagnosis and those with a diagnosis but no symptoms showed higher rates of smoking than individuals with neither condition. However, individuals with both a diagnosis and symptoms of major depression showed the highest rates of smoking.

Thus, there is now evidence that symptoms, as well as a diagnosis of major depression, are associated with cigarette smoking. These data are somewhat more complex than is readily apparent. It might seem that symptoms of depression and major depression alone are approximately equal in their likelihood of being associated with cigarette smoking. However, it is probable that the cases of major depression in the major depression-only group will be less severe and less likely to be recurrent than those cases in the group with both major depression and present symptoms of depression.

Recurrent major depression has regularly been shown to have higher levels of interepisode depressive symptomatology (Keller et al. 1983; Dalack et al. 1995) than single episode cases. Thus, it seems probable that the major depression-only group will contain a greater proportion of single episode cases of major depression.

Cases of single episodes of major depression have already been shown in both clinical (Glassman et al. 1993) and epidemiological (Covey et al. 1994) research to be less strongly associated than recurrent major depression with cigarette smoking.

As a result, it would seem likely that both individuals with symptoms of depression and individuals with a single episode of major depression are more likely to be smokers than individuals with no history of either condition. In addition, the association between smoking and depression will be strongest among those individuals with either recurrent major depression or major depression and high levels of chronic depressive symptoms.

There is also evidence that a similar step function exists with the intensity of smoking. At least among women, Kendler and associates (1993) have replicated the finding that heavier smoking is associated with an increasing likelihood of a lifetime history of major depression, and Breslau and associates (1993) have shown that this same association is greater in dependent than in nondependent smokers.

One of the issues not dealt with adequately in any of these three large data sets is the role of other psychiatric diagnoses. Breslau has examined 1,200 young adults (Breslau et al. 1991) and Kendler has data on 1,566 female twins (Kendler et al. 1993).

Breslau replicates the previously observed associations between major depression and both smoking and smoking cessation. Kendler does not examine cessation, but does find a strong association between smoking and a lifetime diagnosis of major depression. However, these studies provide information that earlier data sets were not designed to address.

As a major example, both Breslau and Kendler demonstrated that the relationship between major depression and smoking persists even after controlling for both alcohol and anxiety disorders.

Both also showed that the association was most robust among heavier or more dependent smokers.

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NIDA Research Monograph, Number 172
  

Treatment of Depression in Drug-Dependent Patients: Effects on Mood and Drug Use

Edward V. Nunes and Frederic M. Quitkin

INTRODUCTION

Symptoms of depression and anxiety are common in patients with substance use disorders (Meyer 1986; Schuckit 1986). In the general population, mood and anxiety disorders convey increased risk for substance use disorders (Regier et al. 1990).

Further, mood disordered substance abusers have poor prognoses (Rounsaville et al. 1982b, 1986b, 1987; Weissman et al. 1976; Kosten et al. 1986; LaPorte et al. 1981; Loosen et al. 1990; Carroll et al. 1993).

Thus, evaluation and appropriate management of affective disorders should be a useful treatment adjunct with the potential of improving outcome of substance abuse. Nevertheless, controversy continues to surround this clinical problem, and approaches vary widely among clinicians. Further, the problem of the depressed substance abuser raises important theoretical questions about the etiology and pathogenesis of substance abuse disorders.

Mood syndromes observed in substance dependent patients often resolve soon after abstinence or the initiation of specific treatment such as methadone (Weddington et al. 1990; Rounsaville et al. 1986a; Schuckit 1986; Willis and Osbourne 1978; DeLeon et al. 1973), suggesting a "substance-induced" (American Psychiatric Association 1994) syndrome (i.e., toxicity or withdrawal) or transient adjustment reactions.

However, in 10 percent or more of these patients in various clinical samples, depression persists (Nakamura et al. 1983; Johnson and Perry 1986; Rounsaville et al. 1986a; Croughan et al. 1981). These persons may have a mood disorder that is independent of substance abuse.

Because both substance abuse and mood disorders are common in the general population, it can be expected that some individuals will have both disorders by chance alone. Another possibility is that a subgroup has mood disorders that contribute to the etiology of substance abuse.

In fact, a self medication hypothesis has been advanced (Khantzian 1985; Quitkin et al. 1972) suggesting that some individuals use drugs because they provide temporary relief from symptoms of depression or anxiety.

Depression or anxiety may be the sole etiology or one of several causal factors, including other genetic and environmental vulnerabilities, in substance abuse. Also, depression or anxiety may alter the course of substance abuse.

For example, depression is a frequent internal cue triggering drug craving (Marlatt and Gordon 1985; Daley and Marlatt 1992). Thus, an initially independent depressive disorder, through classical conditioning (Childress et al. 1994), may become linked to relapse and perpetuate substance abuse.

The evidence that the self-medication hypothesis plays a contributory role in some substance abuse stems mainly from clinical observations (Khantzian 1985; Marlatt and Gordon 1985) and epidemiologic data (Regier et al. 1990). However, the strongest test of the hypothesis would be one that directly addresses its clinical utility, namely, whether treatment of depression or anxiety alters the course and outcome of substance abuse.

Specifically, if depression contributes to the etiology of substance abuse, then antidepressant treatment should improve substance abuse outcome. Relatively few studies of this type have been undertaken, and most have methodologic problems.

This chapter reviews this literature as well as the authors' recent studies, drawing tentative conclusions and developing suggestions for future research. The present approach to evaluating the literature is summarized in table 1 (Nunes et al., in press).

Studies evaluated are those in which patients with substance use disorders who also display evidence of depression receive antidepressant medication treatment. If there is no medication-placebo difference in both mood and substance use outcome (right column, table 1), and particularly if the placebo-mood response is high, a transient substance-induced mood syndrome or adjustment reaction is suggested.

If mood improves on medication compared to placebo, but substance use does not (middle column, table 1), it suggests a true mood disorder that is independent of substance abuse.

Finally, if both mood and substance use improve on medication (left column, table 1), it suggests that the depression contributes to the etiology of substance abuse, as in self-medication.

Antidepressant Treatment in Alcoholism In the 1960's and 1970's, nine placebo-controlled studies of antidepressant medications (mainly tricyclics) (TCAs) in alcoholic patients were reported. These studies have been reviewed extensively by Ciraulo and Jaffe (1981) and by Liskow and Goodwin (1987).

No study demonstrated superiority of TCAs except for some short-lived effects, probably attributable to amelioration of withdrawal symptoms. However, both research pairs concluded that the studies were seriously flawed and that further study of antidepressant medication treatment of depressed alcoholics was needed.

Both the doses of TCAs and the trial lengths (mostly 3 weeks or less) were inadequate. Outcome measures were narrowly focused on either depression or drinking behavior, but not both. Methods of diagnosing affective disorder were either unspecified or based on cross-sectional scales, which are not adequate measures of primary affective disease in the setting of alcoholism (Keeler et al. 1979).

One promising pilot study did demonstrate successful open treatment with imipramine of a small series of alcohol and sedative abusers with panic disorder (Quitkin et al. 1972). This study had the advantage of a carefully diagnosed, homogeneous sample, but required replication in larger controlled trials. In a first replication attempt, Nunes and colleagues (1993) conducted an open-label trial of imipramine followed by double-blind, placebocontrolled discontinuation for responders.

Subjects were outpatients who currently met criteria for Diagnostic and Statistical Manual of Mental Disorders, 3d ed. revised (DSM-III-R) (American Psychiatric Association 1987) alcohol abuse or dependence and also had DSM64 III-R major depression or dysthymia.

Experienced research psychiatrists interviewed and diagnosed the patients. Depressive syndromes were either chronologically primary, antedating the onset of alcohol abuse on a lifetime basis, had persisted during past abstinent periods, or were chronic.

Eighty-five patients met inclusion criteria and entered the trial, and 60 completed the minimum adequate trial of 6 weeks of imipramine. The mean dose of imipramine was 263+77 mg/day and the mean blood level was 368+264 nanograms per milliliter (ng/mL).

In addition to weekly visits with a treating psychiatrist, each patient received one weekly session of alcoholism counseling, and all patients were encouraged to attend Alcoholics Anonymous. Of the 60 completers, 27 (45 percent) were rated as "responders" to open imipramine after the initial 12 weeks with a substantial improvement in both mood Clinical Global Impression (CGI) change score of 2, "much improved," or 1, "very much improved," and drinking behavior.

A rating of substantial improvement in drinking required either abstinence (18 cases, 30 percent) or a substantial reduction in quantity consumed and an absence of functional impairment. Another three patients responded after increases in imipramine dosage, and five more responded after brief courses of disulfiram, so that a total of 35 (58 percent) were ultimately called responders.

Twenty-three of the responders entered and completed the 6-month, double-blind discontinuation phase in which they were randomized either to remain on imipramine or taper off imipramine onto placebo. The principal endpoint was relapse during the 6-month followup period, defined as loss of either mood response or drinking response or both.

The relapse rate was lower on imipramine (31 percent, 4/13) than on placebo (70 percent, 7/10), a difference that approached statistical significance (Fisher's exact p = 0.09, two-tailed). Most relapses involved near-simultaneous return of both depression and drinking.

This study differed from previous research by providing a medication trial of adequate dosage and duration, and by selecting depression via syndromal criteria rather than cross-sectional symptoms.

The results suggest that antidepressant medication treatment is useful in depressed outpatient alcoholics, both in treating depression and in inducing remission of drinking and preventing relapse.

The findings provide preliminarily support for the hypothesis that depression plays some role in the etiology of drinking in a selected subgroup. Replication is clearly needed in larger controlled trials, along with further work on developing criteria for selecting medication responsive depressed alcoholics.

The majority of patients selected for this trial had depression that was chronologically primary, because the investigators felt that this history would characterize self-medicators.

Interestingly, Mason and Kocsis (1991) recently completed a methologically sound, placebo-controlled trial of desipramine in alcoholics who all had depression that was chronologically secondary, but had persisted during inpatient detoxification. Their results also suggested that desipramine was useful in treating both depression and drinking (Mason and Kocsis 1991).

This suggests that the primarysecondary distinction may be of limited utility as a selection criterion, since both primary and secondary depressions appear to respond to medication.

Persistence of depression after inpatient detoxification may be more useful, although in practice it is not always possible to arrange hospitalization.

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NIDA Research Monograph, Number 172
  

The Course and Treatment of Substance Use Disorder in Persons With Severe Mental Illness

Kim T. Mueser, Robert E. Drake, and Keith M. Miles

There is now a widespread acceptance that persons with severe mental illness are at increased risk to develop substance use disorders (alcohol and drug abuse/dependence).

Reviews of the prevalence of substance use disorders in clients with schizophrenia (Mueser et al. 1990), bipolar disorder (Goodwin and Jamison 1990), and the young, chronically mentally ill (Safer 1987) indicate a wide range of prevalence estimates, from as low as 10 percent to over 65 percent.

Variability in prevalence rates can be attributed to differences across studies in factors such as the setting in which clients are sampled (e.g., community mental health center, acute inpatient, chronic inpatient), methods for assessing psychiatric and substance use disorders (e.g., structured clinical interview, chart review), and the demographic mix of the study sample (e.g., proportion of males) (Galanter et al. 1988; Mueser et al. 1995).

Despite the variability in prevalence estimates, strong evidence indicates that the rate of comorbid substance use disorders in people with severe mental disorders is substantially greater than in the general population. The most compelling evidence supporting this is provided by the Epidemiological Catchment Area (ECA) study (Regier et al. 1990), which assessed psychiatric and substance use disorders in over 20,000 persons living in the community and in various institutional settings.

The results of this study indicated that persons with a psychiatric disorder were at increased risk for developing a substance use disorder over their lifetime. Of particular importance, people with severe mental illness were especially vulnerable to substance use disorders.

For example, those with schizophrenia were more than four times more likely to have had a substance use disorder during their lifetime than persons in the general population, and those with bipolar disorder were more than five times as likely to have such a diagnosis.

The high rate of substance use disorders among persons with severe mental illness has important clinical implications, because their substance abuse is associated with an array of negative outcomes.

Common negative consequences include increased vulnerability to 87 relapses and rehospitalizations, greater depression and suicidality, violence, housing instability and homelessness, noncompliance with medications and other treatments, increased vulnerability to human immunodeficiency virus (HIV) infection, increased family burden, and higher service utilization and costs (Bartels et al. 1993; Clark 1994; Bartels et al. 1992; Cournos et al. 1991; Drake et al. 1989; Yesavage and Zarcone 1983).

However, evidence also suggests that as dual-diagnosis clients attain stable remission, their vulnerability to these negative outcomes lessens (Bartels et al. 1993; Zisook et al. 1992).

Thus, interventions that are successful at reducing substance abuse in clients with severe psychiatric disorders may also confer positive benefits in such areas as symptomatology, community functioning, service utilization, and costs of treatment.

In this chapter the authors begin with a discussion of issues in the assessment of substance use disorders in persons with severe psychiatric disorders. Following this, an overview provides a natural history of substance use disorders in both the general population and among the chronically mentally ill.

Next, the failure of the parallel treatment system for dually diagnosed clients is briefly reviewed, followed by a description of more recently developed integrated substance abuse and mental health methods. Preliminary data are then presented from a 3-year study by the New Hampshire-Dartmouth Psychiatric Research Center of integrated treatment for dual-diagnosis clients.

The implications of research on integrated treatment approaches for policy decisions are discussed in a concluding section, as are future directions for research in this area.

ASSESSMENT

Several common difficulties arise when assessing substance disorders among persons with severe mental illness (Drake et al. 1993a; Drake and Mercer-McFadden 1995; Stone et al. 1993). The most common problem is that mental health clinicians often do not obtain a thorough history of substance use (Ananth et al. 1989).

Even when interviewed thoroughly, however, persons with dual disorders are subject to the usual problems of denial, distortion, and minimization that attend self-reports of substance use, especially the use of illicit drugs, in the general population (Aiken 1986; Galletly et al. 1993; Stone et al. 1993). Psychiatric clients are also prone to individual distortions arising from the cognitive, emotional, and other aspects of their mental illness (Mueser et al. 1992). 

Another important factor that complicates assessment is the fact that the usual dimensions of substance abuse—pattern, consequences, dependence syndrome, and subjective distress—are qualitatively different in substance abusers who have mental illness compared to those who do not (Drake et al. 1990; Lehman et al. 1994; McHugo et al. 1993).

Specifically, compared with non-mentally ill substance abusers, those with dual disorders use lower amounts of alcohol and drugs, experience different consequences, are less likely to develop a dependence syndrome, and have less subjective distress.

For example, the typical consequences of substance abuse among people with a mental disorder are difficulties with money management, destabilization of illness, unstable housing, and inability to participate in rehabilitation, but not with the items on the Michigan Alcohol Screening Test (Selzer 1971) or the Alcohol Dependence Scale (Skinner and Horn 1984).

Standard instruments, such as the Addiction Severity Index (McLellan et al. 1980), are relatively insensitive to clinically important levels of abuse among persons with psychiatric disorders. One last but critical problem is that dual-disordered clients are typically in a premotivational state regarding their substance abuse, even if they are well engaged in mental health treatment (Drake et al. 1990).

To be useful for treatment planning and monitoring, assessment instruments must be sensitive to stages of motivation and to changes that occur prior to attaining abstinence. The authors and others, thus, recommend the use of multiple tests (Carey, this volume; Drake et al. 1990), multimodal testing (Stone et al. 1993), and an explicit assessment of the stage of treatment (McHugo et al. 1995).

Furthermore, there is a need to develop new instruments sensitive to the presence of substance use disorders in the population of persons with severe psychiatric disorders (Drake et al. 1993a; Lehman et al. 1993b).

NATURAL HISTORY OF SUBSTANCE USE DISORDERS

As a backdrop to understanding the longitudinal course of psychiatric and substance use disorders, it is helpful to review what is known about the course of primary alcohol and drug use disorders. Vaillant's (1983) seminal work on the natural history of alcoholism provides compelling evidence that for most clients the disorder is lifelong and is associated with a substantial risk for early mortality.

Despite the overall negative (and often progressively negative) longterm outlook for alcoholics, a cumulative proportion of individuals 89 achieve abstinence, even in the absence of professional treatment. Vaillant (1983) estimated that approximately 3 percent of alcoholics become abstinent each year without the benefit of formal treatment programs, and between 1 and 2 percent of abstinent alcoholics resume social drinking.

Although the efficacy of treatment for alcoholism continues to be debated, Vaillant (1983) estimated that treatment of alcoholics increases their recovery rate to approximately 6 percent yearly. Fewer data are available on the longitudinal course of primary drug use disorders, although in general the findings are compatible with those reported by Vaillant (1983) for alcoholism (Vaillant 1973, 1988; Simpson et al. 1986).

In one of the largest and longest longitudinal studies published to date, Hser and associates (1993) reported 24-year outcomes for 581 narcotics addicts who had been admitted to the California Civil Addict Program between 1962 and 1964.

Data on the long-term outcome of these patients' drug use disorders revealed high mortality rates and a rate of spontaneous remission in the absence of treatment that was somewhat lower than that reported by Vaillant (1983) for alcoholics.

At the end of the followup period, 28 percent of the sample were dead, and only 19 percent had attained stable abstinence, which was defined as not using drugs for the prior 3 years.

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NIDA Research Monograph, Number 172
  

Substance Use and HIV Risk Among People With Severe Mental Illness

Francine Cournos and Karen McKinnon

People with severe mental illness are often overlooked in the acquired immunodeficiency syndrome (AIDS) epidemic.

For a long time it was assumed that those with schizophrenia, the most common diagnosis in public treatment settings, were too disorganized or withdrawn to engage in the drug use and sexual behaviors related to human immunodeficiency virus (HIV) exposure (Carmen and Brady 1990).

The extent of these risk behaviors was unknown and uninvestigated. Unfortunately, this inattention may have facilitated the spread of HIV infection among people with the most severe psychiatric disorders. This chapter reviews the literature on the role of substance use in HIV risk among people treated in public mental health settings who have recurrent or persistent psychotic illness and significant functional impairments.

Most of these people have had multiple psychiatric admissions and courses of psychotropic medications. The majority are unemployed and rely on social welfare benefits. Some are homeless. They typically fit poorly into existing health care and substance abuse treatment programs—they receive inferior medical care, have higher morbidity and mortality, and are unwelcome in traditional treatment programs (Gelberg and Linn 1984; Kroll et al. 1986).

THE EMERGENCE OF THE AIDS EPIDEMIC IN THE PSYCHIATRIC POPULATION

In 1983, a 25-year-old woman hospitalized at a state psychiatric center in Brooklyn, New York developed a low white blood cell count. It was assumed to be caused by the antipsychotic medication she was taking, which was immediately stopped.

However, her blood count did not improve. Ten months later she developed pneumonia and was transferred to a general hospital. There was no HIV antibody test at the time, but the organism causing her pneumonia was pneumocystis carinii, and a diagnosis of AIDS was made. This woman was one of the first of a series of patients who would make it clear that AIDS could have a significant impact on the psychiatric population.

This was a shock to psychiatric institutions. Clinicians and hospital administrators of the time thought of AIDS as a disease of men who either had sex with other men or injected drugs. In 1983, there were only 143 newly diagnosed cases of AIDS among women in the entire country, and one of them was at a public psychiatric hospital in New York City. In fact, the majority of early cases reported in the psychiatric literature were women (Cournos et al. 1990; Gewirtz et al. 1988; Horwath et al. 1989).

Well into the second decade of the AIDS epidemic, such case reports were the only information in the peerreviewed literature about HIV infection among psychiatric patients. To what extent these cases were typical or represented an accurate picture of the epidemic in this population was unknown.

THE PREVALENCE OF HIV INFECTION AMONG ADULTS WITH SEVERE MENTAL ILLNESS

The first published study of the prevalence of HIV infection among a psychiatric population appeared in 1991 (Cournos et al. 1991a). There are now 11 studies in the peer-reviewed psychiatric literature on the rates of HIV infection among psychiatric patients in treatment in the United States, 10 conducted in New York City and 1 in Baltimore. Rates of infection range from 4.0 to 22.9 percent (Cournos et al. 1991a; Empfield et al. 1993; Lee et al. 1992; Meyer et al. 1993; Sacks et al. 1992a; Silberstein et al. 1994; Volavka et al. 1991).

One small study conducted outside a hospital setting found that 19.4 percent of mentally ill men attending a day program in a large homeless shelter had a positive antibody test noted in their records (Susser et al. 1993). Unfortunately, little peer-reviewed research examines seroprevalence among a defined psychiatric population in the United States outside New York City.

Anecdotal reports suggest elevated rates of infection in comparison to the general population in other geographic areas (personal communications). Although some psychiatric hospitals have conducted seroprevalence studies without external funding, results have not appeared in scientific journals, possibly because of flawed methods of data collection.

Methodological Issues in Estimating Prevalence

Estimating how many people with severe mental illness are infected with HIV requires identifying a group to study, learning their demographic and risk characteristics, and obtaining blood samples to test. Differences in the HIV infection rates obtained in seroprevalence studies may be due to differences in sampling and methodology.

Sampling. To map the distribution of HIV and the factors that influence it in the psychiatric population, a representative sample is required. The published seroprevalence studies are all limited by the selection of populations in treatment in hospital settings, who represent only some of those with severe psychiatric disorders.

In addition, all were conducted in New York City, where AIDS case rates are higher than in other parts of the United States. In these studies, sampling was carried out over varying timeframes, ranging from 3 (Meyer et al. 1993) to 18 months (Empfield et al. 1993). Changes in rates among subgroups of patients have not been reported and information on the number of new cases (incidence) of HIV infection occurring in the population has not appeared.

Method. Anonymous serosurveys have been described in detail elsewhere (Cournos et al. 1991a). Such surveys have several advantages over studies in which patients consent to testing. They capture a larger and more representative proportion of the population under investigation because they sample all patients, not specifically those selected either because they request testing, are urged to have it because of a history of HIV-related risk behaviors, or are capable of giving informed consent.

Larger sample sizes increase the statistical power to assess relationships between independent and dependent variables. In addition, infected patients are not individually identified, so there is little direct impact on staff and patients. Anonymous testing does not interfere with clinical judgments about the risks and benefits of testing, and pre- and posttest counseling can be tailored to individual patients. This method is best suited to hospital settings in which large patient pools permit anonymous blood collection.

By comparison, the major advantage of the open testing method, which is contingent on patient capacity to give informed consent, is the possibility of conducting structured diagnostic and risk assessment interviews to obtain detailed and reliable information that can be linked to HIV status. Open testing can be carried out in any setting.

In summary, the number of studies attempting to estimate HIV infection among people with severe mental illness is small. All were conducted in New York City and limited in the type and reliability of information obtained and by the selection of hospitalized people.

Nevertheless, they represent the state of the art, and must be used as a basis for further research.

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NIDA Research Monograph, Number 172
 

Depression, Substance Use, and Sexual Orientation as Cofactors in HIV-1 Infected Men: Cross-Cultural Comparisons

Paul Satz, Hector F. Myers, Mario Maj, Fawzy Fawzy, David L. Forney, Eric G. Bing, Mark A. Richardson, and Robert Janssen

INTRODUCTION

The co-occurrence of major depression in medical populations has been the subject of much controversy in the past decade.

Although some investigators have suggested that reports of an increased prevalence of depression may, in part, be due to misclassification based on physician reliance on self-report methods (Perez-Stable et al. 1990) or on failure to adjust for symptoms induced by physical illness (Plumb and Holland 1977), most studies have suggested that the prevalence of depression is high, although often undetected by the primary care physician (Perez-Stable et al. 1990; Schulberg et al. 1985).

Schulberg and colleagues (1985) state that it is unclear whether this oversight reflects true limitations in the physician's diagnostic acumen, his/her lack of concern for social implications, or whether it is an artifact of existing classification procedures.

Regardless of the reasons for its underreporting, the detection and treatment of depression is crucial, especially for medically ill patients, because depressive disorders may adversely affect survival, length of hospital stay, compliance with therapy, ability to care for oneself, and quality of life (Schulberg et al. 1985).

These concerns are particularly relevant to human immunodeficiency virus type 1 (HIV-1), where the co-occurrence of major depression has received only limited recent attention. Based on initial reports using chart reviews (Perry and Tross 1984), it has been suggested that over 83 percent of hospitalized acquired immunodeficiency syndrome (AIDS) patients have significant disturbances in mood.

Unfortunately, anecdotal studies such as this fail to use structured diagnostic interviews to distinguish transitory dysphoria in response to the clinical condition and its treatment from syndromal depression. The latter disorder is more serious and merits direct clinical intervention because it may be predictive of more accelerated course and early mortality.

In addition, such reporters do not investigate 131 other cofactors that could account for the co-occurrence of depression in HIV-1 disease. The purpose of this chapter, therefore, is to examine the evidence of the co-occurrence of major depression in persons infected with HIV- 1, with special attention to the potential role that cofactors such as substance use and sexual orientation (i.e., being gay or bisexual) might play in accounting for the association.

The chapter is organized into two parts. Part I presents a brief summary of the literature on syndromal depression in HIV-1 that was part of a larger review on the assessment of mood disorder in medical populations (Satz et al., in press).

Part II presents a reanalysis of data from two large recent cohort studies of HIV-1 in populations in the United States and abroad, the World Health Organization (WHO) Multicentre Study of HIV-1 (Maj et al. 1994a, 1994b). The latter provides a more direct test of the relationship of syndromal depression in HIV-1, with special focus on substance use and sexual orientation as important cofactors.

PART I Syndromal Depression and HIV-1 (Summary Review)

There are eight studies in the literature that report the prevalence of current and/or lifetime major depression in HIV-infected adults. Each study used structured diagnostic interview instruments and Diagnostic and Statistical Manual of Mental Disorders, 3d ed. revised (DSM-IIIR), or ICD-10 criteria to define syndromal disorder.

The results from these studies, which are summarized in table 1, indicate two general findings. The first is that none of the studies found an association of HIV-1 with lifetime depression, and only one found an association with current (1 month) depression (Baldeweg et al. 1993).

In addition, none of the studies reported an association between either lifetime or current depression and early (presymptomatic) HIV-1 infection. The second finding is that, despite the general lack of association between major depressive disorders (MDD) and HIV-1, the rates for both current and lifetime depression in HIV-infected persons were significantly higher than the prevalence rates for depression in the general population reported in both the Epidemiologic Catchment Area (ECA) study (Regier et al. 1988) and in the more recent National Comorbidity Survey (NCS) (Kessler et al. 1994).

The average prevalence rates for lifetime MDD in HIV seropositive men (23.7 percent) was approximately fivefold higher than the average rate reported for men in the ECA (4.6 percent) and 1.8 times higher than reported for men in the NCS (13 percent).

With respect to current depression, the observed rates were approximately 3.8 times higher than reported for 1-month ECA rates for men (2.3 percent). NCS rates for current major depression were available only for the past 12 months. Comparisons are presented for men only because the studies of HIV-1 included primarily well-educated, white, gay, male volunteers, which reflects the population most affected in the first wave of the disease.

For example, in five of the studies the participants were described as gay or bisexual (Tross et al. 1987; Atkinson et al. 1988; Williams et al. 1991; Baldeweg et al. 1993; Perkins et al., in press). Given the population trends for this disease, it is very likely that the majority of the participants in these early studies were gay or bisexual.

Despite the generally null findings regarding the association between MDD and HIV-1, one must note that few studies contrasted the spectrum of HIV-1 infection (Tross et al. 1987; Atkinson et al. 1988; Baldeweg 1993), while other studies pooled cases of presymptomatic and sympto- matic HIV-1 infection (Perry 1990; Pace et al. 1990).

The pooling of early stage and advanced stage patients could attenuate the HIV-MDD association if the latter is more likely to be present in advanced cases. Also, most studies had small sample sizes, which restricts power to detect an association between these putative comorbid outcomes.

The consistently high rates of MDD across studies, regardless of serostatus, raises the question of whether sexual orientation or other factors may be unexamined independent risk factors for major depression.

Only one study (Atkinson et al. 1988) explored this hypothesis by including two small samples of noninfected gay (N = 11) and heterosexual (N = 22) controls. This study was the first to show an elevated rate of MDD in the gay and bisexual groups, independent of serostatus, suggesting that sexual orientation and lifestyle may be risk factors for major depression.

It is also noteworthy that despite evidence of significant substance abuse among those at highest risk for HIV-1 infection (Donahoe 1990; Parker and Carballo 1992), none of these studies investigated whether the increased prevalence of depression in their samples may have been attributable, either directly or indirectly, to the widespread abuse of alcohol and other substances.

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NIDA Research Monograph, Number 172
  

George E. Woody, David Metzger, Helen Navaline, Thomas McLellan, and Charles P. O'Brien

INTRODUCTION

Previous work done at the Addiction and Research Center of the University of Pennsylvania and elsewhere has shown that the intensity and frequency of psychiatric symptoms is related to treatment outcome for patients with substance use disorders (McLellan et al. 1983; Rounsaville et al. 1986; 1987).

These studies have found that patients with high symptom levels (high-severity patients) generally do poorly in standard, addiction-focused treatment. In contrast, patients with low to moderate symptom levels (low- or mid-severity patients) usually benefit considerably from addiction-focused treatments without the need for additional professional services.

High-severity patients are typically characterized by significant levels of anxiety and depression and usually meet diagnostic criteria for other axis I psychiatric disorders, particularly mood disorders as described in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (APA 1994).

These patients are identified as having a dual diagnosis, and most clinicians feel that their treatment outcome can be improved by adding psychiatrically focused therapy to the addiction-focused treatment that they typically receive.

Several studies have now been completed, or are in progress, to examine the benefits that may result from adding psychiatric treatments to standard drug counseling for high-severity patients. One study examined the efficacy of supportive-expressive or cognitive-behavioral psychotherapy when added to paraprofessional drug counseling in a methadone program.

The results showed that high-severity patients who received only drug counseling made few gains while those who received additional psycho-therapy made a number of significant gains that persisted even 6 months after therapy ended (Woody et al. 1983, 1987). A recently completed followup study gave similar results (Woody et al. 1995).

Other recent studies have examined the effect of imipramine with depressed alcoholic or opiate-addicted patients. In these, in contrast to most earlier antidepressant studies with addicts and alcoholics, the investigators have been careful to select patients whose depression either predated their addiction or has been persistent (i.e., duration of 6 months or longer) in the context of the dependence.

Preliminary results indicate that imipramine treatment has a significant effect on reducing the depression and a weaker, though measurable, effect on substance use (Nunes et al. 1991, this volume). Taken together, this research indicates that psychiatrically impaired addicts and alcoholics (Mason and Kocsis 1991) can be helped in clinically meaningful ways by adding psychotherapy, pharmacotherapy, or combinations of both to addiction-focused treatments.

An additional line of research has examined the effect of axis II disorders, particularly antisocial personality disorder (ASPD), on outcome. Several of these suggest that patients with significant antisocial traits or a diagnosis of ASPD, like those with high levels of anxiety and depression, generally do poorly in treatment (Sturup 1948; Gibbens et al. 1959; Shamsie 1981).

However, other studies also indicate that ASPD is a heterogeneous category (Gibbens et al. 1959) and that some patients with this disorder are much more responsive to treatment than others (Adams 1981). For example, Woody and colleagues (1985) found that a diagnosis of ASPD does not necessarily mean that treatment will be ineffective, although much of the available data and opinion argue that this disorder is generally associated with a less than optimal outcome.

These two types of psychiatric problems, general psychiatric severity and a diagnosis of ASPD, are often associated with poor judgment, impulsive behavior, higher levels of drug use, and other factors that increase the risk for human immunodeficiency virus (HIV) infection (Brooner et al. 1993; Metzger et al. 1993).

Thus, they are a logical focus for studies attempting to identify individuals within an intravenous drug-using (IVDU) population who may be at particularly high risk for HIV infection. Put another way, these personal characteristics may provide information about why some addicts continue to share needles and engage in other behaviors that put them at risk for HIV infection, even when they know that these actions can have disastrous consequences.

Data from a study that this center has been conducting since 1989 indicate that there is a significant relationship between psychiatric symptoms and risky behavior among opioid addicts, showing that the intensity and frequency of psychiatric symptoms (i.e., psychiatric severity) is highly associated with continued needle sharing and other risky behavior among opioid-dependent patients (Metzger et al. 1993).

This finding is especially important because all of the subjects were receiving pre- and posttest HIV counseling about risky behaviors as part of an HIV testing protocol, and were well aware of the types of behaviors that put them at risk for HIV infection.

Another recent study examined HIV risk and seroconversion among heroin addicts with ASPD. This was also a prospective study involving injection drug users (IDUs) who were both in and out of methadone maintenance treatment.

Results showed that addicts with ASPD engaged in significantly higher levels of needle sharing and other acquired immunodeficiency syndrome (AIDS) risk behaviors than those without this diagnosis. Moreover, subjects with ASPD became HIV positive (i.e., seroconverted) at significantly higher rates than those without the diagnosis (Brooner et al. 1993).

Overall, these studies indicate that the same factors that are associated with poor treatment outcome (i.e., high levels of psychiatric symptoms and ASPD) are also associated with higher levels of risky behavior and with actual infection by HIV.

PROCEDURES

New data on the association between psychiatric symptoms, risky behavior, and seroconversion are being obtained from the longitudinal study of heroin and cocaine addicts in Philadelphia discussed above (Metzger et al. 1993).

This study is now in its fifth year and has had an 84 percent followup rate after 4 years, thus providing data continuously over an extended period of time. The project began in 1989 at the Girard Medical Center in Philadelphia, the largest methadone program in Pennsylvania.
 
Subject recruitment began with a random selection of 153 heroin addicts from among the 450 patients in the methadone program. After obtaining their informed consent, these 153 in-treatment (IT) subjects were asked to refer someone who "is just like you but who had been out of treatment for at least the last 10 months."

Through this patientreferral method of recruitment, an additional 102 out-of-treatment (OT) subjects were identified, providing a total initial cohort of 255. All subjects were evaluated at baseline and every 6 months with a range of measures that included interviewer- and self-reported measures of HIV risk behavior, the Beck Depression Inventory (BDI) (Beck and Beck 1972), the Hopkins Symptom Checklist-90 (SCL-90) (Derogatis et al. 1959), the Addiction Severity Index (ASI) (McLellan et al. 1980), and blood tests for HIV and human T-cell lymphocytotropic virus (HTLV) types I and II.

RESULTS

Retention As noted, retention in this longitudinal study has been approximately 84 percent for the combined IT and OT cohorts over the first 48 months. Twenty-six subjects died during the first 4 years of the study from a range of conditions that included AIDS, homicide, drug overdose, pneumonia, and liver failure.

Treatment course for many individuals has not been stable: Approximately half of the IT subjects have left treatment at some point, and approximately half of the OT subjects have entered treatment. The proportions of subjects in and out of treatment at each evaluation point are shown on figure 1.

Seroconversion

Seroconversion has been the highest (significantly so) among those who have remained out of treatment continuously and lowest among those who have continuously remained in treatment. Figure 2 shows that 30 percent of the OT subjects who began the study as seronegative and who remained out of treatment have seroconverted over the first 48 months.

This compares with only 8 percent seroconversion among those IT subjects who began and remained in treatment. The two groups also showed marked differences in levels of risky behaviors such as drug use, needle sharing, visiting shooting galleries, and having unprotected sex.

As seen in figure 2, seroconversions among those who moved in and out of treatment were found at rates that were not significantly different from those who continuously remained in treatment. Psychiatric Symptoms The intensity and frequency of psychiatric symptoms (i.e., psychiatric severity) was examined using the SCL-90, the BDI, and the psychiatric severity scale of the ASI.

These measures were then studied in relation to treatment involvement, treatment entry, drug injection and needle sharing, and seroconversion. Similar relationships between each of these domains and psychiatric symptoms were found for all measures; therefore, the SCL-90 findings will be used to demonstrate the findings. 

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NIDA Research Monograph, Number 172