ABSTRACT. Objective: While much is known about the clinical patterns and family histories of individuals with alcoholism or stimulant (cocaine and amphetamine) dependence, there are few data that describe men and women with concomitant alcohol and stimulant dependence. Method: As part of the Collaborative Study on the Genetics of Alcoholism, structured interviews were administered to 3,882 (2,432 male) DSM-III-R defined alcohol and/or stimulant dependent subjects. The characteristics and family histories of four groups were compared: Group 1 (26%), with the onset of alcohol before stimulant dependence; Group 2 (10%), with alcohol dependence simultaneously with or after stimulant dependence; Group 3 (58%), with alcohol dependence only; Group 4 (6%), with stimulant dependence only. Results: Individuals with concomitant alcohol and stimulant dependence (Groups 1 and 2) reported more general life problems (e.g., marital instability), a higher rate of antisocial personality disorder and more substance-induced mood disorders, additional drug dependencies and substance-related difficulties than those with dependence on one substance only. People with alcohol dependence before stimulant dependence had the most severe clinical patterns. In addition, alcohol dependence and stimulant dependence were found to breed true in families of subjects with these concomitant disorders. The major findings were confirmed with logistic regression analyses, and were independent of ASPD and gender. Conclusions: It is important for clinicians to be aware of the severe clinical characteristics of patients with concomitant alcohol and stimulant dependence. In addition, the data consistent with drug-specific heritability in this heterogeneous population may be useful to researchers. (J. Stud. Alcohol 61: 728-735, 2000)
THE TWO CLASSES of substances (other than nicotine and marijuana) that are most frequently used in the United States are alcohol and stimulants (amphetamines and cocaine) (Schuckit, 2000; Substance Abuse and Mental Health Services Administration, 1998). According to the 1997 National Household Survey on Drug Abuse, more than 80% of people age 12 and older reported ever drinking alcohol, 10.5% endorsed prior cocaine use and 4.5% had used amphetamines (Substance Abuse and Mental Health Services Administration, 1998). Most stimulant users took their drug while also consuming alcohol (Grant and Harford, 1990).
Reflecting these high levels of use, alcohol- and stimulant-related problems are also common. Two large-scale national studies reported that the lifetime rate of alcohol dependence was about 15%, and it was approximately 2% for stimulant dependence (Helzer and Pryzbeck, 1988; Kessler et al., 1997). Among those with cocaine abuse or dependence, 85% met criteria for alcohol abuse or dependence; for those with amphetamine abuse or dependence the figure was 62% (Regier et al., 1990). It has been reported that alcoholics had a 35-times greater risk than nonalcoholics of developing cocaine dependence and were 11 times more likely to become dependent on other stimulants (mainly amphetamine) (Helzer and Pryzbeck, 1988).
There are several reasons why it is important to better characterize individuals with both alcohol and stimulant dependence. First, when alcohol and cocaine are mixed a new product called cocaethylene is formed, which has a longer half-life, a more intense high and possibly more severe consequences than cocaine alone (Jatlow et al., 1991; McCance-Katz et al., 1993; Randall, 1992). In addition, men and women with both disorders have high rates of morbidity and mortality, perhaps greater than those with either dependency alone. The combination of alcohol and stimulants is the most common drug combination seen in emergency room visits (Salloum et al., 1996) and the one most likely to be associated with violent behavior (Denison et al., 1997), cardiotoxicity (Mendelson et al., 1995; Nicolas et al., 1996; Salloum et al., 1996) and sudden death (Salloum et al., 1996).
Several authors have reported that groups with dependence on both categories of substances (compared to dependence on alcohol or stimulants alone) had more frequent drinking, intoxication and use of other drugs; a larger number of substance-related problems; higher rates of past treatment (Carroll et al., 1993b; Higgins et al., 1994; Miller et al., 1993; Schmitz et al., 1997); and a greater percentage of individuals with antisocial personality disorder (ASPD; Carroll et al., 1993b). Consistent with these findings, other studies have revealed poorer outcomes at 1 year among those with both disorders (Brower et al., 1994; Carroll et al., 1993a; Miller et al., 1990). This pattern of more severe problems appeared to be especially marked in subjects who were dependent on cocaine before alcohol (Carroll et al., 1993b).
Characterizing individuals with these concomitant dependencies might also impact research on the genetic influences of substance use disorders. In genetic studies, it is imperative that the purest phenotypes are identified in order to minimize this source of heterogeneity; it is possible that people with both dependencies represent a unique phenotype. Several recent reports (Bierut et al., 1998; Merikangas et al., 1998; Tsuang et al., 1998) indicated that while relatively independent factors might confer susceptibility to alcohol and drug dependence, additional overarching genetic influences might also be shared by these disorders.
The results from these descriptive (Carroll et al., 1993b; Higgins et al., 1994; Miller et al., 1990; Schmitz et al., 1997) and genetic (Merikangas et al., 1998; Tsuang et al., 1998) studies are informative; however, there are some methodological problems that limit the impact of the conclusions. These include the need for large sample sizes and a full complement of comparison groups. In addition, in the absence of personal, face-to-face interviews that use a time-line approach to diagnosis, independent and substance-induced psychiatric syndromes can be difficult to distinguish from each other. Substances of abuse can cause behavioral syndromes that could be mistaken for independent conditions (Raimo and Schuckit, 1998; Schuckit et al., 1997a). It is also important to control for the presence of ASPD; individuals with this disorder run a severe clinical course of substance use disorders and often have multiple drug dependencies (Hesselbrock et al., 1984; Hesselbrock and Hesselbrock, 1992; Hesselbrock et al., 1985).
This report presents data on the clinical characteristics, substance-related problems and family histories of a large group of men and women with both alcohol and stimulant dependence, along with comparison groups who are dependent on one substance only. Two subgroups with concomitant alcohol and stimulant dependence, differing in the sequence of onsets of the dependencies, are also characterized.
Method
The data come from the Collaborative Study on the Genetics of Alcoholism (COGA), a national pedigree investigation of alcohol dependent men and women, controls, their first-degree relatives and extended-family members (Schuckit et al,, 1997a,b,c, 1998). Index subjects, or probands, were recruited from consecutive admissions to inpatient or outpatient treatment programs at the six participating centers, and each proband had to have met DSM-III-R lifetime criteria for alcohol dependence and Feighner criteria for definite alcoholism (Feighner et al., 1972). Potential subjects were excluded if they did not speak English, if they had any immediate life-threatening diseases (e.g., AIDS), if they had repeatedly used intravenous drugs in the recent past or if they had no relatives that were available for a clinical interview. No exclusions were based on comorbid psychiatric diagnoses. Control index subjects were selected at the six sites through a variety of means including random mailings to university students and drivers' license records; some were selected from patients receiving care for nonpsychiatric disorders. After the alcoholic probands and control index subjects were recruited, all of their possible relatives were sought for clinical interviews. Probands, controls and their relatives with DSM-III-R diagnoses of alcohol dependence and/or stimulant dependence were included in the present analyses, and all first-degree relatives with complete diagnostic information were used for the family history evaluations.
The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA; Bucholz et al., 1994) was administered to all appropriate probands, controls and their available family members after they had received a full explanation of the details of the study and provided written informed consent. The SSAGA is a face-to-face diagnostic instrument that was developed from several validated epidemiologic research tools, including the Diagnostic Interview Schedule (DIS; Helzer and Robins, 1988) and the Schedule for Affective Disorders and Schizophrenia (SADS; Endicott and Spitzer, 1978). The interview, which has excellent test-retest reliability, establishes 17 DSM-III-R Axis I psychiatric diagnoses and ASPD, including substance use disorders (Bucholz et al., 1994; Hesselbrock et al., 1999); along with another assessment, it also reviews the family histories of all of these conditions (Rice et al., 1995). The SSAGA uses a time-line approach to diagnosis to delineate the sequence of onsets of disorders, and can define the onset of dependence as the age at which three or more of the nine DSM-III-R criteria for dependence on the relevant drug have occurred. The tool documents physical, psychological and social manifestations of substance use disorders and major psychiatric illnesses, and yields a list of 39 alcohol problems (e.g., legal, professional, health) (Raimo et al., 1999) and 36 stimulant-related adverse events that can be analyzed. In addition, the SSAGA discriminates substance-induced behavioral syndromes from independent psychiatric diagnoses (Schuckit et al., 1997a) and chronicles treatment histories (if any). All interviews are performed by carefully trained examiners and reviewed by on-site editors; when clarification is needed, subjects are reprobed.
The present analyses characterized individuals with lifetime histories of both alcohol and/or stimulant dependence. Four groups were created for these comparisons: Group 1, onset of alcohol dependence before stimulant dependence; Group 2, onset of alcohol dependence during the same year as or after the onset of stimulant dependence; Group 3, alcohol dependence only; Group 4, stimulant dependence only. Because probands recruited for the COGA study were required to have an alcohol dependence diagnosis, men and women in the stimulant-dependent-only category (Group 4) were all nonprobands (i.e., family members of index subjects) or were from control families.
Statistical comparisons between groups were carried out using a series of chi-square analyses for categorical data and ANOVAs for continuous variables. Overall statistics were done first, to detect the presence of any group differences; when the results were significant, specific groups were compared using post hoc tests (e.g., the post hoc test for proportions and Tukey's honestly significant difference post hoc test of pairwise comparisons). Logistic regression analyses were performed to determine which of the characteristics that significantly differentiated groups at the univariate level remained robust in the context of other related variables.
The family history analyses were carried out using the approach of prior COGA studies (Schuckit et al., 1997a). To avoid overlapping relationships among individuals, these comparisons were limited to interviewed first-degree relatives of probands. Group 4 (stimulant dependence alone) contained nonprobands only; thus, family histories were not analyzed in this group. It is also important to note that the diagnoses of the relatives came from direct assessment of these individuals, using the SSAGA, and not from historical information provided by the probands.
Results
Data were available on 3,882 subjects (2,432 men) from Master File 80 of the COGA project, who met DSM-III-R (American Psychiatric Association, 1987) lifetime criteria for alcohol and/or stimulant dependence. This population was divided into: Group 1 (26%), those who developed alcohol dependence before stimulant dependence; Group 2 (10%), those with alcohol dependence established during the same year as or after stimulant dependence; Group 3 (58%), those with alcohol dependence only; and Group 4 (6%), those with stimulant dependence alone.
Table 1 offers data regarding demographic and diagnostic patterns from univariate comparisons across the four groups. Overall, the groups were similar on age and race with the exception of Group 3 individuals (alcohol dependent only), who were older and more likely to be white, and Group 4 subjects (stimulant dependent only), who were more likely to be black and female. In addition, people with dependence on one drag only (Groups 3 and 4) were less likely to be divorced or separated; those in Group 3 had the highest educational levels; and Group 1 members (alcohol before stimulant dependence) were the least likely to be employed.
TABLE 1. Demographics and associated diagnoses in 3,882 alcoholics with concomitant stimulant dependence and comparison subjects
Alcohol dep. Alcohol dep.
before with or after
stimulant dep. stimulant dep.
(Group 1) (Group 2)
Demographics n = 1,020 (26.3%) n = 378 (9.7%)
Age, mean (SD) 34.2 (6.88) 34.4 (7.65)
Female (%) 32.4 39.9
Proband (%) 53.1 41.0
Ethnicity (%)
White 71.4 77.2
Black 24.5 19.6
Other 4.1 3.2
Marital status (%)
Married 28.6 33.3
Widowed 1.0 1.1
Divorced or separated 31.0 31.7
Never married 39.4 33.9
Highest grade completed,
mean (SD) 12.2 (2.01) 12.3 (2.00)
Presently employed
full-time (%) 48.6 59.5
Associated diagnoses (%)
Conduct disorder 40.0 28.8
ASPD 32.0 21.2
Sedative dep. 21.3 17.5
Opiate dep. 23.3 16.7
Marijuana dep. 64.6 51.6
Smoked daily at least 1
pack/day for [is greater
than or equal to] 6 months 57.1 56.1
Substance-induced
depression 43.3 34.4
Independent major depression 13.7 16.4
Independent mania 3.7 2.9
No. health problems
(9), mean (SD) 1.3 (1.24) 1.3 (1.37)
Stimulant dep.
Alcohol dep. only
only (Group 3) (Group 4)
Demographics n = 2,250 (58.0%) n = 234 (6.0%)
Age, mean (SD) 40.1 (13.74) 32.7 (7.41)
Female (%) 35.9 68.8
Proband (%) 25.6 na
Ethnicity (%)
White 84.6 67.1
Black 13.1 30.3
Other 2.3 2.6
Marital status (%)
Married 47.8 43.2
Widowed 2.0 1.3
Divorced or separated 23.2 20.1
Never married 27.0 35.5
Highest grade completed,
mean (SD) 12.8 (2.40) 12.2 (1.87)
Presently employed
full-time (%) 63.2 60.7
Associated diagnoses (%)
Conduct disorder 15.6 12.8
ASPD 8.1 8.1
Sedative dep. 3.3 5.1
Opiate dep. 2.5 6.0
Marijuana dep. 18.8 39.3
Smoked daily at least 1
pack/day for [is greater
than or equal to] 6 months 52.6 38.0
Substance-induced
depression 23.6 19.7
Independent major depression 16.6 14.1
Independent mania 2.2 0.4
No. health problems
(9), mean (SD) 1.2 (1.24) 0.8 (1.07)
Demographics Statistic F or [chi square]
Age, mean (SD) 90.07([double dagger])
Female (%) 112.90([double dagger])
Proband (%) 242.09([double dagger])
Ethnicity (%) 135.82([double dagger])
White 100.31([double dagger])
Black 92.01([double dagger])
Other 8.38(*)
Marital status (%) 155.16([double dagger])
Married 116.86([double dagger])
Widowed 6.07
Divorced or separated 33.43([double dagger])
Never married 53.22([double dagger])
Highest grade completed,
mean (SD) 18.08([double dagger])
Presently employed
full-time (%) 62.00([double dagger])
Associated diagnoses (%)
Conduct disorder 255.91([double dagger])
ASPD 320.42([double dagger])
Sedative dep. 298.35([double dagger])
Opiate dep. 377.03([double dagger])
Marijuana dep. 699.36([double dagger])
Smoked daily at least 1
pack/day for [is greater
than or equal to] 6 months 29.28([double dagger])
Substance-induced
depression 147.11([double dagger])
Independent major depression 5.05
Independent mania 11.37(*)
No. health problems
(9), mean (SD) 9.70([double dagger])
Demographics Group differences
Age, mean (SD) b,d,f,g,h
Female (%) a,c,e,f,h
Proband (%) a,b,d,g
Ethnicity (%)
White a,b,d,e,f,g
Black b,d,e,f,g,h
Other b,g
Marital status (%)
Married b,c,d,e,g,h
Widowed NA
Divorced or separated b,c,d,e,g,h
Never married b,d,f,g
Highest grade completed,
mean (SD) b,d,f,g
Presently employed
full-time (%) a,b,c,g,h
Associated diagnoses (%)
Conduct disorder a,b,c,d,e,g,h
ASPD a,b,c,d,e,g,h
Sedative dep. b,c,d,e,g,h
Opiate dep. a,b,c,d,e,f,g,h
Marijuana dep. a,b,c,d,e,f,g,h
Smoked daily at least 1
pack/day for [is greater
than or equal to] 6 months b,c,e,f,h
Substance-induced
depression a,b,c,d,e,g,h
Independent major depression NA
Independent mania b,c,e,g,h
No. health problems
(9), mean (SD) b,c,e,f,g,h
Notes. a = post hoc comparison of Group 1 vs Group 2, p < .05; b = post hoc comparison of Group 1 vs Group 3, p < .05; c = post hoc comparison of Group 1 vs Group 4, p < .05; d = post hoc comparison of Group 2 vs Group 3, p < .05; e = post hoc comparison of Group 2 vs Group 4, p < .05; f = post hoc comparison of Group 3 vs Group 4, p < .05; g = post hoc comparison of Groups 1 + 2 vs Group 3, p < .05; h = post hoc comparison of Groups 1 + 2 vs Group 4, p < .05.
(*) Overall test, p < .05;
([double dagger]) overall test, p < .001.
While the differences in demography across groups were fairly modest, diagnostic patterns were more divergent. Subjects with concomitant alcohol and stimulant dependence (Groups 1 and 2) were more likely to have fulfilled criteria for conduct disorder as children and for ASPD as adults, a pattern that was most prominent in Group 1. In addition, Groups 1 and 2 had the highest proportion of individuals with sedative, opiate and marijuana dependence; a relatively high percentage of Group 4 participants (stimulant dependence only) also had marijuana dependence. Participants with dependence on both alcohol and stimulants were more likely to have had substance-induced depressive episodes; however, the four groups did not differ significantly on the proportion who had experienced a major depressive episode independent of periods of active heavy drinking or drag intake. Subjects from Group 4 reported the lowest rate of regular smoking (i.e., smoking at least one pack per day for at least 6 months) and the fewest number of health problems.
Table 2 offers data regarding the substance use patterns across the four groups. Regarding alcohol, members of Group 1 had the earliest ages of onset of drinking and alcohol dependence, the highest number of 39 alcohol-related problems and the greatest maximum number of drinks; they were also most likely to have ever been treated for alcoholism. Group 2 individuals also had more severe alcohol characteristics than those dependent on alcohol only (Group 3). Similar results were apparent for stimulants, in that a more intense clinical picture was shown for subjects with dependence on multiple substances. Men and women with both diagnoses (Groups 1 and 2) reported a greater number of 36 stimulant problems, more frequent stimulant use and higher rates of past rehabilitation. In addition, they were more likely to be dependent on both cocaine and amphetamines than were members of Group 4 (stimulant dependence only).
TABLE 2. Substance use characteristics in 3,882 alcoholics with concomitant stimulant dependence and comparison subjects
Alcohol dep. Alcohol dep.
before with or after
stimulant dep. stimulant dep.
Substance use (Group 1) (Group 2)
characteristics n = 1,020 (26.3%) n = 378 (9.7%)
Alcohol,(1) mean (SD)
Age first drunk 14.0 (3.35) 15.6 (4.75)
Age began drinking
regularly 15.7 (3.23) 18.0 (5.20)
Age of onset
alcohol dep. 18.9 (4.37) 23.5 (6.89)
No. DSM-III-R criteris
for alcohol dep. (9) 7.1 (1.76) 6.2 (2.05)
No. alcohol problems,
total (39) 23.3 (7.05) 19.5 (7.85)
Maximum no. drinks/
24 hours, lifetime 34.6 (25.52) 31.6 (24.08)
Treated for alcohol
problem (%) 77.0 60.3
Stimulants (cocaine or
amphetamine),(2) mean (SD)
Age first used stimulants 22.0 (6.19) 21.4 (5.67)
Age of onset stimulant
dep.(3) 26.2 (6.59) 21.7 (5.45)
No. DSM-III-R criteria
for stimulant dep. 7.5 (1.88) 6.4 (2.27)
No. stimulant
problems (36) 21.4 (6.56) 17.5 (7.10)
No. times used
stimulants, lifetime(4) 1209.0 (2073.03) 966.5 (1790.01)
Treated for a drug
problem (%) 67.1 47.6
Cocaine dep. (%) 88.0 67.7
Amphetamine dep. (%) 41.9 47.4
Both cocaine and
amphetamine dep. (%) 29.9 15.1
Alcohol dep. Stimulant dep.
only only
Substance use (Group 3) (Group 4)
characteristics n = 2,250 (58.0%) n = 234 (6.0%)
Alcohol,(1) mean (SD)
Age first drunk 16.6 (4.81) 16.2 (5.02)
Age began drinking
regularly 18.3 (5.52) 16.8 (7.61)
Age of onset 24.6 (9.05) NA
alcohol dep.
No. DSM-III-R criteris
for alcohol dep. (9) 5.5 (2.07) 1.1 (0.90)
No. alcohol problems,
total (39) 16.4 (7.81) 3.5 (2.94)
Maximum no. drinks/
24 hours, lifetime 24.4 (17.30) 12.2 (11.35)
Treated for alcohol
problem (%) 43.1 NA
Stimulants (cocaine or
amphetamine),(2) mean (SD)
Age first used stimulants 22.8 (6.69) 21.8 (5.53)
Age of onset stimulant
dep.(3) NA 24.0 (6.25)
No. DSM-III-R criteria
for stimulant dep. 0.2 (0.55) 6.0 (2.21)
No. stimulant
problems (36) 0.7 (1.71) 15.5 (6.81)
No. times used
stimulants, lifetime(4) 79.2 (287.38) 716.5 (1435.67)
Treated for a drug
problem (%) NA 27.4
Cocaine dep. (%) NA 70.9
Amphetamine dep. (%) NA 37.6
Both cocaine and
amphetamine dep. (%) NA 8.5
Substance use Statistic F or Group
characteristics [chi square] differences
Alcohol,(1) mean (SD)
Age first drunk 113.70([double dagger]) a,b,d,g
Age began drinking
regularly 99.33([double dagger]) a,b,g
Age of onset 188.34([double dagger]) a,b,d,g
alcohol dep.
No. DSM-III-R criteris
for alcohol dep. (9) 217.56([double dagger]) a,b,d,g
No. alcohol problems,
total (39) 291.24([double dagger]) a,b,d,g
Maximum no. drinks/
24 hours, lifetime 92.87([double dagger]) a,b,d,g
Treated for alcohol
problem (%) 330.16([double dagger]) a,b,d,g
Stimulants (cocaine or
amphetamine),(2) mean (SD)
Age first used stimulants 1.16 NA
Age of onset stimulant
dep.(3) 59.32([double dagger]) a,c,e,h
No. DSM-III-R criteria
for stimulant dep. 73.03([double dagger]) a,c,e,h
No. stimulant
problems (36) 96.96([double dagger]) a,c,e,h
No. times used
stimulants, lifetime(4) 6.48([dagger]) c,h
Treated for a drug
problem (%) 138.95([double dagger]) a,c,e,h
Cocaine dep. (%) 91.07([double dagger]) a,c,h
Amphetamine dep. (%) 6.11(*) e
Both cocaine and
amphetamine dep. (%) 67.44([double dagger]) a,c,e,h
(1) Analyses on Groups 1-3 only (alcohol dependent subjects; n = 3,648);
(2) analyses on Groups 1, 2, 4 (stimulant dependent subjects; n = 1,632);
(3) n = 1,522;
(4) n = 1,486.
Notes: a = post hoc comparison of Group 1 vs Group 2, p < .05; b = post hoc comparison of Group 1 vs Group 3, p < .05; c = post hoc comparison of Group 1 vs Group 4, p < .05; d = post hoc comparison of Group 2 vs Group 3, p < .05; e = post hoc comparison of Group 2 vs Group 4, p < .05; g = post hoc comparison of Groups 1 + 2 vs Group 3, p < .05; h = post hoc comparison of Groups 1 + 2 vs Group 4, p < .05.
(*) Overall test, p < .05;
([dagger]) overall test, p < .01;
([double dagger]) overall test, p < .001.
Table 3 presents data on the family histories of substance use disorders for Groups 1-3. High rates of alcohol dependence were seen in the first-degree relatives of all three groups of alcoholic probands, with a significantly greater proportion in the families of Group 3 men and women (alcohol dependent only). Stimulant dependence, however, was highest in relatives of probands who themselves had stimulant dependence (Groups 1, 2). The greatest proportion of relatives with concomitant alcohol and stimulant dependence (in the same person) was also found in Groups 1 and 2 (highest in Group 1). In addition, to determine if any of the groups demonstrated familial aggregation of other substance use disorders or regular smoking, family histories for other drug dependencies and regular smoking were analyzed. Group 1 had the highest percentage of relatives with marijuana dependence (16.6% vs 12.7% vs 11.8%, for Groups 1-3, respectively; overall [chi square] = 21.28, 2 df, p [is less than] .001), whereas there were no significant group differences in the familial rates of opiate or sedative dependence, or regular smoking.
TABLE 3. Family history of alcohol and/or stimulant dependence in 1,272 subjects with concomitant alcohol and stimulant dependence and comparison subjects
Alcohol dep. Alcohol dep.
before with or after
stimulant stimulant
dep. dep.
(Group 1) (Group 2)
N (%)(1) 542 (42.6) 155 (12.2)
No. of relatives(2) 2,027 584
Relatives diagnoses (%)
Alcohol dep. 22.1 20.5
Stimulant dep. 4.2 4.3
Both alcohol and stimulant
dep. in the same relative 13.0 9.4
Alcohol dep.
only
(Group 3) [chi square]
N (%)(1) 575 (45.2)
No. of relatives(2) 2,295
Relatives diagnoses (%)
Alcohol dep. 25.1 8.20(*)
Stimulant dep. 2.0 19.91
([double dagger])
Both alcohol and stimulant
dep. in the same relative 7.6 35.56
([double dagger])
Group
differences
N (%)(1)
No. of relatives(2)
Relatives diagnoses (%)
Alcohol dep. b,c,d
Stimulant dep. b,c,d
Both alcohol and stimulant
dep. in the same relative a,b,d
(1) Probands only;
(2) directly interviewed first-degree relatives.
Notes: a = post hoc comparison of Group 1 vs Group 2, p < .05; b = post hoc comparison of Group 1 vs Group 3, p < .05; c = post hoc comparison of Group 2 vs Group 3, p < .05; d = post hoc comparison of Groups 1 + 2 vs Group 3, p < .05.
(*) Overall test, p < .05;
([double dagger]) overall test, p < .001.
Tables 1-3 compare groups on demographic, diagnostic and substance-related items, but these univariate statistics do not evaluate how each variable performs in the context of the others. Table 4 presents a series of logistic regression analyses using all the characteristics that significantly differentiated the relevant groups in Tables 1 and 2. Because the data on family history could be analyzed on only a subset of individuals, these variables were not included in the regression analyses.
TABLE 4. Logistic regression analyses of characteristics significantly associated with concomitant alcohol and stimulant dependence and alcohol before stimulant dependence
Concomitant alcohol and stimulant
dep. among alcohol dependent
subjects (n = 3,648)(a)
Predicting [chi square]
characteristic (10 df) OR (95% CI)
Age at interview 80.93(*) 0.96 (0.95-0.97)
Female gender
Proband 7.17([dagger]) 1.33 (1.08-1.63)
White 74.25 0.42 (0.34-0.51)
([double dagger])
Divorced or separated 6.65([dagger]) 1.29 (1.06-1.56)
ASPD 34.70 1.99 (1.58-2.49)
([double dagger])
Marijuana dep. 215.60(dagger]) 1.39 (1.33-1.45)
Sedative dep. 27.54 2.41 (1.74-3.35)
([double dagger])
Opiate dep. 57.60 3.75 (2.66-5.27)
([double dagger])
Ever smoked daily at
least 1 pack/day for
[is greater than or
equal to] 6 months
Substance-induced
depression 5.45(*) 1.24 (1.04-1.49)
Total alcohol problems 29.99 1.04 (1.03-1.06)
(n = 39) ([double dagger])
Ever treated for an 11.94 1.51 (1.20-1.91)
alcohol problem ([double dagger])
Total stimulant problems
(n = 36)
Ever treated for a drug
problem
Both cocaine and
amphetamine dep.
Concomitant alcohol and
stimulant dep. among
stimulant dependent subjects
(n = 1,632)(b)
Predicting [chi square]
characteristic (8 df) OR (95% CI)
Age at interview 12.68 1.04 (1.02-1.07)
([double dagger])
Female gender 45.59 0.33 (0.24-0.45)
([double dagger])
Proband
White 9.81([dagger]) 1.79 (1.24-2.58)
Divorced or separated
ASPD 12.06 2.50 (1.49-4.19)
([double dagger])
Marijuana dep.
Sedative dep.
Opiate dep.
Ever smoked daily at
least 1 pack/day for
[is greater than or 10.44 1.70 (1.23-2.34)
equal to] 6 months ([double dagger])
Substance-induced 15.07 2.09 (1.44-3.02)
depression ([double dagger])
Total alcohol problems
(n = 39)
Ever treated for an
alcohol problem
Total stimulant problems 12.22 1.05 (1.02-1.08)
(n = 36) ([double dagger])
Ever treated for a drug 27.27 2.80 (1.90-4.12)
problem ([double dagger])
Both cocaine and
amphetamine dep. 7.87([dagger]) 2.09 (1.25-3.51)
Alcohol before simulant
dep. among subjects with
concomitant alcohol and stimulant
dep. (n = 1,398)(c)
Predicting [chi square]
characteristic (2 df) OR (95% CI)
Age at interview
Female gender
Proband
White
Divorced or separated
ASPD
Marijuana dep.
Sedative dep.
Opiate dep.
Ever smoked daily at
least 1 pack/day for
[is greater than or
equal to] 6 months
Substance-induced
depression
Total alcohol problems 28.29 1.05 (1.03-1.07)
(n = 39) ([double dagger])
Ever treated for an
alcohol problem
Total stimulant problems 40.82 1.06 (1.04-1.08)
(n = 36) ([double dagger])
Ever treated for a drug
problem
Both cocaine and
amphetamine dep. 8.61([dagger]) 1.64 (1.18-2.27)
(a) Overall regression chi square = 1,374.68, 10 df, p < .001; variance accounted for by predictor variables = 22.1%.
(b) Overall chi square = 287.56, 8 df, p < .001; variance accounted for by the predictor variables = 17.6%.
(c) Overall chi square = 127.92, 2 df, p < .001; variance accounted for by the predictor variables = 7.3%.
Note:
OR (95% CI) = odds ratio (95% confidence interval).
(*) Overall test, p < .05;
([dagger]) overall test, p < .01;
([double dagger]) overall test, p < .001.
The first two data columns of Table 4 list the items that were significantly associated with concomitant stimulant dependence among alcoholics. Subjects with both diagnoses were younger and less likely to be white; they were more likely to be probands and divorced or separated. In addition, alcoholics with stimulant dependence were more likely to fulfill criteria for ASPD, dependence on additional drugs (in particular, opiates and sedatives) and substance-induced depression. They reported more alcohol-related problems and were more likely to have had treatment for an alcohol problem. These items together explained 22.1% of the variance in group classification (p [is less than] .001). Similar demographic characteristics along with ASPD, evidence for more severe stimulant-related problems and a history of regular smoking predicted concomitant alcoholism among stimulant dependent people, although fewer variables entered the final equation and they accounted for a lower proportion (17.6%; p [is less than] .001) of the variance. Within the combined group of subjects with concomitant disorders (Groups 1 and 2), Group 1 membership (alcohol before stimulant dependence) was associated with more alcohol- and stimulant-related adverse events, with an equation that explained 7.3% of the variance (p [is less than] .001).
The analyses reported in Tables 1-3 were repeated on subgroups of subjects to control for factors that might influence [he severity of substance use disorders. These results were obtained by limiting the analyses, in turn, to: non-ASPD subjects; men; women; probands (i.e., a group of unrelated individuals with more severe disorders); nonprobands; those without stimulant abuse in Group 3 (alcohol dependence only); and those without alcohol abuse in Group 4 (stimulant dependence only). In addition, repeated analyses were performed after excluding subjects who had dependence on drags other than alcohol, stimulants or nicotine. The data were, finally, evaluated separately for individuals dependent on amphetamines and for those dependent on cocaine. The major group differences reported in the tables were supported in each of these separate evaluations, and most maintained statistical significance (data not shown). A noteworthy finding is that, while a high percentage of the subjects in Groups 1 and 2 were probands, the subanalyses on nonprobands revealed similar univariate and multivariate results to those for the entire population. In addition, the multivariate results for these subsamples also closely resembled those for the emir. e sample; most of the predictors maintained statistical significance and the direction remained the same for those that did not.
Discussion
These analyses demonstrate that subjects with concomitant alcohol and stimulant dependence had lower levels of life stability and more severe alcohol and stimulant-related problems than those with dependence on either drug alone. In addition, men and women who had developed alcohol dependence before stimulant dependence had the most intense clinical patterns. These findings remained robust even after controlling for factors that can influence the severity of substance use disorders (e.g., the presence of ASPD). The data are consistent with other reports that have found more substance-related adverse events (Carroll et al., 1993b; Higgins et al., 1994; Miller et al., 1993; Schmitz et al., 1997) and poorer outcomes (Brower et al., 1994; Miller et al., 1990) in people with concomitant alcohol and stimulant dependence.
The data also reveal that alcoholic subjects had high rates of alcoholic relatives, while the groups with stimulant dependence were more likely to have family histories of stimulant dependence. In addition, stimulant dependent subjects reported high familial rates of marijuana dependence, although no group differences were seen for the family histories of sedative and opiate dependence or regular smoking. Thus, these data are consistent with other articles that have generally supported drug-specific heritability (Bierut et al., 1998; Merikangas et al., 1998; Tsuang et al., 1998).
The conclusion that individuals with the onset of alcohol dependence before stimulant dependence had the most severe clinical characteristics deserves additional comment. This result might be related to the fact that this group had the earliest onset of dependence on any substance, as earlier onsets have been reported to be associated with a more severe clinical course (Irwin et al., 1990). In any event, this finding emphasizes the need for additional studies to better understand the clinical course for individuals with both dependencies.
These data are also consistent with a pattern of mood disorders that has been described in several recent studies. The groups with concomitant alcohol and stimulant dependence endorsed the highest rates of substance-induced mood disorders, whereas no group differences were found for independent major depression. Other studies have consistently demonstrated the highest rates of substance-induced mood syndromes for groups with the most intense clinical patterns of dependence on alcohol and/or drugs (Raimo et al., 1999; Schuckit et al., 1997a).
As with any study, the conclusions must be viewed in light of the methods used. First, although all subjects and their relatives received personal, face-to-face interviews, these cross-sectional and retrospective data provide limited information about future clinical course. Second, because of the way original subjects are recruited for the COGA project, the group with stimulant dependence alone contained no probands. However, the major conclusions held for subanalyses that excluded probands from all groups. Third, one of the COGA exclusion criteria is recent, repeated intravenous drug use, which could have biased the sample toward less functionally impaired individuals. Last, while the COGA study places an emphasis on perhaps the most salient personality disorder (ASPD) that is related to the clinical course of substance use disorders, other personality traits and disorders have also been associated with the severity of substance problems (Cloninger et al., 1988; Links et al., 1995).
Individuals with concomitant alcohol and stimulant dependence had more severe clinical characteristics than those with dependence on either substance alone, and alcohol dependence and stimulant dependence were found to breed tree in families of this understudied population. These conclusions provide a better understanding of the substance use patterns and problems in people with both alcohol and stimulant dependence, and contribute to the knowledge of the familial nature of these disorders.
References
AMERICAN PSYCHIATRIC ASSOCIATION. Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R), Washington, DC, 1987.
BIERUT, L.J., DINWIDDIE, S.H., BEGLEITER, H., CROWE, R.R., HESSELBROCK, V., NURNBERGER, J.I., JR., PORJESZ, B., SCHUCKIT, M.A. AND REICH, T. Familial transmission of substance dependence: Alcohol, marijuana, cocaine, and habitual smoking: A report from the Collaborative Study on the Genetics of Alcoholism. Arch. Gen. Psychiat. 55: 982-988, 1998.
BROWER, K. J., BLOW, F.C., HILL, E. M. AND MUDD, S.A. Treatment outcome of alcoholics with and without cocaine disorders. Alcsm Clin. Exp. Res. 18: 734-739, 1994.
BUCHOLZ, K.K., CADORET, R., CLONINGER, C.R., DINWIDDIE, S.H., HESSELBROCK, V.M., NURNBERGER, J. I., JR., REICH, T., SCHMIDT, I. AND SCHUCKIT, M.A. A new, semi-structured psychiatric interview for use in genetic linkage studies: A report on the reliability of the SSAGA. J. Stud. Alcohol 55: 149-158, 1994.
CARROLL, K.M., POWER, M.E, BRYANT, K. AND ROUNSAVILLE, B.J. One-year follow-up status of treatment-seeking cocaine abusers: Psychopathology and dependence severity as predictors of outcome. J. Nerv. Ment. Dis. 181: 71-79, 1993a.
CARROLL, K.M., ROUNSAVILLE, B.J. AND BRYANT, K.J. Alcoholism in treatment-seeking cocaine abusers: Clinical and prognostic significance. J. Stud. Alcohol 54: 199-208, 1993b.
CLONINGER, C.R., SIGVARDSSON, S. AND BOHMAN, M. Childhood personality predicts alcohol abuse in young adults. Alcsm Clin. Exp. Res. 12: 494-505, 1988.
DENISON, M.E., PAREDES, A. AND BOOTH, J.B. Alcohol and cocaine interactions and aggressive behaviors. In: GALANTER, M. (Ed.) Recent Developments in Alcoholism, Vol. 13: Alcohol and Violence, New York: Plenum Press, 1997, pp. 283-303.
ENDICOTT, J. AND SPITZER, R.L. A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia. Arch. Gen. Psychiat. 35: 837-844, 1978.
FEIGHNER, J.P., ROBINS, E., GUZE, S. B., WOODRUFF R.A., JR., WINOKUR, G. AND MUNOZ, R. Diagnostic criteria for use in psychiatric research. Arch. Gen. Psychiat. 26: 57-63, 1972.
GRANT, B.F. AND HARFORD, T.C. Concurrent and simultaneous use of alcohol with cocaine: Results of national survey. Drug Alcohol Depend. 25: 97-104, 1990.
HELZER, J.E. AND PRYZBECK, T.R. The co-occurrence of alcoholism with other psychiatric disorders in the general population and its impact on treatment. J. Stud. Alcohol 49: 219-224, 1988.
HELZER, J.E. AND ROBINS, L.N. The Diagnostic Interview Schedule: Its development, evolution, and use. Social Psychiat. Psychiatric Epidemiol. 23: 6-16, 1988.
HESSELBROCK, M., EASTON, C., BUCHOLZ, K.K., SCHUCKIT, M. AND HESSELBROCK, V. A validity study of the SSAGA: A comparison with the SCAN. Addiction 94: 1361-1370, 1999.
HESSELBROCK, M.N. AND HESSELBROCK, V.M. Relationship of family history,
antisocial personality disorder and personality traits in young men at risk for alcoholism. J. Stud. Alcohol 53: 619-625, 1992.
HESSELBROCK, M.N., HESSELBROCK, V.M., BABOR, T.F., STABENAU, J.R., MEYER, R.E. AND WEIDENMAN, M. Antisocial behavior, psychopathology, and problem drinking in the natural history of alcoholism. In: GOODWIN, D.W., VAN DUSEN, K.T. AND MEDNICK, S.A. (Eds.) Longitudinal Research of Alcoholism, Boston: Kluwer-Nijhoff, 1984, pp. 197-214.
HESSELBROCK, V.M., HESSELBROCK, M.N. AND STABENAU, J.R. Alcoholism in men patients subtyped by family history and antisocial personality disorder. J. Stud. Alcohol 46: 59-64, 1985.
HIGGINS, S.T., BUDNEY, A.J., BICKEL, W.K., FOERG, F.E. AND BADGER, G.J. Alcohol dependence and simultaneous cocaine and alcohol use in cocaine-dependent patients. J. Addict. Dis. 13: 177-189, 1994.
IRWIN, M., SCHUCKIT, M. AND SMITH, T.L. Clinical importance of age at onset in type 1 and type 2 primary alcoholics. Arch. Gen. Psychiat. 47: 320-324, 1990.
JATLOW, P., ELSWORTH, J.D., BRADBERRY, C.W., WINGER, G., TAYLOR, J.R., RUSSELL, R. AND ROTH, R.H. Cocaethylene: A neuropharmacologically active metabolite associated with concurrent cocaine-ethanol ingestion. Life Sci. 48: 1787-1794, 1991.
KESSLER, R.C., CRUM, R.M., WARNER, L.A., NELSON, C.B., SCHULENBERG, J. AND ANTHONY, J.C. Lifetime co-occurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey. Arch. Gen. Psychiat. 54: 313-321, 1997.
LINKS, P.S., HESLEGRAVE, R.J., MITTON, J.E., VAN REEKUM, R. AND PATRICK, J. Borderline psychopathology and recurrences of clinical disorders. J. Nerv. Ment. Dis. 183: 582-586, 1995.
MCCANCE-KATZ, E.F., PRICE, L.H., MCDOUGLE, C.J., KOSTEN, T.R., BLACK, J.E. AND JATLOW, P.I. Concurrent cocaine-ethanol ingestion in humans: Pharmacology, physiology, behavior, and the role of cocaethylene. Psychopharmacology 111: 39-46, 1993.
MENDELSON, J., JONES, R.T., UPTON, R. AND JACOB, P., 3RD. Methamphetamine and ethanol interactions in humans. Clin. Pharmacol. Therapeut. 57: 559-568, 1995.
MERIKANGAS, K.R., STOLAR, M., STEVENS, D.E., GOULET, J., PREISIG, M.A., FENTON, B., ZHANG, H., O'MALLEY, S.S. AND ROUNSAVILLE, B.J. Familial transmission of substance use disorders. Arch. Gen. Psychiat. 55: 973-979, 1998.
MILLER, N.S., MILLMAN, R.B. AND KESKINEN, S. Outcome at six and twelve months post inpatient treatment for cocaine and alcohol dependence. Adv. Alcohol Subst. Abuse 9: 101-120, 1990.
MILLER, N.S., SUMMERS, G.L. AND GOLD, M.S. Cocaine dependence: Alcohol and other drug dependence and withdrawal characteristics. J. Addict. Dis. 12: 25-35, 1993.
NICOLAS, J.M., RUBIN, E. AND THOMAS, A.P. Ethanol and cocaine cause additive inhibitory effects on the calcium transients and contraction in single cardiomyocytes. Alcsm Clin. Exp. Res. 20: 1077-1082, 1996.
RAIMO, E.B., DAEPPEN, J.B., SMITH, T.L., DANKO, G.P. AND SCHUCKIT, MA. Clinical characteristics of alcoholism in alcohol-dependent subjects with and without a history of alcohol treatment. Alcsm Clin. Exp. Res. 23: 1605-1613, 1999.
RAIMO, E.B. AND SCHUCKIT, M.A. Alcohol dependence and mood disorders. Addict. Behav. 23: 933-946, 1998.
RANDALL, T. Cocaine, alcohol mix in body to form even longer lasting, more lethal drug. JAMA 267: 1043-1044, 1992.
REGIER, D.A., 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 Epidemiological Catchment Area (ECA) study. JAMA 264: 2511-2518, 1990.
RICE, J.P., REICH, T., BUCHOLZ, K.K., NEUMAN, R.J., FISHMAN, R., ROCHBERG, N., HESSELBROCK, V.M., NURNBERGER, J.I. JR., SCHUCKIT, M.A. AND BEGLEITER, H. Comparison of direct interview and family history diagnoses of alcohol dependence. Alcsm Clin. Exp. Res. 19: 1018-1023, 1995.
SALLOUM, I.M., DALEY, D.C., CORNELIUS, J.R., KIRISCI, L. AND THASE, M.E. Disproportionate lethality in psychiatric patients with concurrent alcohol and cocaine abuse. Amer. J. Psychiat. 153: 953-955, 1996.
SCHMITZ, J.M., BORDNICK, P.S., KEARNEY, M.L., FULLER, S.M. AND BRECKENRIDGE, J.K. Treatment outcome of cocaine-alcohol dependent patients. Drug Alcohol Depend. 47: 55-61, 1997.
SCHUCKIT, M.A. Drug and Alcohol Abuse: A Clinical Guide to Diagnosis and Treatment, 5th Edition, New York: Plenum Press, 2000.
SCHUCKIT, M.A., SMITH, T.L., DAEPPEN, J.B., ENG, M., LI, T.K., HESSELBROCK, V.M., NURNBERGER, J.I., JR. AND BUCHOLZ, K.K. Clinical relevance of the distinction between alcohol dependence with and without a physiological component. Amer. J. Psychiat. 155: 733-740, 1998.
SCHUCKIT, M.A., TIPP, J.E., BERGMAN, M., REICH, W., HESSELBROCK, V.M. AND SMITH, T.L. Comparison of induced and independent major depressive disorders in 2,945 alcoholics. Amer. J. Psychiat. 154: 948-957, 1997a.
SCHUCKIT, M.A., TIPP, J.E., BUCHOLZ, K.K., NURNBERGER, J.I., JR., HESSELBROCK, V.M., CROWE, R.R. AND KRAMER, J. The life-time rates of three major mood disorders and four major anxiety disorders in alcoholics and controls. Addiction 92: 1289-1304, 1997b.
SCHUCKIT, M.A., TIPP, J.E., SMITH, T.L. AND BUCHOLZ, K.K. Periods of abstinence following the onset of alcohol dependence in 1,853 men and women. J. Stud. Alcohol 58: 581-589, 1997c.
SUBSTANCE ABUSE AND MENTAL HEALTH SERVICES ADMINISTRATION. Preliminary Results from the 1997 National Household Survey on Drug Abuse, DHHS Publication No. (SMA) 98-3251, Rockville, MD: Office of Applied Studies, 1998.
TSUANG, M.T., LYONS, M.J., MEYER, J.M., DOYLE, T., EISEN, S.A., GOLDBERG, J., TRUE, W., LIN, N., TOOMEY, R. AND EAVES, L. Co-occurrence of abuse of different drugs in men: The role of drug-specific and shared vulnerabilities. Arch. Gen. Psychiat. 55: 967-972, 1998.
ERIC B. RAIMO, M.D., TOM L. SMITH, PH.D., GEORGE P. DANKO, PH.D., KATHLEEN K. BUCHOLZ, PH.D.,([dagger]) AND MARC A. SCHUCKIT, M.D.
Department of Psychiatry, University of California, San Diego & San Diego Veterans Affairs Medical Center, 3350 La Jolla Village Drive, 116A, San Diego, California 92161
Received: November 1, 1999. Revision: January 21, 2000.
(*) The Collaborative Study on the Genetics of Alcoholism (H. Begleiter, State University of New York, Health Sciences Center at Brooklyn, principal investigator; T. Reich, Washington University, co-principal investigator) includes six different centers in which data collection takes place. The six sites, with principal investigator and co-investigators listed respectively for each, are: Indiana University (J.I. Nurnberger, Jr., T.-K. Li, P.M. Conneally, H. Edenberg); University of Iowa (R. Crowe, S. Kuperman); University of California at San Diego and Scripps Institute (M.A. Schuckit, F. Bloom); University of Connecticut (V.M. Hesselbrock); State University of New York, Health Sciences Center at Brooklyn (H. Begleiter, B. Porjesz); Washington University in St. Louis (T. Reich, C.R. Cloninger, J. Rice); Howard University (R. Taylor); Rutgers University (J. Tischfield); and Southwest Foundation (L. Almasy). This national collaborative study is supported by National Institutes of Health grant U10AA08403 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). This research was also supported by NIAAA grant 05526, National Institute of Mental Health grant 5T32 MH18399 and by the Veterans Affairs Research Service.
([dagger]) Kathleen K. Bucholz is with the Department of Psychiatry, Washington University, St. Louis, MO.
COPYRIGHT 2000 Alcohol Research Documentation, Inc.
