Skip to main content
PMC home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2010 Jan 1.
Published in final edited form as: Drug Alcohol Depend. 2008 Sep 4;99(1-3):193–203. doi: 10.1016/j.drugalcdep.2008.07.004

Association of Psychiatric and Substance Use Disorder Comorbidity with Cocaine Dependence Severity and Treatment Utilization in Cocaine-Dependent Individuals

Julian D Ford 1, Joel Gelernter 2, Judith S DeVoe 1, Wanli Zhang 1, Roger D Weiss 3, Kathleen Brady 1, Lindsay Farrer 5, Henry R Kranzler 1,*
PMCID: PMC2745327  NIHMSID: NIHMS90554  PMID: 18775607

Abstract

The relations among psychiatric and substance dependence disorders and treatment utilization are of clinical interest both for their clinical management and for health services. We examined these relations using six self-reported indices of cocaine dependence severity and three self-reported measures of treatment utilization and self-help group participation for cocaine dependence. The sample consisted of dyads: namely, a cocaine dependent adult proband (N=449) and a cocaine dependent sibling (N=449). Psychiatric and substance use disorders were assessed with the Semi-structured Assessment for Drug Dependence and Alcoholism. We controlled for the nesting within families of proband-sibling dyads and for demographic features using generalized estimating equation linear and logistic regression analyses. We found that psychiatric disorders were associated with an increased likelihood of cocaine dependence treatment or self-help group participation, but with only one of six indices of cocaine dependence severity. Bipolar disorder and antisocial personality disorder were associated with greater past heavy cocaine use, and with utilizing self-help but not treatment. Major depressive disorder and posttraumatic stress disorder were associated with treatment utilization and overall services utilization, respectively. The presence of other substance use disorders (SUDs) was the strongest correlate of cocaine dependence severity. Results suggest that co-occurring substance dependence and psychiatric disorders warrant attention in cocaine dependence assessment, treatment, and self-help.

Keywords: Cocaine, Dependence, Psychiatric, Comorbidity, Services Utilization

1. Introduction

Cocaine use is widespread, affecting as many as one in six adults across a wide range of socioeconomic strata and ethnocultural groups in the United States (Shaffer and Eber, 2002) and internationally (http://www.who.int/substance_abuse/facts/cocaine/en/ accessed May 15, 2008). Cocaine dependence, while less prevalent, may affect as many as 3% of the adult U.S. population (Shaffer and Eber, 2002) and is associated with substantial social, vocational, and medical impairment and healthcare and legal costs to the individual and society.

Cocaine use often is associated with psychiatric comorbidity, e.g., antisocial personality disorder (ASPD; 24%), major depressive disorder (MDD; 18%), posttraumatic stress disorder (PTSD; 12%) (Falck et al., 2004), and a threefold risk of panic attacks (O’Brien et al., 2005). Studies have shown that almost half of patients in treatment for a cocaine use disorder may have comorbid ASPD (Carroll et al., 1997), one-third to one-half a history of PTSD (Back et al., 2000; Brady et al., 2004; Mills et al., 2005), and 20% an affective disorder (Carroll et al., 1997). ASPD (Arndt et al., 1994) and depression (Carroll et al., 1997; Ziedonis & Kosten, 1991) have been shown to be associated with poorer response to addiction or psychiatric treatment by cocaine abusing or dependent adults. PTSD similarly has been shown to be associated with poorer response to addiction treatment by opiate dependent (Hien et al., 2000) and mixed substance use disorder (Ouimette et al., 2003) patients, including higher rates of cocaine use (Hien et al., 2000).

In addition to frequently being comorbid with substance use disorders (SUDs), psychiatric disorders may be associated with an increased severity of these disorders (Cacciola et al., 2001; Compton et al., 2005b; Mills et al., 2007; Skinstad and Swain, 2001; Watkins et al., 2004). Further, substance dependence disorders may be associated with increased severity of anxiety disorders such as agoraphobia and PTSD (Grant et al., 2006), major depressive disorder (MDD; Kandel et al., 2001; Kessler et al., 2005; Kessler et al., 1994; Regier et al., 1990), bipolar disorder (Cassidy et al., 2001; Kessler et al., 1994; Regier et al., 1990), and Cluster B personality disorders, especially antisocial personality disorder (ASPD; Kandel et al., 2001).

However, the relationship between psychiatric and SUD comorbidity and illness severity and impairment is not necessarily consistent across domains of illness severity and impairment and may be the result of multiple concurrent psychiatric disorders rather than a single comorbid psychiatric disorder. For example, Mills and colleagues (2007) reported that opiate dependent treatment recipients with PTSD (compared to those who did not meet criteria for PTSD) were less likely to be employed, more impaired physically and psychosocially, and more likely to have a history of overdose or suicidality, but they also reported using heroin less frequently in the past month, reduce heroin use as successfully, and did not report higher levels of other drug use. Participants with PTSD in the Mills et al. (2007) study also were 1.6–2.5 times more likely than those without PTSD to meet criteria for major depression, ASPD, and borderline personality disorder as well as PTSD. Another study of opiate dependent treatment recipients found that PTSD was associated with a longer history of drug use and more severe psychiatric symptoms than patients not diagnosed with PTSD, but comparable reductions in heroin, cocaine, and alcohol use and better treatment attendance and retention (Trafton et al., 2006).

Given the serious morbidity and costs of cocaine dependence, this study was designed to examine the relationship to severity of cocaine dependence of both specific comorbid psychiatric disorders and the added burden that may occur when multiple comorbid psychiatric disorders are present. Although the study’s focus was on psychiatric comorbidity and cocaine dependence, the presence of other substance dependence diagnoses also was assessed. Symptom severity and psychosocial impairment tend to be heightened with polysubstance dependence, as well as the risk of exposure to traumatic stressors, PTSD, and other psychiatric morbidity (Salgado et al., 2007). Therefore, it is important to distinguish between the effects of psychiatric versus SUD comorbidity when examining potential correlates of cocaine dependence severity.

The rationale for focusing on the severity of cocaine dependence is that there is a nascent research literature showing potential relationships between psychiatric or SUD comorbidity and SUD severity. MDD was associated with risky behavior and cocaine use in a community study (Wild et al.,2005). In a clinical sample, bipolar disorder co-occurred commonly with substance use disorder, with an increased likelihood of mixed and rapid cycling mania, a chronic clinical course, medical disorders including liver disease, and both suicide attempts and completed suicides (Krishnan, 2005). PTSD has been associated with suicide attempts; co-occurring mood, anxiety, and personality disorder; overall psychiatric morbidity; family and social problems; marital violence; self-reported employment problems; and the number of episodes of substance abuse treatment--in both treatment samples (Back et al., 2000; Tarrier and Sommerfield, 2003; Wasserman et al., 1997) and non-treatment samples (Parrott et al., 2003; Thevos et al., 1993). ASPD also has been shown to be related to the severity of alcohol, psychiatric, and legal problems and risky sexual behavior among cocaine-abusing research treatment recipients (Ladd and Petry, 2003) and of SUD symptoms in community samples (Goldstein et al., 2007).

However, no study has examined the relationship of psychiatric and SUD comorbidity specifically with cocaine dependence severity, nor across a range of psychiatric disorders and a range of indices of impairment. Studies show evidence of more social, vocational, and legal problems when psychiatric disorders co-occur with cocaine dependence than with alcohol dependence (Brady et al., 2004; Thevos et al., 1993), suggesting that psychiatric morbidity may be particularly related to exacerbated symptom severity or impairment in cocaine dependence. In the present study, cocaine dependency severity was operationalized by specific indices that are consistent with the DSM-IV (American Psychiatric Association, 1994) criteria for substance dependence and psychometric measures of dependence severity (Miele et al., 2000), i.e., the number of withdrawal symptoms and of other dependence symptoms (Sofuoglu et al., 2003). In addition, additional measures were used to characterize the increasingly heavy and dangerous use over a long time period that occurs when dependence is severe (i.e., number of days during the period of heaviest cocaine use ever; age of first heavy use of cocaine; history of over-doses). A criterion feature of substance abuse, adverse legal consequences (i.e., arrest related to cocaine use), was included because of the severe impact of involvement in the criminal justice system.

A second objective of the present study was to examine the association of psychiatric and SUD comorbidity with the utilization of treatment and self-help for cocaine dependence. The severity of cocaine dependence (Kampman et al., 2004) and mental distress (Dennis et al., 2005) has been associated with SUD treatment outcomes. However, the role of psychiatric comorbidity in the utilization of SUD treatment services has not been well studied (Chassler et al., 2006; Grella et al., 2003; Hansen et al., 2004; Van Ness et al., 2004). Cocaine or alcohol dependence severity at entry to SUD treatment has been shown to be associated with less treatment use in the next six months (Carpenter et al., 2002), but the only study examining psychiatric comorbidity found that PTSD was associated with more treatment use and retention (Trafton et al., 2006). The present study was designed to extend those findings by being the first, to our knowledge, to test the relationship between a range of psychiatric comorbidities and SUD treatment utilization.

Although self-help support program participation has been associated with sustained recovery from SUDs (Staines et al., 2003), few robust predictors of the use of self-help programs have been identified in past studies with individuals having alcohol use disorders (Carpenter et al., 2002; Weiss et al., 2000). Studies of cocaine dependent individuals have shown that the severity of substance dependence is associated with self-help program attendance (Carpenter et al., 2002; Weiss et al., 2000), and suggest that cocaine dependent persons without a religious preference may be inclined to attend self-help programs (Weiss et al., 2000). These studies primarily involved treatment-seeking persons, and have not examined psychiatric diagnoses as a potential correlate of self-help program participation. Therefore, this study also serves as a first test of the relationship of psychiatric comorbidity to SUD self-help support program attendance.

The study’s two hypotheses were that, among cocaine dependent adults, after controlling for the effects of demographics and lifetime history of co-occurring substance dependence diagnoses, a history of one or more psychiatric disorders would be associated with: (1) greater cocaine dependence severity, and (2) a higher likelihood of utilization of cocaine-related treatment and participation in SUD self-help groups. To the extent that psychiatric morbidity is associated with increased cocaine dependence severity (Hypothesis 1), the findings of Carpenter and colleagues (2002) suggest that psychiatric comorbidity may be associated with less treatment use. However, Trafton and colleagues’ (2006) specific finding of increased SUD treatment use by patients with PTSD, along with the generally positive association between psychological distress and SUD self-help participation support the hypothesis of a positive relationship between psychiatric comorbidity and SUD treatment or self-help utilization. The present study also extends the research literature on predictors of SUD treatment or self-help utilization by assessing utilization as a dichotomous variable, i.e., whether treatment or self-help were used at all, rather than the prior studies’ focus on the amount of treatment or self-help utilization. 2.

2. Method

2.1 Participants and Recruitment

The sample was drawn from a cohort of pairs of adult siblings who were cocaine-dependent and recruited to participate in genetic linkage studies of cocaine (Gelernter et al., 2005) or opioid dependence (Gelernter et al., 2006). Probands and siblings were recruited at the University of Connecticut Health Center (Farmington, CT); Yale University School of Medicine (APT Foundation; New Haven, CT); Harvard Medical School (McLean Hospital; Belmont, MA); and the Medical University of South Carolina (Charleston, SC). Informed consent was obtained as approved by each institutional review board and subjects were paid for their participation. A certificate of confidentiality was obtained from the National Institute on Drug Abuse. For the present analysis, probands with cocaine dependence were selected if they had at least one sibling with cocaine dependence. Participants with a clinical diagnosis of schizophrenia or schizoaffective disorder were excluded (Gelernter et al., 2005; Gelernter et al., 2006). A total of 449 proband/sibling pairs were identified. If probands had more than one cocaine dependent full sibling, the sibling closest in age to the proband was selected for the analysis.

The demographic features of the proband and affected sibling samples are shown in Table 1. The average age of probands was 38.6 years (SD=7.4) and 51% were women. The average age of siblings was 38.9 years (SD=7.5), and 48% were women. The majority of subjects (~85%) were not married (i.e., divorced, separated, or widowed). The self-reported ethnic/racial distribution of the proband sample was 45.9% African-American (AA), 34.7% European-American (EA), 13.8% Hispanic, and 5.6% Native American, Pacific Islander or other minority groups. The sibling sample’s self-reported ethnic/racial distribution was comparable but not identical to that of probands (Table 1). Most participants had either entered or attended but not completed high school, and most (63%) were unemployed, disabled, retired, or a student.

Table 1.

Demographics and Lifetime Prevalence of Substance Use and Psychiatric Disorders in a Sample of Cocaine Dependent Probands and Siblings

Full Sample Probands Siblings
Race/Ethnicity
 African-American 412(45.0) 206(45.9) 206(45.9)
 Hispanic 117(13.0) 62(13.8) 55(12.2)
 European-American 314(35.0) 156(34.7) 158(35.2)
 Other 55(6.1) 25(5.6) 30(6.7)
Gender
 Male 451(50.2) 218(48.6) 233(51.9)
 Female 447(49.8) 231(51.4) 216(48.1)
Marital Status
 Married 134 (14.9) 61(13.6) 73(16.3)
 Not Married 764(85.1) 388(86.4) 376(83.7)
Employment Statusa
 Employed 566(66.1) 298(66.2) 268(59.7)
 Not Employed 331(36.9) 150(33.8) 181(40.3)
Age 38.74(7.5) 38.62 (7.4) 38.86(7.5)
Years of Education 11.39(2.10) 11.47(2.03) 11.31(2.17)
Lifetime Diagnoses
Alcohol Dependence 446(49.7) 221(49.2) 225(50.2)
Opioid Dependencea 406(45.3) 226(50.4) 180(40.1)
Cannabis Dependence 268(30.1) 124(27.9) 144(32.3)
Sedative Dependence 78(8.8) 38(8.6) 40(8.9)
Stimulant Dependence 65(7.3) 31(7.0) 34(7.6)
MDD 123(14.4) 52(12.3) 71(16.4)
Bipolar disorder 47(5.4) 23(5.3) 24(5.5)
PTSD 107(12.4) 59(13.6) 48(11.2)
Agoraphobia/ Panic 45(5.3) 22(5.1) 23(5.4)
ASPD 123(14.3) 60(13.9) 63(14.6)
Open in a new tab

Note: N(%) or M(SD) (for Age, Education) are presented. MDD = Major Depressive Disorder; PTSD = Posttraumatic Stress Disorder; ASPD Antisocial Personality Disorder.

a

Chi-square test for difference between proband and sibling sub-samples, p < .05

Psychiatric and substance use disorders were evaluated using the Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA; Pierucci-Lagha et al., 2005; Pierucci-Lagha et al., 2007). The most common lifetime DSM-IV (APA, 1994) psychiatric and substance dependence disorders are shown in Table 1. Combined psychiatric comorbidity was defined as having two or more psychiatric diagnoses. The preponderance of participants with multiple psychiatric disorders had only two such disorders, and therefore additional categories reflecting more extensive psychiatric morbidity could not be analyzed. The proband and sibling sub-samples had a comparable distribution of psychiatric diagnoses: 10–15% had histories of each of MDD, ASPD, and PTSD, while 5% had a history of each of panic disorder and agoraphobia or panic disorder and bipolar disorder.

The proband and sibling sub-samples also had a comparable distribution of lifetime substance dependence disorders—except that more probands reporting opioid dependence histories—with approximately half reporting alcohol or opioid dependence, more than a quarter positive for cannabis dependence, and fewer than 10% positive for dependence on sedatives or stimulants other than cocaine. Cocaine use in the past year by self-report was variable: one third of the sample reported no use; 20% of the sample reported infrequent use, less than once every two weeks on average; 15% of the sample reported using on average approximately once weekly; and a third of the sample reported frequent use, between two times a week on average to several times a day. Thus, about two-thirds of the sample appeared to be in full or partial remission from cocaine dependence, and one-third may still have been cocaine dependent.

2.2 Measures

Based on the limited prior research findings in this area, five psychiatric disorders were selected as potential influences on cocaine dependence severity: MDD, bipolar disorder, PTSD, panic/ agoraphobia, and ASPD. Indices of cocaine dependence severity were selected to reflect the extent of recent and past cocaine use, chronicity of cocaine use (i.e., age of onset), the degree of physiological and psychological addiction (i.e., number of dependence and withdrawal symptoms), and potential for severe harm to the individual (i.e., overdose, arrests).

The SSADDA was administered in a computer-assisted format to obtain lifetime psychiatric diagnoses. The SSADDA has been shown to have good inter-rater reliability (κ = 0.50–0.60, with the exception of bipolar disorder, κ = 0.43) and good-to-excellent retest reliability at an approximately two-week interval (κ = 0.50–0.76, with the exception of MDD, κ = 0.49) for the five index psychiatric diagnoses in this study. The SSADDA had excellent inter-rater reliability for cocaine and opioid dependence (κ = 0.83 and 0.91, respectively) and fair-togood inter-rater reliability for alcohol, cannabis, and stimulant dependence (κ = 0.48–0.66), as well as good-to-excellent retest reliability (κ = 0.66–0.94) for these diagnoses (Pierucci-Lagha et al., 2005, 2007). Although designed based on the specific diagnostic criteria of the American Psychiatric Association’s (1994) DSM-IV for each psychiatric disorder, the validity of the SSADDA for psychiatric disorders and substance dependence disorders has not been established. In addition to using the five psychiatric diagnostic categories as variables, a separate variable was constructed based on the presence of more than one psychiatric disorder (i.e., multiple psychiatric comorbidity), in light of findings from Mills and colleagues (2007).

SSADDA scores used as dependent variables in study analyses included indices selected to represent: (a) severity of cocaine use, and (b) use of treatment or self-help resources for cocaine dependence. Continuous measures of cocaine use severity included: number of days during the period of heaviest cocaine use; age of first heavy use of cocaine; and number of lifetime (a) withdrawal symptoms, and (b) cocaine dependence symptoms excluding withdrawal. Withdrawal and dependence symptoms were separated based on prior evidence that cocaine withdrawal symptoms are associated with more severe dependence (Sofuoglu et al., 2003). Dichotomous measures included history of cocaine overdose or arrest related to cocaine use. Finally, dichotomous scores were used to assess the utilization of services or supports for cocaine dependence, including any receipt of cocaine dependence treatment and any attendance in cocaine dependence self-help support programs.

2.3 Statistical Analyses

Descriptive analyses were conducted to characterize the sample demographically and clinically, and we report data on psychiatric disorders with ≥ 5% prevalence in the sample (Table 1). Based on an examination of the distributions of the cocaine-related and psychosocial impairment variables, all variables were approximately normally distributed. The primary study analyses were generalized estimating equation (GEE) linear and logistic regression analyses conducted to test the effect of psychiatric and substance dependence diagnoses and combined psychiatric comorbidity on cocaine-related impairment and service utilization. GEE is widely used as a method of dealing with correlated data in fitting the generalized linear model (Liang and Zeger, 1986). We used GEE to fit the model to account for the potential dependence among individuals within the same nuclear family. Analyses were conducted on a multivariate basis adjusting for proband versus sibling status, for demographics (i.e., gender, age, race/ethnicity, marital status, education, employment), for a history of other substance dependence diagnoses and multiple other substance dependence diagnoses, and for a history of each psychiatric diagnosis or multiple psychiatric diagnoses.

Each severity or treatment/self-help variable was treated as a dependent variable, and all demographic and diagnostic variables were entered simultaneously as independent variables in each multivariate GEE analysis. When the independent variable was dichotomous and the dependent variable was continuous, the raw mean and standard deviation (M[SD]) of the dependent variable are reported for the sub-group that was negative (labeled “No” in the Table column headers) for each independent variable (i.e., not African-American, unemployed, unmarried, not male; no history of the diagnosis) versus for the sub-group that was positive (labeled “Yes” in the Table column headers) for each independent variable (i.e., African-American, male; employed, married, past history of the diagnosis). When both the independent and dependent variables were dichotomous, the raw proportions of respondents endorsing the dependent variable were compared (and are shown in the two columns at the far right of the Table) for the sub-group that was negative (“No”) for each independent variable (i.e., not African-American, not male; unemployed, unmarried, no history of the diagnosis) versus for the sub-group that was positive for each independent variable (i.e., African-American, male; employed, married, past history of the diagnosis). When both the dependent and independent variables were continuous, the raw correlation between the variables is reported. All statistical tests are based upon adjusted regression coefficients, while the numbers in the Table columns labeled “No” and “Yes” show the raw (unadjusted) Mean (SD) or proportion. Although multiple (10) regression tests were conducted, each with several dependent variables, the exploratory nature of the investigation and the conservative use of multivariate models led to our decision to report findings at the conventional p < 0.05 level rather than using a downward Bonferroni-like adjustment of the p level required for statistical significance.

3. Results

Results of the multivariate GEE analyses are reported in Table 2 for variables reflecting the severity of cocaine dependence, and Table 3 for treatment or self-help participation variables.

Table 2.

Multivariate Demographic, Psychiatric Disorder, and Substance Dependence Disorder Correlates of Cocaine Dependence Severity in a Sample of Cocaine Dependent Probands and Siblings

2a. Continuous Measures of Cocaine Dependence Severity
Independent Variable No1M(SD) Yes1M(SD) Chi-Square Pearson r
Days of Cocaine Use in Heaviest Month of Use
Age 5.48* 0.106
African-American 24.71(7.37) 26.00(6.28) 6.09*
Education 6.60* −0.108
ASPD 25.14(6.96) 25.76(6.81) 5.67*
Bipolar Disorder 25.19(6.97) 25.81(6.45) 4.93*
Opioid Dependence 24.57(7.21) 26.17(6.46) 14.88***
Alcohol Dependence 24.89(7.11) 25.70(6.70) 5.41*
Age of First Heavy Cocaine Use
Age 112.76*** 0.586
Employed 28.51(7.70) 27.28(7.24) 7.07**
Opioid Dependence 28.57(7.31) 27.45(7.82) 11.43***
Number of Lifetime Cocaine Dependence Criteria Excluding Withdrawal
Opioid Dependence 5.05(1.10) 5.22(1.02) 3.86*
Cannabis Dependence 5.03(1.09) 5.34(0.97) 6.73**
Alcohol Dependence 4.90(1.16) 5.36(0.92) 27 43***
Sedative Dependence 5.09(1.08) 5.59(0.78) 4.91*
Number of Lifetime Cocaine Withdrawal Criteria
Gender (Male=Yes) 4.89(2.77) 4.47(2.71) 3.95*
Cannabis Dependence 4.45(2.75) 5.20(2.68) 4.16*
Stimulant Dependence 4.57(2.77) 6.06(2.01) 4.62*
Alcohol Dependence 4.24(2.71) 5.12(2.73) 15.53***
2b. Dichotomous Measures of Cocaine Dependence Severity
No1 Yes1 Chi-Square
Proportion Ever Had Cocaine-Related Overdose
Opioid Dependence 0.094 0.229 7.33**
Proportion Ever Arrested Related to Cocaine Use
Gender (Male = Yes) 0.430 0.570 14.72***
Opioid Dependence 0.462 0.544 6.97**
Cannabis Dependence 0.511 0.466 5.16*
Open in a new tab
1

Mean(Standard Deviation) of the continuous severity indices, or raw proportion of respondents answering positively for the dichotomous severity indices, where No = in the sub-group who were not African-American, employed, married, or male or did not have the index diagnosis; Yes = in the sub-group that was African-American, employed, married, male, or had the index diagnosis. Note: Results are adjusted for proband/sibling status. Bold numbers are the larger proportion for each comparison of “No” v. “Yes” sub-groups; ASPD=Antisocial Personality Disorder.

*

p < .05

**

p < .01

***

p < .001

Table 3.

Multivariate Demographic, Psychiatric Disorder, and Substance Dependence Disorder Correlates of Utilization of Cocaine Dependence-related Treatment or Self-help Services

Independent Variable No1 Yes1 Chi-Square
Proportion of Participants Who were Ever in Cocaine Dependence Treatment or Self-Help
MDD 0.623 0.650 9.28**
PTSD 0.620 0.674 7 74**
ASPD 0.611 0.712 15.10***
Bipolar Disorder 0.624 0.643 7.62**
Alcohol Dependence 0.587 0.670 9.23**
Proportion of Participants Who were Ever in Cocaine Dependence Treatment
MDD 0.278 0.357 4.96*
Alcohol Dependence 0.248 0.349 4.45*
Proportion of Participants Who were Ever in Cocaine Dependence Self-Help
African-American 0.548 0.658 4.72*
ASPD 0.587 0.659 5.88*
Bipolar Disorder 0.592 0.681 5.26*
Alcohol Dependence 0.567 0.632 7.70**
Sedative Dependence 0.593 0.641 4.50*
Open in a new tab
1

No = the raw proportion of respondents who were not African-American or did not have the index diagnosis and received treatment or self-help; Yes = the raw proportion of respondents who were African-American or had the index diagnosis and received treatment or self-help Note: Results are adjusted for proband/sibling status. Bold numbers are the larger proportion receiving cocaine dependence treatment or self-help for each comparison of the “Yes” v. “No” sub-groups. MDD=major depressive disorder; PTSD=posttraumatic stress disorder, ASPD=antisocial personality disorder.

*

p < .05

**

p < .01

***

p < .001

3.1 Severity of Cocaine Dependence

For the continuous variables reflecting severity of cocaine dependence, more days of cocaine use in the period of heaviest use was associated with older age; less education; being African-American; and a history of bipolar disorder, ASPD, and alcohol or opioid dependence (Table 2). Later age of first heavy cocaine use was associated with being older and unemployed, and with the absence of past opioid dependence. A greater number of lifetime cocaine dependence criteria (excluding withdrawal symptoms) was associated with a history of opioid, cannabis, alcohol, or sedative dependence. A greater number of lifetime cocaine withdrawal symptoms was associated with being female and with a history of cannabis, alcohol, or stimulant dependence.

Of the dichotomous variables reflecting cocaine dependence severity, past cocaine-related overdose was associated only with a history of opioid dependence. Past arrest for cocaine-related crimes was associated with male gender, a history of opioid dependence and the absence of a history of cannabis dependence.

3.2 Utilization of Treatment and Self-Help for Cocaine Dependence

Use of either treatment or self-help support programs for cocaine dependence was related to a history of MDD, PTSD, ASPD, bipolar disorder, and alcohol dependence (Table 3). Utilization of cocaine dependence treatment specifically was associated with a history of MDD and alcohol dependence. Self-help program attendance was associated with a history of ASPD, bipolar disorder, and alcohol or sedative dependence, as well as African-American ethnicity.

4. Discussion

In this sample of cocaine dependent adults who were recruited as sibling pairs for a genetics study, contrary to Hypothesis 1, psychiatric comorbidity was associated increased severity of cocaine dependence on only one of six cocaine dependence severity indices: “Days of Use in the Heaviest Period of Use.” However, consistent with Hypothesis 2, several psychiatric disorders were associated with an increased likelihood of participation in cocaine dependence treatment or self-help programs. These findings were obtained after controlling for any non-independence of data from the proband and sibling sub-samples, and for demographics and history of other substance dependence diagnoses. SUD comorbidity was the most consistent correlate of cocaine dependence severity, though the direction of the relationship varied depending on the specific SUD and index of cocaine dependence severity. African-American, male, less educated, unemployed, or unmarried participants tended to report higher degrees of cocaine dependence severity, but these demographic factors were unrelated to use of treatment or self-help programs for cocaine dependence, except that African-Americans were more likely than others to report having attended self-help programs.

4.1 Hypothesis One: Relationship of Psychiatric Comorbidity with Cocaine Dependence Severity

Bipolar disorder and ASPD were the only psychiatric disorders associated with any index of cocaine dependence severity. The finding that both were associated with more days of cocaine use during the period of heaviest cocaine use suggests that severe Axis I or Axis II morbidity may exacerbate cocaine use during heavy periods of use by cocaine dependent individuals. This findings is consistent with recommendations that ASPD (Compton et al., 2005a) and bipolar disorder (Weiss et al., 2007) be carefully assessed in cocaine dependent persons. This has treatment implications, since patients with comorbid ASPD and cocaine dependence were more likely to be abstinent from cocaine immediately after treatment and at six-month and one-year follow-up if they received a contingency management intervention in combination with methadone maintenance than if they received methadone maintenance alone (Messina et al., 2003). The need for differential treatment based on ASPD comorbidity was suggested by findings that cognitive behavior therapy was not effective in cocaine dependent patients with comorbid ASPD but was more effective than contingency management with non-ASPD cocaine dependent patients (Messina et al., 2003).

The finding that bipolar disorder also was associated with more days of use in the period of heaviest cocaine use also suggests that bipolar disorder should be carefully assessed with cocaine dependent individuals. With comorbid cocaine dependence and bipolar disorder, targeted psychotherapy has been found to be effective (Weiss et al., 2007), and open-label lamotrigine has shown promising results (Brown et al., 2006). Thus, identifying cocaine dependent persons bipolar disorder comorbidity also may lead to enhanced treatment planning and outcomes.

There are several potential explanations for the lack of association of psychiatric disorders with most of the cocaine dependence severity indices examined here. First, the most obvious explanation is that there is no relationship—or at most a circumscribed relationship— between psychiatric disorders and the severity of cocaine dependence. Prior studies have shown a mixed pattern of results, often finding that psychiatric disorders are associated with severity of or impairment due to SUDs on some indices (e.g., employment problems, suicide risk) but not on others (e.g., response to treatment) (Ladd & Petry, 2003; Mills et al., 2007; Trafton et al., 2006; Wild et al., 2005). SUD severity in particular has been quite variably related to psychiatric comorbidity, and thus the present findings tend to support the view that psychiatric comorbidity should not be assumed to lead to more severe cocaine dependence.

However, the null finding may be an artifact of statistical collinearity. MDD, bipolar disorder (Skinstad and Swain, 2001), PTSD, panic/agoraphobia disorder, and ASPD (Markon and Krueger, 2005) frequently are comorbid with most of the substance dependence diagnoses assessed in this study. Thus, the strong relationship of those other substance dependence diagnoses with cocaine dependence may have obscured the relationship of ASPD or bipolar disorder with cocaine dependence severity. The finding in previous studies of a relationship between psychiatric morbidity (e.g., PTSD; Parrott et al., 2003) and increased substance dependence severity or impairment was evident in unadjusted bivariate analyses (results not reported here but available from the first author), in which each psychiatric disorder assessed in this study was significantly associated with at least one (and usually several) indices of cocaine dependence severity. This suggests that research may be needed to determine where indirect relationships link psychiatric and substance dependence disorders with cocaine dependence severity (e.g., using structural equation modeling). For example, dependence on substances (e.g., alcohol, cannabis, opioids) that are often used to self-medicate PTSD-related anxiety (Tarrier and Sommerfield, 2003) could mediate a relationship between PTSD and cocaine dependence severity that was not detected in the present study’s multivariate regression models.

A third possible explanation for the null relationship between psychiatric morbidity and cocaine dependence severity is that the relatively low self-reported levels of recent cocaine use by two-thirds of the sample suggest that this non-clinical sample is comprised primarily of individuals in recovery from cocaine dependence, with a sub-group still dependent. The finding that almost two-thirds have been in self-help support programs and one-third in treatment is consistent with this view, suggesting that a majority of study participants have been able to get help for their cocaine dependence. For the participants currently in remission, their self-reports of cocaine dependence severity are not only retrospective but may involve a gap of several years, and thus may be insensitive to potential exacerbating factors such as psychiatric disorders. The fact that psychiatric morbidity was assessed lifetime rather than currently raises the possibility that the psychiatric disorders also may have improved or been in remission. Thus, this sample may have under-represented the sub-group of actively cocaine dependent persons with current psychiatric illnesses, and it is possible that these are the cocaine dependent adults for whom psychiatric morbidity may have the greatest impact on cocaine dependence severity.

Finally, it is possible that respondents with psychiatric disorders received mental health treatment, which unfortunately was not assessed by the SSADDA. Mental health treatment could indirectly reduce the severity of cocaine dependence by enhancing the individual’s functioning and emotional and behavioral regulation, as well as potentially leading to the identification of cocaine dependence and participation in substance dependence treatment or self-help. The finding that four of the five psychiatric disorders were associated with participation in either treatment or self-help supports the possibility that psychiatric disorders may lead to individuals receiving help for cocaine dependence and thus indirectly reduce cocaine dependence severity.

4.2 Hypothesis Two: Relationship of Psychiatric Morbidity with Treatment/Self-Help Participation

Consistent with Hypothesis 2, psychiatric morbidity was positively related to treatment utilization (in the case of MDD). MDD, although unrelated to severity of cocaine dependence, was associated with the receipt of cocaine dependence treatment. The difference between this finding and those of Carpenter et al. (2002), who found that substance dependence severity at treatment entry was related to less treatment utilization, may be explained in several ways. First, psychiatric morbidity and cocaine dependence severity were not related in the present findings. Second, participants were not treatment seeking. Third, the current study’s findings are retrospective, in contrast to the prospective design in Carpenter et al. (2002).

Depression may either pre-exist and exacerbate cocaine dependence (“independent depression”), or be a sequela of cocaine-related psychobiological dysregulation (“substance induced depression”) (Leventhal et al., 2006). Cocaine dependent persons also may have trouble with emotion regulation soon after abstinence (Fox et al., 2007), and often are depressed when entering treatment (Carroll et al., 2003). Thus, depression may lead cocaine dependent individuals to seek or be referred for cocaine dependence treatment even though it does not necessarily increase the severity of the dependence per se. Correspondingly, pharmacotherapy for depression may reduce potential contributing factors to cocaine use (e.g., craving ,euphoria), but it has not been shown to reduce cocaine use (Nunes et al., 1995; Schmitz et al., 2001; Ziedonis and Kosten, 1991). Whether depression increases the risk of cocaine dependence, as has been shown for alcohol dependence (Kuo et al., 2006), remains to be investigated.

Also consistent with Hypothesis 2, psychiatric morbidity was positively associated with the likelihood of self-help program participation. Specifically, ASPD and bipolar disorder, although unrelated to cocaine dependence treatment utilization, were positively related to self-help participation. The relationship of both bipolar disorder and ASPD with one index of cocaine dependence severity—the extent of use in the period of heaviest cocaine use—suggests that heavy cocaine use may be a link between these disorders and self-help participation. However, individuals with comorbid cocaine dependence and ASPD or bipolar disorder may not be identified (or self-identify) as being in need of cocaine dependence treatment. Thus, self-help may be a means to obtain support for sobriety in relation to cocaine use that may be more acceptable, or more often recommended or required, for cocaine dependent individuals who also have ASPD or bipolar disorder. Given the initial evidence of efficacy of psychological treatments for comorbid cocaine dependence and bipolar disorder or ASPD, it may be important to encourage cocaine dependence self-help programs to provide educational information or materials about evidence-based treatment options for comorbid cocaine dependence and ASPD or bipolar disorder. However, caution is suggested in relation to pharmacotherapy of comorbid SUD and ASPD, based on the finding that antidepressant pharmacotherapy was beneficial only with cocaine dependent adults who did not have comorbid ASPD diagnoses (Arndt et al., 1994).

PTSD, although also unrelated to cocaine dependence severity, was the only anxiety disorder that was associated with an increased likelihood of having received cocaine dependence treatment or participated in cocaine dependence self-help groups. Comorbid PTSD is associated with poorer treatment outcomes than cocaine dependence without PTSD across a variety of measures (Najavits et al., 2007). Pharmacotherapy has not been evaluated for comorbid cocaine dependence and PTSD, but several psychotherapy models have been developed and one— Seeking Safety (Najavits et al., 2006)—has shown evidence of efficacy in several open and randomized clinical trials (Schafer and Najavits, 2007).

Multiple psychiatric comorbidity was not associated with cocaine dependence treatment or self-help participation, in contrast to prior findings (Bruce et al., 2005). This null finding may reflect a ceiling effect, such that the presence of even a single psychiatric disorder may be sufficient to account for increased utilization. Alternately, cocaine dependent persons with multiple psychiatric disorders may preferentially seek mental health services.

4.3 Co-Occurring Substance Use Disorders and Cocaine Dependence Severity and Services

The multivariate findings consistently showed that a history of other substance dependence diagnoses was strongly related to the indices of cocaine dependence severity and both treatment and self-help participation. Consistent with prior studies’ findings, opioid dependence was associated with past heavy cocaine use, lifetime dependence severity, past risky behaviors (i.e., overdose, arrests), and earlier age of onset of heavy cocaine use (Galea et al., 2006; Lynskey et al., 2004). Prior studies have also shown cocaine dependence to be associated with more severe opioid dependence (Bandettini Di Poggio et al., 2006), but this is the first to show that opioid dependence is associated with more severe cocaine dependence. The inverse relationship of opioid dependence suggests that heavy use of cocaine and opioids may not occur simultaneously, with each drug predominant at different times depending upon environmental conditions or the trajectory of the dependence syndrome and the role of self-medication.

Alcohol dependence also was associated with heavy past cocaine use and lifetime dependence severity, as well as lifetime withdrawal severity--consistent with prior findings of more severe medical (Salloum et al., 2004) and psychosocial problems (Flannery et al., 2004) among individuals with comorbid alcohol and cocaine dependence. Also, alcohol dependence was associated with the use of treatment or self-help for cocaine dependence. However, co-occurring alcohol and cocaine dependence may be less amenable to change through treatment or self-help programs than cocaine dependence alone (Schmitz et al., 2004) or alcohol dependence alone (Flannery et al., 2004). The increased cocaine dependence severity associated with co-occurring alcohol dependence may lead to treatment seeking and self-help participation, while also reducing cocaine dependent persons’ responsiveness to treatment or self-help services.

Sedative use disorders have been associated with increased cocaine dependence severity (Chutuape et al., 1997), consistent with the present study’s finding, but not with other indices of cocaine dependence severity. Sedative dependence was prevalent among alcohol dependent persons (Schuckit et al., 2002); thus any possible relationship between sedative dependence and other indices of cocaine dependence severity may have been obscured by the collinear effect of alcohol dependence. Sedative use was unrelated to treatment utilization but was positively associated with cocaine dependence self-help participation. Co-occurring sedative and cocaine use has been associated with poorer retention and drug use outcomes in patients in methadone maintenance (DeMaria et al., 2000). Thus, cocaine dependent persons who also are dependent on sedatives may seek self-help as an alternative to formal treatment.

4.4 Study Strengths and Limitations

The study had several methodological strengths including the large, demographically diverse community sample of cocaine dependent adults and closely age-matched siblings. Also, psychiatric and substance dependence disorders were diagnosed using a standardized structured interview (Pierucci-Lagha et al., 2005; 2007). Further, a range of indices of cocaine dependence severity was utilized rather than a single measure of symptom or impairment severity.

Study limitations include use of a convenience sample comprised of affected sibling pairs, which is not generalizable to all cocaine dependent adults. The reliability of SSADDA psychiatric diagnoses is less than that for substance dependence diagnoses and the validity of these diagnoses has not been formally demonstrated. Because individuals with a clinical diagnosis of schizophrenia were excluded from participation, there are limitations to the applicability of these findings to a more severely mentally ill patient population. Several variables were used to represent cocaine dependence severity, which may have led to false positive findings, although the use of a conservative multivariate analysis strategy increases the likelihood that relationships between psychiatric comorbidity and cocaine dependence severity are meaningful. Study variables were self-report, which may not accurately describe dependence severity or treatment and self-help program use. Replication is needed with broader samples of cocaine users, confirmation of substance dependence (e.g., toxicology), and external measures of dependence severity (e.g., legal or work records) and service utilization (e.g., medical records).

4.5 Conclusion

After accounting for the effects of demographic factors and other substance dependence disorders, only bipolar disorder and ASPD were related to cocaine dependence severity. The presence of a co-occurring SUD consistently was associated with cocaine dependence severity, although some co-occurring SUDs were associated with increased cocaine dependence severity (e.g., opioids, alcohol) and others were associated with decreased cocaine dependence severity (e.g., marijuana). More specifically study findings suggest that severe psychiatric disorders such as bipolar disorder or ASPD may be associated with extended periods of heavy cocaine use. Therefore, interventions are needed to prevent extended heavy cocaine use when cocaine dependence co-occurs with serious mental illness or ASPD.

Moreover, in addition to bipolar disorder and ASPD, MDD and PTSD were associated with an increased likelihood of cocaine dependence treatment or self-help participation. While mood and anxiety disorders may not increase cocaine dependence severity, they may add psychosocial burden that could motivate cocaine dependent adults to seek treatment or self-help. This finding underscores the importance of targeted psychotherapy or pharmacotherapy for mood or anxiety disorders when they co-occur with cocaine dependence.

Acknowledgements

The authors thank Ms. Amy Stomsky and Ms. Camille Haddad for assistance in the preparation of the manuscript.

Funding for this study was provided by NIH grants R01 DA12849, R01 DA12690, K24 DA15105, K24 DA02288, and K24 AA13736. NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Footnotes

Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Conflict of Interest: none for any of the authors

References

  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th Ed. Washington, DC: American Psychiatric Press; 1994. [Google Scholar]
  2. Arndt IO, McLellan AT, Dorozynsky L, Woody GE, O’Brien CP. Desipramine treatment for cocaine dependence; role of antisocial personality disorder. J Nerv Ment Dis. 1994;182:151–156. doi: 10.1097/00005053-199403000-00004. [DOI] [PubMed] [Google Scholar]
  3. Back S, Dansky BS, Coffey SF, Saladin ME, Sonne S, Brady KT. Cocaine dependence with and without posttraumatic stress disorder: A comparison of substance use, trauma history and psychiatric comorbidity. Am J Addict. 2000;9:51–62. doi: 10.1080/10550490050172227. [DOI] [PubMed] [Google Scholar]
  4. Bandettini Di Poggio A, Fornai F, Paparelli A, Pacini M, Perugi G, Maremmani I. Comparison between heroin and heroin-cocaine polyabusers: a psychopathological study. Ann N Y Acad Sci. 2006;1074:438–445. doi: 10.1196/annals.1369.044. [DOI] [PubMed] [Google Scholar]
  5. Brady KT, Back SE, Coffey SF. Substance abuse and posttraumatic stress disorder. Current Directions in Psychological Science. 2004;13:206–209. [Google Scholar]
  6. Brown ES, Perantie DC, Dhanani N, Beard L, Orsulak P, Rush AJ. Lamotrigine for bipolar disorder and comorbid cocaine dependence: a replication and extension study. J Affect Disord. 2006;93:219–222. doi: 10.1016/j.jad.2006.02.001. [DOI] [PubMed] [Google Scholar]
  7. Bruce SE, Yonkers KA, Otto MW, Eisen JL, Weisberg RB, Pagano M, Shea MT, Keller MB. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. Am J Psychiatry. 2005;162:1179–1187. doi: 10.1176/appi.ajp.162.6.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cacciola JS, Alterman AI, McKay JR, Rutherford MJ. Psychiatric comorbidity in patients with substance use disorders: Do not forget Axis II disorders. Psychiatric Annals. 2001;31:321–331. [Google Scholar]
  9. Carpenter KM, Miele GM, Hasin DS. Does motivation to change mediate the effect of DSM-IV substance use disorders on treatment utilization and substance use? Addict Behav. 2002;27:207–225. doi: 10.1016/s0306-4603(00)00178-7. [DOI] [PubMed] [Google Scholar]
  10. Carroll KM, Nich C, Rounsaville BJ. Variability in treatment-seeking cocaine abusers: Implications for clinical pharmacotherapy trials. NIDA Res Monograph. 2007;175 [PubMed] [Google Scholar]
  11. Carroll KM, Rounsaville BJ. Bridging the gap: a hybrid model to link efficacy and effectiveness research in substance abuse treatment. Psychiatr Serv. 2003;54:333–339. doi: 10.1176/appi.ps.54.3.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cassidy F, Ahearn EP, Carroll BJ. Substance abuse in bipolar disorder. Bipolar Disord. 2001;3:181–188. [PubMed] [Google Scholar]
  13. Chassler D, Lundgren L, Lonsdale J. What factors are associated with high-frequency drug treatment use among a racially and ethnically diverse population of injection drug users? Am J Addict. 2006;15:440–449. doi: 10.1080/10550490600998500. [DOI] [PubMed] [Google Scholar]
  14. Chutuape MA, Brooner RK, Stitzer M. Sedative use disorders in opiate-dependent patients: association with psychiatric and other substance use disorders. J Nerv Ment Dis. 1997;185:289–297. doi: 10.1097/00005053-199705000-00002. [DOI] [PubMed] [Google Scholar]
  15. Compton WM, Conway KP, Stinson FS, Colliver JD, Grant BF. Prevalence, correlates, and comorbidity of DSM-IV antisocial personality syndromes and alcohol and specific drug use disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. J Clin Psychiatry. 2005a;66:677–685. doi: 10.4088/jcp.v66n0602. [DOI] [PubMed] [Google Scholar]
  16. Compton WM, Thomas YF, Conway KP, Colliver JD. Developments in the epidemiology of drug use and drug use disorders. Am J Psychiatry. 2005b;162:1494–1502. doi: 10.1176/appi.ajp.162.8.1494. [DOI] [PubMed] [Google Scholar]
  17. Cottler LB, Campbell W, Krishna VAS, Cunningham-Williams RM, Abdullah AB. Predictors of High Rates of Suicidal Ideation Among Drug Users. J Nerv Ment Dis. 2005;193:431–437. doi: 10.1097/01.nmd.0000168245.56563.90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. DeMaria PA, Jr., Sterling R, Weinstein SP. The effect of stimulant and sedative use on treatment outcome of patients admitted to methadone maintenance treatment. Am J Addict. 2000;9:145–153. doi: 10.1080/10550490050173217. [DOI] [PubMed] [Google Scholar]
  19. Dennis ML, Scott CK, Funk R, Foss MA. The duration and correlates of addiction and treatment careers. J Subst Abuse Treat. 2005;28 Suppl 1:S51–S62. doi: 10.1016/j.jsat.2004.10.013. [DOI] [PubMed] [Google Scholar]
  20. Falck RS, Wang J, Siegal HA, Carlson RG. The prevalence of psychiatric disorder among a community sample of crack cocaine users: an exploratory study with practical implications. J Nerv Ment Dis. 2004;192:503–507. doi: 10.1097/01.nmd.0000131913.94916.d5. [DOI] [PubMed] [Google Scholar]
  21. Flannery BA, Morgenstern J, McKay J, Wechsberg WM, Litten RZ. Co-occurring alcohol and cocaine dependence: recent findings from clinical and field studies. Alcohol Clin Exp Res. 2004;28:976–981. doi: 10.1097/01.alc.0000128232.30331.65. [DOI] [PubMed] [Google Scholar]
  22. Fox HC, Axelrod SR, Paliwal P, Sleeper J, Sinha R. Difficulties in emotion regulation and impulse control during cocaine abstinence. Drug Alcohol Depend. 2007;89:298–301. doi: 10.1016/j.drugalcdep.2006.12.026. [DOI] [PubMed] [Google Scholar]
  23. Galea S, Nandi A, Coffin PO, Tracy M, Markham Piper T, Ompad D, Vlahov D. Heroin and cocaine dependence and the risk of accidental non-fatal drug overdose. J Addict Dis. 2006;25:79–87. doi: 10.1300/J069v25n03_10. [DOI] [PubMed] [Google Scholar]
  24. Gelernter J, Panhuysen C, Weiss R, Brady K, Hesselbrock V, Rounsaville B, Poling J, Wilcox M, Farrer L, Kranzler HR. Genomewide linkage scan for cocaine dependence and related traits: significant linkages for a cocaine-related trait and cocaine-induced paranoia. Am J Med Genet B Neuropsychiatr Genet. 2005;136:45–52. doi: 10.1002/ajmg.b.30189. [DOI] [PubMed] [Google Scholar]
  25. Gelernter J, Panhuysen C, Wilcox M, Hesselbrock V, Rounsaville B, Poling J, Weiss R, Sonne S, Zhao H, Farrer L, Kranzler HR. Genomewide linkage scan for opioid dependence and related traits. Am J Hum Genet. 2006;78:759–769. doi: 10.1086/503631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Goldstein RB, Compton WM, Pulay AJ, Ruan WJ, Pickering RP, Stinson FS, Grant BF. Antisocial behavioral syndromes and DSM-IV drug use disorders in the United States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Drug Alcohol Depend. 2007;90:145–158. doi: 10.1016/j.drugalcdep.2007.02.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Grant BF, Hasin DS, Stinson FS, Dawson DA, Goldstein RB, Smith S, Huang B, Saha TD. The epidemiology of DSM-IV panic disorder and agoraphobia in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2006;67:363–374. doi: 10.4088/jcp.v67n0305. [DOI] [PubMed] [Google Scholar]
  28. Grella CE, Hser YI, Hsieh SC. Predictors of drug treatment re-entry following relapse to cocaine use in DATOS. J Subst Abuse Treat. 2003;25:145–154. doi: 10.1016/s0740-5472(03)00128-4. [DOI] [PubMed] [Google Scholar]
  29. Hansen H, Alegria M, Caban CA, Pena M, Lai S, Shrout P. Drug treatment, health, and social service utilization by substance abusing women from a community-based sample. Med Care. 2004;42:1117–1124. doi: 10.1097/00005650-200411000-00011. [DOI] [PubMed] [Google Scholar]
  30. Hien DA, Nunes E, Levin FR, Fraser D. Posttraumatic stress disorder and short-term outcome in early methadone maintenance treatment. J Subst Abuse Treat. 2000;19:31–37. doi: 10.1016/s0740-5472(99)00088-4. [DOI] [PubMed] [Google Scholar]
  31. Kampman KM, Pettinati HM, Volpicelli JR, Oslin DM, Lipkin C, Sparkman T, O’Brien CP. Cocaine dependence severity predicts outcome in outpatient detoxification from cocaine and alcohol. Am J Addict. 2004;13:74–82. doi: 10.1080/10550490490265389. [DOI] [PubMed] [Google Scholar]
  32. Kandel DB, Huang FY, Davies M. Comorbidity between patterns of substance use dependence and psychiatric syndromes. Drug Alcohol Depend. 2001;64:233–241. doi: 10.1016/s0376-8716(01)00126-0. [DOI] [PubMed] [Google Scholar]
  33. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:617–627. doi: 10.1001/archpsyc.62.6.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:8–19. doi: 10.1001/archpsyc.1994.03950010008002. [DOI] [PubMed] [Google Scholar]
  35. Kidorf M, Disney ER, King VL, Neufeld K, Beilenson PL, Brooner RK. Prevalence of psychiatric and substance use disorders in opioid abusers in a community syringe exchange program. Drug Alcohol Depend. 2004;74(2):115–122. doi: 10.1016/j.drugalcdep.2003.11.014. [DOI] [PubMed] [Google Scholar]
  36. Krishnan KR. Psychiatric and medical comorbidities of bipolar disorder. Psychosom Med. 2005;67:1–8. doi: 10.1097/01.psy.0000151489.36347.18. [DOI] [PubMed] [Google Scholar]
  37. Kuo PH, Gardner CO, Kendler KS, Prescott CA. The temporal relationship of the onsets of alcohol dependence and major depression: using a genetically informative study design. Psychol Med. 2006;36:1153–1162. doi: 10.1017/S0033291706007860. [DOI] [PubMed] [Google Scholar]
  38. Ladd GT, Petry NM. Antisocial personality in treatment-seeking cocaine abusers: Psychosocial functioning and HIV risk. J Subst Abuse Treat. 2003;24:323–330. doi: 10.1016/s0740-5472(03)00042-4. [DOI] [PubMed] [Google Scholar]
  39. Leventhal AM, Mooney ME, DeLaune KA, Schmitz JM. Using addiction severity profiles to differentiate cocaine-dependent patients with and without comorbid major depression. Am J Addict. 2006;15:362–369. doi: 10.1080/10550490600860148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Liang KY, Zeger SL. Longitudinal Data Analysis Using Generalized Liner Models. Biometrika. 1986;73:13–22. [Google Scholar]
  41. Lynskey MT, Glowinski AL, Todorov AA, Bucholz KK, Madden PA, Nelson EC, Statham DJ, Martin NG, Heath AC. Major depressive disorder, suicidal ideation, and suicide attempt in twins discordant for cannabis dependence and early-onset cannabis use. Arch Gen Psychiatry. 2004;61:1026–1032. doi: 10.1001/archpsyc.61.10.1026. [DOI] [PubMed] [Google Scholar]
  42. Markon KE, Krueger RF. Categorical and continuous models of liability to externalizing disorders: a direct comparison in NESARC. Arch Gen Psychiatry. 2005;62:1352–1359. doi: 10.1001/archpsyc.62.12.1352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Messina N, Farabee D, Rawson R. Treatment responsivity of cocaine-dependent patients with antisocial personality disorder to cognitive-behavioral and contingency management interventions. J Consult Clin Psychol. 2003;71:320–329. doi: 10.1037/0022-006x.71.2.320. [DOI] [PubMed] [Google Scholar]
  44. Miele GM, Carpenter KM, Cockerham MS, Trautman KD, Blaine J, Hasin DS. Substance Dependence Severity Scale (SDSS). Reliability and validity of a clinician-administered interview for DSM-IV substance use disorders. Drug Alcohol Dep. 2000;59:63–75. doi: 10.1016/s0376-8716(99)00111-8. [DOI] [PubMed] [Google Scholar]
  45. Mills KL, Teesson M, Ross J, Darke S, Shanahan M. The costs and outcomes of treatment for opioid dependence associated with posttraumatic stress disorder. Psychiatr Serv. 2005;56:940–945. doi: 10.1176/appi.ps.56.8.940. [DOI] [PubMed] [Google Scholar]
  46. Mills KL, Teesson M, Ross J, Darke S. The impact of post-traumatic stress disorder on treatment outcomes for heroin dependence. Addiction. 2007;102:447–454. doi: 10.1111/j.1360-0443.2006.01711.x. [DOI] [PubMed] [Google Scholar]
  47. Najavits LM, Gallop RJ, Weiss RD. Seeking safety therapy for adolescent girls with PTSD and substance use disorder: A randomized controlled trial. J Behav Health Serv Res. 2006;33:453–463. doi: 10.1007/s11414-006-9034-2. [DOI] [PubMed] [Google Scholar]
  48. Najavits LM, Harned MS, Gallop RJ, Butler SF, Barber JP, Thase ME, Crits-Christoph P. Six-month treatment outcomes of cocaine-dependent patients with and without PTSD in a multisite national trial. J Stud Alcohol Drugs. 2007;68:353–361. doi: 10.15288/jsad.2007.68.353. [DOI] [PubMed] [Google Scholar]
  49. Nunes EV, McGrath PJ, Quitkin FM, Ocepek-Welikson K, Stewart JW, Koenig T, Wager S, Klein DF. Imipramine treatment of cocaine abuse: Possible boundaries of efficacy. Drug Alcohol Depend. 1995;39:185–195. doi: 10.1016/0376-8716(95)01161-6. [DOI] [PubMed] [Google Scholar]
  50. O’Brien MS, Wu LT, Anthony JC. Cocaine use and the occurrence of panic attacks in the community: a case-crossover approach. Subst Use Misuse. 2005;40:285–297. doi: 10.1081/ja-200049236. [DOI] [PubMed] [Google Scholar]
  51. Ouimette PC, Moos RH, Finney JW. PTSD treatment and 5-year remission among patients with substance use and posttraumatic stress disorders. J Consult Clin Psychol. 2003;71:410–414. doi: 10.1037/0022-006x.71.2.410. [DOI] [PubMed] [Google Scholar]
  52. Parrott DJ, Drobes DJ, Saladin ME, Coffey SF, Dansky BS. Perpetration of partner violence: effects of cocaine and alcohol dependence and posttraumatic stress disorder. Addict Behav. 2003;28:1587–1602. doi: 10.1016/j.addbeh.2003.08.036. [DOI] [PubMed] [Google Scholar]
  53. Pierucci-Lagha A, Gelernter J, Chan G, Arias A, Cubells JF, Farrer L, Kranzler HR. Reliability of DSM-IV diagnostic criteria using the semi-structured assessment for drug dependence and alcoholism (SSADDA) Drug Alcohol Depend. 2007;91:85–90. doi: 10.1016/j.drugalcdep.2007.04.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Pierucci-Lagha A, Gelernter J, Feinn R, Cubells JF, Pearson D, Pollastri A, Farrer L, Kranzler HR. Diagnostic reliability of the Semi-structured Assessment for Drug Dependence and Alcoholism (SSADDA) Drug Alcohol Depend. 2005;80:303–312. doi: 10.1016/j.drugalcdep.2005.04.005. [DOI] [PubMed] [Google Scholar]
  55. Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264:2511–2518. [PubMed] [Google Scholar]
  56. Salgado D, Quinlan K, Zlotnick C. The relationship of lifetime polysubstance dependence to trauma exposure, symptomatology, and psychosocial functioning in incarcerated women with comorbid PTSD and substance use disorder. J Trauma Dissociation. 2007;8:9–26. doi: 10.1300/J229v08n02_02. [DOI] [PubMed] [Google Scholar]
  57. Salloum IM, Douaihy A, Ndimbie OK, Kirisci L. Concurrent alcohol and cocaine dependence impact on physical health among psychiatric patients. J Addict Dis. 2004;23:71–81. doi: 10.1300/J069v23n02_05. [DOI] [PubMed] [Google Scholar]
  58. Schafer I, Najavits LM. Clinical challenges in the treatment of patients with posttraumatic stress disorder and substance abuse. Curr Opin Psychiatry. 2007;20:614–618. doi: 10.1097/YCO.0b013e3282f0ffd9. [DOI] [PubMed] [Google Scholar]
  59. Schmitz JM, Averill P, Stotts AL, Moeller FG, Rhoades HM, Grabowski J. Fluoxetine treatment of cocaine-dependent patients with major depression. Drug Alcohol Depend. 2001;63:207–214. doi: 10.1016/s0376-8716(00)00208-8. [DOI] [PubMed] [Google Scholar]
  60. Schmitz JM, Stotts AL, Sayre SL, DeLaune KA, Grabowski J. Treatment of cocaine-alcohol dependence with naltrexone and relapse prevention therapy. Am J Addict. 2004;13:333–341. doi: 10.1080/10550490490480982. [DOI] [PubMed] [Google Scholar]
  61. Schuckit MA, Smith TL, Kramer J, Danko G, Volpe FR. The prevalence and clinical course of sedative-hypnotic abuse and dependence in a large cohort. Am J Drug Alcohol Abuse. 2002;28:73–90. doi: 10.1081/ada-120001282. [DOI] [PubMed] [Google Scholar]
  62. Shaffer HJ, Eber GB. Temporal progression of cocaine dependence symptoms in the US National Comorbidity Survey. Addiction. 2002;97:543–554. doi: 10.1046/j.1360-0443.2002.00114.x. [DOI] [PubMed] [Google Scholar]
  63. Skinstad AH, Swain A. Comorbidity in a clinical sample of substance abusers. Am J Drug Alcohol Abuse. 2001;27:45–64. doi: 10.1081/ada-100103118. [DOI] [PubMed] [Google Scholar]
  64. Sofuoglu M, Dudish-Poulsen S, Brown SB, Hatsukami DK. Association of cocaine withdrawal symptoms with more severe dependence and enhanced subjective response to cocaine. Drug Alcohol Depend. 2003;69:273–282. doi: 10.1016/s0376-8716(02)00328-9. [DOI] [PubMed] [Google Scholar]
  65. Staines G, Magura S, Rosenblum A, Fong C, Kosanke N, Foote J, Deluca A. Predictors of drinking outcomes among alcoholics. Am J Drug Alcohol Abuse. 2003;29:203–218. doi: 10.1081/ada-120018847. [DOI] [PubMed] [Google Scholar]
  66. Tarrier N, Sommerfield C. Alcohol and substance use in civilian chronic PTSD patient seeking psychological treatment. J Substance Use 8. 2003;8:8. [Google Scholar]
  67. Thevos AK, Brady KT, Grice D, Dustan L. A comparison of psychopathology in cocaine and alcohol dependence. Am J Addict. 1993;2:279–286. [Google Scholar]
  68. Trafton J, Minkel K, Humphreys J. Opioid substitution treatment reduces substance use equivalently in patients with and without posttraumatic stress disorder. Journal of Studies on Alcohol. 2006;67:228–235. doi: 10.15288/jsa.2006.67.228. [DOI] [PubMed] [Google Scholar]
  69. Van Ness PH, Davis WR, Johnson BD. Socioeconomic marginality and health services utilization among Central Harlem substance users. Subst Use Misuse. 2004;39:61–85. doi: 10.1081/ja-120027766. [DOI] [PubMed] [Google Scholar]
  70. Wasserman DA, Havassy BE, Boles SM. Traumatic events and post-traumatic stress disorder in cocaine users entering private treatment. Drug Alcohol Depend. 1997;46:1–8. doi: 10.1016/s0376-8716(97)00048-3. [DOI] [PubMed] [Google Scholar]
  71. Watkins KE, Hunter SB, Wenzel SL, Tu W, Paddock SM, Griffin A, Ebener P. Prevalence and characteristics of clients with co-occurring disorders in outpatient substance abuse treatment. Am J Drug Alcohol Abuse. 2004;30:749–764. doi: 10.1081/ada-200037538. [DOI] [PubMed] [Google Scholar]
  72. Weiss RD, Griffin ML, Gallop R, Luborsky L, Siqueland L, Frank A, Onken LS, Daley DC, Gastfriend DR. Predictors of self-help group attendance in cocaine dependent patients. J Stud Alcohol. 2000;61:714–719. doi: 10.15288/jsa.2000.61.714. [DOI] [PubMed] [Google Scholar]
  73. Weiss RD, Griffin ML, Kolodziej ME, Greenfield SF, Najavits LM, Daley DC, Doreau HR, Hennen JA. A randomized trial of integrated group therapy versus group drug counseling for patients with bipolar disorder and substance dependence. Am J Psychiatry. 2007;164:100–107. doi: 10.1176/ajp.2007.164.1.100. [DOI] [PubMed] [Google Scholar]
  74. Wild TC, el-Guebaly N, Fischer B, Brissette S, Brochu S, Bruneau J, Noel L, Rehm J, Tyndall M, Mun P. Comorbid depression among untreated illicit opiate users: Results from a multisite Canadian study. Can J Psychiatry. 2005;50:512–517. doi: 10.1177/070674370505000903. [DOI] [PubMed] [Google Scholar]
  75. Ziedonis DM, Kosten TR. Depression as a prognostic factor for pharmacological treatment of cocaine dependence. Psychopharm Bull. 1991;27:337–343. [PubMed] [Google Scholar]

RESOURCES