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Comorbidity With Substance Abuse

  • Authors: Kathleen T Brady, MD, PhD
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This activity is intended for physicians, pharmacists, nurses, and healthcare professionals.

The goal of this activity is to provide clinicians with the latest scientific and clinical information in substance abuse.

Upon completion of this activity, participants should be able to:

  1. Review the current scientific data on substance abuse.
  2. Discuss the impact of comorbid psychiatric diagnosis on the prognosis and management of substance abuse.
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  • Kathleen T Brady, MD, PhD

    Professor and Director, Clinical Neuroscience Division, Medical University of South Carolina, Charleston, South Carolina


    Disclosure: Dr. Brady has disclosed that she has received grants for clinical research, education activities, and served as an advisor or consultant to Lilly within the last 12 months. She holds financial interests with Pfizer, Eli Lilly, Abbott Labs, and Bristol-Myers Squibb.

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Comorbidity With Substance Abuse

Authors: Kathleen T Brady, MD, PhDFaculty and Disclosures



This interesting session provided an overview of recent findings in the diagnosis and treatment of several psychiatric disorders that commonly co-occur with substance use disorders. Several epidemiologic survey studies conducted in the past 15 years have demonstrated that many psychiatric disorders and substance use disorders co-occur far more commonly than would be expected by chance alone. In the Epidemiologic Catchment Area Study,[1,2] an estimated 45% of individuals with an alcohol use disorder and 72% of individuals with a drug use disorder had a least one co-occurring psychiatric disorder. In the National Co-Morbidity Study (NCS),[3] probably the best known of the recent survey studies, it was found that approximately 78% of alcohol-dependent men and 86% of alcohol-dependent women met criteria for another psychiatric disorder, including drug dependence and antisocial personality disorder. Interest in the co-occurrence of psychiatric and substance use disorders is clinically important because comorbidity has been found to have a negative impact on the course, treatment outcome, and prognosis of both syndromes. In this symposium, the relationship between substance use disorders and specific anxiety and mood disorders and ADHD was explored.

Depression and Substance Use Disorders

In the first talk, Dr. Edward Nunes,[4] a Professor of Psychiatry from Columbia University School of Medicine, spoke about the comorbidity of depression and substance use disorders. Dr. Nunes pointed out that depressed mood, dysthymia, and major depressive episode are among the most common symptoms and disorders seen in individuals with substance use disorders. This comorbidity has also been the subject of a great deal of research focused on issues concerning differential diagnosis and pharmacotherapeutic and psychotherapeutic treatment. In spite of this, there are still many unanswered questions. With regard to diagnosis, there is a great deal of symptom overlap between symptoms of depression and withdrawal symptoms from alcohol and many drugs of abuse. This can make differential diagnosis difficult.

Studies in treatment-seeking samples have resulted in variable estimates of the comorbidity of affective illness with substance use disorders. Estimates of the prevalence of depressive disorders in treatment-seeking, alcoholic individuals range from 15% to 67%. In studies of cocaine-dependent individuals, estimates of affective comorbidity range from 33% to 53%. Bipolar disorders appear to be more prevalent (20% to 30%) among cocaine-dependent individuals than among alcoholic individuals. In opiate-dependent samples, rates of lifetime affective disorder (primarily depressive disorders) range from 16% to 75%.

While there has been a great deal of discussion about distinguishing primary vs secondary depression, depending on the relative order of onset of the disorders, there is not much evidence that the primary/secondary distinction makes a difference in terms of treatment response. There have been a number of studies of both pharmacotherapeutic and psychotherapeutic treatments for individuals with co-occurring depression and substance use disorders. Several studies have indicated that tricyclic antidepressants are efficacious in the treatment of comorbid depression with alcohol-, cocaine-, and opiate-dependent individuals. Unfortunately, in many of these studies, there was improvement in depression, but not in substance use-related outcomes. In some studies, medication was initiated in individuals while they were still actively using substances. The medications improved symptoms of depression even in individuals who were actively using at the time of medication initiation. Dr. Nunes also presented some interesting findings from a research group[5] studying the impact of cognitive behavioral therapy (CBT) in alcohol-dependent individuals with comorbid major depression. In the study, the efficacy of an integrated CBT that was specifically designed for alcoholism and depression was compared with a relaxation training control group. The authors found that those individuals treated with the integrated treatment approach had better outcomes with regard to both alcohol consumption and symptoms of depression at the 3- and 6-month follow-up visits.

ADHD and Substance Use Disorders

The next speaker was Dr. Tim Wilens,[6] from Harvard University, discussing the comorbidity of attention-deficit/hyperactivity disorder (ADHD) and substance use disorders. Dr. Wilens spoke about the increasing awareness of ADHD in both children and adults and the evidence that ADHD is commonly comorbid with substance use disorders. In some studies, it has been demonstrated that the link between ADHD and substance use disorders is usually through conduct disorder or antisocial personality disorder. Both ADHD and substance use disorders are commonly comorbid with conduct disorders and most often those individuals with ADHD who develop substance use disorders also have a conduct disorder. For those individuals with ADHD who do not have conduct disorder, the comorbidity with substance use disorders is not nearly as striking. Dr. Wilens also addressed the controversial area of the use of stimulant drugs in children with ADHD and in adults with ADHD and comorbid substance use disorders. There has been some speculation that because stimulant drugs used in the treatment of ADHD, such as methylphenidate, have abuse potential, the link between ADHD in children and the development of substance use disorders in adolescents and adults may be causal. In other words, the use of stimulants in children may predispose them to the development of substance use disorders as adults. Dr. Wilens and colleagues recently published a thorough review of the literature[7] in which they concluded that the majority of the literature supports the idea that medication treatment of ADHD in childhood actually has a protective effect with regard to the development of substance use disorders during adolescence or adulthood. They hypothesized that this protective effect may be a result of the fact that treatment of ADHD makes it more likely that a child will be successful in school and other areas, therefore making them less likely to be at risk for the development of a substance use disorder.

PTSD and Substance Use Disorders

Dr. Kathleen Brady,[8] from the Medical University of South Carolina, spoke next about the co-occurrence of posttraumatic stress disorder (PTSD) and substance use disorders. Victimization, violence, and trauma are often a part of the life history of individuals with substance use disorders. PTSD is one of the most common anxiety disorders in individuals with substance use disorders. In the NCS, the odds ratio for substance use disorders was 2-3 for men and 2.5-4.5 for women with PTSD. In treatment settings for substance use disorders, a number of studies have reported rates of current PTSD between 20% and 45%. Individuals with comorbid PTSD and substance use have a worse course of illness with more hospitalizations, less compliance with aftercare treatment, and poorer functional improvement.

For many years, the conventional wisdom in substance abuse treatment settings was to aggressively treat the substance use disorder but not address trauma-related issues until an individual had several months of abstinence. Unfortunately, many individuals suffering with symptoms of PTSD cannot attain sobriety because PTSD symptoms, such as sleep disturbance and intrusive thoughts, can drive continued substance use. Therefore, the development of treatments specifically tailored to address trauma-related issues during early recovery has been a focus of much recent investigation. One of the most widely used manualized psychotherapy, which uses a combination of techniques from both the addiction and PTSD fields, is Seeking Safety, developed by Lisa Najavits from Harvard University.[9] This is a 12-24 session group or individual therapy that focuses on understanding trauma-related symptoms, healthy behaviors, and relapse prevention. This therapy is under investigation in a multisite trial sponsored by the National Institute on Drug Abuse.

Dr. Brady then presented some data from a study conducted by her research group from the Medical University of South Carolina on the efficacy of sertraline in the treatment of co-occurring PTSD and alcohol dependence. Sertraline has demonstrated efficacy in the treatment of PTSD in nonalcohol-dependent individuals. In this study, sertraline had a modest impact on the symptoms of PTSD. When the data from the group were analyzed as a whole, sertraline did not have an impact on alcohol-related outcomes. In a post-hoc analysis, however, the study sample was divided into a group who had early onset PTSD, later onset alcohol abuse, and a group who had early onset alcohol abuse, later onset PTSD. Sertraline was very efficacious in improving alcohol-related outcomes in the early onset PTSD group, but not in the early onset alcohol abuse group. These data suggest that subtyping comorbid populations for the purpose of treatment matching could be important in choosing the most efficacious treatment for a specific patient.

Social Phobia and Substance Use Disorder

The next speaker was Dr. Hugh Myrick,[10] from the Medical University of South Carolina. Dr. Myrick's presentation focused on the comorbidity of social phobia and substance use disorders. Dr. Myrick began with an overview of the characteristics of social phobia and the substantial functional impairment associated with this disorder. Social anxiety disorder is defined as a marked and persistent fear of situations in which an individual is exposed to unfamiliar people or to the scrutiny of others. Fear of being embarrassed or evaluated negatively is the hallmark of the disorder. This fear often leads to avoidance of feared situations and results in impairment in academic, occupational, and social functioning. In spite of the prevalence and high price of social phobia, it is often unrecognized and/or trivialized as just "shyness."

A number of studies have emphasized the high comorbidity of social phobia with a number of other psychiatric disorders, including substance use disorders. Studies of treatment-seeking alcoholics and drug-dependent individuals also indicate a high percentage of individuals meeting criteria for social phobia (approximately 10% to 15%), but the disorder is rarely diagnosed in substance abuse treatment settings. Early recognition of the individual with comorbid social anxiety disorder and substance use is paramount to an improved chance of recovery because the social anxiety disorder may interfere with an individual's ability to engage effectively in treatment.

In an interview study of socially phobic, alcohol-dependent individuals, most reported the onset of social phobia was earlier than the onset of drinking. They also reported using alcohol to make themselves more comfortable in social situations, but generally not using alcohol in a work setting or any other settings in which performance would be evaluated. Dr. Carrie Randall and colleagues,[11] also at the Medical University of South Carolina, has conducted both a pharmacotherapy and a psychotherapy study of the treatment of alcohol-dependent individuals with social phobia. In the psychotherapy study, they compared a 12-session manualized treatment that combined social phobia CBT with relapse prevention techniques from the alcohol treatment field with CBT relapse prevention for alcohol only. Surprisingly, the group that received the combined treatment actually had poorer outcomes. The investigators speculate that aggressive treatment of social phobia may make it difficult for individuals to concentrate on their sobriety. They suggest that it may be an issue of timing -- perhaps treatment of social phobia following relapse prevention treatment would be a better strategy. This area clearly needs further study.

In another pilot study, Dr. Randall and colleagues[12] studied the use of paroxetine in socially phobic alcohol-dependent individuals. They found that the group treated with paroxetine had better outcomes in terms of social phobia and a trend toward better alcohol-related outcomes. The trial was brief (8 weeks), and many of the treatment effects were just beginning to emerge at the end of the trial. They are now conducting a longer and larger double-blind, placebo-controlled trial funded by the National Institutes of Health.

The discussion was conducted by Richard Rosenthal, a Professor of Psychiatry at Columbia University School of Medicine and the current president of the American Academy of Addiction Psychiatry. Dr. Rosenthal pointed out some of the common themes of the talks in the symposium. The idea of integrated treatment has been a critical part of treatment of comorbidity. In all of the presentations, new advances in treatment integration, both pharmacotherapeutic and psychotherapeutic, were presented. Dr. Rosenthal also stressed the idea of subtyping substance dependent individuals for the purposes of individualizing treatment. For a long time, substance abuse treatment has followed the "one size fits all" model. Particularly with regard to psychiatric comorbidity, it is clear that this approach does not work. Careful psychiatric diagnosis and appropriate treatment of psychiatric symptoms are critical to maximizing patient outcomes.


  1. essler RC, Nelson CB, McGonagle KA, et al. The epidemiology of co-occurring addictive and mental disorders: implications for prevention and service utilization. Am J Orthopsychiatry. 1996;66:17-31. Abstract
  2. Eaton WW, Regier DA, Locke BZ, Taube CA. The Epidemiologic Catchment Area Program of the National Institute of Mental Health. Public Health Rep. 1981;96:319-325. Abstract
  3. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264:2511-2518. Abstract
  4. Nunes EV. Substance abuse and depression. Program and abstracts of the American Psychiatric Association 156th Annual Meeting; May 17-22, 2003; San Francisco, California. Abstract S103A.
  5. Brown RA, Evans DM, Miller IW, et al. Cognitive-behavioral treatment for depression in alcoholism. J Consult Clin Psychol. 1997;65:715-726. Abstract
  6. Wilens TE. Substance abuse and ADD. Program and abstracts of the American Psychiatric Association 156th Annual Meeting; May 17-22, 2003; San Francisco, California. Abstract S103C.
  7. Wilens TE, Faraone SV, Biederman J, Gunawardene S. Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics. 2003;111:179-185. Abstract
  8. Brady KT, Sonne S, Killeen T, McRae A. Substance abuse and PTSD. Program and abstracts of the American Psychiatric Association 156th Annual Meeting; May 17-22, 2003; San Francisco, California. Abstract S103B.
  9. Najavits LM, Weiss RD, Liese BS. Group cognitive-behavioral therapy for women with PTSD and substance use disorder. J Subst Abuse Treat. 1996;13:13-22. Abstract
  10. Myrick H. Substance abuse and social phobia. Program and abstracts of the American Psychiatric Association 156th Annual Meeting; May 17-22, 2003; San Francisco, California. Abstract S103D.
  11. Thevos AK, Roberts JS, Thomas SE, Randall CL. Cognitive behavioral therapy delays relapse in female socially phobic alcoholics. Addict Behav. 2000;25:333-345. Abstract
  12. Randall CL, Johnson MR, Thevos AK, et al. Paroxetine for social anxiety and alcohol use in dual-diagnosed patients. Depress Anxiety. 2001;14:255-262. Abstract