Introduction: Comorbidity, Cognition, and Pharmacotherapies

Psychiatric TimesPsychiatric Times Vol 28 No 6
Volume 28
Issue 6

In this Special Report, Helen M. Pettinati, PhD, and William D. Dundon, PhD, discuss prevalence, assessment, clinical features, and treatment issues with respect to individuals with co-occurring major depression and alcohol dependence.

Substance use disorders are arguably a leading category of health problems in the United States. Of the proposed top 5 health problems in terms of economic costs (in decreasing order: drug abuse, mental illness, heart disease, alcohol use disorders, and nicotine use), 3 are substance use disorders.1 Substance use disorders are commonly encountered in every domain of psychiatric practice. Yet psychiatrists often feel limited in their ability to recognize and manage these disorders. In this Special Report, accomplished authors provide focal reviews on topics central to the psychiatric treatment of substance use disorders.

Raymond F. Anton, MD, reviews the COMBINE study and the short- and long-term implications for the use of medication combined with behavioral interventions for alcohol dependence. Dr Anton discusses recently emerging genetic data from the COMBINE study that are furthering a path toward personalized medicine in the pharmacotherapy for alcohol use disorders. He makes the salient point that interest in addiction-specialty care and medication is actually quite substantial among patients when they are offered such services in their local communities. Yet research findings indicate that only 23% of publicly funded addiction treatment programs use any of the FDA-approved pharmacotherapies for managing addiction.2 The results of one study show that fewer than 50% of privately funded addiction treatment programs with access to physicians use medication-assisted treatments. For opioid or alcohol dependence (for which there are a variety of FDA-approved medications), these numbers are just 34% and 24%, respectively.3 There is a significant gap between research and practice. Dr Anton provides lumber for bridging this gap: the matching of endophenotypes of disease with genetic markers for pharmacotherapy response.

Cognitive dysfunction, particularly fronto-executive deficits, has increasingly been recognized as problematic for patients with substance use disorders. Not only may there be preexisting trait-dependent deficits that portend risk for the onset of addiction disorder, but also there has been increasing interest in the pathophysiology and progression of state-dependent cognitive deficits that negatively impact the clinical course. We now understand that in addition to pathology in the reward, motivation, and memory/learning circuits, addiction disorders are characterized by dysfunctional cognition/decision-making circuits wherein the brain overvalues reward, undervalues risk, and fails to learn from repeated errors.4Antonio Verdejo-Garca, PhD, points out that cognitive dysfunction in patients with substance use disorders is associated with negative treatment outcomes (poorer adherence, shorter retention, and greater risk of relapse). Herein, Dr Verdejo-Garca provides brief, practical advice for the office psychiatrist on how to assess for cognitive dysfunction in patients who have substance use disorders as well as how to personalize treatment interventions in accordance with cognitive limitations.

Despite evidence for efficacy, medications continue to be underused in the treatment of alcohol dependence. A “double-whammy” often exists in clinical practice when depression and alcohol dependence co-occur. Not only may providers not offer medications for alcohol dependence, but they may also be reluctant to prescribe medication for depression until they are assured that the symptoms of depression are not substance-induced. Often, however, the net effect is that the patient ei-ther leaves treatment or the clini-cian fails to follow up on the option of medication-and opportunities are lost. Given that comorbid depression is considered one of the strongest relapse risk predictors for alcohol dependence, the results can be disastrous.

In this Special Report, Helen M. Pettinati, PhD, and William D. Dundon, PhD, discuss prevalence, assessment, clinical features, and treatment issues with respect to individuals with co-occurring major depression and alcohol dependence. This discussion extends from their recent and highly cited study, which showed that combined medications for co-occurring alcohol dependence and depression can make very positive contributions to outcomes for patients.

We are hopeful that you will find these articles practical and helpful, ideally assisting you in the translation of research into clinical practice.

Disclaimer-The contents do not represent the views of the Department of Veterans Affairs or the United States government.



1. Office of National Drug Control Policy. The Economic Costs of Drug Abuse in the United States, 1992-2002. Washington, DC: Executive Office of the President; 2004. Publication 207303.

2. Knudsen HK, Roman PM, Oser CB. Facilitating factors and barriers to the use of medications in publicly funded addiction treatment organizations. J Addict Med. 2010;4:99-107.

3. Knudsen HK, Abraham AJ, Roman PM. Adoption and implementation of medications in addiction treatment programs. J Addict Med. 2011;5:21-27.

4. Volkow ND, Baler RD, Goldstein RZ. Addiction: pulling at the neural threads of social behaviors. Neuron. 2011;69:599-602.

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