Comorbid Depression and Alcohol Dependence

New Approaches to Dual Therapy Challenges and Progress

By Helen M. Pettinati, PhD and William D. Dundon, PhD | June 9, 2011

Dr Pettinati is a Research Professor in the department of psychiatry and Division Director in the Center for Studies of Addiction and the Treatment Research Center at the University of Pennsylvania School of Medicine in Philadelphia. Dr Dundon is Director of Operations and Clinical Services in the Center for Studies of Addiction and the Treatment Research Center. Dr Pettinati reports that she receives research support from Alkermes, Inc. Dr Dundon reports no conflicts of interest concerning the subject matter of this article.

Psychosocial treatment for major depression and alcohol(Drug information on alcohol) dependence

There have been 3 approaches to psychosocial interventions for treating comorbid disorders:

• Sequential: treating the primary disorder initially, followed by treating the other disorder

• Parallel: treating both disorders at the same time but in different settings

• Integrated: simultaneously treating both disorders

Although research and experience have been limited, integrated approaches have been shown to be superior to other approaches.¹⁷ Hesse¹⁸ identified only 5 randomized clinical trials that focused on the treatment of comorbid substance abuse and depressive disorders: those trials showed that integrated treatment programs had statistically superior alcohol and drug outcomes compared with addiction treatment only. Measures of depression outcomes and treatment retention also appeared to favor integrated treatment programs, although these results did not reach statistical significance. 

Pharmacotherapy

Research has been sparse on integrated psychosocial approaches and even less information is available on how to use pharmacotherapy for co-occurring major depression and alcohol dependence. Moreover, no evidence-based guide exists on how to integrate psychosocial and pharmacotherapy approaches in depressed alcohol-dependent patients. Major depression is generally responsive to pharmacological treatment, and antidepressants can be lifesaving for individuals at risk for suicide. However, studies that supported FDA approvals for these antidepressants typically excluded patients with comorbid alcohol dependence. Thus, the depression literature does not adequately address questions such as: Are antidepressants actually effective for reducing depressive symptoms in this patient population? Will antidepressants help reduce alcohol drinking, either directly or indirectly, by reducing depression? Would an antialcohol medication, singly or in combination with an antidepressant, reduce clinical symptoms for either or both disorders?

Historically, long-term drinkers were denied medications (except for detoxification) because of long-standing stigmas about alcohol-dependent patients taking any medications (“treating a drug with a drug”). Fortunately, this attitude is fading as scientists impart knowledge to professionals and the public about the possibilities of correcting the neurobiology of addiction by treating the addicted brain with certain medications. In addition, there are legitimate safety concerns about the potential interaction of medications with alcohol, or the potential for antidepressant overdose in depressed intoxicated patients.

The advent of SSRIs, many of which are FDA-approved, mitigated many of the safety concerns about depressed alcohol-dependent patients taking antidepressants. If a patient drinks alcohol or feels suicidal, SSRIs are better tolerated and are generally thought to be safer than, for example, tricyclic antidepressants (TCAs). In addition, the frequency of adverse effects is relatively low and the severity of most ad-verse effects is mild or moderate. Investigators have been more willing to examine the efficacy of SSRIs in alcohol-dependent patients, and clinicians have been more likely to prescribe SSRI medications than drugs in other classes for depression in alcohol-dependent patients because of the safety profile of these agents.

The Table summarizes the results of recent, well-controlled, double-blind, placebo-controlled studies of pharmacotherapies for comorbid depression and alcohol dependence. Typically, these trials have provided antidepressant medication and some form of weekly psychosocial treatment or counseling. (See also earlier reviews by Nunes and Levin¹⁹ and Pettinati.²⁰)

Six of the 9 studies (67%) that compared an antidepressant medication with placebo found a relationship between the medication and reductions in depressive symptoms, irrespective of type of antidepressant (eg, TCAs, SSRIs). Only 3 of the 9 studies (33%) found an advantage for the medication over placebo in reducing drinking in depressed alcohol-dependent patients. In the largest (N = 345) multicenter trial of sertraline(Drug information on sertraline) (50 to 150 mg/d for 10 weeks), the drug provided no advantage over placebo in reducing depressive symptoms, nor did it reduce drinking, compared with placebo.²¹ Because of this trial’s size, the results challenged those of all the other trials, indicating that antidepressants alleviate depression in depressed patients with alcohol dependence.

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by Chevies Newman | October 26, 2012 9:53 PM EDT

PS
I meant to say it is difficult to determine medicine requirements long term until the opiod "hole" is plugged. Certainly one can and should do whatever appropriate in the short term.

by Chevies Newman | October 26, 2012 9:46 PM EDT

The thinking on addiction, in general, was also dramatically altered with the successful use of suboxone for those with opiod addiction. The paradigm may shift, for some, to one of less use and less problematic use. Topirimate and 5Ht-3 antagonists also demonstrate promise in drinking reduction; Physical dependence is probably a different physiologic burdon in which complete abstinence would be essential.

Naltrexone reduces satisfaction by blocking opiod receptors. Drinking becomes less pleasurable long enough to get the reward mechanism retuned. It is not antabuse.

Consider the at risk drinker, say 4 solid cocktails a night, who has anxiety and issues of insomnia. There is no apnea or legal problems. Alcohol and benzos both target GABA neurons. Would a long acting benzo, say 1 mg of clonazepam, help control the insomnia and reduce the drinking or is there a greater risk of worsening the problem? Would the addition of topirimate, Mirtazapine, and naltrexone along with the benzo at night help reduce the risk of progression.

I deal with the medications not hammerring too hard on the booze. I see much more opiod dependence and combined substance use as Peter below has said. In contrast, I thought the article good. It brings to light the interconnectedness of the brain that by blocking opiod receptors, satisfaction is diminished from a gabanergic drug. A life of exclusion is difficult to imagine for any addict. The old model of "higher power" therapy must accomidate broadening scientific views. Addiction psychiatry is not easy, but one cannot really begin the pharmacology until the opiod issue is managed. Suboxone is a godsend and plugs in the gap.

I wonder what happens to alcohol use in those with comorbid addictions treated with an opiod partial agonist?
If it decreases, well, uh, just maybe suboxone...

by Karen Fowler | October 24, 2012 8:04 AM EDT

HI, I have been nursing since 1986 and it saddens me that we are still talking about treating dual diagnosis. This was a topic and an obvious solution for me since 1986. Why does practice still need to keep educating professionals of this importance. Why are systems still only treating the one at time. Holistic approach is not new. It makes me sad. I am tired of hearing "we are now going to treat both", "we are now going to set up a practice that includes both". Yet the system does not. I live in NS and it seems like things have gone backwards for those struggling with mental health issues and addiction issues.

by Peter Weiser | October 18, 2012 10:48 AM EDT

"...This combined pharmacotherapy, with some platform counseling that integrates support and advice for both disorders, can provide an aggressive approach to treating co-occurring depression and alcohol dependence."

The efficacy of both drugs on their own for treating depression and alcohol abuse is rather weak. The authors give little credit to the effective therapy of motivational therapy combined with CBT on both alcohol abuse and depression.

Single drug abuse, especially just alcohol abuse, is rare in this culture. "Medical"and recreational use of marijuana is widespread and very rarely does one in actual clinical practice see a "pure alcoholic."

In my opinion the article is overly simplistic and as such not particularly helpful in clinical practice.

by Barrie March | October 11, 2011 11:32 AM EDT

Either bupripion or stimulant drugs in combination with naltrexone would make more sense from a physiologic standpoint for the treatment of depression in the active alcoholic than do TCAs or SSRIs..

Also in this Special Report

Introduction: Comorbidity, Cognition, and Pharmacotherapies

Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence

Novel Therapies for Cognitive Dysfunction Secondary to Substance Abuse

Comorbid Depression and Alcohol Dependence

Comorbid Depression and Alcohol Dependence

New Approaches to Dual Therapy Challenges and Progress

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