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Home » Major Depressive Disorder

Psychiatric Times. Vol. 28 No. 6
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SUBSTANCE ABUSE: ADDICTION & RECOVERY 

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.

New treatment strategy

We recently published the results of a double-blind, placebo-controlled, 14-week trial of 170 alcohol(Drug information on alcohol)-dependent patients with major depressive disorder. Two FDA-approved medications were evaluated, one for depression (sertraline) and one for alcohol dependence (naltrexone).22 An important aim of the study was to compare mood and drinking outcomes with the combined medications with those with placebo and with single-medication treatment. Patients received either 200 mg/d of sertraline(Drug information on sertraline), 100 mg/d of naltrexone(Drug information on naltrexone), a combination of the two, or a double placebo for 14 weeks while receiving weekly cognitive-behavioral therapy.

(MORE: Novel Therapies for Cognitive Dysfunction Secondary to Substance Abuse)

The sertraline-naltrexone combination produced a higher alcohol abstinence rate (53.7%; P = .001; odds ratio [OR] = 3.7) and a longer delay before relapse to heavy drinking (median delay, 98 days; P = .003; Cohen d = .54) than the other treatments: naltrexone (21.3% abstinent; delay, 29 days), sertraline (27.5% abstinent; delay, 23 days), or placebo (23.1% abstinent; delay, 26 days). A trend was also seen in the relief of depression symptoms in the medication combination group by the end of treatment (83.3% not depressed; P = .014; OR = 3.6) compared with the single-medication or placebo group.

The patients treated with an SSRI and an opiate antagonist achieved greater abstinence from alcohol, delayed relapse to heavy drinking, and relief of depression symptoms by the end of treatment than did patients who received naltrexone or sertraline alone or placebo. As with other initial findings from clinical trials, the results await replication in other settings with different patient populations and with other antidepressants.

Summary and future directions

Empirical data that support effective treatments for co-occurring depression and alcohol dependence are long overdue. Comorbid prevalence rates are formidable, and numerous reports describe patients with comorbid depression and alcohol dependence as clinically more severely ill and more difficult to keep well than patients who are either depressed or alcohol-dependent. Positive outcomes may depend on both the type and timing of the medication and psychosocial interventions needed to treat both disorders to symptom remission, as well as a solid doctor-patient relationship, attention to treatment compliance, and a commitment to treat both the alcohol dependence and the mood disorder.

While it seems logical to prescribe antidepressants for patients who are depressed, some alcohol-dependent patients—as well as some clinicians who treat them—are unwilling to use a medication. Fortunately, bias is fading as scientists learn more about treating the addicted brain with certain medications and correcting the neurobiology of addiction. Over the past 20 years, results from the majority of well-controlled trials have showed that antidepressants reduced depressive symptoms in patients with depression and alcohol dependence. However, in most of the trials, these medications had virtually no effect on reducing excessive drinking.

Recently published results of a controlled trial indicate that combining a medication to treat alcohol (naltrexone) with the antidepressant sertraline might be the optimal course of treatment for co-occurring depression and alcohol dependence.22 While these findings require replication, they provide a practical recommendation to integrate or combine 2 medications—1 for treating alcohol dependence and 1 for treating depression. 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.

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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





Acknowledgment—We thank Amy Leshner for technical assistance.

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13. Niciu MJ, Chan G, Gelernter J, et al. Subtypes of major depression in substance dependence. Addiction. 2009;104:1700-1709.

14. Ries RK, Demirsoy A, Russo JE, et al. Reliability and clinical utility of DSM-IV substance-induced psychiatric disorders in acute psychiatric inpatients. Am J Addict. 2001;10:308-318.

15. Reis RK, Yuodelis-Flores C, Comtois KA, et al. Substance-induced suicidal admissions to an acute psychiatric service: characteristics and outcomes. J Subst Abuse Treat. 2008;34:72-79.

16. Nunes EV, Liu X, Samet S, et al. Independent versus substance-induced major depressive disorder in substance-dependent patients: observational study of course during follow-up. J Clin Psychiatry. 2006;67:1561-1567.

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18. Hesse M. Integrated psychological treatment for substance use and co-morbid anxiety or depression vs. treatment for substance use alone. A systematic review of the published literature. BMC Psychiatry. 2009;9:6.

19. Nunes EV, Levin FR. Treatment of depression in patients with alcohol or other drug dependence: a meta-analysis. JAMA. 2004;291:1887-1896.

20. Pettinati HM. Antidepressant treatment of co-occurring depression and alcohol dependence. Biol Psychiatry. 2004;56:785-792.

21. Kranzler HR, Mueller T, Cornelius J, et al. Sertraline treatment of co-occurring alcohol dependence and major depression. J Clin Psychopharmacol. 2006;26:13-20.

22. Pettinati HM, Oslin DW, Kampman KM, et al. A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence. Am J Psychiatry. 2010;167:668-675.

23. Mason BJ, Kocsis JH, Ritvo EC, Cutler RB. A double-blind, placebo-controlled trial of desipramine for primary alcohol dependence stratified on the presence or absence of major depression. JAMA. 1996;275:761-767.

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