Karen Drexler, M.D. ALCOHOLISM AND DEPRESSION

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1 Karen Drexler, M.D. for the DUMC Alcohol Awareness Task Force ALCOHOLISM AND DEPRESSION

2 Overview What is major depression? What is alcohol dependence? Does depression lead to alcohol dependence? Does alcohol dependence lead to depression? Is there effective treatment for both?

3 What is Major Depression?

4 Depression in the Bible My God, my God, why have you forsaken me?... I cry by day, but you do not answer; and by night, but find no rest I am a worm, and not human My heart is like wax; it is melted within my breast; my mouth is dried up I can count all my bones. Psalm 22

5 What is Major Depression?

6 What is Major Depression? Persistently depressed mood Diminished interest or pleasure Sleep disturbances Appetite and weight changes Marked fatigue Worthlessness Poor ability to concentrate Disturbance of spontaneous movement Thoughts of death

7 What is Alcohol Dependence?

8 Alcohol in the Bible Noah was the first to plant a vineyard. He drank some of the wine and became drunk, and he lay uncovered in his tent Gen 9:20 you shall offer one fourth of a hin of wine as a drink offering with the eburnt offering Num 15:5 55 but he said to me, You shall conceive and bear a son. So then drink no wine or strong drink. Judges 13:7 Woe to those who are heroes at drinking wine and champions at mixing drinks Isa 25: Stop drinking only water, and use a little wine because of your stomach... 1 Tim 5:23

9 How much is too much? WHO and NIAAA recommend: For men < 65 years, No more than 14 drinks per week No more than 4 drinks per day For men >65 years and women of any age, g, No more than 7 drinks per week No more than 3 drinks per day

10 WHAT S A STANDARD DRINK? What s a Standard Drink? What s a Standard Drink? In the U.S., a standard drink is any drink that contains about 14 grams of pure alcohol (about 0.6 fluid ounces or 1.2 tablespoons).

11 Choice The voluntary act of selecting from two or more things that which is preferred How do we decide what is preferred? Sensory input Memory With or without conscious deliberation Driving Hunting 11

12 12

13 DSM IV Alcohol l Dependence Tolerance Withdrawal Larger amountsthan intended Efforts to cut down or controluse Great deal of timespent drinking or recovering Important t activitiesgiven iti i upor reduced d Use despite psychological or physical problemcaused d by or exacerbated btd by use 13

14 How do Alcohol and Depression Relate in the Bible? I tried cheering myself with wine and embracing folly Ecc 2:3

15 How Do Alcoholism and Depression Relate? Depression Alcohol dependence Alcohol: mood initially Depressed mood becomes a trigger for alcohol craving and relapse Alcohol dependence Depression Alcohol is a CNS depressant (Schukitt et al) Depression improves in patients in treatment for alcoholism over 2 to 4 weeks

16 Prevalence of SMI in Patients with SUDs Gen Pop 15 AUD 10 DUD 5 0 Mood D/O BPD MDD Anxiety D/O Grant et al: 2004

17 Prevalence of Major Depression General Pop 6 SUDs Compton 2006 NLAES, NESARC

18 What About Treatment? Alcohol Dependence Medications Disulfiram (Antabuse ) Naltrexone (Revia ) Acamprosate (Campral ) Psychotherapy Cognitive behavioral therapy Twelve step facilitation Motivation enhancement Behavioral family therapy Major Depression Medications Serotonin specific reuptake inhibitors (SSRIs) Broad spectrum reuptake inhibitors Psychotherapy Cognitive behavioral therapy Psychodynamic psychotherapy

19 Alcohol Metabolism CH 3 -CH 2 -OH (ethanol) Alcohol Dehydrogenase CH 3 -CH = O (acetaldehyde) Aldehyde Dehydrogenase (*inhibited by disulfiram) CO 2 + H 2 O + energy 19

20 Alcohol Metabolism CH 3 -CH 2 -OH CH 3 -CH = O (Acetaldehyde) Alcohol Dehydrogenase Aldehyde Dehydrogenase CO 2 + H 2 O + energy

21 Disulfiram (Antabuse ) Mechanism of action: Irreversibly inhibits aldehydedehydrogenase Disulfiram Ethanol Reaction Common: HR, BP, HA, flushing, nausea, vomiting, shortness of breath Severe: confusion, shock, cardiac arrhythmias or arrest Risk of severe reaction increases with increasing dose of disulfiram and of alcohol

22 Disulfiram Dose: 250 mg to 500 mg p.o. per day Adverse events Metallic taste, sedation, HA, drowsiness, rash Hepatitis, peripheral neuropathy Caution: DO NOT take with alcohol

23 Naltrexone Acts at Opioid Receptors

24 Naltrexone (Revia ) Mechanism of action: μ Opioid receptor blocker Consistent effect on reducing relapse Dose: 25 mg first dose, then 50 mg q day Must be opioid free for 7 10 days Less side effects if alcohol free l for 5 days Adverse events (partial) Nausea, headache, dizziness, nervousness, insomnia, pain and cramping

25 Good clinical outcome: Naltrexone Project COMBINE Percentage Placebo Naltrexone

26 Disulfiram and Naltrexone in Alcohol Dependence and Depression 254 patients with mental illness and alcohol dependence; 139 had current major depression Randomized to receive 12 weeks of: Disulfiram and naltrexone Disulfiram and placebo Naltrexone alone Placebo alone All continued to receive usual treatment for co occurring occurring conditions Pt Petrakis et al: 2007

27 Percent Days Abstinent Depression No depression 0 Petrakis et al: 2007

28 Change in Depression Severity Pre Tx Depression Post Tx Depression Pt Petrakis et al: 2007

29 Acamprosate (Campral ) Mechanism of action: May act by ing NMDA glutamate activity Eliminated through kidney, not liver Early European trails showed strong effect 4 multisite clinical trials have shown no effect Dose: 333 mg 666 mg three times daily Adverse events: Headache, diarrhea, nausea, vomiting

30 Treatment for Depression and Alcohol Dependence SSRIs (Prozac, Zoloft, Celexa, etc.) Improve mood reactivity and neurovegetative signs of depression Consistently reduce alcohol consumption in rats Reduces alcohol use and improves depression in patients with depression and alcohol dependence 30

31 Summary Alcohol dependence and major depression are common medical conditions They commonly occur together Both respond to treatment Combining medication for both conditions Co b g ed cat o o bot co d t o s improves outcome for both disorders

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