Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood...

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Advances in Diagnosis, Neurobiology, and Treatment of Mood Disorders June 13 - 14, 2016 Field House Coral Gables University of Miami Coral Gables, FL

Transcript of Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood...

Page 1: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Advances in Diagnosis, Neurobiology, and Treatment of Mood Disorders June 13 - 14, 2016 Field House Coral Gables University of Miami Coral Gables, FL

Page 2: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Alcohol and Substance Abuse and Their Comorbidity with Mood Disorders Ihsan M. Salloum, MD, MPH, DFAPA Professor of Psychiatry Chief, Division of Alcohol and Drug Abuse: Treatment and Research Director, Addiction Psychiatry Fellowship Program Department of Psychiatry University of Miami Miller School of Medicine Miami, FL

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Ihsan M. Salloum, MD, MPH, DFAPA

●  Research Support: The National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute of Drug Abuse (NIDA)

●  Consultant: Orexigen Therapeutics Inc.; Takeda Pharmaceuticals U.S.A., Inc.

Disclosures

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Acknowledgment

● Research Supported by ● The National Institute on Alcohol Abuse and

Alcoholism (NIAAA) ● The National Institute of Drug Abuse (NIDA) ● The National Institute of Mental Health

(NIMH) ● The Department of Veterans Administration

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Learning Objectives

● Describe the relationship between mood disorders and substance use disorders.

● Implement evidence-based, best-practice options for treatment of mood disorders and comorbid alcohol and substance use disorders.

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Audience Response

How confident are you in identifying clinical signs and symptoms of common mood disorders when treating alcohol and substance use disorder patients? A.  Extremely confident B.  Confident C.  Somewhat confident D.  Not at all confident

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Audience Response

What percentage of people with alcohol dependence report having depressive symptoms? A.  40% B.  50% C.  70% D.  80%

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Audience Response

Which of the following are common measures used in addiction for withdrawal symptoms?

A.  CIWA, COWS B.  CIWA, OCDS C.  COWS, CAGE D.  OCDS, CAGE

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Agenda

1.  Significance of the problem ● Prevalence & Consequences

2.  Challenges ● Diagnostic & Treatment Issues

3.  Pharmacotherapy Trials 4.  Summary

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Disease Burden

● Mood disorders and substance use disorders are among the most frequent causes of disability worldwide

Murray, CJ, et al. Lancet. 2012;380(9859):2063-2066. PMID: 23245602.

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Disease Burden DALY

0 2 4 6 8 10 12 14 16 18 20

HIV/AIDS Hearing Loss, adult onset

Schizophrenia Migraine

Bipolar Disorder Self Inflicted Injuries Drug Use Disorders

Road Traffic Accidents Alcohol Use Disorders

Unipolar Depressive Disorders

Disability Adjusted Life Year (DALY), 15 – 44 yr olds

USA, Canada, and West Europe, 2000

WHO – Burden of Disease Statistics. http://www.who.int/healthinfo/global_burden_disease/en/

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46.2  

39.2  33.7  

28.7  24  

21  16.5   13.5  

0  

10  

20  

30  

40  

50  

Pro

porti

on (%

)

Diagnosis

Lifetime Rates of Alcoholism in Major Psychiatric Disorders

BP = bipolar disorder; Schiz = schizophrenia’ PD=Panic disorder, OCD = obsessive compulsive disorder; MDD = major depression Regier DA, et al. JAMA 1990;264(19):2511–2518.

BP I BP II MDD Gen Pop OCD Dysthymia PD Schiz

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Mood Disorders and Substance Abuse

9.1

21.1

2.1 0.8

6.9

14.1

0

5

10

15

20

25

Alcohol Abuse

Alcohol Dep

Cannabis Use

Cannabis Abu/Dep

Benzo Abuse

Benzo Dep

MDD Mania Bip II

Merikangas, KR, et al. Arch Gen Psychiatry 2008;65(1):47-52.

20 Yrs Follow-Up: The Zurich Cohort Study

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Substance Use and Mood Disorders

AL = Alcohol; Dr = Drugs; DP = Dependence, AB = Abuse; GP = General Population N = 42,000 (NESARC) Odds Ratio Grant BF, et al. Arch Gen Psychiatry. 2004;61(8):807-816.

4.9 5.7

13.9

1.4

4.2

0 0 2 4 6 8

10 12 14 16

Any SUD AI DP Dr DP AL AB Dr AB GP

Mania Hypomania

12 Months Likelihood (ORs) of an Additional SUD in Mania and Hypomania

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Depression is Very Common in Alcohol Dependence

Those with alcohol dependence: ● 80% report depressive symptoms ● 33% have MDD diagnosis ● Women > men

Kessler R, et al. Arch Gen Psychiatry. 1997;54(4):313-321.

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Alcohol Dependence with Comorbid Major Depression or Dysthymia

OR MDD = Men: 2.95; Women: 4 – OR DYS = Men: 3.8; Women: 8 Kessler R, et al. Arch Gen Psychiatry. 1997;54(4):313-321.

24.3

12.7 11.2

4.8

48.5

21.3 20.9

3.63

0 5

10 15 20 25 30 35 40 45 50

% MDD % GP MDD % DYSTH % GP DYS

Men Women

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Alcoholism in Bipolar Men and Women

2.8  

7.35  

0  

1  

2  

3  

4  

5  

6  

7  

8  

Men   Women  *Odds ratio compared to ECA sample weighted by age, race, gender; BP men OR=2.8 (95% CI: 1.59-4.81); BP women OR= 7.35 (95% CI: 3.32-16.26) † P < .0001 Frye MA, et al. Am J Psychiatry 2003;160:883-889.

Odd

s R

atio

* (O

R)

† •  N = 267 •  116 men, 151 women

•  Rates of alcoholism: •  BP men = 49% •  BP women = 29%

Odd

s R

atio

* (O

R)

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The Challenge of Mood Disorders–SUD comorbidity

● Complicated course (Rec/Relap/polysympt.) ● Suicidality and increased mortality ● Dysfunctions (family, social, emp/edu) ● Multiple morbidities (Medical & psychiatric) ●  Unstable housing and homelessness ● Violence, legal problems, incarceration ● More service use (days in hospital, ER visits,

use of SUD and MH services)

Salloum IM, Thase M. Bipolar Disorders 2000;2(32):269-280. Salloum & Thase. Bipolar Disorders 2000;2(32):269-80

SUD = substance use disorder, MH = mental health

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Reciprocal Negative Impact MD SUD

● Diagnostic confusion

● Treatment compliance

● Treatment response

● Course and outcome of illness

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Diagnostic Issues

● Drinking vs. alcoholism; sadness vs. depression; alcohol induced vs. primary ● Rating scales & structured interviews ● DSM-5 guidelines ● Prior or during abstinence from alcohol ● Better accounted for by depression ● Does not occur only during intoxication/

withdrawal ● Prior episodes & family history

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Diagnostic Accuracy & Medications in the Context of Alcoholism & SUD

● Diagnostic Accuracy ● Duration of drug free observational period:

4 vs....... 1 week? ● Advantage & disadvantage of initiating

medication ● Studies of depressed alcoholics

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Limited Change in Depressive Symptoms on Placebo (HAMD-24)

Cornelius JR, Salhoum, IM, et al. Arch Gen Psychiatry. 1997;54(8):700-705.

N=25 N=26

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Alcohol & SUDs Impact on the Course of Mood Disorders

Mood Disorders Course

Alcohol & SUD Impact

Response Worsens respond to medication

Remission Prolong sick state

Recovery Maintain persistent symptom & impair coping skills

Relapse Increase risk for depression relapse

Recurrence Maintain sub-syndromal state; Psychosocial stress

Cornelius JR, Salloum IM, et al. Addict Behav. 2000;25(2):307-310.

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Mood Disorders as a Risk for Alcohol & SUDs Relapse

● Alcohol & substance use as “self-medicating” the symptoms of mood disorders?

● Mood disorders increases vulnerability to alcohol relapse by decreasing stress coping abilities

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Depression as a Risk for Alcohol & SUDs Relapse

● Stressors that exceed the adaptation capacity of the individual lead to relapse

● Depression impacts multiple areas of adaptation abilities predictive of relapse

● Effect of stress on alcohol problem was found to be mediated by depression

Brown SA, et al. J Stud Alcohol 1995;56(5):538-545.

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Depression Impacts on Adaptation Capacity Which Predicts Relapse

● Impairment in coping skills

● Impairment in self-efficacy

● Influence availability of social support

● Cognitive distortion

● Irrational beliefs

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Major Depression & Gender Predict Relapse

Greenfield SF, et al. Arch Gen Psychiatry. 1998;55(3):259-265.

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Untreated Depression Leads to Early Relapse

Mason BJ, et al. JAMA. 1996;275(10):761-767.

N=71

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Untreated Depression Leads To Early Relapse

Greenfield SF, et al. Arch Gen Psychiatry. 1998;55(3):259-265.

N=40 women N=61 men

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Fluoxetine in Depressed Alcoholics One Year Follow-up

Cornelius JR, G, Salloum IM, et al. Addict Behav. 2004;29(5):1035-1038.

0

20

40

60

80

100

120

HAM-D-24 Days Intoxicated GAS

Fluoxetine Placebo

N=116

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Bipolar SUDs Relationship

SUD on Bipolar ● Course Modifier ● Earlier onset ● Shorter cycle length ● Persistent symptom ● Delayed recovery ● Rapid cycling?

● Episode Modifier ● More symptoms ● Worsens depression ● Mixed episodes ● Episode switch?

Bipolar on SUD ● Bipolar as risk factor ● Bipolar predate SUD ● Mood states (mania) ● Impulsivity ● Self-medication ● Impaired coping skills ● Neurobiological factors

● Adolescent onset BPD

Salloum IM, Thase ME. Bipolar Disorders 2000;2(32):269-280.

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Bipolar Multi-Symptoms Disorder

Goodwin FK, Jamison KR. Manic-Depressive Illness. New York, NY: Oxford University Press; 1990:85-125

•  Euphoria/ Grandiosity •  Pressured speech •  Impulsivity •  Excessive libido •  Recklessness •  Social intrusiveness •  Decrease need for sleep •  Hyperactivity

MANIA

•  Depression •  Anxiety •  Irritability •  Hostility •  Violence or suicide

DEPRESSION

PSYCHOSIS •  Delusions •  Hallucinations

COGNITION •  Racing thoughts •  Distractibility •  Disorganization •  Inattentiveness

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Long-term Natural History of the Weekly Symptomatic Status of Bipolar I Disorder

52.7  31.9  

9.3  5.9  

Asymptoma9c  

Depression  

Mania  

Cycling/Mixed  

%  Follow-­‐up  Weeks  

Judd LL, et al. Arch Gen Psychiatry. 2002;59(6):530-537.

Percentage of Follow-up Weeks Spent at Specific Affective Symptom During Long-term Follow-up of 146 Patients With Bipolar I Disorder

Page 34: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Residual Symptoms Increase Future Episode Relapse Risk

Judd LL, et al. Arch Gen Psychiatry. 2008;65(4):386-394.

Time from End of Intake MDE/Mania to Next Major Affective Episode, wk

Par

ticip

ants

Rem

aini

ng F

ree

of

Maj

or A

ffect

ive

Epi

sode

R

elap

se/R

ecur

renc

e, %

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Etiology: Pathophysiology

Koob GF. Alcohol Clin Exp Res, 2003, 27(2):232-243.

+Risk Factors: Genetic, Environmental, Stress

Positive Reinforcement

Negative Reinforcement

Hypomania Impulsivity Sensation-seeking Mood Instability

Page 36: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Reward Transmitters Implicated in the Motivational Effects of Drugs of Abuse

Koob GF. Alcohol Clin Exp Res, 2003, 27(2):232-243.

Dopamine … “dysphoria”

Opioid peptides ... pain

Serotonin … “dysphoria”

GABA … anxiety, panic attacks

Dopamine

Opioid peptides

Serotonin

GABA

Positive Hedonic Effects

Negative Hedonic Effects of Withdrawal

Mania: Positive hedonic state

Depression: Negative hedonic state

Page 37: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Medical Burden in Patients with Severe Psychopathology

● Major depression ● Bipolar disorder ● Schizophrenia ● Alcoholism and other

substance use disorders

Obesity Diabetes Cardiovascular Chronic resp.

HIV / V.Hep / STD/ TB Trauma, Suicide

Chronic mental disorders are associated with physical disorders and excess mortality

Salloum IM, et al. Ann of General Psych. 2008.

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Mortality in Unipolar, Bipolar, and Schizophrenia for Females (SMR)

SMR = standardized martality ratio (# of observed cases / # of expected) Osby U, et al. Arch Gen Psychiatry. 2001;58(9):844-50. Osby U, et al. Schizophr Res. 2000;29;45(1-2):21-8.

13.2

1.6 2.7

12.7

2.1 2.7

0

2

4

6

8

10

12

14

Unnatural Natural All Causes

Unipolar Bipolar Schizophrenia

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Death by Injury

OMI = other mental illness; SUD = substance use disorders Dickey B, et al. J Behav Health Serv Res. 2004;31(1):75-85.

3.55

8.11

2.84

6.09

3.57

0 1 2 3 4 5 6 7 8 9

Psychosis Psychosis + SUD

OMI OMI + SUD SUD only

Adjusted Odds of Death by Injury in Medicaid Beneficiaries

Odd

s R

atio

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Management of Mood Disorders with Comorbid SUD

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Treatment Integration for Comorbid Bipolar & Addictive Disorders

● System Integration ● From financing to access

● Provider Factors ● Training and commitment

● Interventions ● Medications and psychosocial interventions

● Consumer Factors ● Recognition of interrelationship of the two

diseases

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0

5

10

15

20

25

30

initial discharge 3month

Time

BD

I M

ean

Sco

re

depression

bipolar

0

5

10

15

20

initial discharge 3month

Time

Mean

OC

DS

sco

res

depression

bipolar

0

5

10

15

20

25

30

initial discharge 3month

Time

Mean

BA

I S

co

res

depression

bipolar

0

1

2

3

4

5

6

7

initial discharge 3month

Time

Mean

YM

S S

co

res

depression

bipolar

Integrated RX at the Programmatic Level Outcome of “FIRESIDE” program, Alcoholism + Mood (N = 228 adults) Abstinence rates: 60% @ 3m; 50% @ 6m

Slide Courtesy of Dr. Conor Farren Farren C, McElroy S. J Affect Disorder. 2008;106(3):265-272.

Depression Craving

Mania Anxiety

Page 43: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Common Measures Used in Addiction

● Short screening & syndrome measures: ●  CAGE, AUDIT, AUDIT-C, DUDIT, TLFB,

DSM-5 checklist ● Measures of craving: ● Penn Alcohol Craving Scale, OCDS

● Measures of consequences/severity: ● SIP, ASI (alcohol, drug, social, family,

medical, employment and legal) ● Measures of withdrawal syndromes: ● CIWA, COWS

SAMHSA-HRSA. Clinical Practice Screening Tools. SAMHSA Website: http://www.integration.samhsa.gov/clinical-practice/screening-tools

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Alcohol Use Disorder Identification Test-C (Score 0-12) ●  How often did you have a drink containing alcohol in

the past year? ●  0: never, 1: 1 or less month, 2: 2-4 month, 3: 3x week, 4: 4-5/

week, 4: 6 x week ●  How many drinks did you have on typical day when you

were drinking in the past year? ●  0: 0 or 1-2 drinks, 1: 3-4, 2: 5-6, 3: 7-9 , 4: 10 or more

●  How often did you have 6 or more drinks on one occasion in the past year? ●  0: never, 1: <1/month, 2: monthly, 3: weekly, 4: daily

AUDIT-C: BushK, et al. Arch Intern Med. 1998;158(16):1789-1795.

Score of 3: Sensitivity: 90% active abuse/dep; 98% heavy drinkers; Specificity 60%; Score of 4: 86% specificity heavy drinking; 72% for abuse/dependene

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Stabilization of Bipolar Disorder and Substance Abuse

● Aggressive acute stabilization ● Mania ● Depression ● Rapid cycling ● Alcohol/SUD

withdrawal

● Relapse Prevention ● Maintenance mood

stabilization ● DBSupportAlliance ● Alcohol relapse

prevention ● AA/DD support

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Treatment of Alcohol Withdrawal in Psychiatric Patients ●  Goals

●  Prevent complications ●  Alleviate withdrawal

symptoms ●  Initiate process of

recovery “window of opportunity”

●  Principles ●  Medication half-life ●  Symptom-triggered

therapy ●  Effective in preventing

complications

76

10 9 5

0

10

20

30

40

50

60

70

80

0 20 40-100 >120

WAS Symptom Triggered Diazepam

Loading Dose

Diazepam loading dose/ CIWA-Ar (Seller, et al. 1983) Salloum IM, et al. Psychopharm Bull.1995;31(2):305-310.

% P

atie

nts

Diazepam Dose

Page 47: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Paradigms of Medications Trials for Mood Disorders & SUD

Monotherapy Trials: 1 med. – 2 outcomes ●  Medications Bipolar Dis.

●  Mood Stabilizers (Lithium, Anticonvulsants) ●  Valproic acid,

carbamazepine (ER), lamotrigine

●  Antipsychotics (Atypical) ●  Quetiapine, aripiprazole

risperidone, olanzapine, ziprasidone, clozapine

●  Antidepressants SSRIs, SNRIs, TCAs,

Combined meds: 2 meds. – 2 outcomes ●  Medications for SUD

●  Alcoholism ●  Disulfiram*, Naltrexone*

(PO, IM), Acamprosate*, Topiramate, Gabapentin

●  Tobacco ●  Varenicline, bupropion,

NPT ●  Cocaine ●  Cannabis ●  Opioid ●  Methadone, suboxone,

naltrexone * FDA approved for SUD

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Placebo-Controlled Trials in Bipolar Disorder and Cocaine Use Disorder

Study Medication N Wks Design Cocaine outcome

Brown et al, 2007 Citicoline 44 12 D-blind Advantage over PBO

Brown et al., 2012 Citicoline 60 12 D-blind

Advantage* Methamphetamine

Depression(BP&MDD)

Brown et al., 2012 Lamotrigine 112 110 D-blind Advantage on money

spent on cocaine

Brown et al., 2015 Citicoline 130 12 D-blind Advantage on + urine

early in trial

Brown ES, et al., 2007. J Clin Psychopharmacol. 27 (5): 498-502.; Brown ES, et al., 2012. J Affect Disord. 143(1-3): 257-260.; Brown ES, et al., 2012. Neuropsychopharmacology. 37 (11):2347-2354.; Brown ES, et al. 2015. Am J Psychiatry. 172(10):1014-1021.

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Placebo-Controlled Trials in Bipolar (I-II) Disorders and Alcoholism

Study Medication N Wks Design Alcohol outcome

Salloum et al., 2005 Valproic acid 59 24 D-blind Advantage over PBO

Brown et al., 2008 Quetiapine 115 12 D-blind No advantage

Brown et al., 2009 Naltrexone 50 12 D-blind Trend toward advantage

Stedman et al., 2010 Quetiapine 362 12 D-blind No advantage

Tolliver et al., 2012 Acamprosate 33 12 D-blind No advantage

Brown et al., 2014 Quetiapine* 90 12 D-blind No Advantage

Salloum IM, Olagunju Y. Current Psychiatry Reviews 2008, 4: 14-27. *Brown ES, et al. Alcoh Clin Exp Res 2014, 38 (7):2113-2118.

Page 50: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Divalproex Impact on Heavy Drinking Days

p = .02 Salloum IM, et al. Arch.Gen.Psychiatry. 2005;62(1):37-45.

0.19

0.09

0

0.1

0.2

PBO (n = 25) Valproate (n = 27)

Divalproex Significantly Decreases % of Heavy Drinking Days

Pro

porti

on o

f H

eavy

Drin

king

Day

s

Page 51: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Divalproex Efficacy in Alcohol Use Disorder

P = .02*; *Medication adherence as covariate in the Mixed Model Salloum IM, et al. Arch.Gen.Psychiatry 2005;62(1):37-45.

10.2

5.59

0

2

4

6

8

10

12

PBO (n = 25) Valproate (n = 27)

Divalproex Significantly Decreases # of Drinks per Heavy Drinking Days

Num

ber o

f Drin

ks p

er

Hea

vy D

rinki

ng D

ays

Page 52: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Figure 1

Study Day

2001000

Pro

port

ion

Not

Rel

apsi

ng to

Sus

tain

ed H

eavy

Drin

king

1.0

.8

.6

.4

.2

0.0

Relapse to Sustained Heavy Drinking

Salloum IM, et al. Arch Gen Psychiatry. 2005;62(1):37-45.

Kaplan-Meier log rank 3.90, p < .05

Valproate: mean 93 days to relapse

Placebo: mean 62 days to relapse

Page 53: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Valproate vs. Placebo Effect on Glutamyl Transpeptidase (GTP)

p = .045 Salloum IM, et al. Arch. Gen. Psychiatry 2005;62(1):37-45.

81

66

0 10 20 30 40 50 60 70 80 90

PBO (n = 25) Valproate (n = 27)

GTP

(IU

/L)

Page 54: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

SSRIs Studies in Comorbid MDD & Alcoholism

Study Medication N Wks Design Conclusion

Kranzler, 2006 Sertraline 328 12 D-blind No advantage

Gual, 2003 Sertraline 83 24 D-blind No advantage*

Moak, 2003 Sertraline 82 12 D-blind No advantage**

Pettinati , 2001 Sertraline 100 14 D-blind - if MDD hx ***

Roy, 1998 Sertraline 36 6 D-blind ↓ MDD

Cornelius, 1997 Fluoxetine 51 12 D-blind ↓ MDD, ↓ AL

Kranzler, 1995 Fluoxetine 101 12 D-blind ↓ MDD, ↓ AL***

Adamson, 2015 Nalt ± Citalopram 130 12 D-blind No advantage

*+ on MDD for severe sub.; ** ↓ MDD in females, ↓ # D/DD ; *** Alcohol dep. sample Salloum IM, Olagunju Y. Current Psychiatry Reviews 2008;4:14-27.

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Non-SSRI Studies in Comorbid MDD and Alcoholism

Study Medication N Wks Design Conclusion

Garcia-Portilla, 2005 Venlafaxine 90 24 Open Label Improved MDD/AL

Hernandex-Avila, 2005 Nefazadone 40 10 D-blind Improved AL

Roy-Byrne, 2000 Nefazadone 64 12 D-blind Improved MD

McGrath, 1996 Imipramine 69 12 D-blind Improved MD

Mason, 1996 Desipramine 71 (28) 24 D-blind Improved MDD/AL

Nunes, 1993 Imipramine 60 12 D-blind Improved MDD/AL

Altamura, 1990 Viloxazine 31 12 D-blind Improved MDD/AL

Salloum IM, Olagunju Y. Current Psychiatry Reviews 2008;4:14-27.

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Comorbid MDD and Opioid

Study Medication N Wks Design Conclusion

Carpenter, Brooks, et al., 2004 Sertraline 95 12 D-blind

No advantage Role of environment

Dean et al. 2002 Fluoxetine 49 12 D-blind No advantage

Petrakis et al, 1998 Fluoxetine 44 12 D-blind No advantage

Nunes, 1998 Imipramine 84 12 D-blind Decreased depression less so drug

Kleber et al, 1998 Imipramine 48 8 D-blind No advantage

All in methadone maintenance population Salloum IM, Olagunju Y. Current Psychiatry Reviews 2008, 4: 14-27.

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Comorbid MDD and Cocaine

Study Medication N Wks Design Conclusion

Schmitz et al., 2001 Fluoxetine 68 12 D-blind No advantage

Ciraulo et al. 2005 Nefazadone 69 8 D-blind Dec cocaine*

McDowell et al, 2005 Desipramine 111 12 D-blind Dec depression but not

cocaine

Nunes, 1995 Imipramine 113 12 D-blind Dec depression but not cocaine

*Groups not balanced at baseline Salloum IM, Olagunju Y. Current Psychiatry Reviews. 2008;4:14-27.

Page 58: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Effect of Antidepressant Medication on Outcome of Depression (Hamilton Depression Scale)

Nunes EV. et al. JAMA 2004;291:1887-1896.

Page 59: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Effect of Antidepressant Medication on Outcome of Substance Use

Nunes EV. et al. JAMA 2004;291:1887-1896.

Page 60: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Combined Sertraline and Naltrexone in MDD + Alcoholism

98

29 23 26

0

20

40

60

80

100

120

SER + NTX SER NTX PBO

Time to Relapse to Heavy Drinking (days)

N = 170, 14 wks, 4 grps (Sertraline (SER) 200 mg, Naltraxone (NTX) 100 mg, Placebo (PBO), SER + NTX)

Pettinati HM, et al. Am J Psychiatry. 2010;167(6):668-675.

53.7

27.5 21.3 23.1

83.3

48.1

68.8

56

0 10 20 30 40 50 60 70 80 90

SER + NTX SER NTX PBO

Abstinence Rate Not Depressed

Page 61: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Summary

● Bipolar disorder with comorbid alcoholism is still an area of treatment needs

● No clear medication of choice although published data so far favors anticonvulsants use

● Naltrexone may be a promising adjunctive medication

● Multisite trials are needed for this population ●  Innovative technologies and methods may

enhance identification of markers of treatment response

Page 62: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Summary

●  Antidepressants in general decrease depression but are less effective for SUD in comorbid MDD+SUDs pts

●  There are no clear antidepressants of choice for DD ●  Lack of response is likely due to SUD-related behavior

vs. true treatment resistance ●  Maximizing MDD treatment helps prevent SUD relapse ●  Clarifying the nature of depression still relies on

historical information ●  structured clinical assessment is more helpful than self-report

●  Psychotherapy for DD is important ingredient of clinical care

DD=Dual diagnosis

Page 63: Advances in Diagnosis, Neurobiology, and Treatment of Mood ... · The Challenge of Mood Disorders–SUD comorbidity Complicated course (Rec/Relap/polysympt.) Suicidality and increased

Audience Response

What percentage of people with alcohol dependence report having depressive symptoms? A.  40% B.  50% C.  70% D.  80%

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Audience Response

Which of the following are common measures used in addiction for withdrawal symptoms? A.  CIWA, COWS B.  CIWA, OCDS C.  COWS, CAGE D.  OCDS, CAGE

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Thank You