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John Tsuang, M.D., M.S.
Associate Clinical Professor
Department of Psychiatry,
University of California Los Angeles
Director of Dual Diagnostic
Treatment Program
Harbor - UCLA Medical Center
[email protected]
Outline
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Prevalence
Psychiatric symptoms and abstinence
Diagnosis of dual diagnosis patients
Pharmacological Treatment
Prevalence of dual diagnosis
patients
Prevalence of Dual Diagnosis
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Epidemiological Catchment Area (ECA) Study
N= 20291
lifetime prevalence rates for alcohol, drug, and mental
disorders
32.7%
lifetime prevalence rates for any non-substance abuse
mental disorders
22.5%
Alcohol disorders
13.5%
Other drug disorders
6.1%
*Regier, AJ Psych 1990
Mental Disorder Patients:
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Life prevalence of additive disorders
29% (OR = 2.7)
Alcohol disorders
22% (OR = 2.3)
Other drug disorders
15% (OR = 4.5)
45%-70% abuse alcohol or drugs
Affective Disorders (8.3%)
Substance Abuse Disorders 32% (OR =2.6)
Alcohol 22%
Drug 19%
Subtypes of Affective Disorders
Bipolar I Disorder
Substance Abuse Disorders 61% (OR = 7.9)
Alcohol 46%
Drug 40%
Unipolar major depression
Substance Abuse Disorders 27% (OR = 1.7)
Alcohol 16%
Drug 18%
Anxiety Disorder (14.6%)
Substance Abuse Disorders 23.7% (OR = 1.7)
Alcohol 18%
Drug
12%
Subtypes of Anxiety Disorders
Panic Disorder (10.6%)
Substance Abuse Disorders 35.8% (OR = 2.9)
Obsessive-Compulsive Disorder(2.5%)
Substance Abuse Disorders 32.8% (OR = 2.5)
Phobia (12.6%)
Substance Abuse Disorders 22.9% (OR = 1.6)
Schizophrenia Spectrum Disorders
(1.5%)
Substance Abuse Disorders 47% (OR = 4.6)
Alcohol 33.7%
Drug
27.5%
Antisocial Personality Disorder (2.6%) -
Substance Abuse Disorders
83.6%
Alcohol 74%
Drug
42%
Borderline Personality Disorder
(0.2%-1.8%)
Second only to mood disorders, ASPD
 25-67% of BPD receiving treatment have
substance use disorders
 57% when not used substance abuse as a
criteria
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• Miller, 1994, Dulit, 1990, Dimeff, Principles of Addiction
Medicine, 3rd Ed, Chase, 2003
Alcohol Disorders
(%Mental Disorders= 36.6%)
Anxiety Disorder 19%
ASPD
14%
Affective Disorders 13%
Schizophrenia
4%
OR
1.0
21.0
1.9
3.3
Drug Disorders
(% mental disorders= 53%)
OR
Anxiety Disorders
Affective Disorders
ASPD
Schizophrenia
28%
26%
18%
7%
2.5
4.7
13.4
6.2
Relationship between Psychiatric
Symptoms and Abstinence
Moderate Depression
% Patients with
40%
Remission of Depressive
Symptoms
with Abstinence
30%
N=177, no pre-existing
mood syndrome
20%
10%
0%
Abstinence 1
2
3
Weeks
4
Brown S, Schuckit M. J Stud Alcohol. 1988;49:412-417.
16
Hamilton depression scores
during 4 weeks of hospitalization
20
18
16
14
12
10
8
6
4
2
0
1st week
2nd week
3rd week
Brown S, Schuckit M. J Stud Alcohol. 1988;49:412-417.
4th week
Anxiety scores during 4 weeks of
hospitalization
40
39
38
37
36
35
34
33
32
31
30
29
1st week
2nd week
3rd week
Brown S, Irwin, M. Schuckit M. J Stud Alcohol.
1991;52:55-61.
4th week
Diagnostic Issues
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A PERIOD OF ABSTINENCE (JAIL/ PRISON, HOSPITAL)
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SUSTAINED PSYCHIATIRC SYMPTOMS DURING
ABSTINENCE (AMOUNT OF TIME REQUIRED??)
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ONSET OF PSYCHIATRIC SYMPTOMS VERSUS
SUBSTANCE ABUSE PROBLEMS (PRIMARY VS.
SECONDARY)
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FAMILY HISTORY OF PSYCHITRIC ILLNESSES
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CROSS SECTIONAL VERSUS LONGITUDINAL DIAGNOSIS
Psychotic symptoms and
abstinence
165 chronic psychotic patients with cocaine
abuse or dependence
 6 weeks of abstinence needed for diagnosis
of schizophrenia
 81% could not make a definitive diagnosis
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 78%
insufficient abstinence, 24% poor memory
 After 18 months, 75% still diagnostic uncertain
 Shaner,
Psych Ser, 1996
Diagnosis of Dual Diagnosis
Patients
Heterogeneous Population of
Dual Diagnosis Patients
Addiction Only
 Mildly-Moderately Severe
 Highly Severe
 Diagnostic Uncertainty
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• Mee-Lee, David (2001) ASAM PPC-2R. ASAM
• Tsuang, J, Shaner, 1997
Addiction Only Patients
Patients with substance abuse or
dependence problems
 No axis I and/or II psychiatric diagnosis or
mental health issues
 Need addiction service only
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Mildly to Moderately Severe
Sub threshold diagnosis (traits of Axis I or
II psychiatric disorders)
 Diagnosis of Axis I or II, stable on
treatment
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 Anxiety
or mood disorders- stable
 Bipolar mood disorder- resolving
 Need primary substance abuse treatment,
available psychiatric treatment capability
Highly Severe
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Axis I or II psychiatric diagnosis-unstable
 Schizophrenia
spectrum disorders
 Severe mood disorders with psychosis
 Severe anxiety disorders
 Severe personality disorders
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Needs concurrent psychiatric and substance
abuse treatment
Diagnosis Uncertainty
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Time
Additional information
Newer, effective and safe medications
Treat unclear diagnosis?
Integrated Treatment Program
Treatment approach
Combine mental health/Substance abuse treatment
- Outpatient/inpatient
- Comprehensiveness
- Medication management
- Outreach
- Social support
-
Drake, Psych Ser 2001, Tsuang, Psych Ser 1999, Ho, AJP 1999
Pharmacological Treatment of
Dual Diagnosis Patients
Pharmacological Treatment of
Affective Disorders
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Tertiary/Secondary Amines (Serotonin/NE)Amitriptline, Desipramine
Monoamine Oxidase Inhibitors (Serotonin/
NE/Dopamine)- Phenelzine,
tranlcypromine
Selective Serotonin Reuptake Inhibitors
(Serotonin)- Fluoxetine, Paroxetine,
Sertraline, Fluvoxamine, Citalopram
(Celexa)
Pharmacological Treatment of
Affective Disorders
NE-Dopamine Reuptake Inhibitors Bupropion
 Nontricylic Serotonin-NE Reuptake
Inhibitors-Venlafaxine
 Serotonin Antagonist& Reuptake InhibitorsNefazodone, Trazodone
 NE-Serotonin Antagonist-Mirtazapine
(Remeron)
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Treatment of Depression and
Alcohol Addiction
TCSs (Imipramine, desipramine)
 SSRIs (fluoxetine, sertraline, nefazodone)
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 McGrath,
1996, Mason, 1996, Gorelick 1989,
Cornelius, 1997, Pettaniti, 2000, Boy-Byrne,
2000)
Treatment of Depression and
Opioid Addiction
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TCAs (doxepin, amitriptyline, desipramine,
imipramine) for methadone patients
 Brady,
2003 ASAM
Treatment of Depression and
Cocaine Addiction
TCAs (desiprmaine)
 NE-Dopamine Reuptake Inhibitors Bupropion
 Nontricylic Serotonin-NE Reuptake
Inhibitors-Venlafaxine
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 Rao,
1995, Weiss, 1989, Kosten, 1989
Pharmacological Treatment of
Bipolar Patients
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Lithium Carbonate
Valproic acid (Depakote)
Chlorpromazine
Olanzapine (Zyprexa)
Risperidone (Risperidal)
Quetiapine (Seroquel)
Lamotrigine (Lamictal)
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Carbamazepine (tegretol)
Gabapentin (neurontin)
Oxcarbazepine (trileptal)
Tiagabine (gabitril)
Topirmate (topamax)
Tarascon PP 2002
Treatments of Substance Abuse
and Bipolar Disorder
Lithium
 Valproate (Depakote)
 Carbamazepine (Tegretol)
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 Brady,
2003 ASAM, Tohen, 1990, Bowden,
1995, O’Connell, 1991, Brady, 1995
Pharmacological Treatment of
Anxiety Disorders
Benzodiazepines- Chlordiazepoxide,
Clonazepam, Diazepam, Lorazepam
 Anticholingeric/AntihistaminergicDiphenhydramine, Hydroxyzine
 Barbiturates
 Others-Buspirone, Chloralhydrate,
Zolpidem (Ambien), Zaleplon (Sonata)
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Treatment of substance abuse and
anxiety disorders
Antidepressants (SSRIs, Trazadone, TCAs)
 Anticonvulsants
 Antihypertensives
 Atypical antipsychotic medications
 Buspirone
 Bendiazepines (contraindicated)
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 Nitenson, ASAM
2003
Pharmacological Treatment of
Schizophrenia
Dopamine Antagonists
Haloperidol, Fluphenazine
 Serotonin/Dopamine Receptor Antagonists
Clozaril, Risperidone, Olanzapine,
Quetiapine, ziprasidone, aripiprazole
 Depo
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Treatment of Substance Abuse
and Psychotic Symptoms
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Newer Atypical Agents
 Reduce
negative symptoms
 Reduce cognitive deficits
 Reduce severity of detoxification
 May improve abstinence
 Cravings for substances of abuse
 Not a magic bullet!!
 Ziedonis, ASAM
2003, Buckley, 1998, Smelson,
1997, Farren, 2000, Tsuang, 2001, Tsuang, 2004
Treatment Recommendations
A period of abstinence is optimal (wait after
detoxification)
 Duration to wait (??)
 If symptoms mild, diagnosis unclear, can
wait
 If symptoms severe, no remission during
abstinence, early treatment justified
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Avoid These Agents for Treatment of
Substance Dependence
MAOI
 Opiates
 Barbiturates
 Stimulants
 Short Acting BZDs
 Tricyclics (metabolism, cardiac conduction)
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Pharmacological Strategies
for Treatment of
Substance Use Disorders
Initiate and Facilitate Abstinence
 Treat Withdrawal Symptoms
(acute/protracted)
 Relapse Prevention
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 Treat Associated
Psychiatric Syndromes
 Decrease Craving
 Aversive Agents
Current Pharmacological Agents for
Treatment of Stimulant Dependence
Dopaminergic Agents (Agonist, partial
agonist, antagonist)-Bromocriptine,
Levodopa, Amantadine
 Serotonergic Agents-Sertraline, Fluoxetine,
Desipramine
 Others- Carbamazepine, Bupropion,
Selogiline, Modafinil (Provigil), Disulfiram
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Current Pharmacological Agents for
Treatment of Alcohol Dependence
BZD, Anti-Seizure Medications, AntiHypertensive Medications for Withdrawal
 Disulfiram/Calcium Carbamide
 Naltrexone (ReVia)
 Acamprosate (Amino Acid Derivative)Mimics GABAa Receptor/Amino Acid
derivative
 Ondansetron-SHT3 antagonist
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Current Pharmacological Agents for
Treatment of Opiate Dependence
Clonidine for Withdrawal
 BZDs for Withdrawal
 Naltrexone for Withdrawal and
Maintenance
 Methadone for Maintenance
 LAAM for Maintenance
 Buprenorphine for Withdrawal and
Maintenance
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