Download Adolescent Substance Abuse: New Strategies

Co-occurring Psychiatric and
Substance Use Disorders:
The Concept of Comorbidity
Ricardo Restrepo, MD; MPH
The Addiction Institute of NY
St. Luke’s-Roosevelt Hospitals
VI Simpósio Internacional de Alcoologia e Outras Drogas
Vila Serena Bahia
Outline
 Epidemiology
 Neurobiology
 Overview of comorbidity
 Theories
 Dual diagnosis principles
 Comorbid treatment: Anxiety Disorders, Affective Disorders,
Psychotic Disorders, and Personality Disorders
 Conclusions
Which came first?
Psychiatric Symptoms or Substance Abuse
In the ECA study an estimated 45 % of individuals with alcohol use disorders
and 72% of individuals with drug use disorders had at least one co-occurring
psychiatric disorder
ECA Odds Ratios of SUD’s in persons with
Mental Illness
Mental disorder
Odds ratio
(Risk for Substance Abuse Increase)
 Bipolar Disorder
6.6
 Schizophrenia
4.6
 Panic Disorder
2.9
 Major Depression
1.9
 Anxiety Disorder
1.7
Epidemiologic Catchment Area (ECA) Study (Regier 1990) Regier, D. A., Farmer,
M. E., Rae, D. S., Locke, B. Z., Keith, S. J., Judd, L. L., & Goodwin, F. K.
(1990). Comorbidity of mental disorders with alcohol and other drug abuse:
Results from the Epidemiologic Catchment Area (ECA) study. Journal of the
American Medical Association, 264, 2511–2518.
Comorbidity: Other biological factors
contribute to Addiction
Conway KP, Compton W, Stinson FS, Grant BF. J Clin Psychiatry. 2006;67(2):247.
Reward Pathway: Comorbid activation
from mesolimbic to mesocortical
Prefrontal cortex
Thalamus
Nucleus
accumbens
Ventral
tegmental
area
Locus
Coeruleus
Role of Dopamine: Comorbidity
 Psychoactive substances may 1) increase DA
release, 2)inhibit reuptake, 3) act as DA agonist
 Acute increases in DA in both mesolimbic and
mesocortical pathways are thought to be essential
to the initial liking and reinforcement of drug
taking (The Reward Pathway)
 Chronic use
Global decrease in DA
Role of Dopamine: Comorbidity
 Corticotropin Releasing Factor (CRF) and the
hypothalamic-pituitary-adrenal (HPA) axis (stress
response)
 In response to drug use and more precisely, activation of
the mesolimbic DA system, CRF and the HPA axis are
upregulated
 In acute withdrawal this leads to physiological and
psychological withdrawal
 However, increases in cortisol, CRF, NE in addition to
neuropeptide Y, nociceptin, vasopressin are thought to
persist weeks/months into sobriety leading to anxiety
dysphoria that is called protracted withdrawal
Why Do Drug Abuse and Mental
Disorders Commonly Co-occur?
 Overlapping genetic vulnerabilities
 Overlapping environmental triggers
 Involvement of similar brain regions
 Drug abuse and mental illness are
developmental disorders
How Can Comorbidity Be Diagnosed
and Treated?
 The health care systems in place to treat substance abuse and
mental illness are typically disconnected, hence inefficient.
Physicians tend to treat patients with mental illnesses, whereas
a mix of clinicians with varying backgrounds deliver drug abuse
treatment.
 Some substance abuse treatment centers are biased against
using any medications, including those necessary to treat
patients with severe mental disorders.
 Clinicians and researchers generally agree that broad-spectrum
diagnosis and concurrent therapy (pharmacological and
behavioral) will lead to better outcomes for patients with
comorbid disorders.
Psychosocial treatment for comorbid
disorders and substance use disorders
 Single: treating the primary d/o resolved the
other one
 Sequential: treating the primary d/o initially,
followed by treating the other disorder
 Parallel: treating both disorders at the same time
but in different settings
 Integrated: simultaneously treating both disorders
What is Comorbidity and What Are Its
Causes?
 When two or more disorders or illnesses occur simultaneously in
the same person, they are called comorbid. Surveys show that
drug abuse and other mental illnesses are often comorbid. They
can occur at the same time or one after the other
 Three scenarios that we should consider:
 Drug abuse can cause a mental illness (Causal Effect)
 Mental illness can lead to drug abuse (Self-medication)
 Drug abuse and mental disorders are both caused by other
common risk factors (Common or correlated causes)
Hypothesis 1: Alcohol and drug abuse can
cause mental illness (Causal Effect)
 Galanter et al. (1988): Drug & ETOH abuse: 1/3 of patients
receiving acute psychiatric services
 Kosten and Kleber (1988): Specific drugs/alcohol may result
in tendency for the development of mental d/o’s
 National Institute of Drug Abuse –NIDA- (1991): Prolonged
abuse of specific drug combinations : direct causal role/
hasten development of psychiatric d/o’s
 Miller and Gold (1991): acute & chronic actions of alcohol &
drugs can produce symptoms similar to psychiatric disorders
(ie. depression, anxiety, personality disorders & psychosis)
Hypothesis 1: Alcohol and drug abuse can
cause mental illness (Causal Effect)
 Stimulants & cocaine: dose dependent agitation, anxiety, panic & psychosis
during acute intoxication; depression post-withdrawal
 Hallucinogens & cannabis: psychotic symptoms
 Adverse psychiatric reactions to marijuana/THC: panic attacks, anxiety
reactions, severe MDD, psychosis
 Chronic opiate administration: high rates of major & minor depressions
 Lysergic acid diethylamide (LSD): severe panic & anxiety reactions, bipolar
manic disorders, schizoaffective disorders & MDD
 Irritability & anger attacks, depressed mood, and decreased social interaction
may be seen in patients taking BZ or drinking alcohol.
Hypothesis 2: Mental illness can cause
alcohol and drug abuse (Self-medication)
- Drug of choice: interaction between psychopharmacologic
actions of the drug & dominant painful feelings
- Opioid abuse: powerful muting action of opioids on the
disorganizing & threatening affects of rage & aggression
- cocaine: relieves distress from depression, hypomania &
hyperactivity
- psychopathology can alter course of any addictive disorder
- most support based on clinical experience
McLellan and Druley (1977)
Case Presentation….what to do?
(Common or correlated causes)
 ID: Ms. B; 32 y/o, single, female student from Salvador.
 CC: I am depressed and hopeless after terminating my
relationship and since I’ve not been able to find a job.
“sometimes I cut my self to relieve the pain when I am high”
 HPI: Depressed, reports use of alcohol and other drugs including
cocaine and heroin to relieve the depressed mood. Patient
describes self cutting behavior since age 15 during stressful
times.
Past Psych Hx: 2 hospitalizations for depression and suicidal
attempts
Past SA Hx: ETOH use since age 13, THC use since age 15,
cocaine and heroin use since age 20
Treating a Biobehavioral Disorder Must
Go Beyond Just Fixing the Chemistry
We Need to Treat the Person
Pharmacological Treatment
Behavioral Therapies
(Medications)
Medical Services
Social Services
Dual Diagnosis Principles
 Dual Diagnosis is an expectation, not an exception
 Successful treatment is based on empathic, hopeful, integrated
and continuing relationships.
 Treatment must be individualized utilizing a structured
approach to determine the best treatment. The consensus
“four quadrant” model for categorizing individuals with cooccurring disorders can be a first step to organizing treatment
matching.
Dual Diagnosis Principles
Both High Severity
Mental Illness Low Severity
Substance use disorder High
Severity
MI High Severity
SUD Low Severity
Both Low Severity
Determining Level of Care
 Level I: Outpatient treatment
 Level II: Intensive outpatient treatment, including
partial hospitalization
 Level III: Residential/medically monitored
intensive inpatient treatment
 Level IV: Medically managed intensive inpatient
treatment
Dual Diagnosis Principles
 Case management and clinical care (in which we
provide for individuals that which they cannot
provide for themselves) must be properly
balanced with empathic detachment,
opportunities for empowerment and choice,
contracting, and contingent learning.
 When mental illness and substance use disorder
co-exist, each disorder is “primary”, requiring
integrated, properly matched, diagnosis specific
treatment of adequate intensity.
Dual Diagnosis Principles
 Both serious mental illness and substance
dependence disorders are primary biopsychosocial
disorders that can be treated in the context of a
“disease and recovery” model. Treatment must
be matched to the phase of recovery (acute
stabilization, engagement/motivational
enhancement, active treatment/prolonged
stabilization, rehabilitation/recovery) and stage
of change or stage of treatment for each disorder.
Dual Diagnosis Principles
 There is no one correct approach (including
psychopharmacologic approach) to individuals
with co-occurring disorders. For each individual,
clinical intervention must be matched according
to the need for engagement in an integrated
relationship, level of impairment or severity,
specific diagnoses, phase of recovery and stage of
change.
Case Presentation part 2
 Patient and clinicians agree with an Integrated
treating program where simultaneously both
disorders (Comorbid treatment program) are
treated:
- Pharmacotherapy
- Psychotherapy (Intensive outpatient treatment)
including
- DBT, Dual dx group among others
Pharmacotherapy and Psychotherapy in
comorbid psychiatric disorder and
substance abuse disorders
 Double Blind Controlled Trial Data IS ALMOST NON-EXISTENT
How do I determine if my addiction patient
has a co-morbid psychiatric disorder?
 History of symptoms (current history may not be as
important as past history)
 Family history
 No blood tests, physical exam, imaging studies are
diagnostic
 Must conduct a clinical interview
(remember that a ‘mental status examination’ is a presentstate assessment; the key is to get the longitudinal
course, the natural history of the condition)
Comorbid Psychiatric Disorder and
Substance Use Disorder
 The following scenarios suggest an independent
psychiatric disorder:
- Psychiatric disturbance precedes substance use
- Psychiatric disturbance persists following prolonged
abstinence
- Psychiatric disturbance occur in excess of those
typically seen considering the quantity and frequency
of substance consumption
Comorbid Anxiety and Substance Use
Disorder
 Patients with an anxiety disorder
 36% alcohol or illicit drug abuse
 26% of substance dependent pt’s: PTSD *
 Exposure to Traumatic Events Puts People at Higher Risk of Substance Use
Disorders. Recent epidemiological studies suggest that as many as half of
all veterans diagnosed with PTSD also have a co-occurring substance use
disorder (SUD)
 Primary vs. secondary
* substance use → anxiety
* substance withdrawal → anxiety
* anxiety → symptom relief w/ substance use
•Merikangas KR, Whitaker A, et al. Comorbidity and boundaries of affective disorders with anxiety disorders and substance misuse; results of
an international task force. Br J Psychiatry 1996; 168 (Suppl 30): 58-67
12-Month prevalence rates of drug and alcohol dependence
in patients with anxiety disorder compared with the
general population
NESARC: National Epidemiological Survey on Alcohol and Related Conditions 2004
Treatment of Anxiety & Substance abuse
disorders

SSRIs are the first-line therapy for anxiety disorders with Psychotherapy (CBT)

Use of nonaddictive medications, with the exception of treating withdrawal
symptoms

Other antianxiety medications to consider in patients being treated for
comorbid SUD: hydroxyzine, gabapentin, quetiapine

Cravings or preoccupation w/ ETOH: naltrexone, acamprosate and disulfiram
*Benzodiazepines
- popular “mainstay” of treatment, but…
- highest abuse potential (40% of substance abusers seeking treatment)
- concern for prescribers (abuse risk vs. trigger for relapse vs. disinhibition)
Resource : Harvard Psychopharmacology Algorithm Project www.mhc.com Osser DN, Renner JA & Bayog (1999)
Comorbid Mood Disorders and
Substance Use Disorder
 Patients with an affective disorder
 32% alcohol or illicit drug abuse
 Prevalence rate of 20.5% of major depressive disorder in patients
with alcohol dependence
 Among all Axis I conditions, bipolar disorder has the highest
prevalence of comorbid substance use. Prevalence rates of alcohol
or drug abuse in patients with bipolar disorder have been estimated
to range from 21% to 58% (Brady and Lydiard 1992).
Treatment of Mood disorders and
Substance abuse disorder
 SRI (Serotonin Reuptake Inhibitors) are the pharmacotherapeutic
intervention of alcohol dependence and major depression
 Several studies have identified substance abuse as a predictor of
poor response to lithium
 Bipolar patients with concomitant substance use disorders appear
to have more mixed and/or rapid cycling bipolar disorder than
patients with bipolar disorder who do not abuse substances.
Therefore, substance-abusing bipolar patients may respond
better to anticonvulsant medications (for example, valproate)
than to lithium therapy.
 The optimal management of patients with comorbid
schizophrenia and SA involves both psychopharmacology and
psychotherapy
Principles of Addiction Medicine, 3rd Edition
Results of studies of antidepressant use in patients
with comorbid depression and alcohol dependence
Outcomes (med vs. placebo)
STUDY (N)
Medication
Average daily
dose (no wks)
Depression
Drinking
Mason (28)
Desipramine
200 mg (24)
Med< plac
Med < plac
McGrath (69)
Imipramine
260 mg (12)
Med < plac
Med = plac
Cornelliuos (51)
Fluoxetine
20-40 mg (12)
Med < plac
Med < plac
Roy (36)
Sertraline
100 mg (6)
Med < plac
Med = plac
Roy-Byrne (64)
Nefazodone
460 mg (12)
Med < plac
Med = plac
Pettinati (29)
Sertraline
170 mg (14)
Med = plac
Med = plac
Moak (82)
Sertraline
186 mg (12)
Med < plac
Med = plac
Hernandez-Avila Nefazadone
(41)
413 mg (10)
Med = plac
Med < plac
Kranzler (345)
50-100 mg (10)
Med = plac
Med = Plac
Sertraline
New treatment strategy
Study (N)
Medication
Average daily
dose (no.wks)
Depression
Drinking
abstinence
Pettinati (170)
Sertraline and
Naltrexone
200 mg (14)
Med
combination <
Single
medication <
placebo
Med combination <
Single medication <
placebo
100 mg (14)
Single
Medication
Placebo
(Double blind, placebo-controlled trial combining sertraline and naltrexone for treating cooccurring depression and alcohol dependence)
Implication: Combining a medication to treat alcohol dependence (eg, naltrexone)
with an antidepressant (eg, sertraline) with some basic psychosocial support and
advice for both disorders can provide an aggressive approach to treating patients
with co-occuring depression and alcohol dependence
Comorbid Psychotic Disorder and
Substance Use Disorder
 Patients seeking treatment for schizophrenia
 50% alcohol or illicit drug abuse
 70-90% are nicotine dependent
 Symptomatic relief
 Combat hallucinations/paranoia
 Decrease negative symptoms
 Ameliorate adverse effects of medication
 The optimal management of patients with comorbid
schizophrenia and SA involves both psychopharmacology and
psychotherapy
Percent with
schizophreniform disorder at
age 26
Comorbid Psychotic Disorder and
Substance Use Disorder
COMT genotype
Casp A, Moffitt TE, Cannon M, et al., Biol Psychiatry, May 2005
Cannabis and psychosis risk
Hypotheses linking cannabis and psychosis
Hypothesis
Strenght of Evidence for
evidence
Evidence
against
Cannabis worsens
existing psychotic
disorders
Strong
Cannabidiol
and Δ9-THC
improve
symptoms
in some
patients
with
schizophren
ia
•Cannabis is associated with
increased symptoms, relapse, and
treatment nonadherence among
those with schizophrenia
•Patients with schizophrenia are
more vulnerable to cannabisinduced psychosis under
experimental conditions
Zammit S, Moore TH, Lingford-Hughes A, et al. Effects of cannabis use on outcomes of psychotic disorders: systematic review. Br J
.
Psychiatry. 2008;193(5):357–363
Cannabis and psychosis risk
Hypotheses linking cannabis and psychosis
Hypothesis
Strenght of Evidence for
evidence
Evidence
against
Cannabis increases
the risk of chronic
psychosis among
vulnerable
individuals
Strong
Cannabis use
is not always
a risk factor
for conversion
to psychosis
in studies of
prodromal
schizophrenia
•For patients with schizophrenia,
a history of cannabis use is
associated with illness onset 2 to
3 years earlier compared with
non-users.
•Cannabis use is a risk factor for
conversion to psychosis in some
studies of prodromal
schizophrenia
Large M, Sharma S, Compton MT, et al. Cannabis use and earlier onset of psychosis: a systematic meta-analysis. Arch Gen
Psychiatry. 2011;68(6):555–561
Treatment: Comorbid Psychotic
Disorder and Substance Use Disorder
 There are few controlled trials on the use of specific antipsychotics
on people with psychoses and SUD, although it appears that clozapine
(Buckley, Thompson,Way, & Meltzer, 1994) and olanzapine (Conley,
Kelly, & Gale, 1998) have approximately equal effectiveness in
treatment-resistant patients with and without substance abuse.
 Since people taking standard antipsychotic medication have an
increased risk of tardive dyskinesia if they misuse alcohol, cannabis
(Olivera, Kiefer, & Manley, 1990; Salyers & Mueser, 2001; Zaretsky et
al., 1993) and perhaps nicotine (Yassa, Lal, Korpassy, & Ally, 1987), it
may be especially important for these patients to be given
medications with a lower risk of this side-effect.
Comorbid Personality disorder and
Substance Use Disorder
 About 40% to 50% of individuals with a substance use disorder meet
the criteria for antisocial personality disorder (ASPD) and
approximately 90% of individuals diagnosed with ASPD also have a
co‐occurring substance use disorder (Messina, Wish, & Nemes, 1999).
 People with comorbid personality disorder and substance use:
 Have more problematic symptoms of substance use than those without a
personality disorder.
 Are more likely to participate in risky substance-injecting practices that
predispose them to blood borne viruses.
 Are more likely to engage in risky sexual practices and other disinhibited
behaviours
 May have difficulty staying in treatment programs and complying with
treatment plans.
Treatment: Comorbid Personality
disorder and Substance Use Disorder
 Treatment for substance use in people with personality
disorders is associated with a reduction in substance use.
 Treatment for substance use is also associated with a reduction
in the likelihood of being arrested, suggesting a reduction in
criminal activity.
 Psychotherapy is the treatment of choice for personality
disorders but be aware of pharmacological agents available to
help with comorbidity
Evidence-Based Practices
 Motivational Enhancement Therapy (MET)- Initiate and maintain
changes
 Cognitive Behavioral Therapy (CBT)- make and identify the cause and
consequences of changes
 Dialectic Behavioral Therapy (DBT) (Borderline Personality d/o)
 Exposure Therapy (anxiety d/o-Phobia and PTSD)
 Integrated Group Therapy (IGT) (Bipolar d/o and SA)
 Twelve Step Facilitation (TSF)- help to sustain changes
 Other considerations:
 Managing Medications
 Involving the Family
 Encouraging participation in group/individual therapy
Avoid These group of Medications for
Treatment of Substance Abuse disorders
Choosing a pharmacological agent include paying particular
attention to potential toxic interaction of the medication with
drugs and alcohol
 MAOI
 Opiates
 Barbiturates
 Stimulants
 Short Acting BZDs
 Tricyclics (metabolism, cardiac conduction)
When to consider Pharmacotherapy
Consider Precipitant To Treatment And Severity of Associated
Medical/Psychiatric/Psychosocial Problems







Family
Employment
Financial
Medical
Legal
Psychiatric comorbidity (including risk for harm to self or others)
Relapse Potential
 The higher the acuity or severity; greater need for use of
medication treatment (if there is an appropriate
medication intervention available)
When to consider Pharmacotherapy
Indications: To treat psychiatric disorders and minimize potential relapse to
substance use.

Any Primary/Endogenous Psychiatric Disorder

Any Psychosis or mood disorder irrespective of whether drug-induced or
primary (e.g., antipsychotics, mood stabilizers, antidepressants)

Secondary anxiety or mood disorders - If there has been clear, lasting, and
severe past episodes that led to impaired function.

Psychiatric Disorders that last more than 4 weeks after drug/alcohol use
*May need detoxification to ascertain psychiatric diagnosis

Can use psychopharmacotherapy with other medications used to
promote/maintain abstinence (e.g., methadone, acamprosate)
Pharmacology Treatment (Medications)
 Pharmacotherapies that benefit multiple problems:
 Bupropion -----depression and nicotine dependence, might also help
reduce craving and use of the drug methamphetamine
 Pharmacotherapies for Nicotine Dependence:
 Nicotine Substitution (Agonist Therapy): Nicotine
polacrilex gum, Transdermal nicotine patch, Nicotine
nasal spray
 Bupropion
 Varenicline (nicotine partial agonist)
Pharmacology Treatment (Medications)
 Pharmacotherapies for Alcohol dependence (Relapse
Prevention):
 Naltrexone (oral and injectable)
 Disulfiram
 Acamprosate
 Pharmacotherapies for Opiate Addiction
 Methadone (Can’t use outside of a registered narcotic treatment
program)
 Buprenorphine
 Naltrexone
Pharmacology Treatment (Medications)
Alcohol Typologies
• Abstinence rates during a
14-week treatment trial
with sertraline 200 mg
QD.
• Sertraline helped Type A
(Late-Onset) alcoholics
stay abstinent (P=0.004),
but not Type B (EarlyOnset).
Adapted from: Pettinati HM, Volpicelli JR, Kranzler HR, Luck G, Rukstalis MR, Cnaan, A: Sertraline
treatment for alcohol dependence: Interactive effects of medication alcoholic subtype. Alcohol Clin
Exp Res 24:1041-1049, 2000
Tools
 TIP 42 Substance Abuse Treatment For Persons With CoOccurring Disorders Inservice Training based on Treatment
Improvement Protocol (TIP) 42 Substance Abuse Treatment
For Persons With CoOccurringDisorders.http://kap.samhsa.gov/products/trainin
gcurriculums/tip42.htm
 NIDA (National Institute of Drug
Abuse)http://drugabuse.gov/researchreports/comorbidity/
 SAMHSA (Substance Abuse & Mental Health Services
Administration) http://www.samhsa.gov/co-occurring/
Conclusions
 Identify the need of your patients to get treatment
 Addiction and psychiatric disorders are treatable brain diseases
 Research is edifying the biological mechanisms involved
 Increased understanding of neurobiology is allowing for the
development of effective, targeted pharmacotherapies and
psychotherapy
 Comorbidity disorders are multifactorial, be ready for relapses
 Pharmacotherapy and psychotherapy modalities are effective and
scientifically based approaches
 Prevention is based on screening and early Intervention
THANKS! Gracias! Obrigado!
Questions? Comments?