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CO-MORBID PSYCHIATRIC DISORDERS



Patrick W. Gibbons, DO, MSW

Medical Director, Dawn Farm

Medical Director, Michigan Health Professionals Recovery Program

University of Michigan Dept. of Psychiatry, Adjunct Clinical Instructor

Washtenaw County/ Community Support and Treatment services
Declaration of Potential Conflict of Interest




The content of this presentation is non-commercial
and I have no conflict of interest to disclose
Overview



   Definitions
   Epidemiology
   Diagnostic considerations
   Treatment considerations
   Case studies
Co morbidity


Two or more illnesses in the same person at
 the same time, e.g.., bipolar illness and
 alcoholism

One may affect the course or response to
treatment of the other
Psychiatric Disorders

Mood - depression, anxiety, bipolar

Cognitive - autism, ADHD, dementia

Psychotic - schizophrenia, delusional d/o

Somatoform - conversion, somatization d/o
Substance use disorders = abuse or dependence


   Substance use = non- problematic use

   Substance misuse = use in a manner not intended

   Substance abuse = recurrent;
       *life problems, role function affected

        *interpersonal, legal problems

        *use in situations that are physically hazardous to
         the user
4 C’s of Addiction

Control attempts
Compulsive use
Continued use despite consequences
Craving when the drug is stopped

  Addictive disease is obsession + compulsion
  +/- physiologic withdrawal symptoms

 *Drug dependence is physiologic adaptation and
 withdrawal on stopping the drug
Mental Health and Treatment settings 1980’s and 1990’s




substance abuse programs reported co- occuring mental
  disorders in 50 to 75%

Mental health programs reported co-occurring substance
  use disorders in 20 and 50%
 CSAT, SAMHSA (TIP) Series 42. DHHS Publication No. (SMA) 05-3992. 2005,
  Rockville, MD


 21.3% with serious mental illness had a SUD in the past
  year

National Epidemiologic Survey on Alcohol and Related Conditions, 2004
2010 NSDUH : Summary of National Findings
Past Year Substance Dependence or Abuse and Serious Mental Illness
among Adults Aged 18 or Older: 2010
2010 NSDUH : Summary of National Findings
Past Year Substance Dependence or Abuse among Adults Aged 18 or
Older, by Level of Mental Illness: 2010
2010 NSDUH : Summary of National Findings
Co-Occurring Mental Illness and Substance Use Disorder in the Past
Year among Adults Aged 18 or Older, by Age and Gender: 2010
2010 NSDUH : Summary of National Findings
Why do drugs affect mood ?

Most drugs of abuse influence production of
 dopamine and serotonin

Depression is most common symptom during any
 substance withdrawal followed by anxiety and
 irritable mood.

Withdrawal related mood symptoms may last
 weeks to many months depending on the
 substance.
Why is diagnosis difficult?

Alcohol/drugs can cause psychiatric symptoms in anyone
(acute toxicity)

Prolonged A/D use can cause short or long-term
psychiatric illness

A/D use can escalate in episodes of psychiatric illness

Psychiatric symptoms and A/D use can occur in other
psychiatric disorders
  Marc A. Schuckit: Am. J Psychiatry, 143:2 p. 141 – modified
Substance-induced mood disorder DSM IV

  Prominent/persistent mood disturbance

  Develops within 1 month of intoxication or
  withdrawal or medication use is causative

  Not better accounted for by other axis I d/o

  Sx not exclusively during delirium

  Sx cause significant distress or impairment
Substance induced depression?
191 male alcoholics, none with prior major psychiatric Hx.



42% had significant Sx (Ham D > 19) within 48 hrs. of
admission
At 2 weeks, 12% with Ham D score >19
At 4 weeks, 6% with Ham D score > 19

Rapid decline in Sx intensity over first 4 weeks of Tx.,
largest reduction at 2 weeks

Recommended: defer antidepressant Rx prior to first 4
weeks of abstinence*
     (Brown and Schuckit, 1988.)
Chicken or Egg?


25-year longitudinal study, 635 boys, 630 girls, birth
  cohort, general community sample in New Zealand

found that:
problems with alcohol led to increased risk of Major
  Depression

as opposed to:
 a self-medication model in which Major Depression
  led to increased risk of AAD.

Fergusson, Boden, et al, Arch Gen Psychiatry. 2009 Mar;66(3):260-6
Past Year Substance Dependence or Abuse among Adults Aged 18 or Older, by
Major Depressive Episode in the Past Year: 2010
2010 NSDUH : Summary of National Findings
What’s the difference?

Post-Acute Withdrawal               Psychiatric Disorder
Depression                          Major Depression
Anxiety                             Anxiety/Panic Disorder
Mood Lability                       Bipolar Disorder
* normal in early abstinence        *not normal
  resolves with time                 won’t resolve without Tx
  Responds to behavioral measures
                                    12-Steps won’t hurt
  responds to 12-Steps
Early phase psychosis w/ co-morbid substance
use vs. substance induced psychosis ?

N=386, 44% sub induced psychosis, 56% primary
psychosis
Predictors of substance-induced Sx:
parental substance abuse (odds ratio [OR], 1.69; 95%
confidence interval [CI], 1.00-2.85)
diagnosis of dependence on any drug (OR, 9.41; 95%
CI, 5.26-16.85),
visual hallucinations

Caton et al, Arch Gen Psychiatry. 2005;62:137-145.
Quick differential: Psychosis

Visual Hallucinations:
 -hallucinogens, alcohol withdrawal, organic i.e, Lewy body dementia,
   delirium (uncommon with 1º psychosis)
-vague (shadows, etc.) with Axis II

Auditory Hallucinations:
-Schizophrenic or schizoaffective d/o (less common with substances)
-vague sounds (mumbling, name called, etc.) with Axis II

Paranoia:
-substances: cocaine, psych stimulants, occ. THC and ETOH withdrawal
-Axis I: mania, schizophrenia/schizoaffective
-Axis II: paranoid personality disorder (rare)
Mania: simultaneously activated
      behavior, mood and thinking
**medical causes to be considered include thyrotoxicosis, temporal
    lobe epilepsy


   Bipolar, schizoaffective, psychosis, anxiety
    disorders
   Methamphetamine/Cocaine
   Ecstasy (MDMA)
   Hallucinogens
   Alcohol/Benzodiazepine withdrawal?
   Medication induced (i.e. corticosteroids)
Schizophrenia and Marijuana



                                          Up to 2x >risk of developing
                                          schizophrenia
                                          Moore, et al, Lancet 2007; 370: 319–28




Caspi et al., Biol Psychiatry, May 2005
Meier et al. Persistent
cannabis users show
neuropsychological decline
from childhood to midlife
Proc Nat Acad Sci, October 2, 2012 vol.
109 no. 40 E2657 – E2664




   Fig. 2. Adolescent vulnerability. Change in full scale IQ (SD units) from childhood
   to adult. Adolescent onset (black bar) had >IQ decline vs. adult onset. IQ ↓
   approximately -0.55 units (8 IQ points) with 3+ diagnosis over time
Adolescents and marijuana use
   have higher levels of anxiety (Dorard et al., 2008),
    depressive symptoms (Medina et al., 2007),
    suicidality (Pedersen 2008) and externalizing
    behavior (Monshouwer et al., 2006)
    neurocognitive deficits, including intentional,
    learning, memory, and intellectual functioning
    decrements (Fried et al., 2002; Di Forti et al., 2007; Harvey et
    al., 2007; Brook et al., 2008)

   poorer sleep (Bolla et al., 2008), respiratory
    problems (Aldington et al., 2007; Brook et al., 2008), cancer
    (Berthiller et al., 2008)
Personality disorders and substance use


Antisocial PD - highest likelihood of co-morbid
substance use (may facilitate further behavioral
or emotional excursions)

Borderline PD – predictable clinical worsening
(increased externalizing, impulsivity)

Hard to diagnose in presence of early onset
and/or active substance use
What is the most fatal mental disorder?


       Risk Factor              Odds Of Attempting Suicide

   Cocaine use             →    62 times more likely
   Major Depression        →    41 times more likely
   Alcohol use             →     8 times more likely
   Separation or Divorce   →    11 times more likely


                     NIMH/NID
Suicide Thoughts, Plans, and Attempts in the Past Year among Adults
Aged 18 or Older, by Substance Dependence or Abuse: 2010
2010 NSDUH : Summary of National Findings
Eating disorders and substance use


   50% of persons with an eating disorder also
    have problematic drug or alcohol use,
    (compared with 9% of the general population)

   35% of females with a substance use disorder
    report having an eating disorder (compared
    with 1–3% of the general population)


    Root, et al, Int J Eat Disord March 2009; (online pub. )
Eating disorders and substance use


 Alcohol and drug abuse or dependence
 more common in: *mixed binge/purge
                  *purging only eating behaviors

  than in: restrictive only eating behaviors

Treatment outcomes poor unless both conditions addressed

       Root, et al, Int J Eat Disord March 2009; (online pub.)
Red Flags
for co-occurring psychiatric illness include:


 Family history of psychiatric illness

 Onset of psychiatric symptoms before the onset of
 substance use disorder

 Psychiatric symptoms during lengthy periods of abstinence
 in the past

 The longer from last use and acute withdrawal, more likely
 to be seeing a co-morbid process
Implications for treatment

addictive disease is predictive

Exposure kindles “a new biological drive” to use
the drug (success in meeting basic drives
decreases anxiety i.e., not getting fed)

Encouraging self confidence, empowerment as
goals not always desirable

Heritability ranges from 40 – 60%
Amphetamine and cocaine elevate DA in
                           NAS
Drugs of abuse act on:
                         Nicotine acts on cholinergic receptors at
                            cell bodies and terminals of
                            mesolimbic system, increasing DA in
                            NAS


                         PCP blocks NMDA (GLU) increasing DA
                           in NAS.


                         Opiates inhibit the GABAergic cells that
                           normally inhibit the mesolimbic
                           system Increasing dopamine in NAS


                         Barbiturates and benzo’s do the same at
                            some GABAergic level


                         Ethanol and marijuana end with the
                            same results in NAS through
                            unknown mechanisms


                         Caffeine doesn’t involve the same circuit.
DA Receptors and the Response to
                Methylphenidate (MP)
High DA                                 high
receptor




                                                   Dopamine receptor level
                                        low
 Low DA
receptor




As a group, subjects with low receptor levels found MP
pleasant while those with high levels found MP unpleasant
     Adapted from Volkow et al., Am. J. Psychiatry, 1999.
Treatment: generally avoid cross-
dependency producing drugs
 Benzodiazepines Ativan, Xanax, Klonopin, Valium, Librium,
   Restoril, Tranxene, Versed


 Benzodiazepine analogs Ambien, Sonata, Lunesta

 Other Sedative-Hypnotics Soma, meprobamate, chloral
   hydrate, etc.


 Barbiturates Fiorinal, Fioricet, phenobarbital

 Psychostimulants Adderall, Ritalin, etc.

 Opioids codeine, Ultram, Vicodin, methadone, heroin, etc.
How to address sleep and anxiety problems?



 Thorough history, +/- medical evaluation if needed

 Optimize self care * recovery program
                    * sleep
                    * diet, caffeine use
                    * exercise

 Psychiatric referral if necessary
Medical procedures and pain management in
recovering persons:

  Generally, avoid elective procedures in 1st year of recovery

  Co-ordination of care is essential (PCP, surgeon, dentist, etc.)

  Avoid practice outside of specialty (prescribing for conditions
    you don’t have experience with, can’t evaluate or follow)

  Consider non-opioid measures such as long- lasting local
    anesthesia (i.e, bupivicaine), NSAIDS, acetaminophen, anti-
    convulsants for neuropathic pain, topical analgesics,
    physical therapy
ADHD in Recovering Persons

Consider non-stimulants agent first (Strattera®)

Controlled release (i.e. Adderall®, Concerta®) or pro-
drugs (Vyvanse®) have less abuse potential, harder to get
high peak effect by IV or snorting

All activate mesolimbic and mesocortical areas of the brain
involved in addictive disease, kindle craving, obsession
and compulsion, and all have been abused

Of persons having true ADHD diagnosis in childhood, only
30% will carry functional symptoms into adulthood
ADHD in Recovering Persons
General points on pharmacotherapy for
co-occurring disorders

Avoid the trap of reacting to symptoms with
polypharmacy

Many substance-use patients like taking drugs,
any drugs

Decision to medicate should always be with clear
rationale and consideration of alternatives
including psychosocial and behavioral
interventions.
Always weigh risk versus benefit



Persons with persistent anxiety, apathy,
irritability or social withdrawal are describing
barriers to engagement in recovery process
Successful adaptation to the
substance-free state for most means:

   Abstinence plus engagement in a psychosocial
   process which can facilitate a transfer of
   dependency needs to sources of supply which
   are:

    1.   *non-destructive
    2.   *intrinsically rewarding
    3.   *inexhaustible
Meta analysis of literature on AA effectiveness found:
Katsukis, 2009 , Addict Dis. 2009;28(2):145-57.


 (1) magnitude of effect: rates of abstinence about 2x higher
 (2) dose response effect: > attendance associated with >
   rates of abstinence
 (3) consistent effect: these relationships are found for
   different samples and follow-up periods
 (4) temporally accurate effects: prior AA attendance
   predictive of subsequent abstinence
 (5) specific effects: evidence establishing the specificity of
   an effect for AA or Twelve Step Facilitation/TSF is mixed
     *(2 trials+, 1 trial -, 1 trial no effect)
 (6) plausibility: mechanisms of action predicted by theories
   of behavior change are present in AA
AA and Doctors, Medications
   “In the doctor’s (Karl Jung) opinion, he was utterly
    hopeless”

   “Try to remember that though God has wrought
    miracles among us, never belittle a good doctor or
    psychiatrist, their services can be indispensible…”
    p.133

   “No AA member should “play doctor”, all medical
    advice and treatment should come from a qualified
    physician” The AA member – medications and other
    drugs”
AA world services, Inc., ©1984, 2011
Depressive Sx in 20 y.o. male


Past Psych Hx: None beyond HPI

Psych Sx review: Non-contributory

PMH: Non-contributory

FHx:     *Mother: problematic ETOH use,
         *Father -depression ? Dx or Tx.
         *P. cousin (distant), suicide when
          patient age 9
Depressive Sx in 20 y.o. male


   Substance Hx:

    *ETOH, 1st at age 14, daily use 6-10 beers for 9
      mos prior to 11/06 then MIP, tether

    *Marijuana: 1-8 “bong hits” daily for past 2.5 yrs

    *Oxycontin®, first at age 18, 4-5 occ./week, 80-
      120mg/occ. (“snorting”) X 6 mos.
Depressive Sx in 20 y.o. male

Social Hx:

*Only child, parents divorced when patient age 15,
  raised by mother.

*Never married, no long term relationships.

*H.S. grad, “barely”

*On probation for DUI 12/06 (BAC 0.23%), 3 prior
  MIP’s
Depressive Sx in 20 y.o. male, Diagnosis:


  AXIS I: ETOH dep., cannabis dep., opioid dep.,
          all in early full remission
           Substance-induced depressive disorder by HX

  AXIS II: deferred

  AXIS III: no active medical problems

  AXIS IV: mod. to severe inc. legal, social, occupational,
   family, financial

  AXIS V: 58
Depressive Sx in 20 y.o. male, Considerations

   Stable/improving mood, engaging in program


   No prior psychiatric history before onset of substance use


   No self perceived need for medication or investment in
    having a psychiatric diagnosis


   Recommendation:
    1. Taper off Celexa® over 2-4 weeks

    2. Stop trazodone

    3. Continue to monitor mood
Worsening depression in a middle age male

   A 56 year old male is brought to Psych ED by his wife

   1 week worsening depressive Sx, 3 yr. total treatment for
    “resistant depression”, little benefit.

   Clothes are rumpled, he is unshaven, agitated, wringing
    hands, despairing, says, “I just can’t go on like this, I don’t
    know what to do”

   He says the past few days he is having SI with vague plan to
    jump from a parking deck, When asked to talk about what’s
    wrong, mumbles, “I don’t know, everything”
Worsening depression in a middle age male


    No prior suicide attempts, no family history of suicide, or
     psychiatric problems, no pre-morbid psychiatric history

    Second marriage, now 20 years, lives with wife who is
     supportive but feels helpless

    middle class, both are high school teachers

    PMH: hypertension on lisinopril, migraines

    Meds: venlafaxine XR 300mg/d (3 mo.), bupropion SR
     150mg bid (2 wk.), Ambien® 10mg at hs (8 mo.)
Worsening depression in a middle age male

   Labs: TSH, LFT’s, renal function, electrolytes, CBC all
    WNL
  VS on admission: P. 88 b/p 150/84

 *************************************************

 1) what is your differential dx ?
 2) you’ve just spoken with patient, looked at the outpatient
    notes, what is your intuitive diagnosis ?
 3) what would you do next?
 4) any additional information or diagnostics?
Worsening depression in a middle age male


   MAPS report

   Comprehensive Urine Toxicology screen
    (ELISA + GC/MS)

   Interview wife alone - collateral (with patients
    permission)
Worsening depression in a middle age male

 MAPS: 2 Rx’s for small quantities Tylenol #3®
       w/codeine
       3 Rx’ for Ambien® 10mg, #30, at monthly
       intervals

    UDS + for barbiturates (GC/MS identified butalbital)

    Wife concerned, non-drinker but he occasionally slurs
     words in the evenings, says “I’m just tired”

    Arguing more about $$$, she thinks he is hiding it from
     her, they can’t seem to reduce credit card balances,
     thinks he might be having an affair
        What do you think is going on with this patient ?
Urine drug testing
   ELISA (urine dip test) first done, most common

   Be aware of cross reactants (false +) , panel
    contents specific to your test strip (read circular)

   Approach to patient – empathic, clear, ally not
    enemy

   GC/MS to confirm (takes time, $$$, no false +)
Worsening depression in a middle age male

    24 hrs. after admission, increasing agitation, sweaty, P. 110,
     b/p, 170/110, B UE tremor on exam. Asked for repeat
     zolpidem night before, no effect with 1 dose noted by RN.

    When asked to help us understand his barbiturate + urine he
     had “no idea”

    An hour later called the resident to his room, tearfully
     admitted has been buying APAP/butalbital (Fioricet®, Esgic®,
     etc.) over the Internet for 3 1/2 years, 8-16 tabs/day. Stopped
     it 2 days PTA, “I was trying to quit, tired of lying to everyone”

    Met DSM IV for sedative-hypnotic dep.
Great Idea !!!!
Reality……
Worsening depression in a middle age male,
points to consider

     Always ask about substances & get UDS (only reason
      for patient refusal is it’s going to be positive)

     Some drugs aren’t on the Controlled Substance list and
      won’t show on MAPS, i.e., Fioricet (but Fiorinal® , ASA +
      butalbital is CIII), tramadol, Soma ®, etc.

     Many drugs are available w/o Rx on the Internet

     ALWAYS THINK CRITICALLY, are there other possible
      explanations for what you’re seeing ?
Psychiatric Disorders in Chemically Dependent Individuals - October 2012
Worsening depression in a middle age male

    Treatment plan changes:

    stop bupropion (why?)

    start phenobarbital taper, problem solve to access
     substance use treatment on discharge

    Support patient with engaging family, secrets lead to
     relapse!!
Worsening depression in a middle age male,
references

 CE Romero, et al, Barbiturate Withdrawal Following Internet Purchase of
   Fioricet. Archives of Neurology, 2004

 NS Miller, M Gold. Management of Withdrawal Syndromes and Relapse
  Prevention in Drug and Alcohol Dependence. American family
  physician(1970) 58:11, 119-146, American Academy of Family
  Physicians, 1998

 Graham A et al. Principles of Addiction Medicine. American Society of
   Addiction Medicine. 3rd Edition, Chevy Chase , MD , 2003

 RF Forman, DB Marlowe, AT McLellan. The Internet as a source of drugs
   of abuse. Current Psychiatry Reports, 2006 - Springer
Therapy session #20, 30 y.o. woman, panic,
     anxiety and depression

    “stuck” in therapy, little progress, still having panic
     attacks, depressed
    Confesses, “I think I’m hooked on the Xanax my
     doctor gave me, not doing good, feel guilty, tired of
     all the lying”
                     What do you do next?
a.    Tell her to stop it if she can’t take it the way she
      is supposed to.
b.    Increase therapy to deal with her resistance to
      treatment, anxiety
c.    Send her to a doctor or substance use program
d.    Feel guilty, you should have “caught it” sooner
Questions
   Comments ?

   Cases ?
A case of cross dependence
A case of cross dependence

   52 y.o. Veterinarian, stable in recovery for 18 months
    after a 3 year dependence on Ultram® (tramadol).

   4 mo. ago sought help for anxiety, having cravings for
    alcohol (had alcohol abuse history in her early 20’s)

   Citalopram (SRI) started along with baclofen® titrated to
    120mg/d (rec. max is 80mg/d)

   6 weeks ago began asking for early refills, had started
    writing Rx’s for self
A case of cross dependence

   Says baclofen® “really works”, anxiety “goes away” but
    “it doesn't last that long”

   Disclosed that she had felt a sedative effect, “calm,
    relaxed, good” with the first dose, didn’t tell anyone,
    “thought I found a legal high”, increased dose on own to
    150-180mg/d.

   Now can’t reduce her dose without anxiety, tremor,
    sleeplessness, GI upset.

   “I didn’t plan this to happen, I should have known better”
A case of cross dependence

   Baclofen® being used “off label” for suppression of
    ETOH craving, treatment of anxiety in recovering
    alcoholics (1)

   Some evidence for efficacy in small open-label trials,
    case reports, larger double blind study in progress (1,2)

   Side effects include: drowsiness, dizziness (common)
    and euphoria (rare) – no studies of abuse liability in
    persons known to be ETOH or other drug dependent (5)
A case of cross dependence


   Baclofen® being used “off label” to suppress alcohol
    craving, treat anxiety in recovering alcoholics (1,2)

   Some evidence for efficacy in small open-label trials,
    case reports, larger double blind study in progress (1,2)

   Side effects include: drowsiness, dizziness (common)
    and euphoria (rare) (5)

   No studies of abuse liability in persons known to be
    ETOH or other drug dependent (5)
A case of cross dependence

 Abrupt d/c of high dose baclofen® after several
 months or more can produce withdrawal syndrome
 similar to severe ETOH or sedative-hypnotics. Can
 include: seizures, delirium, autonomic instability
 (3,5)

Management:
 Involved family to handle meds

 Tapered off by 10-20mg q 4-7 days

 Patient self reported to MHPRC as “relapsed”,   rec:
 IOP, no clinical practice until re-evaluation
A case of cross dependence,
Caveats:
   Use caution when prescribing drugs that involve (directly
    or indirectly) the patients know receptor pattern
    vulnerability *(even though their brain has never seen
    the new drug)

   Other gaba-ergic drugs such as gabapentin and
    pregabalin have also been abused by recovering
    patients (4,5)

   Limited information on managing withdrawal of these
    agents, most shows poor cross coverage with high dose
    BZD’s, phenobarbital.

   Most effective way is to re-start drug and slowly taper (3)
A case of cross dependence, gaba-
like drugs/some references
(1) Alcohol and Alcoholism, 2002. Baclofen efficacy in reducing alcohol
cravings and intake: a preliminary double-blind study. G Addolorato, F
Caputo, E Capristo

(2)Alcohol and Alcoholism, 2007. Suppression of symptoms of alcohol
dependence and craving using high dose baclofen. W Bucknam

(3) Psychosomatics 46 (6): 503–507 (Nov-Dec 2005). “Delirium Asociated
With Baclofen Withdrawal: A review of Common Presentations and
management Strategies". Leo RJ; Baer D

(4) J Clin Psychiatry. 2007 Mar;68(3):483-4. Gabapentin abuse, and delirium
tremens upon gabapentin withdrawal. C Pittenger, PH Desan

(5)(2009/MICROMEDEX online) Prescribing Information LYRICA®
(pregabalin) Capsules; Drug Abuse and Dependence

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Psychiatric Disorders in Chemically Dependent Individuals - October 2012

  • 1. CO-MORBID PSYCHIATRIC DISORDERS Patrick W. Gibbons, DO, MSW Medical Director, Dawn Farm Medical Director, Michigan Health Professionals Recovery Program University of Michigan Dept. of Psychiatry, Adjunct Clinical Instructor Washtenaw County/ Community Support and Treatment services
  • 2. Declaration of Potential Conflict of Interest The content of this presentation is non-commercial and I have no conflict of interest to disclose
  • 3. Overview  Definitions  Epidemiology  Diagnostic considerations  Treatment considerations  Case studies
  • 4. Co morbidity Two or more illnesses in the same person at the same time, e.g.., bipolar illness and alcoholism One may affect the course or response to treatment of the other
  • 5. Psychiatric Disorders Mood - depression, anxiety, bipolar Cognitive - autism, ADHD, dementia Psychotic - schizophrenia, delusional d/o Somatoform - conversion, somatization d/o
  • 6. Substance use disorders = abuse or dependence Substance use = non- problematic use Substance misuse = use in a manner not intended Substance abuse = recurrent; *life problems, role function affected *interpersonal, legal problems *use in situations that are physically hazardous to the user
  • 7. 4 C’s of Addiction Control attempts Compulsive use Continued use despite consequences Craving when the drug is stopped Addictive disease is obsession + compulsion +/- physiologic withdrawal symptoms *Drug dependence is physiologic adaptation and withdrawal on stopping the drug
  • 8. Mental Health and Treatment settings 1980’s and 1990’s substance abuse programs reported co- occuring mental disorders in 50 to 75% Mental health programs reported co-occurring substance use disorders in 20 and 50% CSAT, SAMHSA (TIP) Series 42. DHHS Publication No. (SMA) 05-3992. 2005, Rockville, MD 21.3% with serious mental illness had a SUD in the past year National Epidemiologic Survey on Alcohol and Related Conditions, 2004
  • 9. 2010 NSDUH : Summary of National Findings
  • 10. Past Year Substance Dependence or Abuse and Serious Mental Illness among Adults Aged 18 or Older: 2010 2010 NSDUH : Summary of National Findings
  • 11. Past Year Substance Dependence or Abuse among Adults Aged 18 or Older, by Level of Mental Illness: 2010 2010 NSDUH : Summary of National Findings
  • 12. Co-Occurring Mental Illness and Substance Use Disorder in the Past Year among Adults Aged 18 or Older, by Age and Gender: 2010 2010 NSDUH : Summary of National Findings
  • 13. Why do drugs affect mood ? Most drugs of abuse influence production of dopamine and serotonin Depression is most common symptom during any substance withdrawal followed by anxiety and irritable mood. Withdrawal related mood symptoms may last weeks to many months depending on the substance.
  • 14. Why is diagnosis difficult? Alcohol/drugs can cause psychiatric symptoms in anyone (acute toxicity) Prolonged A/D use can cause short or long-term psychiatric illness A/D use can escalate in episodes of psychiatric illness Psychiatric symptoms and A/D use can occur in other psychiatric disorders Marc A. Schuckit: Am. J Psychiatry, 143:2 p. 141 – modified
  • 15. Substance-induced mood disorder DSM IV Prominent/persistent mood disturbance Develops within 1 month of intoxication or withdrawal or medication use is causative Not better accounted for by other axis I d/o Sx not exclusively during delirium Sx cause significant distress or impairment
  • 16. Substance induced depression? 191 male alcoholics, none with prior major psychiatric Hx. 42% had significant Sx (Ham D > 19) within 48 hrs. of admission At 2 weeks, 12% with Ham D score >19 At 4 weeks, 6% with Ham D score > 19 Rapid decline in Sx intensity over first 4 weeks of Tx., largest reduction at 2 weeks Recommended: defer antidepressant Rx prior to first 4 weeks of abstinence* (Brown and Schuckit, 1988.)
  • 17. Chicken or Egg? 25-year longitudinal study, 635 boys, 630 girls, birth cohort, general community sample in New Zealand found that: problems with alcohol led to increased risk of Major Depression as opposed to: a self-medication model in which Major Depression led to increased risk of AAD. Fergusson, Boden, et al, Arch Gen Psychiatry. 2009 Mar;66(3):260-6
  • 18. Past Year Substance Dependence or Abuse among Adults Aged 18 or Older, by Major Depressive Episode in the Past Year: 2010 2010 NSDUH : Summary of National Findings
  • 19. What’s the difference? Post-Acute Withdrawal Psychiatric Disorder Depression Major Depression Anxiety Anxiety/Panic Disorder Mood Lability Bipolar Disorder * normal in early abstinence *not normal resolves with time won’t resolve without Tx Responds to behavioral measures 12-Steps won’t hurt responds to 12-Steps
  • 20. Early phase psychosis w/ co-morbid substance use vs. substance induced psychosis ? N=386, 44% sub induced psychosis, 56% primary psychosis Predictors of substance-induced Sx: parental substance abuse (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.00-2.85) diagnosis of dependence on any drug (OR, 9.41; 95% CI, 5.26-16.85), visual hallucinations Caton et al, Arch Gen Psychiatry. 2005;62:137-145.
  • 21. Quick differential: Psychosis Visual Hallucinations: -hallucinogens, alcohol withdrawal, organic i.e, Lewy body dementia, delirium (uncommon with 1º psychosis) -vague (shadows, etc.) with Axis II Auditory Hallucinations: -Schizophrenic or schizoaffective d/o (less common with substances) -vague sounds (mumbling, name called, etc.) with Axis II Paranoia: -substances: cocaine, psych stimulants, occ. THC and ETOH withdrawal -Axis I: mania, schizophrenia/schizoaffective -Axis II: paranoid personality disorder (rare)
  • 22. Mania: simultaneously activated behavior, mood and thinking **medical causes to be considered include thyrotoxicosis, temporal lobe epilepsy  Bipolar, schizoaffective, psychosis, anxiety disorders  Methamphetamine/Cocaine  Ecstasy (MDMA)  Hallucinogens  Alcohol/Benzodiazepine withdrawal?  Medication induced (i.e. corticosteroids)
  • 23. Schizophrenia and Marijuana Up to 2x >risk of developing schizophrenia Moore, et al, Lancet 2007; 370: 319–28 Caspi et al., Biol Psychiatry, May 2005
  • 24. Meier et al. Persistent cannabis users show neuropsychological decline from childhood to midlife Proc Nat Acad Sci, October 2, 2012 vol. 109 no. 40 E2657 – E2664 Fig. 2. Adolescent vulnerability. Change in full scale IQ (SD units) from childhood to adult. Adolescent onset (black bar) had >IQ decline vs. adult onset. IQ ↓ approximately -0.55 units (8 IQ points) with 3+ diagnosis over time
  • 25. Adolescents and marijuana use  have higher levels of anxiety (Dorard et al., 2008), depressive symptoms (Medina et al., 2007), suicidality (Pedersen 2008) and externalizing behavior (Monshouwer et al., 2006)  neurocognitive deficits, including intentional, learning, memory, and intellectual functioning decrements (Fried et al., 2002; Di Forti et al., 2007; Harvey et al., 2007; Brook et al., 2008)  poorer sleep (Bolla et al., 2008), respiratory problems (Aldington et al., 2007; Brook et al., 2008), cancer (Berthiller et al., 2008)
  • 26. Personality disorders and substance use Antisocial PD - highest likelihood of co-morbid substance use (may facilitate further behavioral or emotional excursions) Borderline PD – predictable clinical worsening (increased externalizing, impulsivity) Hard to diagnose in presence of early onset and/or active substance use
  • 27. What is the most fatal mental disorder? Risk Factor Odds Of Attempting Suicide  Cocaine use → 62 times more likely  Major Depression → 41 times more likely  Alcohol use → 8 times more likely  Separation or Divorce → 11 times more likely NIMH/NID
  • 28. Suicide Thoughts, Plans, and Attempts in the Past Year among Adults Aged 18 or Older, by Substance Dependence or Abuse: 2010 2010 NSDUH : Summary of National Findings
  • 29. Eating disorders and substance use  50% of persons with an eating disorder also have problematic drug or alcohol use, (compared with 9% of the general population)  35% of females with a substance use disorder report having an eating disorder (compared with 1–3% of the general population) Root, et al, Int J Eat Disord March 2009; (online pub. )
  • 30. Eating disorders and substance use Alcohol and drug abuse or dependence more common in: *mixed binge/purge *purging only eating behaviors than in: restrictive only eating behaviors Treatment outcomes poor unless both conditions addressed Root, et al, Int J Eat Disord March 2009; (online pub.)
  • 31. Red Flags for co-occurring psychiatric illness include: Family history of psychiatric illness Onset of psychiatric symptoms before the onset of substance use disorder Psychiatric symptoms during lengthy periods of abstinence in the past The longer from last use and acute withdrawal, more likely to be seeing a co-morbid process
  • 32. Implications for treatment addictive disease is predictive Exposure kindles “a new biological drive” to use the drug (success in meeting basic drives decreases anxiety i.e., not getting fed) Encouraging self confidence, empowerment as goals not always desirable Heritability ranges from 40 – 60%
  • 33. Amphetamine and cocaine elevate DA in NAS Drugs of abuse act on: Nicotine acts on cholinergic receptors at cell bodies and terminals of mesolimbic system, increasing DA in NAS PCP blocks NMDA (GLU) increasing DA in NAS. Opiates inhibit the GABAergic cells that normally inhibit the mesolimbic system Increasing dopamine in NAS Barbiturates and benzo’s do the same at some GABAergic level Ethanol and marijuana end with the same results in NAS through unknown mechanisms Caffeine doesn’t involve the same circuit.
  • 34. DA Receptors and the Response to Methylphenidate (MP) High DA high receptor Dopamine receptor level low Low DA receptor As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant Adapted from Volkow et al., Am. J. Psychiatry, 1999.
  • 35. Treatment: generally avoid cross- dependency producing drugs Benzodiazepines Ativan, Xanax, Klonopin, Valium, Librium, Restoril, Tranxene, Versed Benzodiazepine analogs Ambien, Sonata, Lunesta Other Sedative-Hypnotics Soma, meprobamate, chloral hydrate, etc. Barbiturates Fiorinal, Fioricet, phenobarbital Psychostimulants Adderall, Ritalin, etc. Opioids codeine, Ultram, Vicodin, methadone, heroin, etc.
  • 36. How to address sleep and anxiety problems? Thorough history, +/- medical evaluation if needed Optimize self care * recovery program * sleep * diet, caffeine use * exercise Psychiatric referral if necessary
  • 37. Medical procedures and pain management in recovering persons: Generally, avoid elective procedures in 1st year of recovery Co-ordination of care is essential (PCP, surgeon, dentist, etc.) Avoid practice outside of specialty (prescribing for conditions you don’t have experience with, can’t evaluate or follow) Consider non-opioid measures such as long- lasting local anesthesia (i.e, bupivicaine), NSAIDS, acetaminophen, anti- convulsants for neuropathic pain, topical analgesics, physical therapy
  • 38. ADHD in Recovering Persons Consider non-stimulants agent first (Strattera®) Controlled release (i.e. Adderall®, Concerta®) or pro- drugs (Vyvanse®) have less abuse potential, harder to get high peak effect by IV or snorting All activate mesolimbic and mesocortical areas of the brain involved in addictive disease, kindle craving, obsession and compulsion, and all have been abused Of persons having true ADHD diagnosis in childhood, only 30% will carry functional symptoms into adulthood
  • 40. General points on pharmacotherapy for co-occurring disorders Avoid the trap of reacting to symptoms with polypharmacy Many substance-use patients like taking drugs, any drugs Decision to medicate should always be with clear rationale and consideration of alternatives including psychosocial and behavioral interventions.
  • 41. Always weigh risk versus benefit Persons with persistent anxiety, apathy, irritability or social withdrawal are describing barriers to engagement in recovery process
  • 42. Successful adaptation to the substance-free state for most means: Abstinence plus engagement in a psychosocial process which can facilitate a transfer of dependency needs to sources of supply which are: 1. *non-destructive 2. *intrinsically rewarding 3. *inexhaustible
  • 43. Meta analysis of literature on AA effectiveness found: Katsukis, 2009 , Addict Dis. 2009;28(2):145-57. (1) magnitude of effect: rates of abstinence about 2x higher (2) dose response effect: > attendance associated with > rates of abstinence (3) consistent effect: these relationships are found for different samples and follow-up periods (4) temporally accurate effects: prior AA attendance predictive of subsequent abstinence (5) specific effects: evidence establishing the specificity of an effect for AA or Twelve Step Facilitation/TSF is mixed *(2 trials+, 1 trial -, 1 trial no effect) (6) plausibility: mechanisms of action predicted by theories of behavior change are present in AA
  • 44. AA and Doctors, Medications  “In the doctor’s (Karl Jung) opinion, he was utterly hopeless”  “Try to remember that though God has wrought miracles among us, never belittle a good doctor or psychiatrist, their services can be indispensible…” p.133  “No AA member should “play doctor”, all medical advice and treatment should come from a qualified physician” The AA member – medications and other drugs” AA world services, Inc., ©1984, 2011
  • 45. Depressive Sx in 20 y.o. male Past Psych Hx: None beyond HPI Psych Sx review: Non-contributory PMH: Non-contributory FHx: *Mother: problematic ETOH use, *Father -depression ? Dx or Tx. *P. cousin (distant), suicide when patient age 9
  • 46. Depressive Sx in 20 y.o. male  Substance Hx: *ETOH, 1st at age 14, daily use 6-10 beers for 9 mos prior to 11/06 then MIP, tether *Marijuana: 1-8 “bong hits” daily for past 2.5 yrs *Oxycontin®, first at age 18, 4-5 occ./week, 80- 120mg/occ. (“snorting”) X 6 mos.
  • 47. Depressive Sx in 20 y.o. male Social Hx: *Only child, parents divorced when patient age 15, raised by mother. *Never married, no long term relationships. *H.S. grad, “barely” *On probation for DUI 12/06 (BAC 0.23%), 3 prior MIP’s
  • 48. Depressive Sx in 20 y.o. male, Diagnosis: AXIS I: ETOH dep., cannabis dep., opioid dep., all in early full remission Substance-induced depressive disorder by HX AXIS II: deferred AXIS III: no active medical problems AXIS IV: mod. to severe inc. legal, social, occupational, family, financial AXIS V: 58
  • 49. Depressive Sx in 20 y.o. male, Considerations  Stable/improving mood, engaging in program  No prior psychiatric history before onset of substance use  No self perceived need for medication or investment in having a psychiatric diagnosis  Recommendation: 1. Taper off Celexa® over 2-4 weeks 2. Stop trazodone 3. Continue to monitor mood
  • 50. Worsening depression in a middle age male  A 56 year old male is brought to Psych ED by his wife  1 week worsening depressive Sx, 3 yr. total treatment for “resistant depression”, little benefit.  Clothes are rumpled, he is unshaven, agitated, wringing hands, despairing, says, “I just can’t go on like this, I don’t know what to do”  He says the past few days he is having SI with vague plan to jump from a parking deck, When asked to talk about what’s wrong, mumbles, “I don’t know, everything”
  • 51. Worsening depression in a middle age male  No prior suicide attempts, no family history of suicide, or psychiatric problems, no pre-morbid psychiatric history  Second marriage, now 20 years, lives with wife who is supportive but feels helpless  middle class, both are high school teachers  PMH: hypertension on lisinopril, migraines  Meds: venlafaxine XR 300mg/d (3 mo.), bupropion SR 150mg bid (2 wk.), Ambien® 10mg at hs (8 mo.)
  • 52. Worsening depression in a middle age male  Labs: TSH, LFT’s, renal function, electrolytes, CBC all WNL  VS on admission: P. 88 b/p 150/84 ************************************************* 1) what is your differential dx ? 2) you’ve just spoken with patient, looked at the outpatient notes, what is your intuitive diagnosis ? 3) what would you do next? 4) any additional information or diagnostics?
  • 53. Worsening depression in a middle age male  MAPS report  Comprehensive Urine Toxicology screen (ELISA + GC/MS)  Interview wife alone - collateral (with patients permission)
  • 54. Worsening depression in a middle age male MAPS: 2 Rx’s for small quantities Tylenol #3® w/codeine 3 Rx’ for Ambien® 10mg, #30, at monthly intervals  UDS + for barbiturates (GC/MS identified butalbital)  Wife concerned, non-drinker but he occasionally slurs words in the evenings, says “I’m just tired”  Arguing more about $$$, she thinks he is hiding it from her, they can’t seem to reduce credit card balances, thinks he might be having an affair What do you think is going on with this patient ?
  • 55. Urine drug testing  ELISA (urine dip test) first done, most common  Be aware of cross reactants (false +) , panel contents specific to your test strip (read circular)  Approach to patient – empathic, clear, ally not enemy  GC/MS to confirm (takes time, $$$, no false +)
  • 56. Worsening depression in a middle age male  24 hrs. after admission, increasing agitation, sweaty, P. 110, b/p, 170/110, B UE tremor on exam. Asked for repeat zolpidem night before, no effect with 1 dose noted by RN.  When asked to help us understand his barbiturate + urine he had “no idea”  An hour later called the resident to his room, tearfully admitted has been buying APAP/butalbital (Fioricet®, Esgic®, etc.) over the Internet for 3 1/2 years, 8-16 tabs/day. Stopped it 2 days PTA, “I was trying to quit, tired of lying to everyone”  Met DSM IV for sedative-hypnotic dep.
  • 59. Worsening depression in a middle age male, points to consider  Always ask about substances & get UDS (only reason for patient refusal is it’s going to be positive)  Some drugs aren’t on the Controlled Substance list and won’t show on MAPS, i.e., Fioricet (but Fiorinal® , ASA + butalbital is CIII), tramadol, Soma ®, etc.  Many drugs are available w/o Rx on the Internet  ALWAYS THINK CRITICALLY, are there other possible explanations for what you’re seeing ?
  • 61. Worsening depression in a middle age male Treatment plan changes:  stop bupropion (why?)  start phenobarbital taper, problem solve to access substance use treatment on discharge  Support patient with engaging family, secrets lead to relapse!!
  • 62. Worsening depression in a middle age male, references CE Romero, et al, Barbiturate Withdrawal Following Internet Purchase of Fioricet. Archives of Neurology, 2004 NS Miller, M Gold. Management of Withdrawal Syndromes and Relapse Prevention in Drug and Alcohol Dependence. American family physician(1970) 58:11, 119-146, American Academy of Family Physicians, 1998 Graham A et al. Principles of Addiction Medicine. American Society of Addiction Medicine. 3rd Edition, Chevy Chase , MD , 2003 RF Forman, DB Marlowe, AT McLellan. The Internet as a source of drugs of abuse. Current Psychiatry Reports, 2006 - Springer
  • 63. Therapy session #20, 30 y.o. woman, panic, anxiety and depression  “stuck” in therapy, little progress, still having panic attacks, depressed  Confesses, “I think I’m hooked on the Xanax my doctor gave me, not doing good, feel guilty, tired of all the lying” What do you do next? a. Tell her to stop it if she can’t take it the way she is supposed to. b. Increase therapy to deal with her resistance to treatment, anxiety c. Send her to a doctor or substance use program d. Feel guilty, you should have “caught it” sooner
  • 64. Questions  Comments ?  Cases ?
  • 65. A case of cross dependence
  • 66. A case of cross dependence  52 y.o. Veterinarian, stable in recovery for 18 months after a 3 year dependence on Ultram® (tramadol).  4 mo. ago sought help for anxiety, having cravings for alcohol (had alcohol abuse history in her early 20’s)  Citalopram (SRI) started along with baclofen® titrated to 120mg/d (rec. max is 80mg/d)  6 weeks ago began asking for early refills, had started writing Rx’s for self
  • 67. A case of cross dependence  Says baclofen® “really works”, anxiety “goes away” but “it doesn't last that long”  Disclosed that she had felt a sedative effect, “calm, relaxed, good” with the first dose, didn’t tell anyone, “thought I found a legal high”, increased dose on own to 150-180mg/d.  Now can’t reduce her dose without anxiety, tremor, sleeplessness, GI upset.  “I didn’t plan this to happen, I should have known better”
  • 68. A case of cross dependence  Baclofen® being used “off label” for suppression of ETOH craving, treatment of anxiety in recovering alcoholics (1)  Some evidence for efficacy in small open-label trials, case reports, larger double blind study in progress (1,2)  Side effects include: drowsiness, dizziness (common) and euphoria (rare) – no studies of abuse liability in persons known to be ETOH or other drug dependent (5)
  • 69. A case of cross dependence  Baclofen® being used “off label” to suppress alcohol craving, treat anxiety in recovering alcoholics (1,2)  Some evidence for efficacy in small open-label trials, case reports, larger double blind study in progress (1,2)  Side effects include: drowsiness, dizziness (common) and euphoria (rare) (5)  No studies of abuse liability in persons known to be ETOH or other drug dependent (5)
  • 70. A case of cross dependence Abrupt d/c of high dose baclofen® after several months or more can produce withdrawal syndrome similar to severe ETOH or sedative-hypnotics. Can include: seizures, delirium, autonomic instability (3,5) Management: Involved family to handle meds Tapered off by 10-20mg q 4-7 days Patient self reported to MHPRC as “relapsed”, rec: IOP, no clinical practice until re-evaluation
  • 71. A case of cross dependence, Caveats:  Use caution when prescribing drugs that involve (directly or indirectly) the patients know receptor pattern vulnerability *(even though their brain has never seen the new drug)  Other gaba-ergic drugs such as gabapentin and pregabalin have also been abused by recovering patients (4,5)  Limited information on managing withdrawal of these agents, most shows poor cross coverage with high dose BZD’s, phenobarbital.  Most effective way is to re-start drug and slowly taper (3)
  • 72. A case of cross dependence, gaba- like drugs/some references (1) Alcohol and Alcoholism, 2002. Baclofen efficacy in reducing alcohol cravings and intake: a preliminary double-blind study. G Addolorato, F Caputo, E Capristo (2)Alcohol and Alcoholism, 2007. Suppression of symptoms of alcohol dependence and craving using high dose baclofen. W Bucknam (3) Psychosomatics 46 (6): 503–507 (Nov-Dec 2005). “Delirium Asociated With Baclofen Withdrawal: A review of Common Presentations and management Strategies". Leo RJ; Baer D (4) J Clin Psychiatry. 2007 Mar;68(3):483-4. Gabapentin abuse, and delirium tremens upon gabapentin withdrawal. C Pittenger, PH Desan (5)(2009/MICROMEDEX online) Prescribing Information LYRICA® (pregabalin) Capsules; Drug Abuse and Dependence