Illicit Drugs, Medication Misuse, Pain Management, and Pharmacotherapy

1
Illicit Drugs, Medication Misuse, Pain
Management, and Pharmacotherapy

• David W. Oslin, MD
• University of Pennsylvania, School of Medicine
• And
• Philadelphia, VAMC

Hazelden Research Co-Chair on Late Life
Addictions
2
Disclosures

• NIMH
• K08 Award
• ACSIR
• NIDA
• Center for Studies on Addiction
• NIAAA
• R01
• VA
• Merit Early Entry
• MIRECC
• HSRD Merit Award
• Industry Support
• DuPont Pharma
• Forest Labs
• Hazelden Foundation
• Pfizer

3
The Problems

• Alcohol Use
• Medication Misuse
• Cigarette use
• Illicit substances
• Gambling

4
What is the Extent of the Issues?In the Community
5
Illicit Drug Use
6
Relevance to an aging population

• Cohort changes in exposure we will see more
  elderly patients using illicit substances
  (current and past abuse)
• Consequences may be greater in older adults
• Direct toxicity / withdrawal
• Indirect interactions with medications or other
  illnesses
• We dont know much about treatment
• Comorbidity is a significant issue perhaps
  uniquely so for the elderly
• Cognition
• Minor depression
• Suicide
• Anxiety and personality problems

7
The difficulty

• Extremely limited research
• Most epidemiological samples few elderly, ECA
  is gt20 years old
• Drug and alcohol dependence are exclusions to
  most geriatric trials
• Age gt65 is almost always an exclusion for drug
  and alcohol trials

8
Veterans (Age 60 and Over) in Addiction Treatment

• Alcohol Only 51.8
• Street Drugs Only 9.1
• Prescription Medications only 3.6
• Alcohol and Street Drugs 26.4
• Alcohol and Prescription Medications 5.5
• Street Drugs and Prescription Medications
  0.9
• All three categories of substances 1.8
• Missing data 0.9

Sample of 110 subjects in a special
geri-addiction program
Schonfeld et al. 1990
9
Drug Consequences

• Alcohol
• Directly neurotoxic
• Associated with dementia and depression
• Opioids
• Secondary effects via infection
• Acute cognitive effects ?long term effects
• Stimulants
• Acute and chronic depletion of dopamine
• Effects frontal striatum
• Nicotine
• Associated with dementia and depression

10
Treatment Issues

• No clinical trial research
• Very limited observational research
• Some clinical experience by select clinicians
• Many opinions

11
Past History is a Concept We Must Embrace

• Many older adults especially those of the
  Woodstock generation will enter late life with
  a past history of alcohol or drug abuse
• 5 fold increase in late life mental disorders
  (depression and dementia)
• Treatment of late life depression (3-5 yr
  outcomes)
• 88 of those without an alcohol history
  significantly improved
• 57 of those with an alcohol history
  significantly improved

Saunders et al. 1991, Cook et al. 1991
12
Behavioral Health Laboratory (BHL) Links To
Primary Care
13
Research to PracticeBehavioral Health Laboratory

• The BHL is an automated telephone assessment and
  triage service for patients identified by primary
  care providers as having depressive symptoms or
  at-risk drinking.
• The depression and alcohol clinical reminder
  system generates a consultation request to the
  BHL.
• The BHL conducts a brief telephone (20-30
  minutes) assessment generating a report for the
  PCP including diagnosis, severity, and general
  treatment recommendations.

14
Drug Use Among Primary Care Patients with Minor
or Major Depression
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Types of Substance Use Among Older Adults (50)
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Drug Use Among Older Patients with Minor or Major
Depression
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Drug Use Among Older Patients with Minor or Major
Depression
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Medication Misuse So Many Terms Little
agreement

• Abuse
• Inappropriate
• Problematic
• Misuse
• Addiction

• Non-medical use
• Dependence
• Iatrogenic
• Unintended use

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Prescription Medication Use by Seniors - 1996

• Taking 3 or more medications 58
• Taking an antidepressant 8.9
• Taking a benzodiazepine 10.4
• Taking a narcotic analgesic 14.5
• Taking a non-steroidal agent - 17.5

Moxley, E. et.al. 2003
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Benzodiazepine across the age spectrum
Dunbar et al. 1980
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Analgesic Drug Use
Use in the last 2 weeks
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Risks of Non-Specific Use of Medications

• Costs patient, insurance, and employer
• Increased exposure to drug specific adverse
  effects
• General adverse effects such as falls and memory
  impairment
• Increased drug drug interactions
• Increased drug disease interactions

24
Sedative/Hypnotic UseA Disappearing Problem?
MW p 0.0393, Positive Negative p0.002
25
Relationship Between Benzodiazepine Use and
Depression Treatment
Percent Reduction in HAMD p0.091
26
Benzodiazepine Discontinuation
4
2
0
-
2
P
l
a
c
e
b
o
B
e
n
z
o
d
i
a
z
e
p
i
n
e
-
4
(n36)
-
6
6 Months
12 Months
(Habraken et. Al., 1997)
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Medication Misuse

• Think twice before using a medication when the
  target is not well defined or there are
  non-pharmacological alternatives
• Set out with well defined goals for the
  medication
• Dont be afraid to stop medication when there is
  no evidence it is effective
• Educate patients about the limitations of
  medications

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Treating Pain and the Risks of Analgesic Abuse
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Chronic Pain and the Elderly

• Chronic Pain Problems 20 50
• Chronic Pain in NH residents 34 67
• Use Analgesics
• (several times/wk) 18
• Use Analgesics for gt 6 months 11

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Clinician attitudes toward pain management

• Duration of pain or patient demographics are not
  related to opioid prescribing
• Nonverbal expressions of pain were the greatest
  predictors of opioid prescriptions
• Many physicians have negative views about
  patients with chronic pain
• 35 of primary care physicians are unwilling to
  prescribe sustained release opioids for chronic
  pain

Turk et al 1997, Weinstein et al 2000, Potter et
al 2001
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Outcome of Pain for Older Adults

• Depression
• Decreased socialization
• Sleep problems
• Decreased functional capacity
• Increased health care utilization
• 8 of chronic pain patients have seen 3 or more
  physicians in the last 5 years

33
Depression and Pain Complaints
Parmelee et al 1991
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What are the Concerns/Issues?

• Fear of inducing a new addiction by using opioid
  analgesics or benzodiazepines
• Fear of inducing a relapse in those in remission
  from an addiction problem
• Dealing with drug-seeking behavior
• Concern about drug interactions
• Regulatory fears physician mis-prescribing and
  legal consequences
• Rising use of opioid analgesics for medical and
  non-medical use

35
New users of Opioid Analgesics for Non-medical
purposes
1600
1400
1200
1000
Thousands
800
600
400
200
1980
1985
1990
1995
36
Medical Use of Opioid Analgesics
Kgs of use
Joranson et al 2000
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What about the myths?

• Myth
• Using Opioid analgesics will lead to a new
  pattern of addiction
• Reality
• Very limited evidence that this occurs

Chabal et al, 1997, Joranson et al 2000
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What about the myths?

• Myth
• Using Opioid analgesics will lead to a relapse in
  patients already in treatment
• Reality
• No evidence for this
• Consider the converse pain will limit
  improvements in addiction treatment

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What about the myths?

• Myth
• Using Opioid analgesics will promote drug seeking
  behavior
• Reality
• The behavior is predictable
• Current history of polysubstance dependence
• Low social support
• Not currently in addiction treatment

Dunbar and Katz, 1996
40
What about the myths?

• Myth
• Tolerance and physiologic dependence addiction
• Reality
• Many patients will develop tolerance to opioid
  analgesics
• Many patients will experience withdrawal symptoms
  after long term use.
• The majority of these patients will not exhibit
  other symptoms of addiction such as drug seeking,
  using more than prescribed, etc.

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What about the myths?

• Myth
• I will loose my license if I prescribe opioids to
  an addicted individual
• Reality
• Using opioid analgesics in substance dependent
  patients is not illegal
• Rationale for treatment should be well documented
• Treatment outcomes should be well documented.

42
Clinical Trial Data on Pain Management

• 1993
• 83 randomized clinical trials using an NSAID
• 10000 subjects
• 230 subjects gt 65
• 0 subjects gt85

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Pharmacologic Guidelines for older adults

• Acetaminophen
• mild to mod pain
• not to exceed 4000mg/day
• NSAIDs
• use with caution in those with renal failure,
  PUD, bleeding problems.
• High dose long-term should be avoided
• Opioids
• Sustained release preps for chronic pain
• Fixed dose combinations (e.g. T3) for short term
  or break through pain
• For long term use remember a prophylactic bowel
  regimen
• Cognitive impairment, nausea and puritus are all
  common

JAGS 461998
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Choices other than Opioids

• Medications
• Antidepressants
• Mood stabilizers/ anticonvulsants
• NSAIDS
• Cox inhibitors
• Acetametaphin
• tramadol

• Devices and procedures
• Nerve blocks/ablation
• Electrical/magnetic stimulation
• Acupuncture
• Exercise/PT
• Psychotherapy
• Chiropractic treatment
• hypnosis

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Summary

• We all must die. But if I can save someone
  from days of torture, that is what I feel is my
  great and ever new privilege. Pain is a more
  terrible lord of mankind than even death itself.
• Albert Schwietzer, MD

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Pharmacotherapy for Addictive Disorders
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Pharmacological Treatments of Addiction

• FDA Approved
• Antabuse (alcohol)
• Naltrexone (alcohol)
• Methadone (opioids)
• Buprenorphine (opioids)
• Nicotine replacement (nicotine)
• Buproprion (nicotine)

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Naltrexone

• FDA approved for the treatment of alcohol
  dependence
• Functions as an opioid receptor antagonist (mu gtgt
  delta or kappa)
• Development was an example of bench to bedside
  translational science (opioid effects on reward
  pathways)

50
Opioid Neurotransmission and Alcohol

• Alcohol consumption affects the production,
  release, and activity of opioid peptides (Herz,
  1997)
• Opioid peptides mediate some of alcohols
  rewarding effects by enhancing midbrain dopamine
  release
• Opioid antagonists suppress alcohol-induced
  reward (Swift,1999)

51
Naltrexone in the Treatment of Alcohol Dependence
Cumulative Relapse Rate
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
Naltrexone HCL (N35) Placebo (N35)
0.2
0.1
0.0
1
0
2
3
4
5
6
7
8
9
10
11
12
No. of Weeks Receiving Medication
Volpicelli et al, Arch Gen Psychiatry, 1992 49
876-880
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Randomized Placebo Controlled Naltrexone/Nalmafene
Trials
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Younger versus Older Adults
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Translating Positive findings in Aging to Younger
Adults
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For Whom?

• Under what conditions and for which patients will
  naltrexone have the greatest impact?

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Effects of Family History on Naltrexone Response
Days of Heavy Drinking
Monterosso et al 2001
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A118G (Asn40Asp)

• Asp40 allele frequency of 13-20 (24.3 36 of
  European Americans have at least one copy)
• The 118 AgtG exon 1 SNP increases OPRM1 affinity
  for beta-endorphin. The functional significance
  of other variants remains unknown.
• Asp40 variant binds beta-endorphin and activates
  G- protein coupled protein potassium ion channels
  with 3 times greater potency
• Naloxone challenge alters CRF secretion in those
  with the Asp40 variant

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Proportions of Clinical Response in Naltrexone
Treated Subjects
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Proportions of Clinical Response in Placebo
Treated Subjects
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Genetic Polymorphisms and Alcohol Treatment
Naltrexone / Asp40 Allele (A/G, G/G)
Naltrexone Asn40 Allele (A/A)
Cumulative Survival (time to relapse)
Placebo / Asp40 Allele (A/G, G/G)
Placebo / Asn40 Allele (A/A)
Days
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Buprenorphine in Office-Based Opiate Treatment

• Buprenorphine and buprenorphine/naloxone are the
  only opioid agonist medications approved for the
  treatment of opioid dependence in the office
  setting.
• DATA 2000 allow for qualified physicians to treat
  up to 30 patients at any given time with
  buprenorphine by prescription, with appropriate
  ancillary services either in the office or by
  referral.

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Buprenorphine, Methadone, LAAM Treatment
Retention
100
73 Hi Meth
80
60
58 Bup
Percent Retained
40
20
20 Lo Meth
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Study Week
Adapted from Johnson, et al., 2000
63
Buprenorphine, Methadone, LAAMOpioid Urine
Results
100
All Subjects
80
60
Bup
40
Hi Meth
Mean Negative
40
39
Lo Meth
20
19
0
1
3
5
7
9
11
13
15
17
Study Week
Adapted from Johnson, et al., 2000
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Summary

• Buprenorphine and buprenorphine/naloxone are
  effective for the treatment of opiate dependence
  in the office setting.
• Physicians can easily become qualified to
  prescribe buprenorphine.
• Managing patients within the office setting can
  be done with existing resources and minimal
  difficulty.