The Emerging Epidemic of Prescription Drug Abuse

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The Emerging Epidemic of Prescription Drug Abuse

• Friday, May 6, 2005
• Honolulu, Hawaii
• Kevin Kunz, M.D.

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Term Merge

• Illicit use
• Licit use
• Addiction
• Pseudo-addiction
• Comfort use
• Innocent use
• Doesnt meet criteria
• Medical use
• Problem use

• Non-medical use
• Misuse
• Inadvertent use
• Abuse
• Dependence
• Therapeutic dependence
• Current use
• Lifetime use
• Habit

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Whos Fault?

• Consumer?
• Pharmaceutical Industry?
• Physicians?
• Society and Culture?

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End Fault Zone
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Historic waves. of drug problems

• Stimulants
• 1895 medical cocaine, Parke Davis Co.
• 1932 medical amphetamine, Benzadrine
• 1980 crack cocaine
• 1995 methamphetamine, ice
• Opioids/Sedatives
• 1885-1925 opium, medical heroin (Bayer)
• 1950-70 heroin, 4 pure
• 1990 heroin, 48 pure
• Intoxicants
• marijuana, LSD, Club Drugs

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Medicinal to Illicit Drugs

• Cocaine for vitality, alcoholism,
  hay fever
• Marijuana AMA fought MJ Stamp Act
• Heroin Bayers blockbuster for
  cough
• Amphetamine for depression , dieters, drivers
• Morphine Gods own medicine

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The Drug Epidemic Cycle

• Acceptance Acceptance
• Doubt Re-emergence
• Rejection
  Permissiveness
• Sanctions Loosen sanctions
• Hibernation

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New trends, not new drugs

• Route of use (1865 syringe, inhalation, SL,
  lollipop)
• New forms (Miltown/Soma MJ/Marinol/ Sativex
  ER/SR/CR, Pallidone)
• New potency (fentanyl, aprazolam)
• Designer drugs (tramadol, modafanil, new S/H,
  me too)

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Deja vu

• 1860 Hypodermic syringe. 1900 IV same effect
  with less dose, protects against addiction.
  Thus, reasonable for all pain.
• 1920 Nearly 80 of the morphine addicts have
  acquired the habit from legitimate
  medications Dr. A. Lambert, AMA Pres.
• 1930-50s Opioids illegal, unnecessary,
  dangerous
• 1960s Hospice Movement death with dignity

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• 1980s Liberalization of opioids for non-terminal
  pain
• 1996 Oxycontin released, echoes syringe
  situation,
• less addicting, less than 1 addiction rate
• 2000 Oxycontin epidemic, teens to parents,
• dependence, addiction, problem use, death
• 2001 Purdue retracts less addicting, pain
  experts apologize
• 2005 Stage set for cycle of retreat and
  hibernation

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How Many Americans Have a Drug Problem?

• Nicotine 20-30
• Marijuana 14
• Alcohol 6-12
• Opioids ?
• Any illicit drug 8.2
• Prescription drugs 2.7
• Perspective 45 take a RX qd there are
  150,000 OTCs
• 1965 300 Rx drugs 2005 9,000 Rx drugs
  (RxList.com)

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• Nonmedical Use of Prescription Drugs,
• Reported by 6.2 Million Persons in 2002,
• Is Second Only to Marijuana Use

Past Month Users, Ages 12 and Older (in Millions)
14.6
Marijuana
6.2
Prescription Drugs
Cocaine
2.0
(incl. crack)
Crack
0.6
0.7
Ecstasy
0.6
Meth
0.6
Inhalants
0.2
Heroin
0.1
LSD
0
1
3
5
7
9
11
13
15
Source SAMHSA, 2002 National Survey on Drug Use
and Health.
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Non-Medical Use of Selected Pain Pills
(lifetime, 12 and over, 2002)
Darvocet, Darvon, or Tylenol with Codeine
18.9
Vicodin, Lortab or Lorcet
13.1
Percocet, Percodan or Tylox
9.7
6.9
Codeine
Hydrocodone
4.5
2.9
Demerol
2.1
Morphine
1.9
OxyContin
1.1
Dilaudid
1.0
Ultram
0.9
Methadone
Source SAMHSA, NSDUH Report Nonmedical Use of
Prescription Pain Relievers, May 21, 2004.
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New Non-medical Users of Pain Relievers
1965-2002
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As Prescriptions Increase, Emergency Room
Reports Have Increased at the Same or Faster rate
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Increase in Poisoning Deaths Caused by
Non-Illicit Drugs --- Utah, 1991--2003MMWR,
1/21/05

• Figure 3

Figure 3
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High Rates in Non-medical Use of Oxy Vicodin
Source Monitoring the Future Study, 2004.
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Generation Rx

• 18 of teens have abused Vicodin
• 20 tried Ritalin or Adderall without Rx
• 9 abused OTC cough syrup to get high
• Equal or greater abuse of OTC/Rx than cocaine,
  Ecstasy, LSD, ketamine, heroin, GHB, ice
• Rx Meds safer (50), less addictive (33)
• Ease of access medicine cabinets
• Drugs are fun vs Drugs help kids when they are
  having a hard time
• Rx/OTC med abuse has penetrated teen culture
• April 21, 2005. Partnership for a Drug Free
  America. 17th annual study of teen drug abuse.
  N 7,300, error margin /- 1.5

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Why Has the Abuse of Prescription Drugs Been
Increasing?

• Pain and DSM relief
• Production and availability increased
• Marketing and media attention
• Molecular factors
• User characteristics
• Physician factors

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Treat Pain !

• JACHO Guidelines 2000
• Mandate pain assessment and treatment
• Nurse and physician education required
• Pain as the fifth vital sign

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Increased Production DEA Quotas,1990-2000

• Morphine 300
• Hydrocodone 500
• Hydromorphone 600
• Oxycodone 1200
• Fentanyl 1700

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Drug
2003 Rx
Revenue

• Hydrocodone 84M
• Lipitor 69M 6.7B
• Synthroid 49M
• Norvasc 36M
• Zoloft 33M 2.9B
• (Others in the top 130 Xanax, Ambien, Ativan,
  Klonipin, Soma
• Valium, oxycodone, Oxycontin, Darvocet, Ultracet,
  Concerta, Adderal)

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Rx Opioids In Hawaii(Source K. Kamita, Chief,
NED, State of Hawaii. 11/7/03)

• Drug
• APAP/hydrocodone
• Tussionex
• Endocet
• OxyContin
• Morphine sulfate
• Methadone

• Prescriptions
• 2,310,398
• 564,258
• 561,658
• 506,408
• 335,502
• 326,446

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Availability Role of the Internet
!
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Media Attention
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Molecular factors
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( Subutex, Suboxone )

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Mesolimbic Dopamine System and Drug Misuse

• Circuit 1
• LIKE
• Pleasure circuit
• Meso-accumbens
• Circuit 2
• WANT
• Desire and urge circuit
• Basolateral n. of amygdala
• Circuit 3
• Need
• Pathologic desire demand circuit
• Periaqueducal gray of brain stem

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Drug Factors Influencing Abuse Potential

• Rapid onset
• Xanax vs. Tranxene
• High potency/intensity
• Dilaudid vs. Darvon
• Brief duration of action Actig vs. MS Contin
• Purity/Water soluble MS vs. Anexia
• High volatility (smokable)
• Brand name Vicodin vs. HC/APAP

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Commonalities Licit and Illicit Drugs

• Psychoactive potential
• Reinforcement potential
• Decrease negative symptoms
• Increase positive symptoms
• Tolerance and withdrawal potential

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OpioidsIllicit vs. Prescription
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StimulantsIllicit vs. Prescription
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Users At-risk if Exposed

• Genetically vulnerable (60/40)
• Vulnerable by history
• Past problems/consequences with any drugs
• Present problems with any drug (even nicotine)
• Family history of substance abuse
• Mental Health Co-morbidity
• Untreated mood disorders (I.e.anxiety,
  depression, PTSD) Personality disorders
• Psychosocial, Environmental Problems (Axis IV)
• GAF Global Assessment of Functioning (Axis V)

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Rx Misusers

• Adolescents
• MH issues, multiple contacts, AOD, Rates up
  with age
• Pain Patients (seen by specialists)
• 10 misuse, 8 abuse/dependence
• Primary Care Patients
• SA Hx, co-morbid psych condition, believes
  addicted
• Substance Abusers
• Elderly
• PolyRx, nl aging?, metabolism, cognitive
  impairment

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Elderly Misusing Rx

• Higher incidence of chronic pain
• Directions misunderstood
• Medication sharing
• Polypharmacy, alcohol
• Rebound syndromes
• Family/peer enabling
• Misinterpretation of drug effects

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Physician Factors

• Dated
• Duped
• Disabled
• Dishonest
• Medication Mania

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Confused Physicians

• The use of narcotics in terminal cases is to be
  condemnedundesirable side effects. Dominant on
  the list of these unfortunate effects is
  addiction.
• AMA Consensus Paper, 1940
• Physicians told not to feardiscipline for pain
  treatment
• amednews.com 6/16/03

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Medication Mania

• Societal phenomenon, perception of safety
• High efficacy of certain meds
• Patient expectation, pressure to prescribe
• Difficult access, payment for non-pharm Rx

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Pain Treatment Modalities

• Non-pharmacologic
• Psychologic
• Pharmacologic
• Interventional
• Hygenic

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• Strong Opioid consensus
• Use aggressively for severe acute pain
• Use aggressively for terminal pain (cancer, AIDS)
• Trial for severe CNMP
• Weak or no Opioid consensus
• Use in less well-defined syndromes (CRPS, PPS,)
• Use in pain syndromes with moderate pain and
  complex psychosocial components ( FM, LBP)

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Opioid Disorder in Past Four Weeks According to
Different Levels of Pain
Nearly Linear Relationship of Pain and Opioid Use
Disorder
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CHRONIC OPIOID INTAKE BIOLOGICAL RESPONSES

• Transcription factors and 2nd messenger molecules
• cAMP c-fos CREB, ERK
• Neurotrophins
• Ngf,gdnf,bdnf
• Cytokines
• Cannabinoid receptors
• Novel pain pathways
• Opioid System
• Nociceptin, nocistatin, dynorphin

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Dynorphin promotes abnormal pain and spinal
opioid antinociceptive tolerance

• Chronic opioids stimulate dynorphin
• Vanderah, et al. J Neurosci 202074-2079, 2000

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• Recent studies have shown that continuous opioid
  exposure produces exaggerated pain and,
  importantly, such pain occurs while the opioid is
  continuously present in the system
• Vanderah, et al., Pain 925-9, 2001

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Chronic Pain among Chemical Dependent
PatientsRosenblum et al., JAMA, May 14, 2003
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OPIOID THERAPY FOR CHRONIC PAIN ?

• evidence now suggests that prolonged, high-dose
  opioid therapy may be neither safe nor
  effective.It is therefore important that
  physicians make every effort to control
  indiscriminate prescribing, even when they are
  under pressure by patients to increase the dose
  of opioids.
• BALLANTYNE MAO, NEJM, 3491943-53, 2003

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Opioids Decrease D2 Receptors
Source Wang, G-J et al., Neuropsychopharmacology,
16(2), pp. 174-182, 1997.
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Protracted Opioid Withdrawal

• Anergia
• Ahedonia
• Sleep disturbance
• Emotional lability/dysphoria
• Stress incompetence
• Craving
• Can persist for months

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Opioid Withdrawal Options

• 1. Taper by 50 every several days
• Transition to longer acting analgesic
  (propoxyphene, methadone) and taper
• Symptomatic Rx
• Buprenorphine safe, easy, effective
• Rapid Opioid Detox, UROD

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Buprenorphine Summary

• For withdrawal, maintenance, or pain
• Mild withdrawal itself
• Greater safety, and no high
• Lower diversion potential
• Office-based, expands treatment
• 15 Hawaii MDs certified to use

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Sedative Hypnotics

• Alcohol
• Most important drug in this class
• Benzodiazepines
• Xanax, Valium, Klonipin, Ativan, Ambien
• Barbiturates
• Fioricet, Esgic (butalbital), Soma
• Cross-tolerance among all (GABA related)

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APA Guidelines for BNZ Use

• Intermittent use preferable to daily use
• Risk of abuse increases in persons with hx of
  alcoholism or other drug abuse
• At-risk persons should rarely, if ever, be
  treated with BNZ on a chronic basis
• Insomnia rarely should be treated with medication
  except when produced by a short-term stressful
  situation

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Stimulants in Chronic Pain

• Very rarely indicated
• Caffeine is generally safe
• Consider specialty consultation before Rx

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ADHD

• Prevalence children 4-6
• adults 2-4
• Natural History associated with
  substantial impairment
• throughout lifespan
• Prognosis worse with co-morbidity
• oppositional, conduct disorder,
  learning disabilities, mood disorder,
  substance abuse

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ADHD, Stimulants and SUD

• ADHD is a risk factor for substance abuse
• Pharmacotherapy decreases SUD risk
• Nicotine use 2 years earlier in ADHD
• 2.5-5 in HS used Ritalin illicitly
• 22 misused Rx stimulant
• 11 sold prescribed medication
• Stimulants can be snorted, smoked

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Treatment forPrescription Drug Abuse
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Treatment Nothing New

• Match treatment to disease severity
• Complex disorders need comprehensive Rx
• Detox, or stabilization is not treatment

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Standard Treatment

• Same modalities as for all other CD Rx
• Education, IC, IOP, Residential, Aftercare
• Medications may have a place
• Community 12-step, mutual-help
• Psychosocial, Family Therapy
• Functional rehabilitation
• Special attention if need for controlled Rx

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Prevention

• Education and Training
• Physicians, Counselors, Consumers
• Business Outreach Consumer Protection
• Labeling, RiskMAPs, Guidelines, Online commerce,
  Insurance Carriers
• Prescription Monitoring Programs
• Treatment systems, Law enforcement systems
• Combined systems
• Investigation Enforcement
• Internet, Customs Border Protection

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Physician Solutions

• Education, training mandates
• American Pain Society, American Academy of Pain
  Management
• Screening all patients for risk before
  prescribing controlled medications
• Urine Drug Testing
• Peer consultation, review, co-management
• Consent to treat, informed consent forms

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Physician Solutions

• Comprehensive Exam
• Establish firmly that non-controlled Rx has
  failed
• Establish agreed upon goals for treatment
• Shared understanding between MD and Pt the true
  benefits, pitfalls of long-term controlled Rx
• Involve a single prescribing MD and pharmacy
  whenever possible
• Comprehensive follow-up

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Deja vu

• I just minimized or dismissed the issues of
  abuse, addiction and diversion
• ten years later, and we recognize that was a
  big error..we need to talk about the use of
  opioids and other prescription drugs from the
  perspective of two skill setshow to prescribe,
  but at the same time, (doctors) have to have a
  skill set in addiction medicine, how to assess
  the risk of abuse and diversion and addictionor
  they shouldnt use them.
• Dr. Russell Portenoy, ABC National Radio
  12/5/04

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Recovery_at_aesoft.net808-327-4848Kevin Kunz
M.D., M.P.H., C.S.A.C., FASAM