Complexities
of
Prescription Drug
Misuse
Seddon R. Savage MD
Director,
Dartmouth Center on Addiction
Recovery and Education
Pain Medicine Consultant
Manchester VAMC
Associate Professor of Anesthesiology
Adjunct Faculty, Dartmouth Medical School
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Concept of balance, medical and legal
Common misused drugs
Available data on Rx drug misuse
Clinical perspective on Rx drug misuse
Strategies to reduce Rx drug misuse
Prescription Medication
Benefits
Risks
Relief of symptoms
Side effects
Improved function
Toxicity
Restored quality of life
Unintended consequences
Clinical Challenge with
Controlled Substances
Benefits
Relief of pain
Improved function
Restored quality of life
Risks
Side effects
Toxicity
Unintended consequences
Misuse Addiction Diversion
U.S. Controlled Substances Act
”Many of the drugs
included within this
subchapter have a useful
and legitimate medical
purpose and are necessary
to maintain the health and
general welfare of the
American people.”
“The illegal importation,
manufacture, distribution,
and possession and
improper use of controlled
substances have a
substantial and detrimental
effect on the health and
general welfare of the
American people”
Medical Treatment
Controlled Substances
Risks
Benefits
Side effects
Relief of symptoms
Improved function
Restored quality of life
Toxicity
Unintended consequences
Misuse Addiction Diversion
?
Controlled Substance Classes
Classified by
– Relative potential for “abuse”
– Identified current legitimate medical use
– Risk of physical or “psychological”
dependence [sic] - (in appropriate medical terms: “risk of
physical dependence or addiction”)
Controlled Substance Classes
Examples of Inclusions
i. Heroin, marijuana, lsd, psilocybin
ii. Pure mu opioids, topical cocaine
iii. Combination opioids with non-opioid,
stimulants, anabolic steroids
iv. Sedative hypnotics including barbiturates,
benzodiazepines, sleep meds
v. Dilute opioids, pregabalin
Unscheduled: Soma, tramadol
Commonly Misused Rx Drugs
• Medical or pharmacologic classes
– Sedative hypnotics
– Stimulants
– Opioid analgesics
– Narcotics
6.2 Million Americans (~2%) Used
Prescription Drugs Non-Medically Past Month
2008 NSDUH Data
Stimulants
• Clinical indications
– Attention deficit hyperactivity disorder (ADHD)
– Disease- or medication -related sedation
– Narcolepsy
– Depression (rare)
– (Weight loss)
• Commonly prescribed stimulants
– Ritalin (methylphenidate)
– Concerta (long acting methylphenidate)
– Adderall (amphetamine and dextro-amphetamine)
Stimulant Neurobiology
Stimulants
Increase dopamine by:
•Stimulating synthesis
•Releasing from
presynaptic vesicles
•Inhibiting reuptake
Increase noradrenaline by:
•Releasing from
presynaptic vesicles
Image from: Chronic amphetamine use and
abuse. The American Academy of
Neuropsychopharmacology.
http://www.acnp.org/g4/GN401000166/CH1
62.htm.Accessed on 30 January 2003.
Stimulant
Therapeutic Effects
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•
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•
Increased attention
Increase energy
Reduce sleep
Decreased appetite
Euphoria
In ADHD – decreased impulsivity,
reduced hyperactivity
Stimulant
Toxic Effects
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Sleep interference
Anxiety, psychosis
Seizures
Hyperthermia
Elevated blood pressure and heart rate
Heart attack, cardiac arrest and stroke
possible
Stimulant
Withdrawal
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Low energy level
Hypersomnia (or insomnia)
Dysphoria
Anhedonia
Depression
Irritability
Sedative Hypnotics
• Clinical uses: anxiety, sleep induction,
PTSD, alcohol and drug withdrawal
• Action: enhance GABAa activity, calms
CNS
• Types
– Benzodiazepines: Valium, Librium,
Ativan, Klonopin, Xanax etc
– Barbiturates: phenobarbital, butalbitol
– Sleep medis: Ambien, Sonata, Lunesta
– Miscellaneous: Soma (carisoprodol)
Sedative Hypnotic Actions
Reprinted from: Medications for analgesia and sedation in the intensive care unit: an overview.
Diederik Gommers and Jan Bakker, Critical Care 2008 Supplement 3-4 at www.ccforum.com
Sedative Hypnotics Effects
• Relaxation > sedation > stupor
• Dysequilibrium: impaired balance,
coordination, and gait, slurred speech
• Impaired cognition and memory
• Increased risks with opioids and alcohol
• Tolerance, physical dependence
and addiction may occur
Sedative Hypnotic Withdrawal
• Cardiovascular arousal
– Increased pulse or blood pressure
• Neurologic arousal
– Sleeplessness, irritability, agitation, anxiety
– Tremor
– Seizures
• Autonomic arousal
– Sweating
– Nausea and vomiting
Opioid Medications
• Clinical indications
– Analgesia
– Anti-tussive
– Anti-diarrheal
– Teatment of opioid addiction
• Oral, transdermal , transmucosal and
parenteral forms
• Quick onset, short acting vs slower onset
longer acting vs sustained release meds
Opioid Types
• Pure mu opioid agonists:
– Natural or semi-synthetic: morphine, codeine,
hydrocodone, oxycodone, hydromorphine
– Synthetic: fentanyl, methadone,
propoxyphene
• Partial mu agonists:
– Buprenorphine, tramadol
• Kappa opioid agonist/mu antagonists
– Pentazocine, butorphanol, nalbuphine
Opioid Therapeutic Actions
• Analgesia through stimulation central and
peripheral opioid receptors
• Inhibit intestinal motility
• Suppressive cough reflex
• Euphoria, sense of well being
• Mildly sedative, induce sleep
Opioid Side Effects
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•
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Constipation
Respiratory depression
Sedation, cognitive blurring
Sweating, meiosis, urinary retention
Tolerance, physical dependence,
hyperalgesia
• Reward and addiction in vulnerable
Opioid Withdrawal
• Flu-like syndrome: muscle aches, joint
pains, sweating, stomach cramping,
diarrhea
• Irritability, arousal, wakefulness
• Mild increase bp and heart rate
• Mydriasis
• Piloerection (gooseflesh)
Teenagers caught with pills
By AMY AUGUSTINE
Monitor staff
November 05, 2009 - 7:28 am
What happened at Grimes Field on Oct. 12 was troubling, said police Chief Dave
Roarick, who responded about 2 p.m. to a report of suspicious behavior. There, he found a
group of teenagers, ages 13 to 19, hanging out with backpacks. Roarick thought that was
odd because it was Columbus Day and school wasn't in session. The 19-year-old Stephen Martel of Hillsboro - was drinking alcohol and arrested. The rest, whom the police
have not identified because they are minors, were taken into protective custody, he said.
As the teens were brought back to the station, Roarick said the police learned that the
majority of them had taken multiple doses of Benadryl, an antihistamine, and that four had
mixed it with Prozac, an antidepressant.
"We probably found four or five boxes of Benadryl on them . . . and a baggie
containing a lot of Prozac. Some of them had (consumed) alcohol, too," Roarick said. "As
we're finding this, one of the girls appeared to be really out of it, acting very, very strange."
In the weeks before the incident, Roarick said at least one local store owner called the
police to report that the store had been selling a lot of Benadryl. Roarick said he's advised
store owners not to sell to kids if they think something "isn't right."
The Prozac was provided by a teenager who had a prescription and was present among
the group, he said.
Non-Medical Rx Drug Misuse
Motivators
• Self medication of symptoms:
pain, sleep, mood, memories,
withdrawal if physically dependent
• Novelty, experimentation, risk-taking
• Enhance performance
• Elective use for euphoria/reward
• Compulsive use due to addiction
• Diversion for profit
Self Medication or
Performance Enhancement
• Opioid internet survey 3200 college students
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–
–
–
13.9% reported lifetime non-medical use opioids
42% of these reported use exclusively for pain
34% for pain and recreational
24% recreational only
McCabe SE, Boyd CJ, Teter CJ: Drug Alcohol Depend 2009
• Stimulant internet survey 4580 college students
– 8.3% reported lifetime non medical use stimulants
– 65% for concentration, 60% to help study, 48% to
increase alertness.
– 31% to get high, 30% for experimentation
Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ.
Generation Rx
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Rx/OTC med abuse is part of teen culture
18% of teens have non-medically used Vicodin
20% have tried Ritalin or Adderall without a Rx
9% used OTC cough syrup to get high
Equal or greater use of OTC/Rx than cocaine, Ecstasy,
LSD, ketamine, heroin, GHB, ice
• Believe that Rx Meds safer (50%), less addictive (33%)
• Report ease of access: medicine cabinets
• “Drugs are fun” and “Drugs help kids when they are
having a hard time”
April 21, 2005. Partnership for a Drug Free America. 17th annual study of teen drug abuse. N=
7,300, error margin +/- 1.5% (Mooney and Freese, UCLA presentation)
New Non-Medical Users of Rx Drugs
NSDUH Ages 12 and over
Past Month Non-Medical Use of Rx Drugs
NSDUH, Ages 12 and over
Past Month Drug Use Ages 12-17
NSDUH, 2008
Past Month Drug Use Ages 50-59
NSDUH, 2008
Specific Drug Used to Initiate Illicit Drug Use
~30% initiate with Rx Drugs, NSDUH, 2008
Therapeutic Opioid Use
DEA ARCOS Data – U.S.
16000
12000
10000
8000
6000
4000
2000
0
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
gms per 100,000
14000
morphine x2.8
oxycodone x8.0
fentanyl x5.6 (x100)
hydrocodone x3.3
methadone x 12.2
DAWN and New** DAWN Data
Reflects Opioid Misuse/Harm – U.S.
250000
200000
150000
100000
Opioid Analgesic
Related ED Visits
50000
19
96
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
0
**Methodologic differences do
not permit comparisons
between new and old DAWN
DAWN Visits by Rx Drug, 2004
Soma
Flexeril
Methylphenidate
Adderall
TEDS NH – Reflects Addiction
Rx Opioid Deaths in U.S.
Source: U.S. Centers for Disease Control in
Non-Medical Drug Use
Sources (Opioids)
NSDUH, 2006
Source Where Respondent Obtained
Bought on
Drug Dealer/ Internet
0.1%
Stranger
3.9%
More than
One Doctor
1.6%
Other 1
4.9%
One Doctor
19.1%
Free from
Friend/Relative
55.7%
Bought/Took
from Friend/Relative
14.8%
Source Where Friend/Relative Obtained
More than One Doctor
3.3%
Free from
Friend/Relative
7.3%
One
Doctor
80.7%
Bought/Took from
Friend/Relative
4.9%
Drug Dealer/
Stranger
1.6%
Other 1
2.2%
Note: Totals may not sum to 100% because of rounding or because suppressed estimates are not shown.
1
The Other category includes the sources: “Wrote Fake Prescription,” “Stole from Doctor’s
Office/Clinic/Hospital/Pharmacy,” and “Some Other Way.”
Opportunities to Address Rx Drug Misuse
Role of Prescribing
Prescription Drug Misuse
• What is the right amount of prescribing?
• Is there appropriate care and structure
when prescribing controlled substances?
• Do clinicians have the requisite skills and
knowledge to identify and manage
complications of use?
Opioids for Pain
• Acute pain generally adequately treated
– Unused (?excess) pain meds may lend to diversion
• Terminal pain treatment mixed (?)
– Lingering concerns regarding higher opioid doses
– Discarding of excess meds a problem following death
• Chronic non-terminal pain
– Few options for optimum interdisciplinary care
– Balance challenging: overuse and underuse of opioids
– Significant opportunities for misuse and diversion in this
context
– Need for enhanced structure and monitoring
Stimulants
• Over prescribed, under prescribed, or just about
right?
• Does the educational context dictate the need
for treatment?
• Are resources adequate to address behaviors
with non-med approaches?
• Do we too often use medications to counter side
effects of other medications?
Sedative Hypnotics
• Would greater parity for mental health care
reduce use and improve outcomes?
• What role should life individual self
management play in reducing, anxiety,
stress and improving sleep?
• Could we make better use of alternative
medications?
Care in Prescribing
Universal Precautions
• Basic universal precautions to be used
with all patients treated with opioids
• Comprehensive pain, psych, substance
assessment
• Risk stratification (low, medium, high)
• Routine informed consent and agreement
• Regular monitoring of pain, med use, mood, and
function, including drug screens
• Clear and consistent documentation
(Gourlay, Heit 2004)
Care in Prescribing
Treatment Structure Variables
Beyond Universal Precautions
Managing Challenging Clinical Encounters
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Setting of care to match risk level
Selection of treatments
Supply of medications
Supports for recovery
Supervision and monitoring
Savage, 2004 and 2008
Examples of Clinical Tools
in Evolution
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Risk screening tools (SOAPP, ORT)
Misuse screening tools (COMM, PDQ)
Documentation tools (PADT)
Clinical management decision trees (Utah
Guidelines)
• Mentors (PCSS)
Examples of Clinical Tool Initiatives
• State of Utah Guidelines with clinical tools
http://www.useonlyasdirected.org/uploads/65026_UDOH_opioi
dGuidlines.pdf
• ASAM Physician Clinical Support System
www.pcss-mentor.org
– Methadone prescribing
– Buprenorphine prescribing
• Many private websites
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www.painedu.org
www.emergingsolutionsinpain.com
www.pain-topics.org
www.painknowledge.org
www.partnersagainstpain.com
• NIDA web based tools
– In evolution
Clinical Needs
to Manage Complex Patients
• Education in pain management
• Education in addiction medicine
• Reimbursement for collaborative interdisciplinary
care
• More balanced reimbursement for time versus
procedures
– Increased primary care time
– Increased mental health
• Clinical guidelines
State Prescription Drug Monitoring Programs (PDMPs)
VT
ME
WA1
MT
ND
OR
MN
ID
MI
WY
NE
NV
UT
CO
CA
AZ
KS
OK
NM
IA
IL
TX
IN
PA
OH
WV
VA
KY
MO
NC
TN
SC
AR
MS
AK
NY
WI2
SD
NH
MA
RI
CT
NJ
DE
MD
AL
States with operational
PDMPs
GA
LA
FL
States with enacted
PDMP legislation, but program
not yet operational
HI
1Washington
2Legislation
has temporarily suspended its PMP operations due to budgetary constraints.
has been proposed in Wisconsin that ,if passed, would establish a PDMP.
© 2009 Research is current as of June 30, 2009. THE NATIONAL ALLIANCE FOR MODEL STATE DRUG LAWS
(NAMSDL). 1414 Prince St. Suite 312, Alexandria, VA 22314. NJ changed to active PMP by Savage. (Became active 8-09.
Goals of PMPs
• Improve clinical care and public health
through identification of doctors shoppers
– Increase confidence in clinical prescribing
– Identify persons in need of SUD treatment
– Reduce public health harm from diverted
opioids
• Facilitate investigation of possible
controlled substance diversion
Basic PMP Structure
• Pharmacies submit data to a secure database
that tracks at minimum
– Drug, drug dose and dose units
– Date and place dispensed
– Prescriber and patient
• Prescribers and dispensers may query
• Law enforcement may query: established case
vs proactive screening
• Advisory board oversees procedures and
protocols, reviews and revises system
• Outcomes data collected, used to revise and
improve program
Regulatory REMS Requirements
Risk Evaluation and Mitigation Strategies
• Encourages careful decision making and tightly
managed control of higher risk drugs
• FDA currently finalizing plans for opioid REMS
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–
–
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? All schedules vs schedule II vs other
? Educational requirements
? Registration of patients
? Specialty pharmacy requirements
• FDA has negotiated Onsolis REMS
– All the above requirements
– May generalize similar drugs
Public Education
• Key messages
– Dangers of opioid misuse (balanced with
positives of appropriate use)
– Locking of medications
– Need to dispose of unused medications
• Periodic collections vs
• Permanent collection sites
Public Education
>Dangers of misuse
>Lock meds
>Discard unused
med
Professional
Education
>Undergraduate:
pain and addiction
medicine
>CME: opioid issues,
A Comprehensive
other pain tx
Public Policy
>PMPs
>REMS
>Drug disposal
>Parity payment
MH and Addiction
>(CME reqs)
Approach to
Prescription Drug
Misuse
Justice/Law
Enforcement
>Use of PMP info to
aid investigation s
>Drug diversion
programs
>Drug courts
>Drug tx in prisons
Clinical Practice
>Clinical tools
>Practice guidelines
>Systems support
>Interdisciplinary
care for pain
>Tamper proof scripts
> MH/addiction
care
Pharmacy Practice
>ID of CS drug
purchasers
>Disseminate drug
risk information
>Availability of drug
safes