Complexitiesof

Prescription Drug Misuse

Seddon R. Savage MD

Director,Dartmouth Center on Addiction

Recovery and Education

Pain Medicine ConsultantManchester VAMC

Associate Professor of AnesthesiologyAdjunct Faculty, Dartmouth Medical School

• 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

Relief of symptoms

Improved function

Restored quality of life

Side effects

Toxicity

Unintended consequences

Benefits Risks

Clinical Challenge with Controlled Substances

Relief of pain

Improved function

Restored quality of life Side effects

Toxicity

Unintended consequences

Misuse Addiction Diversion

Benefits

Risks

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 TreatmentControlled Substances

Relief of symptoms

Improved function

Restored quality of life

Side effects

Toxicity

Unintended consequences

Misuse Addiction Diversion

BenefitsRisks

?

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 ClassesExamples 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/CH162.htm.Accessed on 30 January 2003.

Stimulant Therapeutic Effects

• Increased attention

• Increase energy

• Reduce sleep

• Decreased appetite

• Euphoria

• In ADHD – decreased impulsivity, reduced hyperactivity

Stimulant Toxic Effects

• Sleep interference

• Anxiety, psychosis

• Seizures

• Hyperthermia

• Elevated blood pressure and heart rate

• Heart attack, cardiac arrest and stroke possible

Stimulant Withdrawal

• 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

• 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 AUGUSTINEMonitor staffNovember 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 MisuseMotivators

• 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 – 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. Pharmacotherapy. 2006 Oct;26(10):1501-10.

Generation Rx

• 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. 17 th annual study of teen drug abuse. N= 7,300, error margin +/- 1.5% (Mooney and Freese, UCLA presentation)

New Non-Medical Users of Rx DrugsNSDUH Ages 12 and over

Past Month Non-Medical Use of Rx Drugs NSDUH, Ages 12 and over

Past Month Drug Use Ages 12-17NSDUH, 2008

Past Month Drug Use Ages 50-59NSDUH, 2008

Specific Drug Used to Initiate Illicit Drug Use~30% initiate with Rx Drugs, NSDUH, 2008

Therapeutic Opioid UseDEA ARCOS Data – U.S.

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morphine x2.8

oxycodone x8.0

fentanyl x5.6 (x100)

hydrocodone x3.3

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Opioid AnalgesicRelated ED Visits

DAWN and New** DAWN DataReflects Opioid Misuse/Harm – U.S.

**Methodologic differences do not permit comparisons between new and old DAWN

DAWN Visits by Rx Drug, 2004

MethylphenidateAdderall

SomaFlexeril

TEDS NH – Reflects Addiction

Rx Opioid Deaths in U.S.

Source: U.S. Centers for Disease Control in

Non-Medical Drug UseSources (Opioids)

NSDUH, 2006

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.”

Bought/Took from Friend/Relative

14.8%

Drug Dealer/Stranger

3.9%

Bought on Internet

0.1% Other 1

4.9%

Free from Friend/Relative

7.3%

Bought/Took fromFriend/Relative

4.9%

OneDoctor80.7%

Drug Dealer/Stranger

1.6%Other 1

2.2%

Source Where Respondent Obtained

Source Where Friend/Relative Obtained

One Doctor19.1%

More than One Doctor

1.6%

Free from Friend/Relative

55.7%

More than One Doctor3.3%

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?

• 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 Universal Precautions

Care in PrescribingTreatment Structure Variables

Beyond Universal PrecautionsManaging Challenging Clinical Encounters

• 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

• 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_opioidGuidlines.pdf

• ASAM Physician Clinical Support System www.pcss-mentor.org – Methadone prescribing– Buprenorphine prescribing

• Many private websites– 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)

© 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.

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States with operational PDMPs States with enacted PDMP legislation, but program not yet operational

1Washington has temporarily suspended its PMP operations due to budgetary constraints.2Legislation has been proposed in Wisconsin that ,if passed, would establish a PDMP.

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– ? 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

Public Policy >PMPs >REMS >Drug disposal >Parity payment MH and Addiction >(CME reqs)

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

Professional Education >Undergraduate: pain and addiction medicine >CME: opioid issues, other pain tx

Pharmacy Practice >ID of CS drug purchasers >Disseminate drug risk information >Availability of drug safes

A Comprehensive Approach to

Prescription Drug Misuse