TheOpioid Epidemic

Some Key issues for Physicians and other Healthcare workers

Richard Ries MDrries@u.washington.edu

Harborview Medical Center and the University of Washington

Seattle, Washington

Len Paul0zzi MD MPHCDC Atlanta Georgia

Ries Conflict of Interest Statement

Dr Ries is on Speaker’s bureaus for Janssen, Reckitt-Benckiser, and Alkermes

Dr Ries has Grant funding from: NIH- NIDA-NIAAA

Contingency Management Alcohol in Mentally Ill

Brief Interventions of Drug Abuse in Prim Care

PTSD-- Exposure +/- Sertraline CM for Alcohol in Native Am Indians RCT of Injectable Naltrexone is Severe

Alc DOD- Suicide Prevention grantRRies 2014

3

Mary presents with serious multiple fractures after an

auto crash

32 y o w female with history of minor traumas (twisted ankle, back spasms), ER scripts 2 years ago for 5 days of oxycodone

Stabilized fractures of L femur and tibia, L wrist, abrasions, but post stabilization on standard opioid pain control, complains of pain, shows sweating, diarhea, feels cold and shakes, blood pressure elevates

Further info from family finds pt is prescribed oxycodone for chronic back pain, also xanax for anxiety, often appears sleepy, they think she might have a drug problem, and may be taking too much medication or maybe not as prescribed

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4

Motor vehicle traffic, poisoning, and drug poisoning (overdose) death rates

United States, 1980-2010

Paulozzi - CDC NCHS Data Brief, December, 2011, Updated with 2009 and 2010 mortality data

1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 20100

5

10

15

20

25

Motor Vehicle Traffic Poisoning Drug Poisoning (Overdose)

Year

Death

s p

er

100,0

00 p

opula

tion

Death Rates for Drug Overdose by State, 2010

3.4 - 10.9* 10.9* - 13.9 14.0 - 28.9

Age-adjusted rate per 100,000 population

10.0

9.6

7.8

8.6

10.6

6.3

3.4

6.7

7.3

13.9

11.8

11.4

9.6

14.4

13.2

15.0

23.8

11.8

10.9

11.4

19.4

10.7

6.812.7

23.6

10.9

12.9

16.9

14.6

16.1

12.9

16.9

15.3

28.9

13.1

17.5

10.4

16.4

17.0

20.7

11.6

NH 11.8VT 9.7MA 11.0RI 15.5CT 10.1NJ 9.8DE 16.6MD 11.0DC 12.912.5

Footnote: *10.9 is in two ranges due to rounding. HI is 10.88 while WI is 10.94RRies 2014

6

Opioid analgesic overdose death rates by sex and race , U.S., 2009

Source: National Vital Statistics System; crude rates

7

Drug overdose deaths by major drug type,

US, 1999-2010

CDC/NCHS National Vital Statistics System, CDC Wonder. Updated with 2010 mortality.

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 20100

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

Opioids HeroinCocaine Benzodiazepines

Year

Num

ber

of

Death

s

Journal of Analytical Toxicology, Volume 27, Number 2 March 2003

Oxycodone Involvement in Drug Abuse Deaths: A DAWN-Based Classification Scheme Applied to an Oxycodone Postmortem Database Containing Over 1000 Cases* Authors: Cone E.J.1; Fant R.V.1; Rohay J.M.1; Caplan Y.H.2; Ballina M.3; Reder R.F.3; Spyker D.3; Haddox J.D.

Of 1014 cases:30 (3.3%) involved oxycodone as the single reported chemical entity; of these,

The vast majority (N = 889, 96.7%) were multiple drug abuse deaths

The most prevalent drug combinations were

oxycodone in combination with benzodiazepines, alcohol, cocaine, other narcotics, marijuana, or antidepressants.

Exhibit 2: Past Year Initiation of Non-Medical Use of Prescription-type

Psychopharmaceutics, Age 12 or Older: In Thousands, 1965 to 20051

0

500

1000

1500

2000

2500

3000N

ew U

sers

(x

1000

)

Analgesics Tranquilizers Stimulants Sedatives

While Opiates have grown fastest, Benzos are not far behind

Source: SAMHSA, OAS, NSDUH data , July 2007

Benzo’s the Hidden Drug

• While there are hundreds of recent articles on Prescription Opiate problems-

• Most literature on Benzo Abuse/Dependence is > 10 years old

• Toxicology studies of Opiate deaths usually find Benzo’s too –respiratory depression is additive.

• Sales of Benzo’s are also increasing dramatically

•Simple Tox screens often miss Clon- and Alprazolam

11

Characteristics of unintentional pharmaceutical overdose deaths

(N=295), West Virginia, 2006

Characteristic Pct.

History of substance abuse 78.3

Other mental illness 42.7

Nonmedical route of administration 22.4

Previous overdose 16.9

TOTAL 100.0

Sources: Hall et al, JAMA, 2008 and Toblin et al, J Clin Psych, 2010

Source Where Pain Relievers Were Obtained for Most Recent

Nonmedical Use among Past Year Users Aged 12 or Older

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 from

Friend/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 Doctor1.6% Free from

Friend/Relative55.7%

More than One Doctor3.3%

2006

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Opioid Abstinence Syndrome

Symptoms: craving, anxiety, irritability, restlessness, nervousness, insomnia, rhinorrhea, lacrimation, nausea, abdominal cramps, myalgias, arthralgias

Signs: tachycardia, hypertension, mydriasis, piloerection, diaphoresis, tremor

  Depending on opioid abused, starts within 4-6

hours, full intensity at 24 to 72 hours, can last for 7-14 days— Eg oxycodone vs methadone

Though less medically dangerous than alcohol or BZP, appears to drive relapse to opioid use at much higher rate.

Clinical Opiate Withdrawal Scale (COWS) 1

Resting Pulse Rate: (record beats per minute)

Measured after patient is sitting or lying for one minute

0 pulse rate 80 or below 1 pulse rate 81-100 2 pulse rate 101-120 4 pulse rate greater than 120 Sweating: over past ½ hour not

accounted for by room temperature or patient activity. 0 no report of chills or flushing 1 subjective report of chills or flushing 2 flushed or observable moistness on

face 3 beads of sweat on brow or face 4 sweat streaming off face Restlessness Observation during

assessment 0 able to sit still 1 reports difficulty sitting still, but is

able to do so 3 frequent shifting or extraneous

movements of legs/arms 5 Unable to sit still for more than a few

seconds

Pupil size 0 pupils pinned or normal size for room

light 1 pupils possibly larger than normal for

room light 2 pupils moderately dilated 5 pupils so dilated that only the rim of the

iris is visible Bone or Joint aches If patient was

having pain previously, only the additional component

attributed to opiates withdrawal is scored 0 not present 1 mild diffuse discomfort 2 patient reports severe diffuse aching of

joints/ muscles 4 patient is rubbing joints or muscles and

is unable to sit still because of discomfort Runny nose or tearing Not accounted

for by cold symptoms or allergies 0 not present 1 nasal stuffiness or unusually moist eyes 2 nose running or tearing 4 nose constantly running or tears

streaming down cheeks

COWS p2 GI Upset: over last ½ hour 0 no GI symptoms 1 stomach cramps 2 nausea or loose stool 3 vomiting or diarrhea 5 Multiple episodes of diarrhea or

vomiting Tremor observation of

outstretched hands 0 No tremor 1 tremor can be felt, but not

observed 2 slight tremor observable 4 gross tremor or muscle

twitching Yawning Observation during

assessment 0 no yawning 1 yawning once or twice during

assessment 2 yawning three or more times

during assessment 4 yawning several times/minute

Anxiety or Irritability 0 none 1 patient reports increasing irritability or

anxiousness 2 patient obviously irritable anxious 4 patient so irritable or anxious that

participation in the assessment is difficult Gooseflesh skin 0 skin is smooth 3 piloerrection of skin can be felt or hairs

standing up on arms 5 prominent piloerrection

Total scores with observer’s initials Score: 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal

                                                                                          

Alcohol WD

CIWA-Ar 10 items

CIWA-AD 8 items

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COWS scale in fill out form ---download

http://www.naabt.org/documents/cows_induction_flow_sheet.pdf

Medically Supervised Opioid Withdrawal

Methadone substitution and taper- not advised for novice doctors….you have to know methadone half lives and build up

Clonidine -2 adrenergic agonist Acts on autoreceptors in locus coeruleus to

decrease noradrenergic output Major side effect hypotension Push dose until withdrawal sx abate or

diastolic BP <60 Use adjunctive benzodiazepines, anti-

emetics, antidiarrheals

BuprenorphineRRies 2014

Key Medications in Acute Opioid Withdrawal

Buprenorphine/Naltrexone 16 mg x 1 16 mg, 8 mg, 4 mg 16 mg maintenance to outpt

Sedation Gabapentin 400 tid – 800 tid esp if BZPs involved Mirtazapine 7.5 or 14 mg ( more is less sedative) Tizanidine to 4-12 mg tid ( muscle spasm and sedation) Quetiapine 200 - 400 HS esp if agitated/psychotic Olazapine 10 mg hs “ “ “

Autonomic stabilization Clonidine .1 tid to 1 mg tid over time

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Journal of Analytical Toxicology, Volume 27, Number 2 March 2003

Oxycodone Involvement in Drug Abuse Deaths: A DAWN-Based Classification Scheme Applied to an Oxycodone Postmortem Database Containing Over 1000 Cases* Authors: Cone E.J.1; Fant R.V.1; Rohay J.M.1; Caplan Y.H.2; Ballina M.3; Reder R.F.3; Spyker D.3; Haddox J.D.

Of 1014 cases:30 (3.3%) involved oxycodone as the single reported chemical entity; of these,

The vast majority (N = 889, 96.7%) were multiple drug abuse deaths

The most prevalent drug combinations were

oxycodone in combination with benzodiazepines, alcohol, cocaine, other narcotics, marijuana, or antidepressants.

Opioids + Benzos

Short acting Opioid and Long acting Benzo ( Clonazepam or Diazepam) Classic opioid WD, migrating to

hyperadrenergic autonomic + anxiety and possible seizures

Though not published, using combination of Bup + anticonvulsant covers this Gabapentin 400 tid, or 600 tid helps

bothRRies 2014

For those with Severe Opioid Dependence -----Withdrawal only (Detox)

---vs. Maintenance vs----Block ?

Withdrawal Only— High Relapse (90+ % ) whether fast or slow

Detox Relapse incurred Morbidity, Mortality, Cost Not only costly, but ethical?

Maintenance Bup/Ntx- Training certification fits ACO Prim

Care Methadone--- only in Federally certified clinics

Block – Naltrexone Oral– adherence issues, but OK after long term

stabilization Injectable– fits in with “abstinence model”, good at inpt

DC

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Treatment duration (days)

Rem

aini

ng in

tre

atm

ent

(nr

)

Bup

0

5

10

15

20

0 50 100 150 200 250 300 350

Control

Buprenorphine

Treatment Retention and more…

Kakko J et al. Lancet 2003

75% retention

75% UTS negative

20% mortality in placebo group

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BMJ. 2003 May 3;326(7396):959-60.

Loss of tolerance and overdose mortality after inpatient opiate detoxification: follow up study.Strang J1, McCambridge J, Best D, Beswick T, Bearn J, Rees S, Gossop M.

Med Sci Law. 1990 Jan;30(1):12-6.

Mortality following release from prison.Harding-Pink D.Author information Abstract. The mortality rate during the first year after release was about 5 deaths/1000 person years, a rate over four times the age-adjusted rate in the general population. The majority of deaths were due to overdose by opiate drugs among young, frequently imprisoned drug abusers, and occurred within the first few weeks after release.

Arch Gen Psychiatry. 2011 Dec;68(12):1238-46. Epub 2011 Nov 7.

Adjunctive Counseling during Brief and Extended Buprenorphine-naloxone Treatment for Prescription Opioid Dependence: a 2-phase Randomized Controlled Trial.Weiss RD, Potter JS, Fiellin DA,.

RESULTS:

Phase 1 ( 2 week detox measured at 12 weeks), 6.6% (43 of 653) had successful outcomes -ie 10 weeks after detox

Phase 2 (12 week detox) 49.2% ie end of detox but still on med

Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference.

.

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Best Treatment by FAR---

• Prevention -- Prevention – Prevention• Avoid Opioids in most non-severe

syndromes• Use Opioids like Steroids…aggressively

with built in short taper for most acute cases

• The US uses more presc opioids than most of the rest of the world combined

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Spine (Phila Pa 1976). 2008 Jan 15;33(2):199-204. doi: 10.1097/BRS.0b013e318160455c.

Early Opioid Prescription and Subsequent Disability among workers with back injuries: the Disability Risk

Identification Study Cohort.Franklin GM1, Stover BD, Turner JA, Fulton-Kehoe D, Wickizer TM; Disability Risk

• To examine whether prescription of opioids within 6 weeks of low back injury is associated with work disability at 1 year.

• Nearly 14% (254 of 1843) of the sample were receiving work disability

• After adjustment for pain, function, injury severity, and other baseline covariates, receipt of opioids for more than 7 days (odds ratio = 2.2; 95% confidence interval, 1.5-3.1) and receipt of more than 1 opioid prescription were associated significantly with work disability at 1 year.

• CONCLUSION: • Prescription of opioids for more than 7 days for workers with acute

back injuries is a risk factor for long-term disability. Further research is needed to elucidate this association.

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Outcomes: Buprenorphine, Methadone, LAAM:

Treatment RetentionP

erce

nt R

etai

ned

0

20

40

60

80

100

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

20% Lo Meth

58% Bup

73% Hi Meth

53% LAAM

Study Week

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-10 -9 -8 -7 -6 -5 -40

10

20

30

40

50

60

70

80

90

100

Intrinsic Activity

Log Dose of Opioid

Full Agonist(Methadone)

Partial Agonist(Buprenorphine)

Antagonist (Naloxone)

Intrinsic Activity: Full Agonist (Methadone), Partial Agonist (Buprenorphine), Antagonist (Naloxone)

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Naltrexone for Opioid Dependence

Most ideal pharmacologic treatment

Requires complete withdrawal before initiation or severe withdrawal will be precipitated

Requires Naloxone challenge test

Risk of OD if medication stopped

In general poor patient compliance with oral form but superb treatment for selected patients

Now available in long acting injectionRRies 2014

Lancet. 2011 Apr 30;377(9776):1506-13.

Injectable Extended-release Naltrexone for Opioid Dependence: a Double-blind, Placebo-controlled, Multicentre Randomised Trial.Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL.

FINDINGS: 6 month study of 250 patients randomly assigned to XR-NTX (n=126) or placebo (n=124).

XR-NTX Placebo Inj% Weeks abstinent 90·0% versus 35·0% (p=0·0002)

Opioid-free days 99·2% versus 60·4% (p=0·0004)

Decreased craving –10.1 versus -0.7 (p<0·0001)

Retention days 168 vs 96 days (p=0·0042)

Two patients in each group discontinued owing to adverse events. No XR-NTX-treated patients died, overdosed, or discontinued owing to severe adverse events.

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12 step facilitation …is a method to help get patients to 12 step meetings and maximize their

benefit Why get people to 12 step meetings?

20-50% of trauma( med-surg) and psychiatric in and outpts will have current, history or episodic substance problems

Substance treatment may be unavailable or even if used, 12 step will likely be involved

Positive effects include not only the group support and socialization, but key psychological/therapeutic content elements.

Addiction is a chronic potentially relapsing disease….Usual TREATMENT is not usually structured for this BUT AA is

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Alcohol Abstinence Rates at 8 Years by Duration of Meeting Attendance in the

First Year

71.3

56.2

42.7

35.3

0

10

20

30

40

50

60

70

80

Per

cent

Abs

tine

nt

Moos, et al., 2004

None 1-16 17-32 33+

Weeks of Participation in AA year 1.

(n = 201) (n = 89) (n = 89) (n = 94)

x 2 = 25.5, p < .01

Best Treatment by FAR--- Prevention -- Prevention –

Prevention

Avoid Opioids in most non-severe syndromes

Use Opioids like Steroids…aggressively with built in short taper for most acute cases

The USA uses more presc opioids than most of the rest of the world combined

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Your Case Examples:

1.

2.

3.