James BellNovember 2014

The three worlds of prescription opioid misuse

• Dr Bell has received funding for research studies, travel to conferences, and hospitality, from ReckittBenckiser, Schering-Plough, Biomed P/L, Pfizer, Martindale, Titan Pharmaceuticals, and Munipharma

Pain and AddictionPain and Addiction

100 million adult Americans have chronic pain

2 million Americans dependent on prescribed opioids (cf ~500,000 heroin addicts)

http://www.drugabuse.gov/news-events/nida-notes/2012/11/qa-dr-david-thomas

Pain and AddictionPain and Addiction

“100 million adult Americans have chronic pain”

2 million Americans dependent on prescribed opioids (cf ~500,000 heroin addicts)

Iatrogenic epidemics driven by unrealistic expectations

Prescription opioids USA, 1995-Prescription opioids USA, 1995-

• 1999 - 2006 fatal poisonings (OD) involving prescription opioids more than tripled

• By 2004, prescription opioids surpassed heroin and cocaine in fatal ODs (Paulozzi and Xi 2008)

• And were increasingly a gateway to heroin addiction (Inciardi, 2009)

• As prescription of opioids for pain increases, non-medical use increases proportionally (Dasgupta, 2006)

Global problemGlobal problem- Similar trends to US identified in Australia, Canada, Europe and Asia

0

100

200

300

400

500

600

700

86 87 88 89 90 91 92 93 94 95

Kg

Year

Oral morphine

Methadone syrup

Other opioids

Australian Opioid prescribing Australian Opioid prescribing 1990s1990s

Opioid overdose presentations to ED, Australia Opioid overdose presentations to ED, Australia (AIHW, 2008)(AIHW, 2008)

0

500

1000

1500

2000

2500

1998/1999 1999/2000 200/2001 2001/2002 2002/2003 2003/2004 2004/2005 2005/2006 2006/2007

Heroin + opium

Prescription opioids

Methadone

An unprecedented epidemic of An unprecedented epidemic of prescription opioid misuse 1995-prescription opioid misuse 1995-

20102010??

~1,000,000 opioid dependent people (1% of population) (Terry and Pellens, 1928)

Most opioids were OTC (Heroin was marketed by Bayer, without prescription)

Diversion was not a problem

Opioid misuse 1860-1900 in USAOpioid misuse 1860-1900 in USA

"The habit in a vast majority of cases is first formed by the unpardonable carelessness of physicians, who are fond of using the little syringe, or relieving every ache and pain by the administration of an opiate”

Report to Iowa Board of Health in 1885 (Quoted in Conrad and Schneider, 1992)

Medical practitioners 1860-1900Medical practitioners 1860-1900

- There is a latent demand for drugs which activate the reward pathway

- Such drugs require different regulation – ethical codes, licensing, taxation, prohibition, guidelines

- Medical profession has uneven record as gatekeepers for access to opioids

Those who ignore history are Those who ignore history are condemned to repeat itcondemned to repeat it

Who misuses prescription opioids?Who misuses prescription opioids?

1. Some people prescribed opioids develop dependence, with escalating pain, distress and escalating doses of opioids

2. Current or former heroin addicts, some of whom use it as maintenance treatment, some who sell to the black market

3. Young people who use and share recreational drugs

1. Prescription opioid dependence1. Prescription opioid dependence

Dependence on prescribed opioids and can contribute to pain, disability and distress

Opioids contribute to pain through 1. Reinforcing unrealistic expectations2. Withdrawal3. OIH (Opioid Induced Hyperalgesia)

2. Diversion2. DiversionDoctors prescribing patterns, USA Doctors prescribing patterns, USA

20092009Prescribing Patterns for All Prescribers

Percentile 10th 50th 90th US Mean

•Prescriptions per Beneficiary 6 1 3 16 •Number of Pharmacies 32 1 17 85

•Percentage of Schedule II Drugs 4% 0% 0% 10% •

Commercial traveller PatientsCommercial traveller Patients

US prescription data (McDonald, 2013) shows US prescription data (McDonald, 2013) shows 0.7% of patients saw> 10 doctors and received 0.7% of patients saw> 10 doctors and received 4% of all prescribed opioids4% of all prescribed opioids

French buprenorphine prescription data French buprenorphine prescription data (Pradel, 2004) – 0.03% of patients obtained (Pradel, 2004) – 0.03% of patients obtained 45% of doctor-shopping medication. (Much of 45% of doctor-shopping medication. (Much of which was probably exported to Georgia) which was probably exported to Georgia)

Aberrant behaviours (ADRBs)Aberrant behaviours (ADRBs)• opioid diversion;• taking doses larger than those prescribed• continued requests for dose escalations;• seeking opioids from different physicians;• resisting urine drug screening or referral• repeatedly losing medications or prescriptions• seeking early refills;• unscheduled visits• misusing alcohol, using illicit drugs• injecting (having track marks) or snorting meds• obtaining medications from multiple doctors

ADRBs in people prescribed opioids ADRBs in people prescribed opioids (Fishbain, 2008)(Fishbain, 2008)

67 studies, pooled data67 studies, pooled data- Most ADRBs occur in people with addiction HxMost ADRBs occur in people with addiction Hx(addiction Hx excluded studies 0.19%; other (addiction Hx excluded studies 0.19%; other

studies, 11.5% ADRBs)studies, 11.5% ADRBs)- Urine testing identifies far more ADRBs than Urine testing identifies far more ADRBs than

clinical assessment clinical assessment - 20.4% of people prescribed opioids for pain had 20.4% of people prescribed opioids for pain had

either no opioid in urine, or additional non-either no opioid in urine, or additional non-prescribed opioidsprescribed opioids

(ex)Heroin users seek prescribed (ex)Heroin users seek prescribed opioidsopioids

• To maintain their habit• To manage withdrawal• A less stigmatized alternative to OST • To sell to the black market• To relieve pain and distress

Pain and Addiction often coexistPain and Addiction often coexist

• Addicted lifestyle may contribute to chronic Addicted lifestyle may contribute to chronic pain (injuries, ulcers, neglect)pain (injuries, ulcers, neglect)

• Opioid-induced hyperalgesia, emotional Opioid-induced hyperalgesia, emotional dysregulation, and somatic focusingdysregulation, and somatic focusing

• Comorbid demoralisation and social Comorbid demoralisation and social marginalisation increase distressmarginalisation increase distress

• Chronic or recurrent opioid withdrawal Chronic or recurrent opioid withdrawal

Mx of Pain in (ex)addictsMx of Pain in (ex)addicts

Structured treatment Structured treatment -Realistic objectivesRealistic objectives-Supervised dispensingSupervised dispensing-Monitoring of injecting sitesMonitoring of injecting sites-Urine toxicologyUrine toxicology

Mx of Pain in (ex)addictsMx of Pain in (ex)addicts

Structured treatment Structured treatment -Realistic objectivesRealistic objectives-Supervised dispensingSupervised dispensing-Monitoring of injecting sitesMonitoring of injecting sites-Urine toxicologyUrine toxicology

But first, identify (ex) addictsBut first, identify (ex) addicts•Drug use history, Drug use history, •Focused physical examinationFocused physical examination

3. Recreational drug users and 3. Recreational drug users and opioid analgesicsopioid analgesics

Tramadol frequently prescribed in UK, and rising Tramadol frequently prescribed in UK, and rising tramadol overdose deaths are a distinct UK issuetramadol overdose deaths are a distinct UK issue

2012 Global drug survey (internet) covered tramadol2012 Global drug survey (internet) covered tramadol-7360 UK respondents (mean age 29, 90% white, 90% 7360 UK respondents (mean age 29, 90% white, 90% working or studying)working or studying)Past-year drug usePast-year drug use-Cocaine 32%, heroin 0.9%, tramadol 5.6%Cocaine 32%, heroin 0.9%, tramadol 5.6%

Recreational drug users and Recreational drug users and opioid analgesicsopioid analgesics

Source of acquisition of tramadol(N = 369)

N (%)Prescribed to me 235 (63.7)From a friend 124 (33.6)From a dealer 12 (3.3)From the internet 10 (2.7)

Reasons given for using Reasons given for using tramadoltramadol

N (%)To relieve pain 276 (74.8)To help me relax 114 (30.9)To help me sleep 104 (28.2)To get high 91 (24.7)To relieve boredom 58 (15.7)To relieve distress 38 (10.3)For work 21 (5.7)For socialising 17 (4.6)To relieve withdrawal 12 (3.3)For sex 7 (1.9)For study 5 (1.4)Other function 29 (7.9)

Reasons given for using Reasons given for using tramadoltramadol

Overall:44% reported reasons other than analgesia44% reported reasons other than analgesia

28% combined tramadol with alcohol or other drugs to 28% combined tramadol with alcohol or other drugs to enhance its effectenhance its effect

19% took doses higher than prescribed19% took doses higher than prescribed

10% reported difficulty stopping10% reported difficulty stopping

SummarySummary

Among young, socially-integrated people sharing and Among young, socially-integrated people sharing and misuse of prescribed pharmaceuticals is not rare in misuse of prescribed pharmaceuticals is not rare in UKUK

Trend towards normalisation of drug useTrend towards normalisation of drug use

In US, this trend among high-school students and late In US, this trend among high-school students and late adolescence appears to have contributed to adolescence appears to have contributed to increasing dependence on pharmaceutical opioidsincreasing dependence on pharmaceutical opioids

Management of chronic painManagement of chronic pain

1. Assessment 1. Assessment • addiction historyaddiction history• social functioningsocial functioning• examination of veinsexamination of veins• urine toxicology (UDS)urine toxicology (UDS)

2. Formulation and treatment objective2. Formulation and treatment objective• NOT pain freeNOT pain free

Mx IIMx II3. Structured Treatment3. Structured Treatment

• Universal precautionsUniversal precautions• Rationale for prescribingRationale for prescribing• Rationalisation of prescribing Rationalisation of prescribing • Expectations – attendance, monitoring, reviewExpectations – attendance, monitoring, review• Dispensing arrangements - supervisionDispensing arrangements - supervision• Shared information with other involved doctorsShared information with other involved doctors

ReferencesReferencesDasgupta N, Kramer D, Zalman M, Carino S, Smith MY, Haddoxa JD, Wright C (2006) Association between non-medical and prescriptive usage of opioids Drug and Alcohol Dependence 82 ; 135–142Fishbain DA, Cole B, Lewis J, Rosomoff HL, Rosomoff RS (2008) What Percentage of Chronic Nonmalignant Pain Patients Exposed to Chronic Opioid Analgesic Therapy Develop Abuse/Addiction and/or Aberrant Drug-Related Behaviors? A Structured Evidence-Based Review Pain Medicine 9; 4:SAMHSA (2012) A Treatment Improvement Protocol. TIP 54 Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders. Substance Abuse and Mental Health Services Administration, Rockville, MD.Bell J, Reed K, Gross S, Witton J (2013) The Management of Pain in people with a past or current history of addiction Action on Addiction, LondonWinstock, A., Bell, J., Borschmann, R. (2014) The non-medical use of tramadol in the UK: findings from a large community sample International Journal of drug Policy doi: 10.1111/ijcp.12429•