Opioids for chronic pain in the prison population– good or bad?

Dr Lesley Colvin Consultant/ Hon Reader in Anaesthesia & Pain Medicine University of Edinburgh

Opioids for severe chronic pain?

Opioids are essential drugs

Patients must have access to effective treatment

Opioids may have long-term problems

•

Evidence of efficacy?

• •

Other long term harms?

Legal & social need to stem diversion and abuse

Efficacy Safety Access to specialist services E.g. pain and addiction

Pain and disability

“ Great news Mr W – you ’ ll still be able to play the harmonica!

”

Evidence for opioid use in chronic pain

Key recommendations 

Strong opioids should be considered for chronic low back pain or osteoarthritis, and only continued if there is ongoing pain relief (B)



Specialist referral or advice if:



concerns about rapid-dose escalation with continued unacceptable pain relief or



>180 mg/day morphine equivalent dose is required (D)



…How do these apply in the context of substance misuse and in the prison population?

Opioids – long term adverse



effects

Central Nervous System – cognitive function  Endocrine  Immune function  Fracture  Cardiovascular  Cancer biology 

Misuse and addiction

Long term harm from opioids?

 No studies of long term outcomes (>1 year) from opioid Rx compared to no opioid  Increased risk of:  Sexual dysfunction [OR 1.45 (CI -1.87)]  Fractures [OR 1.27 (CI 1.21-1.33)]  Myocardial infarction [OR 1.28 (CI 1.19-1.37)]  Abuse [wide range – up to 37%]  Overdose [HR 5.2 (CI 2.1-12.5)]  Motor vehicle accident [OR 1.24-1.42]

Opioid endocrinopathy

 Hypothalamic-pituitary-adrenal axis dysfunction

and/ or

 Hypothalamic-pituitary-gonadal axis  Symptoms of hypogonadism, adrenal dysfunction  Coupled with such disorders as osteoporosis and mood disturbances

Testosterone levels in men – secondary hypogonadism with reduced pituitary hormones (LH, FSH) • Dose related • HADs higher • Fatigue • Poorer survival (OR of death=2.87, p<0.001)

Mx of hypogonadism – necessary?

Discontinue opioid therapy Switch opioid Hormone supplementation

Opioids Pain Peripheral & Central Nervous System response Physiological - analgesia Pathological - hyperalgesia E.g. methadone maintenance

Effect of opioids on

“

wind up

” HV = Healthy volunteers OA = Opioid misuse CNCP= Chronic non malignant pain CP= Cancer pain * p<0.0001

Implications for Rxing pain?

➢

Opioid-associated sensory dysfunction

Bathgate et al, EFIC, Sept 2011

Opioids an the immune system: Toll like receptors

Opioids

Intracellular signaling pathways

Opioids and the immune system: central effects • Opioid activity at TLRs elicit proinflammatory reactivity (similar to endotoxin) from glia, the immunocompetent cells of the central nervous system • Includes release of cytokines and chemokines and associated disruption of glutamate homeostasis ➢ elevated neuronal excitability ➢ decreased opioid analgesic efficacy ➢ heightened pain states Hutchinson MR. Et al. Pharmacological Reviews. 63(3):772-810, 2011; Wang X. et al, Proc Nat Acad Sci.109(16):6325-30, 2012

Opioid effects on cytokines

Cong D et al, SPaRC 2014

Opioids and cancer neurobiology

Colvin et al, BJA, August, 2012

Pain assessment Clinical Challenges in opioid dependence • • Response to opioids: Tolerance ?OIH

Previous experience of healthcare

• •

Opioid misuse

Many studies exclude patients with a Hx of misuse, definitions vary Misuse often not reported – event rate of 0.27% in Cochrane review (Noble, 2010) Low risk Addiction 0.19% Adverse drug-related 0.59% behaviour High risk 3.27% 11.5% (Fishbain, 2008) • Prediction: limited evidence for validated tools or urine drug testing

Increasing Prescription Drug Abuse

3000 2500 2000 number of initiates (in thousands) 1500 1000 500 0 1985 1991 1993 1995 1997 1999 2001

National Household Survey On Drug Use and Health

120000 100000 80000 number 60000 40000 20000 0 1995 1996 1997 1998 1999 2000 2001 2002

Drug Abuse Warning Network Portenoy, Beth Israel, New York

Substance misuse –

“

pain relievers

”  5.1 million users of pain relievers  55% got the pain relievers from a friend or relative for free  11.4 % bought them from a friend or relative (cf 8.9% from 2007-2008)  4.8 % took them from a friend or relative without asking. SAMHSA, 2011

• • • • • Opioid prescribing in Scotland 2003-2012 Total of ~3.7M in 2003 Increase to 5.9M total paid items in 2012 Increase of 63% in 10 years In 2012 >4.8M weak & >1M strong opioid prescriptions

18% of population had opioid script in 2012 Total Prescription (Paid) Items 6 000 000 5 000 000 4 000 000 3 000 000 2 000 000 1 000 000 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

WEAK STRONG

OPIOIDS AND SCOTTISH INDEX OF MULTIPLE DEPRIVATION (SIMD) If in most deprived area 3.5 times more likely to be prescribed a strong opioid 10 000 9 000 8 000 7 000 6 000 5 000 4 000 3 000 2 000 1 000 0 1 SIMD quintiles: 1= most deprived, 5=least deprived STRONG OPIOIDS WEAK OPIOIDS 35 000 30 000 25 000 20 000 15 000 10 000 5 000 0 2 3 SIMD 2012 4 5 1 2 3 SIMD 2012 4 5

Opioid related mortality

Questions?

Which opioid?

 Methadone  Buprenorphine  Subutex  Suboxone (with naloxone)  DHC (unlicensed use) 

Avoid

short acting if possible

Assessment – history: pain

and

substance misuse

  Pain  Is there likely to be a neuropathic component?

Substance misuse history  Stable/ chaotic – prescription? Support?

  IVDA – Hep C/ HIV (BBV) status and Rx Alcohol; stimulants & / or benzos; cannabis; NPAs; gabapentin…   Mental Health Social history/ Child protection issues

Assessment – examination: pain

and

substance misuse

 Pain  Sensory changes/ ? neuropathic  Motor impairment/ impact on function  Substance misuse history  Toxicology – urine / oral swab  Track marks  Intoxication

Management

 Early assessment & explanation  Non-pharmacological – eg TENS (also acupuncture)  Nerve blocks/ regional techniques

Management  Pharmacological  Non-opioids – NSAIDs 

Avoid cyclizine

 ?Gabapentin / Pregabalin  Strong opioids if needed:  monitoring important  split dose  ? buprenorphine

Opioids and cancer neurobiology

• • • Up regulation of MORs (non-small cell lung ca) Rodent studies - MOR over expression increased tumour growth and metastases Peripheral MOR antagonist, methylnaltrexone, prevented tumour growth (similar to silencing MOR expression )

Opioids and cancer

• • Population based study (n=42,000) of patients undergoing colectomy ( 22% -epidural analgesia): 5 year survival better in epidural group cf "traditional pain management” Retrospective study (n=655) of colorectal cancer: increased risk of death up to 5 years later in patients receiving patient controlled analgesia cf epidural analgesia, only in rectal, but not colon cancer. Cummings KC et al. Anesthesiology 2012; 116:797-806.

Gupta A et al. BJA 2011; 107:164-170

Assessment: The effect of patient expectation?

 Remifentanil – a potent opioid analgesic?

 Constant dose – burn - manipulate expectation Behavioural effects of the contextual modulation of opioid analgesia

Bingel U et al. Sci Transl Med 2011;3:70ra14-70ra14

Cortical correlates of behaviour

VAS 6.6/10 VAS 5.5/10 VAS 3.9/10 VAS 6.4/10 Bingel U et al. Sci Transl Med 2011;3:70ra14-70ra14

Pain studies – design problems?

Overestimation of effect Little difference from placebo

Endocrine effects of opioids

 Hypogonadism  Low LH, oestradiol, testosterone (free and total)  Symptoms  Reduced libido, irregular menses  Low energy  Depression  Poor concentration  Reduced physical performance