Preventing and treating narcotic dependence in our IBD patients

Eva Szigethy MD, PhD

Associate Professor of Psychiatry, Pediatrics and MedicineDirector, Visceral Inflammation and Pain (VIP) Center

Division of Gastroenterologyszigethye@upmc.edu

Szigethy: Disclosures

• Grants: NIMH, NIH, CCFA• Consultant: Merck, Abbvie, iHope Networks• Royalties: APPI• Honorarium from GI Health

• Off-label drugs will be discussed and identified as such.

Objectives: Opioids for Chronic Abdominal Pain in IBD

• Rates of use

• Benefits of use

• Risks of use

• Alternatives

Pain: Fifth Vital Sign

• Pain standards of the Joint Commission on Accreditation of Healthcare Organizations

– Pain assessment/management a priority in daily practice

– Pain intensity, temperature, pulse, respiration, BP

– Patients’ rights: full pain work-up when pain is not easily characterized or treated

JCAHO 1999,2000; IOM 2011

Negative aspects of pain as a 5th vital sign

• Increasing prescription drug abuse and deaths

• Unclear that increased opioid use has resulted in proportional improvement in management of pain

Mehendale et al., 2013

Opioids- what?

• Opioid receptors: G protein-coupled receptors throughout body

• Mu (analgesia, GI)• Delta (GI, respiratory)• Kappa (dysphoria, sedation)

• Natural (morphine)• Semi-synthetic (heroine,

oxycodone, hydromorphone)• Synthetic (fentanyl)

Opioid Use in IBD

• Used acutely after surgical resection of the intestinal tract and to treat pain due to inflammation/obstruction in IBD.

• 5–21% of patients with IBD are on chronic narcotics in the outpatient setting.

• 20-70% inpatients with IBD use narcotics

• Risk factors: CD, substance abuse, psychiatric diagnoses, IBS, history of trauma, female gender

Edwards 2001; Cross 2005; Hanson 2009; Long 2011; Szigethy 2014

Benefit of Opioids for chronic non-cancer pain?

• Limited evidence of efficacy for neuropathic pain and chronic back pain and headaches.

• No studies supporting efficacy of long-term opioids for chronic abdominal pain.

• Poor outcomes and high side effects for chronic opioid use for break-thru pain.

Kalso 2007; Chao 2009; Manchikanti 2011; Fine et al., 2010; Devulder et al., 2009

Opioid Side Effects

• Side effects– Nausea/vomiting – Sedation– Constipation– Urinary retention– Pruritis

Opioids- Risk

• Physical dependence• Addiction• Overdose/death• Tolerance: Repeated exposure leads to reduced

therapeutic effect• Opioid-induced hyperalgesia: enhanced pain

response to opioids (narcotic bowel syndrome).– Biphasic mu receptor– NMDA (glutamate) activation– Spinal inflammation

Fernanes 1977; 1997; Vinik 1998; Chu 2006; Hay 2009; Ossipov 2003; Drossman & Szigethy, 2014; Grunkemeimer 2009; Kurlander 2014

Opioid risk management

• State rules and regulations• Random toxicology screens and pill counts• Opioid treatment agreements • Communication with PCPs and pharmacies• Ongoing review and documentation of pain relief,

functional status• Risk assessment instruments: SOAPP-R (Screener and

Opioid Assessment for Patients w/Pain), COMM (Current opioid misuse measure), ABC (Addiction behaviors checklist)

• Take home message- have a risk management plan

Non- Opioid Pain Management

‘Chronification’ of Pain as a DiseasePathology:-Muscle atrophy, weakness;-Bone loss;-Immuno-compromise-Depression

-Less active-Kinesophobia-Decreased motivation-Increased isolation-Role loss

Disability

Pathophysiology of Maintenance:-Radiculopathy-Neuroma traction-Myofascial sensitization-Brain, SC pathology (atrophy, reorganization)

Psychopathologyof maintenance:-Encoded anxiety dysregulation - PTSD-Emotional allodynia-Mood disorder

NeurogenicInflammation:- Glial activation- Pro-inflammatory cytokines- blood-nerve barrier dysruption

Acute injuryand pain

PeripheralSensitization:New Na+ channelscause lower threshold

Central Sensitization-Neuroplastic changes

RM Gallagher, Pain Med, 2009

PHYSICALInflammationObstruction

Surgery

PSYCHOLOGICALMood

Cognitions

Srinath and Szigethy 2012

Peripheral nerve damage

SufferingDisabilitySuicide

Education about Brain-Gut-Pain Connection

Psychosocial Interventions

• Cognitive behavioral therapy (CBT) reduced arthritis pain, fibromyalgia, IBS, headaches

• Meditation and mindfulness techniques reduce pain perception and suffering.

• Hypnosis improved acute and chronic pain across a variety of conditions including IBS and IBD.

• Need adequate dose- 8-12 sessions

Astin 2002,Knittle 2010, Glombiewski 2010; Andrasik 2007; Elkin 2007; Kok 2013; Tang 2013; Palsson & Whitehead 2014; Patterson & Jensen, 2003

Pharmacological (off-label): Visceral PainCLASS TYPE MECHANISMS for PAIN CONTROL

Antidepressants TCAs

SNRIs

Increased NA, SE, endogenous opioid release, anti-inflammatory?

Stimulants MethylphenidateD-amphetamine

Influence NE, SE, DA, endogenous opioids

Mood stabilizers Gabapentin/pregabalin Central voltage-gated calcium channels?

Atypicals Quetiapine? DA, SE, Adrenergic antagonism

Glutaminergic Memantine ? Glutamate antagonism

Anti-inflammatory

Doxcycline ? Central or peripheral inflammation

Ford, 2008; Drossman 2002; Taylor 2007; Houghton 2011; Grover 2009; Szigethy and Drossman, 2014

Rational Approach to Chronic pain

• Address false expectations or beliefs of patients• Provide neurobiological explanation of patient’s

symptoms • Provide information/rationale aligned with

patient’s interests/concerns• Negotiate treatment plan

– Benefit in 4-6 weeks– Most side effects decrease in 1-2 weeks– Consider previous drugs that works and family history of

drug response• Doctor-patient relationship key

Procedural Interventions for Chronic Abdominal Pain ???

• Nerve blocks

• Surgical Interventions- ablation

• Infusion- pumps and intrathecal

• Stimulation units

• Acupuncture

Algorithm for Opioid Detoxification for Patients with Narcotic Bowel Syndrome in IBD

Phase 1Outpatient

• Build a strong therapeutic relationship to improve motivation and reduce resistance.

• Teach behavioral interventions for pain management• Begin appropriate alternative non-opioid pain medications (TCAs,

SNRIs, SSRIs)

Phase 2

Inpatient

• 10-33% daily reduction of i.v. morphine equivalent• Clonidine for withdrawal symptoms; Benzodiazepines for extreme

anxiety• Continue non-opioid pain medications (TCAs, SNRIs, SSRIs)• management of bowel motility

Phase 3Outpatient

• Continue behavioral interventions• Continue non-opioid pain medications• Treat comorbid psychiatric symptoms and conditions• COORDINATION WITH IBD MEDICAL TEAM

Drossman and Szigethy, 2014 in press

Abdominal pain scores improve but high recidivism (Phase 2 only)

6060

5050

3030

1010

00Stayed offnarcotics

n=13

Stayed offnarcotics

n=13

Visual Analog Scale

(0-100)

Visual Analog Scale

(0-100)

4040

2020

Went back onnarcotics

n=10

Went back onnarcotics

n=10

Pre-detox-ification

n=39

Pre-detox-ification

n=39

Post-detox-ification

n=37

Post-detox-ification

n=37

3 month follow-up3 month follow-upDrossman DA et al. Am J Gastro 2012;107:1426

Challenging clinical situations in managing chronic pain

• Misrepresent symptoms• Failure to comply with

medical directives• Repetitive failure of

response to interventions

• Time-consuming• Induce “difficult

feelings within the clinician.

• Severe Axis I psychopathology

• “Abrasive” personality traits (Axis II clusters B & C)

• Childhood adversity (“primed nervous system”)

• < 10% of our patients…but…

Hahn 2000; Jackson 1999; Koekkoek 2011

Managing Challenging Clinical Situations: Suggestions

• Clear explanation of expectations from treatment onset• Empathic listening and repeat back what you heard• Setting consistent limits and clear verbal and written

instructions• Validate anger but redirect toward their helplessness not their

helpers• Re-channel entitlement into realistic expectations of good

care• Arrange regular appointments not based on worsening.

• Manage your countertransference Groves, 1978

So can Prometheus be unbound?

Opioid overuse pain syndrome (OOPS)- Mehendale et al., 2013

Yes with interdisciplinary approach