Management of Addiction Issues in Complex Pain

ACP Maine Chapter 2016 Annual Meeting

Sunday October 2nd, 2016

Jonathan C Fellers, MD Assistant Professor, Department of Psychiatry

Tufts University School of Medicine Director, Integrated Medication-Assisted Therapy Maine Medical Center, Maine Medical Partners

Medical Director, Maine Tobacco Help Line MaineHealth Center for Tobacco Independence

Disclosures

• Relevant financial relationship(s) and nonfinancial relationship(s): – Dr. Fellers, co-editor and author of Treating

Comorbid Opioid Use Disorder in Chronic Pain, is employed by MaineHealth and Maine Medical Center

• Disclosure: – Financial: Author for Springer Publishing, receive

royalty payments – Nonfinancial: I have no relevant nonfinancial

relationship(s) to disclose

Objectives

• Provide background of current theories of pain and addiction

• Describe differences in pain perception by patients with addiction

• Understand how to manage addiction patients with complex pain

Background

• How many people with chronic pain may have addiction?

32% • How many people with opioid use disorder

report chronic pain? 29-60%

CSAT. (2011). Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders. Treatment Improvement Protocol (TIPS) 54. HHS Publication No. (SMA) 12-4671. Rockville, MD: SAMHSA.

Pain Theories

• What is the purpose of pain? – Identifies injury and

disease – Motivates to protect

from further damage – Provides lesson about

the environment

Pain Theories

• Specificity Theory – Pain is an independent sense, with its own unique

receptors, pathways, and “brain center”

• Pattern Theory – Perception of pain depends upon the temporal

and spatial pattern of stimulation

Moayedi, M., & Davis, K. D. (2013). Theories of pain: from specificity to gate control. J Neurophysiol; 109 (1), 5-12.

Pain Theories

• Gate Control Theory – ”Gate" in the spinal cord controls the flow of pain

signals from the periphery to the central nervous system

– i.e. TENS unit

Melzack, R., & Wall, P. D. (1965). Pain mechanisms: a new theory. Science , 50 (3699), 971-9.

Pain Theories

• Biopsychosocial Model – Pain is more than a biological phenomenon – Involves psychological and social factors – Informs multimodal approach to complex pain

Gatchel, R. J., Peng, Y. B., Peters, M. L., Fuchs, P. N., & Turk, D. C. (2007). The biopsychosocial approach to chronic pain: scientific advances and future directions. Psychol Bull; 133(4), 581-624.

Addiction Theories

• Positive reinforcement – Mesocorticolimbic dopamine system involved in reward – Drugs of abuse enhance dopamine release within the

nucleus accumbens, including opioids

• Olds, J., & Milner, P. (1954). Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain. J Comp Physiol Psychol; 47(6), 419-27.

• Nestler, E. J. (2005). Is there a common molecular pathway for addiction? Nat Neurosci; 8(11), 1445-9.

Addiction Theories

• Negative reinforcement – Locus coeruleus noradrenergic system important for

arousal and psychological stress – Opioid withdrawal leads to hyperactivity of system

• Nestler, E. J., Alreja, M., & Aghajanian, G. K. (1999). Molecular control of locus coeruleus neurotransmission. Biol Psychiatry; 46(9), 1131-9.

• Koob, G. F., Buck, C. L., Cohen, A., Edwards, S., Park, P. E., Schlosburg, J. E., et al. (2014). Addiction as a stress surfeit disorder. Neuropharmacology; 76 (Part B), 370-82.

Addiction Theories

• Genetic factors account for between 40 and 60 percent of a person’s vulnerability to addiction – Altered response to the drug – Changes in drug metabolism

• Environmental factors – Each adverse childhood experience increased the

likelihood of early initiation into illicit drug use by 2- to 4-fold

– Peer influences – Drug availability

Pain and Addiction

• Progression to opioid use disorder is not assured – Tolerance and withdrawal will develop

• Opioid use during acute pain is protective against addiction – Pain provides a natural counterbalance to opioid-

induced reward and tolerance

Miller, L. L., Altarifi, A. A., & Negus, S. S. (2015). Effects of repeated morphine on intracranial self-stimulation in male rats in the absence or presence of a noxious pain stimulus. Exp Clin Psychopharmacol;23 (5), 405-14.

Pain and Addiction

• Does chronic exposure to opioids alter pain perception?

• Waccholtz et al looked at four groups (n=30) with chronic pain: – Methadone maintenance – Buprenorphine maintenance – History of opioid maintenance but prolonged

abstinence – Opioid naïve controls

Wachholtz A, Gonzalez G. (2014). Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain. Drug Alcohol Depend; 145: 143-9.

Pain and Addiction

• What did they find? • Differences in the groups:

– Sensitivity to pain and ability to tolerate pain significantly lower among those with an opioid use disorder history compared to opioid naïve

– Prolonged abstinence did not alter it – Prolonged abstinence does improve sense of

control over opioid cravings

Wachholtz A, Gonzalez G. (2014). Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain. Drug Alcohol Depend; 145: 143-9.

Pain and Addiction

Wachholtz A, Gonzalez G. (2014). Co-morbid pain and opioid addiction: long term effect of opioid maintenance on acute pain. Drug Alcohol Depend; 145: 143-9.

Treatment

• What makes treating pain in patients with addiction so challenging?

• Three main challenges: – Rewarding aspect of opioids – Opioid tolerance – Opioid-induced hyperalgesia (OIH)

Opioid Tolerance

• Without use or tolerance, we are at “normal”

• Normal

Opioid Tolerance

• Acute use leads to drug effects

DRUG

• Euphoria • Decreased pain perception • Sedation • Respiratory depression • Constipation • Miosis

• Normal

DRUG Tolerance Tolerance

• Dysphoria • Increased pain perception • Restlessness • Tachypnea • Diarrhea • Mydriasis

• Repeated use lead to tolerance

• No use with tolerance leads to withdrawal

Opioid Withdrawal Symptoms

Early to Moderate Moderate to Advanced

Anxiety, dysphoria, irritability Broken sleep

Fatigue, headache, restlessness, craving Muscle and bone pain

Yawning, lacrimation, rhinorrhea, Myoclonus

Perspiration, piloerection Vasomotor symptoms

Tachypnea Hypertension, tachycardia, hyperthermia

Anorexia Abdominal cramps, nausea, vomiting

Mild mydriasis Severe mydriasis

Opioid Withdrawal Time Course

Drug Effect wear off Start Peak End

Fentanyl 1 hour 3-5 hours 8-12 hours 4-5 days

Meperidine 2-3 hours 4-6 hours 8-12 hours 4-5 days

Oxycodone 3-6 hours 8-12 hours 36-72 hours 7-10 days

Hydromorphone 4-5 hours 4-5 hours 36-72 hours 7-10 days

Heroin 4 hours 8-12 hours 36-72 hours 7-10 days

Morphine 4-6 hours 8-12 hours 36-72 hours 7-10 days

Codeine 4 hours 8-12 hours 36-72 hours 7-10 days

Hydrocodone 4-8 hours 8-12 hours 36-72 hours 7-10 days

Methadone 8-12 hours 36-72 hours 8-12 days 14-21 days

Assessing Opioid Withdrawal

• Clinical Opiate Withdrawal Scale (COWS) • Standardized instrument based on objective

and subjective symptoms

5-12 = Mild 13-24 = Moderate 25-36 = Moderately Severe >36 = Severe

Opioid-Induced Hyperalgesia

• Paradoxical increase in pain sensitivity due to opioid therapy

• Mechanism though to be glutamate (NMDA) dysfunction

• Increase in opioid dose will not improve pain

Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. (2011). A comprehensive review of opioid-induced hyperalgesia. Pain Physician; 14(2): 145-61.

Treatment

• Differs based on type of pain – Chronic – Acute

• Also depends on patient – In recovery – On methadone maintenance – On buprenorphine maintenance – Actively using

Treatment

• General principles: – Complete a thorough assessment – Prioritize non-opioid analgesics

• Acetaminophen • NSAIDs • Antidepressants, anticonvulsants • Regional anesthesia

– Use nonpharmacological treatment • Therapeutic exercise • Physical therapy • Complementary medicine

– Treat comorbidities

Treatment Analgesic Addictive Comments

Acetaminophen No Potentiates analgesia without potentiating respiratory and sedative side effects.

NSAIDs No Are used to relieve numerous types of pain, especially bone, dental, and inflammatory, and enhance opioid analgesia

SNRIs No Are used to relieve several nonstructural types of pain (e.g., migraine, fibromyalgia, low back pain) and probably others

TCAs No Have demonstrated efficacy in migraine prophylaxis, fibromyalgia, many neuropathic pains, vulvodynia, and functional bowel disorders

Anticonvulsants No* Some have demonstrated efficacy in relieving fibromyalgia, migraine prophylaxis, neuropathic pains

CSAT. (2011). Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders. Treatment Improvement Protocol (TIPS) 54. HHS Publication No. (SMA) 12-4671. Rockville, MD: SAMHSA.

Treatment

• When opioids are needed consider: – Avoid opioid patient had trouble with – Avoid IV boluses – Patient-controlled analgesia – Using longer acting opioids

Methadone

• Full agonist at μ opioid receptors, 24 hour half-life • Pain control lasts about 6-8 hours • Potent opioid with excellent oral bioavailability • Has some NMDA antagonism therefore offers some

protection against OIH • Side-effects include weight gain, QTc prolongation,

sex hormone suppression, sedation, constipation

Methadone

• Continue maintenance dose • Consider splitting for 3-4 administrations • Additional opioids may be required fo acute

pain • Will require larger and more frequent

administration

Buprenorphine

• Partial agonist at μ opioid receptors (about 60%), 36 hour half-life

• MUST BE IN WITHDRAWAL to start it • Poor bioavailability, requires sublingual

administration • Combination product includes naloxone, potent μ

opioid receptor antagonist that is not absorbed sublingually

Buprenorphine

• Does have analgesic effects lasting 6-8 hours • Because it is a partial agonist, its dose–response

curve plateaus limiting efficacy in severe pain • May need to be discontinued so that full agonist

opioids for pain can be used • Substitute about methadone 30mg for

buprenorphine 12-16mg

Switch to Buprenorphine

• Patients (n=35) on high-dose opioids (MME=550) with unsatisfactory pain control

• After two months: – Reduction in pain (7.2 3.5, p<0.001) – Quality of life improvement (6.1 7.1, p=0.005)

Daitch D, Daitch J, Novinson D, Frey M, Mitnick C, Pergolizzi J Jr. (2014). Conversion from high-dose full-opioid agonists to sublingual buprenorphine reduces pain scores and improves quality of life for chronic pain patients. Pain Med; 15(12): 2087-94.

Active Substance Use

• Refer for addiction treatment • May begin methadone in hospital to manage

tolerance • Use of adjuvant ketamine peri-operatively

Resources