IMPLICATIONS OF THE OPIOID PANDEMIC FOR CASE

MANAGEMENT

Final Thoughts and Summary

Peter B. Polatin, M.D., M.P.H.

Dallas doctor pleads guilty in pill mill that recruited homeless 'patients'

Dr. X worked as a doctor of osteopathy and owned the XXXXX Medical Clinic in Dallas. The clinic has since closed.

Federal authorities say Dr. X and several co-conspirators hatched a moneymaking scheme to distribute at least 150,000 30-milligram doses of the painkiller oxycodone.

The investigation found that the conspirators often paid homeless people to pose as patients at medical clinics to obtain prescriptions, and then fill them at designated pharmacies.

DALLAS MORNING NEWS, JAN. 15, 2017

2013: 30 million RXs for narcotics(not all by MDs)

• PM&R- 3.18%• ER- 4.29%• Anesthesia- 5.06%• Orthopedics- 5.59%• Nurse practitioner- 6.54%• Physician Assistant- 6.62%• Dentist- 7.50%• Osteopath- 9.65%• Internist- 13.86%• Family practitioner- 16.74%• Others- 20.56%

Original Report: The Initiation of Chronic Opioids: A Survey of Chronic Pain Patients,

Callinan C. Journal of Pain Aug 2016

• Chronic opioid use often starts after surgery or for the treatment of acute injury-related pain

• The continuation of opioids can be attributed to follow-up corrective surgery that is required in many with injury-related pain

• many who started opioids following surgery also report post-op complications

• The main prescribers are surgeons (30%), pain specialists (29%), and primary physicians (21%).

Callinan 2

• 43.5% of patients had concurrent depression

• 23.5% had anxiety

• A history of aberrant drug-related behavior (32.5% )

• Self-reported history of addiction (21.7%)

• Nearly 25% of patients reported taking opioids for a different indication than that for which the drugs were originally prescribed for

Gebhardt S: Pain Relief in Depressive Disorders: A Meta-Analysis of the Effects of Antidepressants; [J Clin

Psychopharmacol] 2016 Dec; Vol. 36 (6), pp. 658-668

• SSRIs & SSNRIs were significantly superior vs. placebo in regards to analgesic effects. All effects were small, however

• A strong positive correlation between pain relief efficacy and positive effect on mood was observed for SSNRIs but this relationship refers to patients with primary depressive disorders and not to patients with primary pain disorders.

• The analgesic effects of SSNRIs and SSRIs in patients with primary depressive disorders can be interpreted as largely equivalent.

• More studies are needed to compare the effects of various antidepressants on pain in patients with depressive disorders.

Pain Processing

Dorsal Horn receives input from periphery

Ascending Pathways: transduction, signaling conscious processing

Descending Pathways: feedback loop

Perception, modulation, relay, & emotion

An unpleasant sensory

and emotional

experience

associated with actual

or potential tissue

damage,

or described in terms

of such damage

Pain

International Association for the Study of Pain, 1994.

Chronic Pain and the Brain

• Chronic pain> neuroplastic changes> increased brain activity

• Morphological and neuroimaging changes seen in the thalamus, dorsal pons, insula, and cingulate and prefrontal cortices

– Examples:

• irritable bowel syndrome> hypothalamus

• fibromyalgia> frontal and cingulate cortices

Pain is associated with psychopathology and dysfunctions

• Depression

• Anxiety

–PTSD

• Substance abuse

• Somatization disorders

• Personality disorders

• Chemical coping

• Progressive deconditioning

• Demoralization • Family

disruption• Secondary gain• Aberrant

behaviors

Chemical Copers

• Drug focused• Fringes of appropriate medication use• Not progressing toward goals• “Accidental overdoses”• Somatization, alexithymia

• Strategy is to de-emphasize meds, focus on physical rehabilitation & psych interventions, structure, frequent visits and toxicology, pill counts, “safer” and longer acting opioids

Psycho-dynamics and chronic pain

Majority of patients have childhood abuse

Chronic pelvic pain = sexual trauma

Repressed anger, marital or job stress

Family history and dynamics are important

Fear-inhibition frequently aided by MD communication or online blogs

Pain has a communication function

• The expression of emotional distress through physical symptoms

• Unconscious

• The language of pain:

– Grimacing

– Groaning

– Rubbing

– Talking about pain

What is Pain?

• Signal (nociceptive impulse)

• Symptom of illness

• Syndrome of behaviors

• Construct for indemnity and litigation

• Chronological sequence: acute>subacute>chronic

Challenges in Pain Management• Identifying psychopathology• Screening for psychosocial determinants• Closing down interventional procedures• Defining an achievable endpoint for therapy• Balancing benefits v.s. side effects of various

treatment interventions• Monitoring opioids, benzodiazepines, and other

potentially addictive substances• Controlling the “gains”• Adhering to a biopsychosocial model

The Medical Model for understanding Illness

Cause(injury, disease)

Effect(illness, disability)

Cure

Chronic pain syndromeHypertensionDiabetesTBI

SUDDepressionAnxietyPersonality disorder

Social withdrawalCollapse of family structureLoss of economic capabilityLoss of social capital

Loss of function

BIO

PSYCHO

SOCIAL

PATIENT WITH

CHRONIC PAIN

Sites of Action of Pain Medications

Opioids

OPIOIDMorphineHydrocodoneOxycodoneOxymorphoneHydromorphoneFentanyl patchActiqFentoraDemerolPentazocineSuboxoneButrans patchTapentadolTramadol

EQUIANALGESIC30 mg22.5 (20-30) mg15 (15-20) mg10 mg7.5 (5-8) mg25 mcg/hr1200 mcg800 mcg300 mg100 mg8 mg SL12.5 mg100 mg300 mg

METABOLISMGlucuronidation2D62D6,3A4GlucuronidationGlucuronidation3A43A43A42B6,3A4,2C19P450,Glucuronide3A4,Glucuronide3A4,GlucuronideGlucuronidation2D6,3A4

RECEPTORMuMuMuMuMuMuMuMuMuKappaPart Mu, K-antPart Mu, K-antNE> wk Mu5HT> NE, wkMu

OPIOID EQUIVALENTS

BUT THERE ARE OTHER OPTIONS!!!

Opioid Risks

Diversion

Misuse

Abuse

Endocrine

Apnea

Accidents

Death

Hyperalgesia

Opioid Tolerance

Neuroadaptation through receptor desensitization resulting in reduced drug effects (and side effects)

Does not develop to constipation or miosis

Occurs more slowly to analgesic effects

Physical Dependence

Characterized by unpleasant withdrawal symptoms upon dose reduction or discontinuation such as nausea, diarrhea, rhinorrea, muscle aches, cramping, restless legs, anorexia, sweating, insomnia, anxiety, dysphoria, mydriasis

Withdrawal can be treated with alpha 2 agonists, substitution, or slow taper

Addiction

Compulsion to use, craving

Loss of control

Withdrawal with dose reduction

Tolerance to effects

Increased time to obtain drug and

neglect of alternative pleasures or interest

Persistent use despite harmful consequences

Opioid induced hyperalgesia (Central Sensitization)

Neurophysiological Changes:

Sensitization of pronociceptive pathways

Abnormal activation of NMDA receptors in CNS

Long term potentiation of synapses between nociceptive C fibers and neurons in the spinal dorsal horn

Patients don’t benefit from high dose opioids

Will get improved pain control with taper, discontinuation, or buprenorphine induction

PREVALENCE OF ABERRANT OPIOID BEHAVIORS IN PAIN PATIENTS

Misuse– 40%(taking other than as directed) Abuse– 20% (illegal use to get high) Addiction- 5% (a chronic neurobiological disease with genetic psychosocial & environmental influences characterized by loss of control, compulsive use, use despite harm & craving )

Diversion- removal of medication from legitimate dispensing channelsPseudoaddiction- abnormal behavior from undertreatmentof pain that ceases with adequate pain relief; misidentified asdrug-seekingPseudotolerance- requiring increased dose because of disease progression

SOAPP-R

Screener and Opioid Assessment for Patients with Pain- Revised

SOAPP-R

LOW RISK (<9) MODERATERISK (10-21)

HIGH RISK (>22)

No past or current abuse history

Treated abuse in past

Active abuse/addiction

No family abuse history

Significant family history of abuse

Major untreated psychiatric or personality disorder

No majoruntreated psychiatric disorder

Past or current comorbid psychiatric disorder

Risk of harm to self or practitioner

S0APP RISK STRATIFICATION

UNIVERSAL PRECAUTIONS IN PAIN MEDICINE

Diagnosis with differentialPsych / Addiction assessment / med recordsInformed consent for Tx & ToxicologyTreatment agreementsPain and functional assessmentsOpioid trialReassessment of pain, function, behavior4 A’s-

analgesia, ADL’s, adverse effects, aberrant behaviors

Periodic review of diagnosis & co-morbiditiesDocumentation

Analgesia

VAS Pain levels : Worst, least, average

Percent pain relieved with medication

30% pain relief is clinically significant

50% pain relief is considered good

Adverse Events

• Nausea / Vomiting• Constipation• Headache• Itching• Fatigue / Sedation• Insomnia• Cognitive changes• Irritability • Edema• Hyperalgesia

Activities of Daily Living

Physical functioning

Family relationships

Social relationships

Mood

Sleep patterns

Work

Sexual function

Progress toward specific goals

Red Flag Behaviors

Intoxication

Sedation

Negative Moods

Alcohol / Illicit drugs

Doctor Shopping

Neglect of Appearance

MVA

Arrest

Hoarding of RXs

Street Drug Culture

Request for specific meds only

Early refills for “lost” or “stolen” RXs

Abnormal Toxicology

Snorting / Crushing

Use for stress

OPIOID AGREEMENT

Legal implications of term “contract”Single MD Rx opioids, possibly BZDsSingle pharmacyRisks/BenefitsPolicy regarding “lost meds” and refillsPill counts / toxicology issuesBehaviors leading to opioid taperingBehaviors leading to termination

MethadoneMethadone has a long half life resulting in rising blood levels over 5-7 days. Highest incidence of apnea. Serotonergic. Dosed q 6-8 hrs for analgesia.Start with 5 mg TID in opioid naïve and low dose patients, half that for geriatrics. Mu agonist; NMDA antagonism reduces hyperalgesia , effective for neuropathic pain. Metabolism through 3A4 and 2D6.

Conversion: Methadone->morphine 1:5Morphine->methadone :

<100 mg 3:1100-300 5:1300-600 10:1600-800 12:1800-1000 18:1>1000 mg 20:1

BuprenorphineSuboxone –buprenorphine/naloxone SL

8/2 mg or 2/.5mg; FDA for opioid dependence

Subutex –buprenorphine SL 8mg or 2 mg

0.5-8 mg TID-QID for pain

Butrans patch weekly 5, 10, 20 ug/hr –approved for pain; 30-70 mcg in Europe

Does not cause hyperalgesia

Antidepressant?

Adjuvant Pharmacotherapy

Somatic/ Musculoskeletal Pain

• NSAIDS –try different families, monitor GI

• Tizanidine- alpha-2 agonist muscle relaxer with sedative and analgesic properties

• Baclofen- GABA angonist, anti-spasticity

• Cyclobenzaprine for FM (TCA-like)

• Avoid carisprodol- metabolizes to meprobamate

• Benzodiazepines should be temporary

• TCA, SNRI work moderately for some

Fibromyalgia

• Pregabalin, gabapentin in adequate doses

• SNRIs- duloxetine, milnacipran, high dose venlafaxine second line, TX MDD as well

• TCAs – NE>5HT for pain in general

• Cyclobenzaprine, tizanidine, Gabitril @HS

– Enhance stage 3 sleep

• Tramadol

• Exercise, stretching, H20, CBT, nutrition

Neuropathic Pain• TCAs, SNRIs

• Gabapentinoids

• Na channel blockers- lidocaine patch, oxycarbamezapine, carbamezapine, mexiletine , lacosamide

• Capsaicin patch (Qutenza)

• Topirimate, zonisamide, Keppra 2nd line

• THC

Antidepressant Issues

Duloxetine 60-120 mg – sedation in a few

Milnacipran 50-200 mg- nausea, HTN

Venlafaxine 225 mg+, Pristiq 100 mg for pain

Amitriptyline- tertiary amines may be more effective but with greater side effects, low doses effective

Protriptyline- noradrenergic, no weight gain

Trimipramine- D2 blocker, low 5HT ,NE, H2 blockade accounts for weigh gain and improved sleep

MAOIs- treats migraine, EMSAM patch selective for MAO-B

Anesthetics

Na channel blockers for neuropathic pain

Lidocaine 5% patch, gel

IV Lidocaine

Mexiletine , Tocainimide antiarrhythmics

Treatment of CRPS

• Neuropathic pain treatments

• Sympathetic blockade with injections or alpha blockers- dibenzyline, terazosin

• Biphosphonates, calcitonin

• Spinal cord stimulators

• Intrathecal pump with opioids, baclofen, anesthetics, ziconotide

• Compounded gels with Ketamine, TCA, NSAID, alpha-2 agonist

• IV/PO ketamine

• PT, ECT , rTMS

The pain is in the brain….

• CBT can change the pain related-

–Thoughts

–Feelings

–Behaviors

–Coping strategies

–Context of discomfort

Clinical Issues

• Overactivity-rest cycle• Intolerance of physical activity• Deconditioning

– Cardio-respiratory endurance– Muscle strength and endurance– Motor control– Proprioception – Balance – Reaction time– Posture

Exercise

• Initially may increase pain

• Ultimately will decrease pain

Cognitive Distortion in Chronic Pain

• Related to general psychological distress (pain, depression, chronic medical illness)

• Characterized by cognitive errors

catastrophizing

selective abstraction

overgeneralization

personalization

Main Goals of CBT for Chronic Pain1. Increased functional activities, despite pain2. Improved mood, despite pain3. Reduced use of analgesic treatments

Essentials of behavioral pain management

• Education

• “Mindfulness” training

• Biofeedback

• Psychosocial support

• Cognitive restructuring

• Behavioral therapy

• Managing “the gains”

• Functional Restoration