Patient Selection What You Must Know 2010 NANS Joel R Saper, MD, FACP, FAAN Director/ Founder Michigan Head Pain & Neurological Institute Ann Arbor, Mi Clinical Professor Neurology, MSU

DISCLOSURE !!! Honoraria: GlxSK, Merck,AstraZ,Allergan, OrthoMcNeil,Elan,Pfizer, Pharmacia Advisory Brd/Consultant: Allergan, OrthoMcNeil,Medtronic, Advanced Bionics, AZ, Ely Lilly, Pfizer, Esai, Pozen Research Grants: GlxSK,Merck,AstraZ,Abbott,Allergan, OrthoMcNeil, Esai, Pfizer, Pharmacia, Elan, Pozen, Medtronic, Advanced Bionics

END OF PRESENTATION!

Interventional Procedure Success, and Adequate Reimbursement, Depend on Fulfillment of Key Clinical Outcomes: Sustained reduction of pain Improved Function Overall cost reduction(utilization) These are achieved…

Successful Outcomes For all Interventional Procedures, and Adequate Reimbursement, Depend on Fulfillment of Key Clinical Outcomes: IDing of proper diagnosis and symptom complex in moderately refractory patients, at a time and evolution of the illness that assures reversibility Surgical/Procedural competence Selecting patients without barriers or conflicts to sustained benefit!

Barriers and Conflicts Wrong Diagnosis In case of headache and occipital n. stim: must be reasonably certain that the occipital nerve stim is a conduit to trigeminal mediated pain via dorsal horn modulation, or in 2 nd and 3 rd order trigeminal neuronal systems. The cervical dorsal horn is a therapeutic locus for trigeminal and occipital pain modulation via the O.N.

C 2-3 & TRIGEMINAL/CERVICAL COMPLEX Stimulation of C 2-3 roots activates trigeminal complex (Goadsby, 2001) Suggests chronic stimulation could sensitize 2nd and 3rd order neurons, activating migraine or other HA mechanisms

Barriers and Conflicts Opioid Dependency

Determine if cervical pain and/or c. pathology are necessary elements favorable response?

Successful Outcomes and Support for this Costly, Surgical Procedure Depend on Fulfillment of Key Clinical Determinants Identification of proper diagnosis and symptom complex in moderately refractory patients, at a time and evolution of the illness that assures reversibility/ control of pathophysiology– implementation at proper “stage” of illness Achieve appropriate surgical competence, device and lead improvements, technique advances

Successful Outcomes and Support for this Costly, Surgical Procedure Depend on Fulfillment of Key Clinical Determinants Identification of proper diagnosis and symptom complex in moderately refractory patients, at a time and evolution of the illness that assures reversibility/ control of pathophysiology--- implementation at proper “stage” of illness Surgical competence, device and lead improvements, technique advances Opioid dependence must be terminated before implantation!

SYNDROME OF MEDICATION OVERUSE HEADACHE Characteristics of Rebound Headache Occurs in patients with pre-existing HA Regular intake, more than 2-3d/wk, for months A self-sustaining rhythm of predictable, reliable & escalating HA frequency & med. use Refractory to otherwise appropriate symptomatic & preventive treatments Med withdrawal results in escalation of HA Saper JR. 1983,1992,1999

MEDICATION OVERUSE HEADACHE, IHS,2004 Diagnostic criteria: Intake (triptans, ergots, opioids) on > 10 d/mo on a regular basis for > 3 mo 15 d/mo for simple analgesics HA has developed or markedly worsened during overuse HA resolves or reverts to previous pattern within 2 mo after D/C Applies to: Ergotamine, triptan, analgesic, opioid, & combination medication overuse HA

Opioids and the Brain Review of literature Opioids can cause receptor hypersensivity, opioid induced hyperalgesia (Mao et al,2002) Glutamate induced apototic cell death(Mao.2002) Induce CGRP increase in dorsal horn( Meng and Porecca, 2004) Morphine activates glia and increases pro- inflammatory cytokines(Watkins, 2002) Pro-nociceptive cholecystokinin (CCK) is upregulated in the rostral ventromedial medulla (RVM) during persistent opioid exposure CCK activates descending RVM pain facilitation, enhancing pain transmission and hyperalgesia (Ossipov,2004)

Opioids and the Brain Review of Literature Long-lasting receptor change after initial exposure to morphine(Lim,et al,Mao, 2005) Numerous endocrine disturbances Age dependant tolerance: exceptional receptor sensitivity and tolerance in adolescents(Buntin- Mushok, 2005) Opioid induced MOH more likely to be unrelieved following D/C than with triptans and ergots(Lake 2005; others) Prevents response to parenteral NSAIDS (Jakubowski,et al 2005)

Opioids: Endocrine/Immune System Effects In animals, opioids increase GH, inhibits LH, FSH, TSH Opioid induced hypogonadism d/t central suppression of gonadotropin releasing hormone 75% of men have clinically significant lowered testosterone levels Loss of muscle strength, compression fractures, osteoporosis, galactorrhea, etc, Katz,et al, 2009, Clin J Pain; Maggi, 1995; Kavelaars,1991

REBOUND: A Neurobehavioral Disorder Not all pts with daily/frequentHA overuse drugs Physical (receptor) alterations ( Srikiatkhachorn, 1998, Mao,2003) Behavioral – excessive/obsessive drug-taking, anticipatory anxiety, fear of pain (cephalgiaphobia), “orality/security dynamic” Saper et al, Cephalalgia,2006

MOH MOH --the phamacokinetic up-regulation of nociceptive system in predisposed patients, in which increased pain reflects receptor hypersensitivity, central sensitization and neuroplasticity,and often behavioral influences (Saper et al. Cephalalgia 2005) Genetics Neuroplasticity (M eng and Porecca, 2004) Neuro-behavioral dynamics

In HA patients, and perhaps others, opioid dependence induces progression of pathology, alterations in personality, a prolonged craving and reliance on the tranquilizing effects, well beyond the analgesic need. Getting better poses a conflict!

Many use drugs to have a life; others to hide from life!

Barriers and Conflicts Opioid Dependency The “PROBLEM PATIENT”

Successful Outcomes and Support for this Costly, Surgical Procedure Depend on Fulfillment of Key Clinical Determinants Identification of proper diagnosis and symptom complex in moderately refractory patients, at a time and evolution of the illness that assures reversibility/ control of pathophysiology--- implementation at proper “stage” of illness Surgical competence, device and lead improvements, technique advances Opioid dependence must be terminated before implantation! Selection of treatable patient, absent barriers to “get better”!

Successful Outcomes and Support for this Costly, Surgical Procedure Depend on Fulfillment of Key Clinical Principles Identification of proper diagnosis and symptom complex in moderately refractory patients, at a time and evolution of the illness that assures reversibility/ control of pathophysiology--- implementation at proper “stage” of illness Surgical competence, device and lead improvements, technique advances Selection of treatable patient, absent barriers to “get better”!

“It not so much what’s done to the head but to whose head it’s done”! Saper, 1992

Identifying the problem patient is critical

PSYCHOBIOLOGY OF PAIN Psychological variables modulate PAG and nociceptive neurons in dorsal horn (Fields, 1997) –Bidirectional control over pain transmission (somatosensory, cortical, limbic via PAG, engaged by psychological factors) –Physiological mechanisms convert psychological distress to painful symptomatology (Fields, 1997) –Limbic enhanced pain via neuroplasticity mechanisms(Rome,2002)

Joel R Saper, MD, FACP, FAAN Michigan Headache & Neurological Institute Ann Arbor, Michigan NINDS, NIH, March 4, 2008 Approach to Intractable Headache Founder/Director

PSYCHOBIOLOGY OF PAIN Psychological variables modulate PAG and nociceptive neurons in dorsal horn (Fields, 1997) –Bidirectional control over pain transmission (somatosensory, cortical, limbic via PAG, engaged by psychological factors) –Physiological mechanisms convert psychological distress to painful symptomatology (Fields, 1997) –Limbic enhanced pain via neuroplastic mechanisms(Rome,2002) –Stress evokes proinflammatory cytokines (Watkins, 2005)

PSYCHOLOGICAL DETERMINANTS OF PAIN 2 Stress & psychotrauma “configure” corticolimbic function Via kindling & neuroplasticity Results in amplification, spontaneity, neuroanatomic spreading, & central sensitization “Limbically Augmented Pain” (Rome, 2000)

Some Barriers Pain communicates Pain controls Pain punishes Pain prevents abandonment Pain protects Pain pays

The Troubled Patient Must be Recognized and Confronted Early Overt drug misuse/ addictive disease Severe anxiety / depression/ somatization “Pain Theater” starring the Drama Queen/King and cast of supporting enablers and sympathizers Missed visits Lost/ “ran short” of scripts Noncompliance Anger Family dysfunction Usually Axis ll, Cluster B

How can some patients say they are better? Disability lost Performance expectations: job, family, marital No more opioids Relinquishing special status/protections/reduced expectations Some spouses/relatives are only attentive when partner is ill Illness can be the glue that binds a weak relationship Chronic impairment and disability, role reversals and drug dependency may lock even motivated people into a sick role

Some patients become “illness locked”! “ I want to feel better, but not necessarily GET better!”

Some patients cannot/won’t get better! They are not good procedural candidates!

Securing Responsible Coverage Through Strong Data Improved product and lead design, and implanting techniques Well targeted, carefully screened and selected study population, with strategic psych. and behavior profile assessments Exclude opioid dependent and “barrier ridden” patients Robust, well considered endpoints Longer trial duration Creative and effective blinding techniques and design Convincing outcome data

For therapeutic stimulation to be cost and clinically effective, we must do a better job of screening, selecting and implanting refractory cases!

Axis ll disorders often prompt the doc to act in unwise and expedient, rather than appropriate, ways. Anything to move on!

“Conversations With Borderlines, Narcissists, Sociopaths, Addicts, Felons and Other Self-Loathing and Good Friends” JRSAPER Highlights from…

TOP 20 QUOTES FROM BPD PTS “Shove your behavior contract up your a-- !”

TOP 20 QUOTES FROM BPD PTS “I want my Demerol”

TOP 20 QUOTES FROM BPD PTS “You’re calling me a drug addict, aren’t you?”

“My Oxy fell down the toilet”

TOP 20 QUOTES FROM BPD PTS “My dog ate my narcotics”

Are there breeds of dogs that love opioids ONLY…? OxyCollie OxyRetriever PercoSpanial VicoCocker Morphi-Yorkie

Dogs That Treat Misuse DetoxerBoxer

“How did that cocaine get in my urine?”

“Nurse Ratshitt, did you put cocaine in Herbie’s urine?!!!!”

“My pain is no better, but I need more Oxycontin because it makes ME feel better”.”

“Let’s face it, I like the buzz!” --a headache patient on Actiq

“Let’s face it, it takes 30 seconds to say yes, but 30 minutes to say no!” Dr Howard Heit, 2004

“Sometimes the best medicine is to stop taking something” Ashleigh Brilliant

“The head speaks when the mouth cannot”! Saper, 2006 (Said in a moment of unrestrained psychobabble!)

“Treating pain is a thinking sport” Dr Jeff Okeson, 2003

“Treating some borderline patients is a blood sport! J Saper, 2006

“What do you mean I have a borderline personality? I’ve never even been to Mexico!” --a perplexed borderline patient

“Justice will be served only when the last lawyer on earth has been strangled with the intestines of the last politician”! George Bernard Shaw

THE BITTER END… at long last