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Optimizing Opioids in Pain Management Roman D. Jovey, M.D. Physician Director Alcohol & Drug Treatment Program Credit Valley Hospital Complex Pain Consultant Mississauga, Ontario, Canada April 1, 2003 An 89-year-old man who smothered his 85year-old wife in her nursing home bed to end her pain will face murder charges, U.S. prosecutors said yesterday. Morris Meyer, who uses a wheelchair, told police his wife had begged him to help her die, so he made his way to her bed and held a pillow over her face. The Dorsal Horn Synapse Endorphins Enkephalins Opioids Clonidine Baclofen 2-methylserotonin GABAB µ § Nociceptor Midozalam GABAA a2 5-HT3 Citalopram Dorsal Horn Cell 5-HT1B Brookoff, 2000 Pain and Suffering The Importance of Genetics GENETICS N O C I C E P T I O N COMT P A MORs I N Placebo Effect COMT Emotions Cognition (vigilance) Environment 2D6 Codeine SUFFERING Clinical Significance of the Basic Science of Pain Not all pains are the same Not all patients have the same pain sensitivities Not all patients have the same pain relief from opioids Not all patients have the same side effects of opioids Not all opioids are the same Not all opioid receptors are the same Not all mu opioid receptors are the same Pasternak, 2001 Why use opioids at all? Chronic Pain- Treatment Options PHYSICAL Normal activities Aquafitness Physio Passive Active Stretching Conditioning Weight training Splinting / Taping TENS TMS / TCNS Massage Chiropractic Acupuncture Dolphin PSYCHOLOGIC Hypnosis Stress Management CognitiveBehavioural Family therapy Psychotherapy MindfulnessBased Stress Reduction PHARMACOLOGIC OTC medication CAM Topical medications NSAIDs / COXIBs DMARDs Immune modulators Tricyclics / AEDs INTERVENTIONAL I.A. steroids I.A. hyaluronan Trigger Pt Therapy IMS / Prolotherapy Nerve Blocks Botox Epidurals Opioids Orthopedic Local anesthetic Neurotomy congeners Neurectomy Muscle relaxants Implantable Sympathetic agents stimulators NMDA blockers Implantable pain CGRP blockers pumps Future Pharmacotherapies CGRP antagonist NMDA blockers Cannabinoids COX inhibitors Bradykinin antagonists Glutamamte antagonists Substance P and Neurokinin antagonists Tetrodotoxin / Omega conotoxins CCK blockers TRPVR1 agonist Opioids continue to be our most potent pain reliever Treating Chronic Pain… Pharmacotherapy BENEFIT RISK Acetaminophen Used for mild-moderate nociceptive pain Good evidence in post-op pain No placebo-controlled evidence in chronic arthritis pain (Case, 2003) Acetaminophen – not a benign drug Hepatotoxicity GI bleeding / perforation Chronic renal failure Hypertension Zimmerman, 1995, 2000; Bromer, 2003; Garcia Rodriguez, 2001; FDA 2004; Health Canada Feb. 2003; Curhan 2002. U.S. Mortality Data, 1997 25000 20000 15000 10000 5000 in s Ho dg k Ca Ce r vix a hm As t lo m a My e MV As s ET OH NS AI D S AI D Le uk em ia 0 Singh G. Am J Med 1998 Wolfe M. NEJM, 1999 If you take an NSAID > 2 mo… 1/5 chance of an endoscopic ulcer 1/70 chance of a symptomatic ulcer 1/150 chance of a bleeding ulcer 1/1200 chance of dying Henry McQuay 10th World Congress on Pain, 2002 http://www.jr2.ox.ac.uk/bandolier/booth/painpag/nsae/nsae.html Approximately 1900 Canadians die annually due to NSAID-related adverse effects * Canadian Arthritis Society www.arthritis.ca * more than the total number of deaths due to MVCs, fires and gunshot wounds combined COXIBs Concurrent ASA nullifies the GI protective effect Increased cardiovascular risk (Vioxx) Howard PA, 2004 Topol E, NEJM 2004 Delayed fracture healing in animals Simon AM. 2002 Gerstenfeld LC, 2004 NSAIDs and COXIBs 10-17% of patients develop increased BP Cheng HF. Hypertension, 2004 Acute and chronic kidney toxicity DeMaria AN. JPSM 2003 Double the risk of hospitalization for CHF Garcia-Rodriguez LA. Epidemiology 2003 Increased miscarriage risk Li DK. BMJ 2003 Adjuvant Analgesics Toxicity Carbamazepine – liver, hematological Valproic Acid – liver, hematological Gabapentin – liver Tricyclics – cardiac, anticholinergic Mexiletine – cardiac, liver, hematological Topiramate - kidney stones Opioids have never been shown to cause organ damage when taken therapeutically. Opioids are physically the safest pain reliever available. Opioids can cause harm when they are misused. Prescription Opioid Abuse DAWN Data – United States 100000 90000 80000 70000 60000 Opioid Analgesic Related ED Visits 50000 40000 30000 20000 10000 1996 1997 1998 1999 2000 2001 New Users of Illicit Drugs in the Past Year Pain Meds THC Cocaine Ecstacy Tranquilizers Heroin 3,500,000 3,000,000 2,500,000 2,000,000 1,500,000 1,000,000 500,000 0 1965 1970 1975 1980 1985 1990 1995 1999 2000 U.S. National Household Survey on Drug Abuse, 2001 Past Year Abuse or Dependence (DSM IV) on Alcohol or Illicit Drugs by Age 25 20 15 % 10 5 >6 5 -64 60 -59 55 -54 50 -49 45 -44 40 -39 35 -34 30 -29 26 -25 24 -23 22 -21 20 -19 18 -17 16 -15 14 12 --1 3 0 Age U.S. National Household Survey on Drug Abuse, 2001 Prescription Opioid Addiction Treatment Episode Data System, TEDS 2.00 1.50 1.00 0.50 20 01 20 00 19 99 19 98 19 97 0.00 19 96 Percent of total admissions 2.50 It really comes down to a question of balance Appropriate Use vs Abuse: Maintaining the Balance The FEW who misuse prescribed opioids should not penalize the OVERWHELMING MAJORITY who use opioids appropriately Treat pain sufferers + minimize drug diversion Assess for risk factors Prescribe carefully Monitor behaviours suggestive of misuse/abuse, or addiction Can we predict who will misuse prescribed opioids? Risk factors for misuse / addiction Family history Previous history of alcohol abuse / addiction Previous history of drug abuse / addiction Serious untreated psychiatric problems Previous criminal behaviour High risk home environment Opioidology 101 Optimizing opioid use for pain When to Consider Opioid Therapy for Chronic Pain … Unrelieved pain + Decreased QoL + Failure of usual treatments Opioids work best when dosed to effect Dosing to effect means… Reasonable pain relief or Unmanageable and persistent side effects Some people respond to a small dose. Others require a much higher dose to adequately treat their pain. Each patient responds uniquely to a given opioid at a given dose with an individual side effect response. Opioid Side Effects Nausea/constipation Sedation during titration (driving, work) Pruritis/sweats Dysphoria/psychotomietic effects Dry mouth/urinary retention Hyperalgesia/myoclonus Opioid-induced edema Hormonal effects Reflux symptoms (Immune dysfunction) Stable dose, titrated, scheduled, LTO does not cause clinically significant cognitive impairment: Hendler N. et al. Amer J Psychiatr 1980 Zacny JP. Exp Clin Psychopharmacol 1995 Vainio A. et al. Lancet 1996 Zacny JP. Addiction 1996 Lorenz J. et. al. Pain 1997 Haythornthwaite JA, et al. JPSM 1998 Sjogren P,et al. Pain; 2000 Galski T, et al. JPSM 2000 Chapman S. Clin J Pain 2002 Sabatowski R. et al. JPSM 2003 Tassain V. et al. Pain; 2003 Fishbain DA. Et al. JPSM 2003 The response to an excess of side effects vs. pain relief is to switch opioids Optimizing Opioid Therapy “In short, we need to move beyond inadequate trials of single opioids at fixed doses to sequential opioid trials, titration for individual patients, and management of side effects.” K. Foley, M.D. NEJM 2003; 348(26):2688-9 Treatment Goals Decrease pain Improve function Minimize adverse effects Opioids are not magic ! Not all pains in all patients will respond. Opioids have side effects - like any other medication High risk patients on therapeutic opioids can manifest abuse / addiction. Prescribed opioids can be diverted. We have a responsibility to society to prescribe and monitor carefully to minimize as much as possible the harm due to misuse and diversion BUT… Opioids are our most potent pain reliever They do not cause organ damage They are underutilized due to exaggerated fears of addiction One cannot predict response without a trial of therapy They work best as part of a multi-modal treatment approach “Men stumble over the truth from time to time, but most pick themselves up and hurry off as if nothing happened.” Winston Churchill
