Presentation on theme: "Managing chronic and breakthrough pain with opioid analgesics Rollin M. Gallagher, MD, MPH Clinical Professor of Psychiatry and Anesthesiology Director,"— Presentation transcript:
Managing chronic and breakthrough pain with opioid analgesics Rollin M. Gallagher, MD, MPH Clinical Professor of Psychiatry and Anesthesiology Director, Center for Pain Medicine, Research and Policy University of Pennsylvania School of Medicine Director of Pain Management Philadelphia Veteran Affairs Medical Center
PRINCIPLES OF TREATMENT: Summary Primary prevention: - avoid injuries and diseases Secondary prevention: - when injuries or diseases occur, prevent or minimize nociception or neural activation of pain pathways with specific, targeted interventions and restore and maintain function Tertiary prevention - manage perpetuating factors, control pain and restore function and quality of life
Challenges of Providing Chronic Pain Care Changing societal laws, customs, values, economies
Over 30 years a major shift occurred in opinion about the use of opioids for chronic pain 1) Emphasis on evidence, not opinion, in clinical medicine 2) Emphasis on cost-containment in managed systems: short-term solutions and cost-shifting 3) Documented clinical experience over several decades: - Cancer pain management - Rehabilitation of disabling back pain - Treatment of severe neuropathic pain (often failed back surgery)
Over 30 years a major shift occurred in opinion about the use of opioids for chronic pain 4) Recognition that: poorly controlled pain damages the nervous system and must be controlled pain as a chronic disease societal health burden of uncontrolled pain exceeds, many fold, the burden of prescription drug abuse 5) Recognition that opioids are: * well-tolerated by many * generally safe (e.g., motor function, driving,etc), compared to other medications for daily use for pain (e.g., in elderly)
7)The demonstration that NSAIDs and acetomenophen, and now Cox-IIs, are potentially dangerous 8)The recognition opioids are effective for pain diseases (e.g., neuropathic pain) 9)The recognition that use of opioids after painful injury may prevent chronic pain. (Secondary prevention) 10)The recognition that opioids for common chronically painful conditions in elderly may improve health outcomes Over 30 years a major shift occurred in opinion about the use of opioids for chronic pain
567 severe single extremity trauma patients Predictors of poor outcome before injury include: Alcohol abuse 1 month before injury (Marker, depression & substance abuse) Older age, lower education, low self efficacy (Gallagher et al Pain 1989) Predictors of poor outcome at 3 months post-injury Acute pain intensity, anxiety, depression and sleep disturbance DOES EARLY TREATMENT HELP?
Opioid protective effect Castillo et al Pain 124(2006), “Patients treated with narcotic medication for pain at three months post-discharge were protected against chronic pain, despite the fact that these patients had higher pain intensity levels and were thus at higher risk.” “The results presented here appear to lend support to the theory that…..early aggressive pain treatment may protect patients from central sensitization and chronic pain.” DID ANY PATIENTS DEVELOP: HYPERALGESIA? TOLERANCE? ADDICTION?
Opioid protective effect: Tertiary Prevention Study of 10,372 nursing home residents –patients appear to function better and more safely when taking opioids for pain –presumably because with better pain control, they are more ambulatory, stronger and less likely to fall Therefore, under clinical conditions where dosing and use is monitored, such as in the Won et al. J Gerontology. 2006; 61A(2):
EFFECTS OF THESE CHANGE IN PERSPECTIVE AND PRACTICE MODELS More opioids prescribed More patients obtaining pain relief More opioids in circulation The Opium Wars, circa 2006
Changes Opioid Prescribing Morphine143% Hydrocodone173% Fentanyl240% Methadone350% Oxycodone430% Meperidine-10% DEA ARCOS data
30% 20% 10% Percentage of U.S. Unintentional Drug Poisoning Deaths† from Opioid Analgesics, Cocaine, and Heroin, 1999 to 2002*
OUR CONUNDRUM Growing societal awareness of: 1. the prevalence of inadequately treated chronic pain 2. its impact on society 3. the need for access to effective pain treatment VS Growing societal awareness of: 1. The rapidly increasing rate of use of opioid prescriptions 2. The increasing rate of prescription drug abuse 3. The increasing rate of prescription drug abuse deaths
New York Times Magazine June 17, 2007, COVER STORY When Is a Pain Doctor a Drug Pusher? By TINA ROSENBERG
QUESTIONS 1)When should I consider treating chronic pain with opioid analgesics? 2)What should guide selection of a long- acting opioid in the treatment of chronic pain? 3)How do I titrate opioid medications and evaluate effectiveness?
QUESTIONS 4) When and how should methadone be used in the treatment of chronic pain? 5) Should use opioids to treat patients with chronic pain who also have a substance abuse history? 6) How should I use treatment agreements? 7)When should I consider stopping opioid therapy in a patient who has been on opioids chronically? How should this be done?
Medication selection in pain is based upon more than just pain severity * Diagnosis Efficacy –Clinical trial data Mechanisms of pain (s) Co morbidities: medical and psychiatric Prior treatment responses Side effect burden, toxicity risk, and the need to maintain function Gallagher RM, Verma S. Sem Neurosurg 2004; 15(1): Sindrup SH, Troels TS. Pain. 1999;83: Galer BS. Neurology. 1995;45(suppl 9):S17-S25.
Efficacy Comparison, Neuropathic Pain: Numbers Needed to Treat Analyses Capsaicin (Sindrup and Jensen, 1999) Gabapentin (Rice and Maton, 2001) Tricyclic Antidepressants (Raja et al, 2002) Opioids (Raja et al, 2002) Lidocaine Patch 5% (Meier et al, 2003) Gabapentin (Rowbotham et al, 1998) Drug or Therapeutic Class Number-needed-to-treat (NNT) Mean ±95% Cl Meier et al. Pain. 2003;106:151–158 ∞
Medication selection in pain is based upon more than just pain severity * Ease of use –dosing –titration –drug-drug interactions –patient acceptability Pain’s psychosocial context and the doctor-patient relationship: - stigma - cost - illness behavior - risk of treatment non-adherence - risk of medication misuse Gallagher RM, Verma S. Sem Neurosurg 2004; 15(1): Sindrup SH, Troels TS. Pain. 1999;83: Galer BS. Neurology. 1995;45(suppl 9):S17-S25.
Opioids have important advantages in the treatment of pain: Opioids relieve the subjective suffering component of pain, without interfering with basic sensation, such as light touch, pinprick, temperature, position. No ceiling effect Actions reversible with antagonists Patients often report: “The pain is still there, but it doesn’t bother me” Opioid Analgesics
What should guide selection of a long-acting opioid in the treatment of chronic pain? Identify the kind of pain: Nociceptive pain Neuropathic pain Visceral pain Myofascial pain Identify the pattern of the pain
Around-the-Clock Medication Breakthrough Pain Over Medication Persistent Pain Time What should guide selection of a long-acting opioid in the treatment of chronic pain? THE PATTERN
CHOOSING MEDICATION Expect partial effects Use multiple agents with different mechanisms: - from different classes - from the same class
Nociceptive pain Neuropathic pain Pain condition Secondary sleep disturbance Secondary depression Primary Depression Short-term NSAIDs, Cox-II (?), opioids Persists after adequate analgesia Evaluate risks Antihistamine, zolpidem, low-dose benzodiazepine Trazodone Low-dose TCA Lidocaine patch; gabapentin & other AED (Ca+ & Na+ channels); alpha 2 agonists (tizanidine, clonidine); opioids Titrate TCAs (Na+ channels and SNRI) : desipramine, nortriptyline, SSRI trial Evaluate risks SNRIs: venlafaxine, duloxetine Algorithm for Medication Selection in Chronic Pain with and without Co-Morbid Depression Gallagher RM, Verma S. Semin Clin Neurosurgery This information concerns uses that have not been approved by the US FDA. Evaluate risks
What should guide selection of a long-acting opioid in the treatment of chronic pain? Establish the goals of treatment: 1)Pain relief and reduced suffering 2)Improved functional capacity & QOL: -Physical functioning -Cognitive functioning -Social functioning -Role functioning To do what? To think about what? To be with and enjoy whom? To accomplish what?
Choices of LA opioid All preparations are mu opioid agonists. All opioids are effective. LA morphine: provides sustained serum levels of active morphine -Q 8-12 hours (MS Contin) -Q hours (Kadian) -Q 24 hours (Avinza) LA oxycodone (Oxycontin): Q 8-12 hours [now manufactured by two companies] Methadone Q 6-12 hours [also has NMDA effect specific for neuropathic pain] Transdermal fentanyl patch: Q hours
Variability Opioid Responsiveness Pain syndromes differ –Somatic versus neuropathic Different patients respond differently –Responsiveness may be genetically mediated Drugs may vary in specific activity –Evidence of sub-mu receptors emerging –Incomplete cross tolerance suggests variable sub-mu activities of different opioids
Genetic variability of morphine analgesia in Mouse Strains Strain Morphine (5 mg/kg) CD-176% Swiss Webster40% BALB/c90% C57/bg J 62% C57/+40% HS62% CXBK 0% Pasternak, G 2003
Opioid Analgesia in CD-1 and CXBK Mice CD-1 Analgesia (% of mice) *P <.004 **P <.001 Rossi GC, et al. Neurosci Lett. 1996;216:1-4. Morphine M6G Heroin, s.c. 6AcMor Morphine, s.c. (-)Methadone Fentanyl All drugs were given i.c.v., unless stated otherwise 6AcMor=6-acetylmorphine CXBK * ** Morphine Morphine, s.c. M6G Heroin, s.c. 6AcMor Fentanyl (-)Methadone Courtesy, G Pasternak 2006
Who is likely to do well on LA opioids? Level 3-4 evidence suggests that the following characteristics predict lower rates of aberrant behavior: Goal-directed, adherent to medical regimens, and functional Takes responsibility for health and multi- modality treatment Understands concepts in opioid use: tolerance, dependence (physical), addiction Bloodworth D, Am J Phys Med & Reh 2005(S);84(3):S64
Who is likely to do well on LA opioids? Level 3-4 evidence suggests that the following characteristics predict lower rates of aberrant behavior: Understands and accepts the need for treatment agreements Absence of severe, chronic psychopathology Absence of personality disorder Rarely overuses medication No illicit drug abuse or alcohol abuse Bloodworth D, Am J Phys Med & Reh 2005(S);84(3)
Which characteristics might predict that a patient might require more structure? 1)Aberrant Behavior: The Opioid Renewal Clinic: A structured approach to managing opioids for pain in primary care (Wiedemer et al PAIN MED 2007) 2) In pain and addiction co-morbidity, managing either addiction or chronic pain alone, without managing the other, is usually futile.
When and how should methadone be used in the treatment of chronic pain? Advantages over other LA opioids moderate NMDA (N-methyl-D-aspartate) receptor antagonist activity, such that in animal studies methadone attenuates the development of tolerance and hyperalgesia theoretically methadone may reduce wind-up and sensitization that leads to tolerance and dosing escalation in neuropathic pain Advantage over morphine lower potential for opioid-induced neurotoxicity lower mu-opioid-receptor affinity absence of active metabolites
Methadone Not prone to conversion to a SA opioid by crushing, as are LA morphine and oxycodone preparations Relatively graduated onset of action reduces the likelihood of a psychoactive effect.
Methadone’s disadvantages Stigmatization due to long association with the treatment of heroin addiction Inexactness of equivalency tables due to the variability of methadone metabolism: SAFETY ISSUE Interactions with other medications due to metabolism by the type I cytochrome P450 (CYP450) group of enzymes - fluoxetine directly inhibit CYP3A4, reducing elimination of methadone - venalafaxine has the lowest probability of interaction with methadone, only marginally inhibiting CYP1A2 May require three or four times daily dosing for pain control
Pharmacokinetic & Pharmacodynamic Properties Long and variable half-life (15 to 150 hours) Elimination half-life does not reflect duration of analgesia Onset of action 1-2 h Peak effect 3-4 h Steady state 5-7 days Analgesic effect - approx 6 to 8 hours
Points to consider regarding equianalgesic conversion ratios Due to inter-individual variability in hepatic metabolism of methadone and potential interactions with other meds: Equianalgesic conversion ratios are imprecise Contrary to logic, methadone appears to be more potent when changing from high doses of other opioids, thus there are dose dependent conversion ratios. Equianalgesic conversion ratio is only one factor in properly dosing methadone or any other opioid. Use the conversion table to get an idea of what the end point of titration might be. It is often lower but depends on many variables.
Dosing Strategies Overall strategy: start low and go slow Opioid naive or on low dose of current opioid –Stop current opioid –Start low : generally 2.5 to 5 mg –Start with one dose or BID on day one. –If tolerated increase to q 6 to 8 hours over the next 2 to 4 days, hold at this level for 5 to 7 days then start with the incremental increases as listed below. –Each 6 or 8 hourly dose may be increased by 2.5 to 5 mg increments every 5 to 7 days If the patient becomes sedated, hold increasing dose until tolerance to sedation develops Once adequate analgesia has been achieved, the same daily dose can be given in divided doses every 8 or 12 hours
Patient education highlights a. Explain that initial dose will often be inadequate for pain relief b. Reassure that the dose will be titrated to adequate analgesia c. Explain that analgesic effect of methadone will probably be felt toward the end of the first week d. Address the stigma of use in heroin addiction up front. Methadone was a pain medication before a heroin addiction medicine ! e. It is " different" than what is used for heroin addiction- it is a pill, not a liquid
Methadone and Torsade de Pointes Methadone is used daily by > 180,000 Americans. The literature reports 17 cases of torsades. Of the 17cases, 10 patients were on other contributing drugs and most were on doses > 100 mg/day.
Methadone and Torsade de Pointes Recommendations: Titrate methadone slowly; Monitor patient for dizziness, lightheadedness, palpitations. Monitor ECG in patients with risk factors (i.e. on medications that have torsades potential) DO NOT use in patients with: - Prolonged QT - Recent conversion from atrial fibrillation - Family history of sudden death
When to stop opioid in a patient If they have adverse reactions to opioids, such as depression or respiratory depression. If they do not achieve reasonable therapeutic goals such as improved physical or social functioning, even with effective pain relief.
When to stop opioid in a patient If they do not adhere to other prescribed treatment that is necessary for a desirable treatment outcome If they exhibit persistent aberrant behavior and are unable to responsibly manage opioids within the constraints of a treatment agreement. If they are diagnosed with an addiction disorder and refuse referral for its treatment.
How to taper opioids? 1)Discuss with the patient and other responsible persons who may be or helpful. 2)Reassure patient and SO of alternative plan for pain control. 3)Patients with aberrant behavior or addiction may refuse to comply and leave treatment, seeking opioids elsewhere. 4)Document discussions and provide a written treatment plan that is given to the patient.
How to taper opioids? 4) The speed depends on the clinical circumstances. A slow taper can be done by reducing the dose by 10 % every two weeks or even longer. A more rapid taper can be accomplished but may require additional medical management of withdrawal symptoms. 5) An alpha 2 agonist such as clonidine can be used to help medically stable patients manage withdrawal symptoms. Some advocate gabapentin as well.
How to taper opioids? 6) Patients and their significant others need to know what to expect – discomfort, anxiety, restlessness, nausea, sweating, etc. – but that controlled withdrawal from opioids is not dangerous in and of itself. 7) If the patient is taking a sedative or benzodiazepine, these should be maintained, as their withdrawal is more difficult and dangerous.
SUMMARY: Using opioids in pain medicine Generate: a)hypotheses about pain diagnosis and mechanisms b)a biopsychosocial formulation of pain c)Identify risk factors for opioid use Prioritize a problem list for each patient, identifying immediate, pivotal and background biopsychosocial problems. Use evidence-based algorithms to treat different types of pain Identify functional outcome goals for treatment
SUMMARY: Using opioids in pain medicine Gradually titrate short acting opioids to effects Replace with Long Acting Opioid to equivalent dose Provide limited amounts of Short Acting Opioids for breakthrough pain Train patient to use other behavioral and physical techniques to manage pain: -Ice -Stretch -TENS -Relaxation -Avoidance -Pacing
SUMMARY: Using opioids in pain medicine If one opioid not tolerated, or loses effectiveness, switch to another If switching to methadone, start very low and go slow, and be aware of drug interactions Be patient and don’t leave the patient short Empower and engage patient:
If I can stop one heart from breaking I shall not live in vain; If I can ease one life the aching Or cool one pain, Or help one fainting robin Unto his nest again, I shall not live in vain Emily Dickinson ABOVE ALL, MAINTAIN INTELLIGENT AND INFORMED EMPATHY – BE PATIENT
The Public Health Problem of Chronic Pain Causes – lack of societal & medical knowledge about chronic pain diseases and conditions primary prevention secondary prevention treatment – education and training deficits – social inequities in access to care – ineffective organizational models of care
Does our system of medical care play a role in creating difficult behavior in a patient with chronic pain ? TIME Inadequate Care >> Pain / Frustration Central sensitization >>Worsening pain >> LOSSES Frustration - Fear- Demoralization- Behavioral Changes Depression >> Worsening Pain
Categories of difficult behavior 1)NON-ADHERENT 2)ABERRANT ON OPIOIDS 3)ANGRY, DEMANDING 4)ENTITLED / VIP 5)PASSIVE 6)SEDUCTIVE
Causes of difficult behavior 1)Non-adherence to prescribed regimen Personality traits – manageable with structure and behavioral contracts Oppositional personality: “I’ll do it my way” Type A personality: “I must win at all costs” Dementia / delerium causing forgetfulness - manageable with environmental structure and support
The John Wayne Syndrome Bite the bullet Be tough Asking for painkillers is a sign of weakness Long-suffering hero “Holing up” Gastric CA in a tough guy
Causes of difficult behavior 1)Non-adherence to prescribed regimen Clinical syndromes causing disorganized behavior – treatable with meds and psychotherapies “Disorganized personality” – ADHD Clinical depression: major, minor, dysthymia Anxiety disorder: GAD, Panic
Causes of difficult behavior 2) ABERRANT BEHAVIOR ON OPIOIDS (early refill calls, lost prescriptions, etc) – behavioral agreements / contract Undertreated pain Tolerance Addiction Personality traits Psychiatric co-morbidities
The tertiary, sequential care model INJURY/SYMPTOM Emergency Services Primary Care Specialty Office #1 Specialty Office #2 Specialty Office #3 TREATMENT FAILURES Specialty Office #4 ALTERNATIVE TREATMENTS TIME (6) (5) Gallagher RM. Med Clin N Am 83(5): , CHASING THE SYMPTOM THROUGH A REDUCTIONISTIC, BIOMEDICAL MODEL
Cost vs Quality ResourceResourceResourceResource Quality of care Excess care Best practice
Pain medicine and primary care community rehabilitation model INJURY/SYMPTOM Emergency Services PrimaryCare: ClinicalAlgorithms Recurrent or persistent pain impairing function Integrated Pain Medicine Eval & Services: Med. trials, PT, Blocks, Behavioral mgmt. Sub-specialty Eval. & mgmt. Treatment Failure Multidisc- iplinary Pain Center (4) Community Support & Services (PT, OT, Voc, behavioral, pharmacy) Gallagher RM. Med Clin N Am 83(5): ,