A SUPPLEMENT TO THE JOURNAL OF FAMILY PRACTICE VOL 62, NO 6 • JUNE 2013

What to do when pain and addiction coexist

Polymyalgia rheumatica and : How best to approach these related diseases

CV1_06.13.indd 1 5/28/13 4:19 PM WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION, and ACCIDENTAL EXPOSURE

Abuse Potential OxyContin® contains oxycodone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit [see Warnings and Precautions (5.1)]. Assess each patient’s risk for opioid abuse or addiction prior to prescribing OxyContin. The risk for opioid abuse is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depressive disorder). Routinely monitor all patients receiving OxyContin for signs of misuse, abuse, and addiction during treatment [see Drug Abuse and Dependence (9)].

Life-Threatening Respiratory Depression Respiratory depression, including fatal cases, may occur with use of OxyContin, even when the drug has been used as recommended and not misused or abused [see Warnings and Precautions (5.2)]. Proper dosing and titration are essential and OxyContin should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. Monitor for respiratory depression, especially during initiation of OxyContin or following a dose increase. Instruct patients to swallow OxyContin tablets intact. Crushing, dissolving, or chewing the tablet can cause rapid release and absorption of a potentially fatal dose of oxycodone.

Accidental Exposure Accidental ingestion of OxyContin, especially in children, can result in a fatal overdose of oxycodone [see Warnings and Precautions (5.3)].

Indications and Usage OxyContin is indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. Limitations of Use OxyContin is not for use: • As an as-needed (prn) analgesic • For pain that is mild or not expected to persist for an extended period of time • For acute pain • I n the immediate postoperative period (the fi rst 24 hours following surgery) for patients not previously taking the drug, because its safety in this setting has not been established • For postoperative pain unless the patient is already receiving chronic opioid therapy prior to surgery, or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time OxyContin 60 mg and 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for patients in whom tolerance to an opioid of comparable potency is established. Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid for one week or longer. Contraindications OxyContin is contraindicated in patients with: • Signifi cant respiratory depression • Acute or severe bronchial in an unmonitored setting or in the absence of resuscitative equipment • Known or suspected paralytic ileus and gastrointestinal obstruction • (e.g., ) to oxycodone

Please read Brief Summary of Full Prescribing Information on the following pages, including Boxed Warning.

©2013 Purdue Pharma L.P., Stamford, CT 06901-3431 A8554-MEDD 4/13

IFC_CHPP_06_13.indd 2 5/17/13 10:59 AM For appropriate patients Medicare Part D coverage can help you meet your patients’ individual needs

To confi rm coverage on patients’ individual plans,

Not actual patients visit PurdueHCP.com/MedD

OxyContin is covered* for the majority† of Medicare Part D patients nationally, including major Part D plans such as: • UnitedHealthcare/AARP/ • Express Scripts Part D • Prime Therapeutics Part D Medicare Rx Preferred • Medco Part D

The preferred branded tier status of OxyContin may enable patients to obtain OxyContin at the lowest available branded co-pay‡ Inclusion on formulary does not imply superior clinical effi cacy or safety.

*Covered represents on formulary (on any tier, with or without restrictions) and may include quantity limits, prior authorizations, and/or step edit restrictions. †Majority is based on data indicating that OxyContin is covered for 63% of Medicare Part D lives nationally. Source: Fingertip Formulary®–database represents 95%-98% of commercial, Medicare, and Medicaid covered lives in the U.S. (4/1/13). Please check with the health plan directly to confi rm coverage for individual patients. Patient costs may vary among plans. ‡ Source: Fingertip Formulary®–database represents 95%-98% of commercial, Medicare, and Medicaid covered lives in the U.S. (4/1/13). Please check with the health plan directly to confi rm coverage for individual patients. Patient costs may vary among plans.

001_CHPP_06_13.indd 3 5/17/13 10:59 AM nists, depending on the patient’s clinical status [see Overdosage (10)]. the medication. 5.14 Cytochrome P450 3A4 Inhibitors and Inducers While serious, life-threatening, or fatal respiratory depression can occur at 4JODFUIF$:1"JTPFO[ZNFQMBZTBNBKPSSPMFJOUIFNFUBCPMJTNPG any time during the use of OxyContin, the risk is greatest during the initiation 0YZ$POUJO ESVHTUIBUBMUFS$:1"BDUJWJUZNBZDBVTFDIBOHFTJODMFBSBODF of therapy or following a dose increase. Closely monitor patients for respira- of oxycodone which could lead to changes in oxycodone plasma concentra- tory depression when initiating therapy with OxyContin and following dose UJPOT*OIJCJUJPOPG$:1"BDUJWJUZCZJUTJOIJCJUPST TVDIBTNBDSPMJEF 10 mg l 15 mg l 20 mg l 30 mg increases. Instruct patients against use by individuals other than the patient antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), for whom OxyContin was prescribed and to keep OxyContin out of the reach and protease inhibitors (e.g., ritonavir), may increase plasma concentrations 40 mg l 60 mg* l 80 mg* of children, as such inappropriate use may result in fatal respiratory depres- PGPYZDPEPOFBOEQSPMPOHPQJPJEFGGFDUT$:1JOEVDFST TVDIBTSJGBNQJO  sion. To reduce the risk of respiratory depression, proper dosing and titration carbamazepine, and phenytoin, may induce the metabolism of oxycodone *60 mg and 80 mg tablets of OxyContin are essential [see Dosage and Administration (2)]. and, therefore, may cause increased clearance of the drug which could lead for use in opioid-tolerant Overestimating the OxyContin dose when converting patients from another to a decrease in oxycodone plasma concentrations, lack of efficacy or, patients only opioid product can result in fatal overdose with the first dose. Respiratory possibly, development of an abstinence syndrome in a patient who had depression has also been reported with use of modified-release opioids developed physical dependence to oxycodone. If co-administration is when used as recommended and not misused or abused. To further reduce necessary, caution is advised when initiating OxyContin treatment in patients UIFSJTLPGSFTQJSBUPSZEFQSFTTJPO DPOTJEFSUIFGPMMPXJOHt1SPQFSEPTJOH DVSSFOUMZUBLJOH PSEJTDPOUJOVJOH $:1"JOIJCJUPSTPSJOEVDFST&WBMVBUF BRIEF SUMMARY OF PRESCRIBING INFORMATION (For complete details and titration are essential and OxyContin should only be prescribed by these patients at frequent intervals and consider dose adjustments until please see the Full Prescribing Information and Medication Guide.) healthcare professionals who are knowledgeable in the use of potent opioids stable drug effects are achieved [see Drug Interactions (7.3), and Clinical GPSUIFNBOBHFNFOUPGDISPOJDQBJOt0YZ$POUJONHBOENHUBCMFUT Pharmacology (12.3)]. 5.15 Laboratory Monitoring Not every urine drug WARNING: ABUSE POTENTIAL, LIFE-THREATENING are for use in opioid-tolerant patients only. Ingestion of these strengths of test for “opioids” or “opiates” detects oxycodone reliably, especially those RESPIRATORY DEPRESSION, and ACCIDENTAL EXPOSURE OxyContin tablets may cause fatal respiratory depression when administered designed for in-office use. Further, many laboratories will report urine drug UPQBUJFOUTOPUBMSFBEZUPMFSBOUUPIJHIEPTFTPGPQJPJETtInstruct patients concentrations below a specified “cut-off” value as “negative”. Therefore, if Abuse Potential to swallow OxyContin tablets intact. The tablets are not to be crushed, urine testing for oxycodone is considered in the clinical management of an OxyContin® contains oxycodone, an opioid agonist and Schedule dissolved, or chewed. The resulting oxycodone dose may be fatal, individual patient, ensure that the sensitivity and specificity of the assay is II controlled substance with an abuse liability similar to other particularly in opioid-naïve individuals. t0YZ$POUJOJTDPOUSBJOEJDBUFE appropriate, and consider the limitations of the testing used when interpret- opioid agonists, legal or illicit [see Warnings and Precautions in patients with respiratory depression and in patients with conditions that ing results. (5.1)]. Assess each patient’s risk for opioid abuse or addic- increase the risk of life-threatening respiratory depression [see 6 ADVERSE REACTIONS The following adverse reactions described else- tion prior to prescribing OxyContin. The risk for opioid abuse Contraindications (4)]. 5.3 Accidental Exposure Accidental ingestion of XIFSFJOUIFMBCFMJOHJODMVEFt3FTQJSBUPSZEFQSFTTJPO[see Boxed Warning, is increased in patients with a personal or family history of OxyContin, especially in children, can result in a fatal overdose of oxycodone. substance abuse (including drug or alcohol abuse or addiction) Warnings and Precautions (5.2, 5.5), and Overdosage (10)]t$/4EFQSFT- 5.4 Elderly, Cachectic, and Debilitated Patients Respiratory depression sion [see Drug Interactions (7.1), and Overdosage (10)] t)ZQPUFOTJWF or mental illness (e.g., major depressive disorder). Routinely is more likely to occur in elderly, cachectic, or debilitated patients as they monitor all patients receiving OxyContin for signs of misuse, effects [see Warnings and Precautions (5.7), and Overdosage (10)]t%SVH may have altered pharmacokinetics or altered clearance compared to abuse, addiction, and dependence [see Drug Abuse and Dependence (9.2, abuse, and addiction during treatment [see Drug Abuse and younger, healthier patients. Therefore, monitor such patients closely, par- 9.3)] [see Warnings and Precautions (5.9, 5.10)] Dependence (9)]. ticularly when initiating and titrating OxyContin and when OxyContin is given t(BTUSPJOUFTUJOBM&GGFDUT [see Warnings and Precautions (5.11)] 6.1 Clinical Trial Life-Threatening Respiratory Depression concomitantly with other drugs that depress respiration [see Warnings and t4FJ[VSFT Experience Because clinical trials are conducted under widely varying Respiratory depression, including fatal cases, may occur Precautions (5.2)]. 5.5 Use in Patients with Chronic Pulmonary conditions, adverse reaction rates observed in the clinical trials of a drug with use of OxyContin, even when the drug has been used as Disease Monitor patients with significant chronic obstructive pulmonary cannot be directly compared to rates in the clinical trials of another drug and recommended and not misused or abused [see Warnings and disease or cor pulmonale, and patients having a substantially decreased may not reflect the rates observed in practice. The safety of OxyContin was respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depres- Precautions (5.2)]. Proper dosing and titration are essential and FWBMVBUFEJOEPVCMFCMJOEDMJOJDBMUSJBMTJOWPMWJOHQBUJFOUTXJUINPEFSBUF OxyContin should be prescribed only by healthcare profession- sion for respiratory depression, particularly when initiating therapy and to severe pain of various etiologies. In open-label studies of cancer pain, titrating with OxyContin, as in these patients, even usual therapeutic doses als who are knowledgeable in the use of potent opioids for the QBUJFOUTSFDFJWFE0YZ$POUJOJOUPUBMEBJMZEPTFTSBOHJOHGSPNNH of OxyContin may decrease respiratory drive to the point of apnea [see management of chronic pain. Monitor for respiratory depres- UPNHQFSEBZ5IFBWFSBHFUPUBMEBJMZEPTFXBTBQQSPYJNBUFMZ sion, especially during initiation of OxyContin or following a dose Warnings and Precautions (5.2)]. Consider the use of alternative non-opioid mg per day. OxyContin may increase the risk of serious adverse reactions increase. Instruct patients to swallow OxyContin tablets intact. analgesics in these patients if possible. 5.6 Interactions with Alcohol, such as those observed with other opioid analgesics, including respiratory Crushing, dissolving, or chewing the tablet can cause rapid CNS Depressants, and Illicit Drugs )ZQPUFOTJPO BOEQSPGPVOETFEBUJPO  depression, apnea, respiratory arrest, circulatory depression, hypotension, or coma or respiratory depression may result if OxyContin is used concomi- release and absorption of a potentially fatal dose of oxycodone. shock [see Overdosage (10)]. 5IFNPTUDPNNPOBEWFSTFSFBDUJPOT   Accidental Exposure tantly with other CNS depressants (e.g., sedatives, anxiolytics, hypnotics, reported by patients in clinical trials comparing OxyContin with placebo are Accidental ingestion of OxyContin, especially in children, can neuroleptics, muscle relaxants, other opioids). When considering the use shown in Table 1 below: of OxyContin in a patient taking a CNS depressant, assess the duration of result in a fatal overdose of oxycodone [see Warnings and use of the CNS depressant and the patient’s response, including the degree TABLE 1: Common Adverse Reactions (>5%) Precautions (5.3)]. of tolerance that has developed to CNS depression. Additionally, consider Adverse OxyContin Placebo the patient’s use, if any, of alcohol and/or illicit drugs that can cause CNS Reaction (n=227) (n=45) 1 INDICATIONS AND USAGE OxyContin is indicated for the management depression. If OxyContin therapy is to be initiated in a patient taking a CNS of moderate to severe pain when a continuous, around-the-clock opioid depressant, start with a lower OxyContin dose than usual and monitor patients (%) (%) analgesic is needed for an extended period of time. Limitations of Use for signs of sedation and respiratory depression and consider using a lower 0YZ$POUJOJTOPUGPSVTFt"TBOBTOFFEFE QSO BOBMHFTJDt'PSQBJOUIBU dose of the concomitant CNS depressant [see Drug Interactions (7.1)]. 5.7 $POTUJQBUJPO    JTNJMEPSOPUFYQFDUFEUPQFSTJTUGPSBOFYUFOEFEQFSJPEPGUJNFt'PSBDVUF Hypotensive Effects OxyContin may cause severe hypotension including /BVTFB    QBJOt*OUIFJNNFEJBUFQPTUPQFSBUJWFQFSJPE UIFGJSTUIPVSTGPMMPXJOH orthostatic hypotension and syncope in ambulatory patients. There is an surgery) for patients not previously taking the drug, because its safety in increased risk in patients whose ability to maintain blood pressure has 4PNOPMFODF    UIJTTFUUJOHIBTOPUCFFOFTUBCMJTIFEt'PSQPTUPQFSBUJWFQBJOVOMFTTUIF already been compromised by a reduced blood volume or concurrent %J[[JOFTT    patient is already receiving chronic opioid therapy prior to surgery, or if the administration of certain CNS depressant drugs (e.g., phenothiazines or postoperative pain is expected to be moderate to severe and persist for an general anesthetics) [see Drug Interactions (7.1)]. Monitor these patients 1SVSJUVT    extended period of time. OxyContin 60 mg and 80 mg tablets, a single dose for signs of hypotension after initiating or titrating the dose of OxyContin. In 7PNJUJOH    HSFBUFSUIBONH PSBUPUBMEBJMZEPTFHSFBUFSUIBONHBSFPOMZGPS patients with circulatory shock, OxyContin may cause vasodilation that can patients in whom tolerance to an opioid of comparable potency is estab- further reduce cardiac output and blood pressure. Avoid the use of OxyContin )FBEBDIF    lished. Patients considered opioid tolerant are those who are taking at least in patients with circulatory shock. 5.8 Use in Patients with Head Injury %SZ.PVUI    NHPSBMNPSQIJOFEBZ NDHUSBOTEFSNBMGFOUBOZMIPVS NHPSBM or Increased Intracranial Pressure Monitor patients taking OxyContin PYZDPEPOFEBZ NHPSBMIZESPNPSQIPOFEBZ NHPSBMPYZNPSQIPOF Asthenia (6) — who may be susceptible to the intracranial effects of CO retention (e.g., day, or an equianalgesic dose of another opioid for one week or longer. those with evidence of increased intracranial pressure or brain tumors) for 4XFBUJOH    4 CONTRAINDICATIONS OxyContin is contraindicated in patients with: signs of sedation and respiratory depression, particularly when initiating t4JHOJGJDBOUSFTQJSBUPSZEFQSFTTJPOt"DVUFPSTFWFSFCSPODIJBMBTUINB therapy with OxyContin. OxyContin may reduce respiratory drive, and the In clinical trials, the following adverse reactions were reported in in an unmonitored setting or in the absence of resuscitative equipment resultant CO retention can further increase intracranial pressure. Opioids QBUJFOUTUSFBUFEXJUI0YZ$POUJOXJUIBOJODJEFODFCFUXFFOBOE t,OPXOPSTVTQFDUFEQBSBMZUJDJMFVTBOEHBTUSPJOUFTUJOBMPCTUSVD- may also obscure the clinical course in a patient with a head injury. Avoid Gastrointestinal disorders: abdominal pain, diarrhea, dyspepsia, gastritis UJPOt)ZQFSTFOTJUJWJUZ FH BOBQIZMBYJT UPPYZDPEPOF [see Adverse the use of OxyContin in patients with impaired consciousness or coma. 5.9 General disorders and administration site conditions: chills, Reactions (6.2)] Difficulty in Swallowing and Risk for Obstruction in Patients at Risk Metabolism and nutrition disorders: anorexia Musculoskeletal and for a Small Gastrointestinal Lumen There have been post-marketing 5 WARNINGS AND PRECAUTIONS 5.1 Abuse Potential OxyContin connective tissue disorders: twitching Psychiatric disorders: abnormal reports of difficulty in swallowing OxyContin tablets. These reports included contains oxycodone, an opioid agonist and a Schedule II controlled sub- dreams, anxiety, confusion, dysphoria, euphoria, insomnia, nervousness, choking, gagging, regurgitation and tablets stuck in the throat. Instruct stance. Oxycodone can be abused in a manner similar to other opioid thought abnormalities Respiratory, thoracic and mediastinal disor- patients not to pre-soak, lick or otherwise wet OxyContin tablets prior to agonists legal or illicit. Opioid agonists are sought by drug abusers and ders: dyspnea, hiccups Skin and subcutaneous tissue disorders: rash placing in the mouth, and to take one tablet at a time with enough water to people with addiction disorders and are subject to criminal diversion. Vascular disorders: postural hypotension The following adverse reactions ensure complete swallowing immediately after placing in the mouth. There Consider these risks when prescribing or dispensing OxyContin in situations occurred in less than 1% of patients involved in clinical trials: Blood have been rare post-marketing reports of cases of intestinal obstruction, and where there is concern about increased risks of misuse, abuse, or diversion. and lymphatic system disorders: lymphadenopathy Ear and labyrinth exacerbation of diverticulitis, some of which have required medical interven- Concerns about abuse, addiction, and diversion should not, however, prevent disorders: Eye disorders: abnormal vision Gastrointestinal tion to remove the tablet. Patients with underlying GI disorders such as the proper management of pain. Assess each patient’s risk for opioid abuse disorders: dysphagia, eructation, flatulence, gastrointestinal disorder, esophageal cancer or colon cancer with a small gastrointestinal lumen are or addiction prior to prescribing OxyContin. The risk for opioid abuse is increased appetite, stomatitis General disorders and administration at greater risk of developing these complications. Consider use of an increased in patients with a personal or family history of substance abuse site conditions: withdrawal syndrome (with and without seizures), edema, alternative analgesic in patients who have difficulty swallowing and patients (including drug or alcohol abuse or addiction) or mental illness (e.g., major peripheral edema, thirst, malaise, chest pain, facial edema Injury, poisoning at risk for underlying GI disorders resulting in a small gastrointestinal lumen. depression). Patients at increased risk may still be appropriately treated and procedural complications: accidental injury Investigations: ST 5.10 Use in Patients with Gastrointestinal Conditions OxyContin is with modified-release opioid formulations; however these patients will depression Metabolism and nutrition disorders: dehydration Nervous contraindicated in patients with GI obstruction, including paralytic ileus. The require intensive monitoring for signs of misuse, abuse, or addiction. system disorders: syncope, , abnormal gait, amnesia, hyperkinesia, oxycodone in OxyContin may cause spasm of the sphincter of Oddi. Monitor Routinely monitor all patients receiving opioids for signs of misuse, abuse, hypesthesia, hypotonia, paresthesia, speech disorder, stupor, tremor, vertigo, patients with biliary tract disease, including acute pancreatitis, for worsening and addiction because these drugs carry a risk for addiction even under symptoms. Opioids may cause increases in the serum amylase. 5.11 Use taste perversion Psychiatric disorders: depression, agitation, deperson- appropriate medical use. Misuse or abuse of OxyContin by crushing, chew- in Patients with Convulsive or Seizure Disorders The oxycodone in alization, emotional lability, hallucination Renal and urinary disorders: ing, snorting, or injecting the dissolved product will result in the uncontrolled OxyContin may aggravate convulsions in patients with convulsive disorders, dysuria, hematuria, polyuria, urinary retention Reproductive system and delivery of the opioid and pose a significant risk that could result in overdose and may induce or aggravate seizures in some clinical settings. Monitor breast disorders: impotence Respiratory, thoracic and mediastinal and death [see Drug Abuse and Dependence (9), and Overdosage (10)]. patients with a history of seizure disorders for worsened seizure control disorders: cough increased, voice alteration Skin and subcutaneous tissue Contact local state professional licensing board or state controlled sub- during OxyContin therapy. 5.12 Avoidance of Withdrawal Avoid the use disorders: dry skin, exfoliative dermatitis 6.2 Postmarketing Experience stances authority for information on how to prevent and detect abuse or of mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and The following adverse reactions have been identified during post-approval use diversion of this product. 5.2 Life-Threatening Respiratory Depression butorphanol) in patients who have received or are receiving a course of of controlled-release oxycodone: abuse, addiction, amenorrhea, cholestasis, Respiratory depression is the chief hazard of opioid agonists, including therapy with a full opioid agonist analgesic, including OxyContin. In these death, dental caries, increased hepatic enzymes, hyperalgesia, hyponatremia, OxyContin. Respiratory depression if not immediately recognized and patients, mixed agonist/antagonist analgesics may reduce the analgesic ileus, muscular hypertonia, overdose, palpitations (in the context of with- treated, may lead to respiratory arrest and death. Respiratory depression effect and/or may precipitate withdrawal symptoms. When discontinuing drawal), seizures, syndrome of inappropriate antidiuretic hormone secretion, from opioids is manifested by a reduced urge to breathe and a decreased OxyContin, gradually taper the dose [see Dosage and Administration (2.4)]. and urticaria. Anaphylaxis has been reported with ingredients contained in rate of respiration, often associated with a “sighing” pattern of breathing Do not abruptly discontinue OxyContin. 5.13 Driving and Operating OxyContin. Advise patients how to recognize such a reaction and when to (deep breaths separated by abnormally long pauses). Carbon dioxide (CO )  Machinery seek medical attention. In addition to the events listed above, the following retention from opioid-induced respiratory depression can exacerbate the OxyContin may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating have also been reported, potentially due to the swelling and hydrogelling sedating effects of opioids. Management of respiratory depression may property of the tablet: choking, gagging, regurgitation, tablets stuck in the include close observation, supportive measures, and use of opioid antago- machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of OxyContin and know how they will react to throat and difficulty swallowing the tablet.

002_CHPP_06_13.indd 2 5/17/13 11:00 AM 7 DRUG INTERACTIONS 7.1 CNS Depressants Concurrent use of tablets. Thus, the usual doses and dosing intervals may be appropriate for undesired effects of drugs, and may develop at different rates for different OxyContin and other central nervous system (CNS) depressants including FMEFSMZQBUJFOUT)PXFWFS SFEVDFUIFTUBSUJOHEPTFUPUPUIFVTVBM effects. Physical dependence results in withdrawal symptoms after abrupt sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, dosage in debilitated, non-opioid-tolerant patients. Respiratory depression discontinuation or a significant dose reduction of a drug. Withdrawal also may and alcohol can increase the risk of respiratory depression, hypotension, is the chief risk in elderly or debilitated patients, usually the result of large be precipitated through the administration of drugs with opioid antagonist profound sedation or coma. Monitor patients receiving CNS depressants initial doses in patients who are not tolerant to opioids, or when opioids are activity, e.g., naloxone, nalmefene, or mixed agonist/antagonist analgesics and OxyContin for signs of respiratory depression and hypotension. When given in conjunction with other agents that depress respiration. Titrate the (pentazocine, butorphanol, nalbuphine). Physical dependence may not TVDIDPNCJOFEUIFSBQZJTDPOUFNQMBUFE TUBSU0YZ$POUJOBUUP dose of OxyContin cautiously in these patients. 8.6 Hepatic Impairment A occur to a clinically significant degree until after several days to weeks of of the usual dosage and consider using a lower dose of the concomitant study of OxyContin in patients with hepatic impairment demonstrated greater continued opioid usage. OxyContin should not be abruptly discontinued [see CNS depressant. 7.2 Muscle Relaxants Oxycodone may enhance the plasma concentrations than those seen at equivalent doses in persons with Dosage and Administration (2.4)]. If OxyContin is abruptly discontinued in a neuromuscular blocking action of true skeletal muscle relaxants and produce normal hepatic function. Therefore, in the setting of hepatic impairment, physically-dependent patient, an abstinence syndrome may occur. Some or an increased degree of respiratory depression. Monitor patients receiving TUBSUEPTJOHQBUJFOUTBUUPUIFVTVBMTUBSUJOHEPTFGPMMPXFECZDBSFGVM all of the following can characterize this syndrome: restlessness, lacrimation, muscle relaxants and OxyContin for signs of respiratory depression that may be dose titration [see Clinical Pharmacology (12.3)]. 8.7 Renal Impairment rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs greater than otherwise expected. 7.3 Agents Affecting Cytochrome P450 In patients with renal impairment, as evidenced by decreased creatinine and symptoms also may develop, including: irritability, anxiety, backache, joint Isoenzymes Inhibitors of CYP3A4 $PBENJOJTUSBUJPOPGBTUSPOH$:1" clearance (<60 mL/min), the concentrations of oxycodone in the plasma are pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, inhibitor ketoconazole, with OxyContin, significantly increased the plasma BQQSPYJNBUFMZIJHIFSUIBOJOTVCKFDUTXJUIOPSNBMSFOBMGVODUJPO'PMMPX diarrhea, or increased blood pressure, respiratory rate, or heart rate. Infants DPODFOUSBUJPOTPGPYZDPEPOF*OIJCJUJPOPG$:1"BDUJWJUZCZJUTJOIJCJUPST  a conservative approach to dose initiation and adjust according to the clinical born to mothers physically dependent on opioids will also be physically such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents situation [see Clinical Pharmacology (12.3)]. 8.8 Gender Differences In dependent and may exhibit respiratory difficulties and withdrawal signs [see (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may prolong pharmacokinetic studies with OxyContin, opioid-naïve females demonstrate Use in Specific Populations (8.9)]. opioid effects. If co-administration is necessary, caution is advised when VQUPIJHIFSBWFSBHFQMBTNBDPODFOUSBUJPOTBOEHSFBUFSGSFRVFODZPG 10 OVERDOSAGE Clinical Presentation Acute overdosage with OxyContin JOJUJBUJOHUIFSBQZXJUI DVSSFOUMZUBLJOH PSEJTDPOUJOVJOH$:1"JOIJCJUPST typical opioid adverse events than males, even after adjustment for body can be manifested by respiratory depression, somnolence progressing to Evaluate these patients at frequent intervals and consider dose adjustments weight. The clinical relevance of a difference of this magnitude is low for stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted until stable drug effects are achieved [see Clinical Pharmacology (12.3)]. a drug intended for chronic usage at individualized dosages, and there was pupils, and in some cases, pulmonary edema, bradycardia, hypotension, Inducers of CYP3A4 A published study showed that the co-administration no male/female difference detected for efficacy or adverse events in clinical partial or complete airway obstruction, atypical snoring and death. Marked of rifampin, a drug metabolizing enzyme inducer, significantly decreased trials. 8.9 Neonatal Opioid Withdrawal Syndrome Chronic maternal mydriasis rather than miosis may be seen due to severe hypoxia in overdose use of oxycodone during pregnancy can affect the fetus with subsequent QMBTNBPYZDPEPOFDPODFOUSBUJPOT$:1JOEVDFST TVDIBTSJGBNQJO  situations. Treatment of Overdose In case of overdose, priorities are the withdrawal signs. Neonatal withdrawal syndrome presents as irritability, carbamazepine, and phenytoin, may induce the metabolism of oxycodone reestablishment of a patent and protected airway and institution of assisted or hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomit- and, therefore, may cause increased clearance of the drug which could controlled ventilation if needed. Employ other supportive measures (including ing, diarrhea and failure to gain weight. The onset, duration and severity of lead to a decrease in oxycodone plasma concentrations, lack of efficacy oxygen, vasopressors) in the management of circulatory shock and pulmonary neonatal withdrawal syndrome vary based on the drug used, duration of use, or, possibly, development of an abstinence syndrome in a patient who had edema as indicated. Cardiac arrest or arrhythmias will require advanced life the dose of last maternal use, and rate of elimination of drug by the newborn. developed physical dependence to oxycodone. If co-administration with support techniques. The opioid antagonists, naloxone or nalmefene, are Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in OxyContin is necessary, caution is advised when initiating therapy with, specific antidotes to respiratory depression resulting from opioid overdose. adults, may be life-threatening and should be treated according to protocols DVSSFOUMZUBLJOH PSEJTDPOUJOVJOH$:1"JOEVDFST&WBMVBUFUIFTFQBUJFOUT Opioid antagonists should not be administered in the absence of clinically developed by neonatology experts. at frequent intervals and consider dose adjustments until stable drug effects significant respiratory or circulatory depression secondary to oxycodone are achieved [see Clinical Pharmacology (12.3)]. Inhibitors of CYP2D6 9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance OxyContin overdose. Such agents should be administered cautiously to persons who 0YZDPEPOFJTNFUBCPMJ[FEJOQBSUUPPYZNPSQIPOFWJB$:1%8IJMFUIJT contains oxycodone, a Schedule II controlled substance with a high potential are known, or suspected to be physically dependent on OxyContin. In such pathway may be blocked by a variety of drugs such as certain cardiovascular for abuse similar to other opioids including fentanyl, hydromorphone, metha- cases, an abrupt or complete reversal of opioid effects may precipitate an acute drugs (e.g., quinidine) and antidepressants (e.g., fluoxetine), such blockade done, morphine, and oxymorphone. OxyContin can be abused and is subject withdrawal syndrome. Because the duration of reversal would be expected has not been shown to be of clinical significance during oxycodone treat- to misuse, addiction, and criminal diversion [see Warnings and Precautions to be less than the duration of action of oxycodone in OxyContin, carefully NFOU)PXFWFS DMJOJDJBOTTIPVMECFBXBSFPGUIJTQPTTJCMFJOUFSBDUJPO7.4 (5.1)]. The high drug content in extended-release formulations adds to the monitor the patient until spontaneous respiration is reliably reestablished. Mixed Agonist/Antagonist Opioid Analgesics Mixed agonist/antagonist risk of adverse outcomes from abuse and misuse. 9.2 Abuse Abuse of OxyContin will continue to release oxycodone and add to the oxycodone load analgesics (i.e., pentazocine, nalbuphine, and butorphanol) should generally OxyContin poses a hazard of overdose and death. This risk is increased GPSUPIPVSTPSMPOHFSGPMMPXJOHJOHFTUJPOOFDFTTJUBUJOHQSPMPOHFE not be administered to a patient who has received or is receiving a course with compromising the tablet and with concurrent abuse of alcohol or other monitoring. If the response to opioid antagonists is suboptimal or not of therapy with a pure opioid agonist analgesic such as OxyContin. In this substances. All patients treated with opioids require careful monitoring for sustained, additional antagonist should be administered as directed in the situation, mixed agonist/antagonist analgesics may reduce the analgesic effect signs of abuse and addiction, since use of opioid analgesic products carries product’s prescribing information. In an individual physically dependent on of oxycodone and may precipitate withdrawal symptoms in these patients. the risk of addiction even under appropriate medical use. Drug addiction is opioids, administration of the usual dose of the antagonist will precipitate 7.5 Diuretics Opioids can reduce the efficacy of diuretics by inducing the a treatable disease, utilizing a multidisciplinary approach, but relapse is an acute withdrawal syndrome. The severity of the withdrawal symptoms release of antidiuretic hormone. Opioids may also lead to acute retention common. Drug abuse is the intentional non-therapeutic use of an over-the- experienced will depend on the degree of physical dependence and the of urine by causing spasm of the sphincter of the bladder, particularly in counter or prescription drug, even once, for its rewarding psychological or dose of the antagonist administered. If a decision is made to treat serious men with enlarged prostates. 7.6 Anticholinergics Anticholinergics or physiological effects. Drug abuse includes, but is not limited to, the following respiratory depression in the physically dependent patient, administration of other medications with anticholinergic activity when used concurrently with examples: the use of a prescription or over-the-counter drug to get “high”, or the antagonist should be begun with care and by titration with smaller than opioid analgesics may result in increased risk of urinary retention and/or the use of steroids for performance enhancement and muscle build up. Drug usual doses of the antagonist. severe constipation, which may lead to paralytic ileus. Monitor patients for addiction is a cluster of behavioral, cognitive, and physiological phenomena signs of urinary retention or reduced gastric motility when OxyContin is used CAUTION that develop after repeated substance use and include: a strong desire to DEA FORM REQUIRED concurrently with anticholinergic drugs. take the drug, difficulties in controlling its use, persisting in its use despite 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category B harmful consequences, a higher priority given to drug use than to other 17 PATIENT COUNSELING INFORMATION See FDA-approved patient There are no adequate and well-controlled studies of oxycodone use dur- activities and obligations, increased tolerance, and sometimes a physical labeling (Medication Guide) Abuse Potential Inform patients that OxyContin ing pregnancy. Based on limited human data in the literature, oxycodone withdrawal. “Drug-seeking” behavior is very common to addicts and drug contains oxycodone, a Schedule II controlled substance that is subject to does not appear to increase the risk of congenital malformations. In animal abusers. Drug-seeking tactics include emergency calls or visits near the end abuse. Instruct patients not to share OxyContin with others and to take steps reproduction and developmental toxicology studies, no evidence of fetal of office hours, refusal to undergo appropriate examination, testing or referral, to protect OxyContin from theft or misuse. Life-Threatening Respiratory harm was observed. Because animal reproduction studies are not always repeated claims of loss of prescriptions, tampering with prescriptions and Depression Discuss the risk of respiratory depression with patients, predictive of human response, oxycodone should be used during pregnancy reluctance to provide prior medical records or contact information for other explaining that the risk is greatest when starting OxyContin or when the only if clearly needed. Teratogenic Effects The effect of oxycodone in human treating physician(s). “Doctor shopping” (visiting multiple prescribers) to dose is increased. Advise patients how to recognize respiratory depression reproduction has not been adequately studied. Studies with oral doses of obtain additional prescriptions is common among drug abusers and people and to seek medical attention if they are experiencing breathing difficul- PYZDPEPOFIZESPDIMPSJEFJOSBUTVQUPNHLHEBZBOESBCCJUTVQUP suffering from untreated addiction. Preoccupation with achieving adequate ties. Accidental Exposure Instruct patients to take steps to store OxyContin NHLHEBZ FRVJWBMFOUUPBOEUJNFTBOBEVMUIVNBOEPTFPGNH pain relief can be appropriate behavior in a patient with poor pain control. securely. Accidental exposure, especially in children, may result in serious day, respectively on a mg/m basis, did not reveal evidence of harm to the Abuse and addiction are separate and distinct from physical dependence and harm or death. Advise patients to dispose of unused OxyContin by flushing fetus due to oxycodone. In a pre- and postnatal toxicity study, female rats tolerance. Physicians should be aware that addiction may not be accom- the tablets down the toilet. Risks from Concomitant Use of Alcohol and other received oxycodone during gestation and lactation. There were no long-term panied by concurrent tolerance and symptoms of physical dependence in CNS Depressants Inform patients that the concomitant use of alcohol with developmental or reproductive effects in the pups [see Nonclinical Toxicology all addicts. In addition, abuse of opioids can occur in the absence of true OxyContin can increase the risk of life-threatening respiratory depression. (13.1)]. Non-Teratogenic Effects Oxycodone hydrochloride was administered addiction. OxyContin, like other opioids, can be diverted for non-medical Instruct patients not to consume alcoholic beverages, as well as prescription orally to female rats during gestation and lactation in a pre- and postnatal use into illicit channels of distribution. Careful recordkeeping of prescribing and over-the-counter drug products that contain alcohol, during treatment toxicity study. There were no drug-related effects on reproductive performance information, including quantity, frequency, and renewal requests as required with OxyContin. Inform patients that potentially serious additive effects may in these females or any long-term developmental or reproductive effects in by state law, is strongly advised. Proper assessment of the patient, proper occur if OxyContin is used with other CNS depressants, and not to use such pups born to these rats. Decreased body weight was found during lactation prescribing practices, periodic reevaluation of therapy, and proper dispensing drugs unless supervised by a health care provider. Important Administration and the early post-weaning phase in pups nursed by mothers given the high- and storage are appropriate measures that help to reduce abuse of opioid Instructions Instruct patients how to properly take OxyContin, including the FTUEPTFVTFE NHLHEBZ FRVJWBMFOUUPBQQSPYJNBUFMZUJNFTBOBEVMU drugs. Risks Specific to Abuse of OxyContin OxyContin is for oral use only. GPMMPXJOHt0YZ$POUJOJTEFTJHOFEUPXPSLQSPQFSMZPOMZJGTXBMMPXFEJOUBDU human dose of 160 mg/day, on a mg/mCBTJT )PXFWFS CPEZXFJHIUPG Abuse of OxyContin poses a risk of overdose and death. Abuse may occur by Taking cut, broken, chewed, crushed, or dissolved OxyContin tablets can these pups recovered. 8.2 Labor and Delivery Opioids cross the placenta taking intact tablets in quantities greater than prescribed or without legitimate SFTVMUJOBGBUBMPWFSEPTFt0YZ$POUJOUBCMFUTTIPVMECFUBLFOPOFUBCMFUBU and may produce respiratory depression and psycho-physiologic effects in purpose, by crushing and chewing or snorting the crushed formulation, or by BUJNFt%POPUQSFTPBL MJDLPSPUIFSXJTFXFUUIFUBCMFUQSJPSUPQMBDJOH neonates. OxyContin is not recommended for use in women immediately injecting a solution made from the crushed formulation. The risk of overdose JOUIFNPVUIt5BLFFBDIUBCMFUXJUIFOPVHIXBUFSUPFOTVSFDPNQMFUF prior to and during labor, when use of shorter-acting analgesics or other or death is increased with concurrent use of OxyContin with alcohol and swallowing immediately after placing in the mouth. Hypotension Inform analgesic techniques are more appropriate. Occasionally, opioid analgesics other central nervous system depressants. Taking cut, broken, chewed, patients that OxyContin may cause orthostatic hypotension and syncope. may prolong labor through actions which temporarily reduce the strength, crushed, or dissolved OxyContin enhances drug release and increases the Instruct patients how to recognize symptoms of low blood pressure and EVSBUJPOBOEGSFRVFODZPGVUFSJOFDPOUSBDUJPOT)PXFWFSUIJTFGGFDUJTOPU risk of overdose and death. With parenteral abuse, the inactive ingredients how to reduce the risk of serious consequences should hypotension occur consistent and may be offset by an increased rate of cervical dilatation, in OxyContin can result in death, local tissue , , pulmonary (e.g., sit or lie down, carefully rise from a sitting or lying position). Driving which tends to shorten labor. Closely observe neonates whose mothers granulomas, and increased risk of endocarditis and valvular heart injury. or Operating Heavy Machinery Inform patients that OxyContin may impair received opioid analgesics during labor for signs of respiratory depression. Parenteral drug abuse is commonly associated with transmission of infectious the ability to perform potentially hazardous activities such as driving a car )BWFBTQFDJGJDPQJPJEBOUBHPOJTU TVDIBTOBMPYPOFPSOBMNFGFOF BWBJM- EJTFBTFT TVDIBTIFQBUJUJTBOE)*7Summary The in vitro data demonstrate or operating heavy machinery. Advise patients not to perform such tasks able for reversal of opioid-induced respiratory depression in the neonate. that OxyContin has physicochemical properties expected to make abuse via until they know how they will react to the medication. Constipation Advise 8.3 Nursing Mothers Oxycodone has been detected in breast milk. Instruct injection difficult. The data from the clinical study, along with support from patients of the potential for severe constipation, including management patients not to undertake nursing while receiving OxyContin. Do not initiate the in vitro data, also indicate that OxyContin has physicochemical properties instructions and when to seek medical attention. Anaphylaxis Inform patients OxyContin therapy while nursing because of the possibility of sedation or UIBUBSFFYQFDUFEUPSFEVDFBCVTFWJBUIFJOUSBOBTBMSPVUF)PXFWFS BCVTF that anaphylaxis has been reported with ingredients contained in OxyContin. respiratory depression in the infant. Withdrawal signs can occur in breast-fed of OxyContin by these routes, as well as by the oral route is still possible. Advise patients how to recognize such a reaction and when to seek medical infants when maternal administration of an opioid analgesic is stopped, or Additional data, including epidemiological data, when available, may provide attention. Pregnancy Advise female patients that OxyContin can cause fetal when breast-feeding is stopped. 8.4 Pediatric Use Safety and effectiveness further information on the impact of the current formulation of OxyContin on harm and to inform the prescriber if they are pregnant or plan to become of OxyContin in pediatric patients below the age of 18 years have not been the abuse liability of the drug. Accordingly, this section may be updated in QSFHOBOU)FBMUIDBSFQSPGFTTJPOBMTDBOUFMFQIPOF1VSEVF1IBSNBT.FEJDBM established. 8.5 Geriatric Use In controlled pharmacokinetic studies in the future as appropriate. OxyContin contains oxycodone, an opioid agonist 4FSWJDFT%FQBSUNFOU  GPSJOGPSNBUJPOPOUIJTQSPEVDU FMEFSMZTVCKFDUT HSFBUFSUIBOZFBST UIFDMFBSBODFPGPYZDPEPOFXBT and Schedule II controlled substance with an abuse liability similar to other slightly reduced. Compared to young adults, the plasma concentrations of opioid agonists, legal or illicit, including fentanyl, hydromorphone, methadone, Purdue Pharma L.P. PYZDPEPOFXFSFJODSFBTFEBQQSPYJNBUFMZ[see Clinical Pharmacology morphine, and oxymorphone. OxyContin can be abused and is subject to Stamford, CT 06901-3431 (12.3)].0GUIFUPUBMOVNCFSPGTVCKFDUT  JODMJOJDBMTUVEJFTPGPYZDPEPOF misuse, addiction, and criminal diversion [See Warnings and Precautions Ï 1VSEVF1IBSNB-1 IZESPDIMPSJEFDPOUSPMMFESFMFBTFUBCMFUT   XFSFBHFBOE (5.1), and Drug Abuse and Dependence (9.1)]. 9.3 Dependence Both 641BUFOU/VNCFST         PMEFS JODMVEJOHUIPTFBHFBOEPMEFS XIJMF  XFSFBHF tolerance and physical dependence can develop during chronic opioid and older. In clinical trials with appropriate initiation of therapy and dose therapy. Tolerance is the need for increasing doses of opioids to maintain         BOE   titration, no untoward or unexpected adverse reactions were seen in the a defined effect such as analgesia (in the absence of disease progression This brief summary is based on OxyContin Prescribing elderly patients who received oxycodone hydrochloride controlled-release or other external factors). Tolerance may occur to both the desired and Information $ 3FWJTFE "

003_CHPP_06_13.indd 3 5/17/13 11:01 AM June 2013 CONTENTS

FEATURE ARTICLES S5 | and : How best to approach these related diseases Angela C. Freeman, PA-C Ronald J. Rapoport, MD

S10 | What to do when pain and addiction coexist S10 Seddon R. Savage, MD, MS

Cover illustration: Steve Dininno

Scan this code with your smartphone or tablet to go to our Web site and read more CHRONIC PAIN PERSPECTIVES articles on pain management. If you register on the site, you will receive a free monthly EDITORIAL BOARD e-newsletter on pain management topics. ROBERT A. BONAKDAR, MD PAUL J. CHRISTO, MD, MBA Board Chairman Associate Professor, Division of Pain Medicine, For information about sponsorship Director of Pain Management, Director, Multidisciplinary Pain opportunities, please contact Scripps Center for Integrative Fellowship Program (2003-2011), Medicine; Assistant Clinical Elaine Coutsouridis at Johns Hopkins University School Professor, Department of Family [email protected] of Medicine, Baltimore, MD or 973-663-1232. and Preventative Medicine, University of California School of Medicine, San Diego, CA For information about submitting manuscripts, please contact Editor at [email protected]. MICHAEL R. CLARK, MD, MPH, MBA Associate Professor and Chronic Pain Perspectives™ is a supplement to Director, Chronic Pain The Journal of Family Practice® and a registered Treatment Program, Johns trademark of Frontline Medical Communications Inc. Hopkins University School Copyright © 2013 Frontline Medical Communications Inc. of Medicine, Baltimore, MD

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CHPP_06.13_TOC.indd 4 5/29/13 10:27 AM FEATURE ARTICLE

Polymyalgia rheumatica and giant cell arteritis: How best to approach these related diseases Each of these painful disorders can be challenging to diagnose, and many patients have both. Adequate dosing and gradual tapering are key to treatment success.

Angela C. Freeman, PA-C Ronald J. Rapoport, MD Truesdale Health, Fall River, Mass

olymyalgia rheumatica (PMR) is a rela- tively common infl ammatory rheumatic Pdisease occurring most often in the elderly population.1,2 It usually causes pain and stiffness in the , pelvic girdle, and neck. Up to 15% of individuals with PMR also have giant cell arteritis (GCA),2 a of medium-size and large arteries that typically occurs in patients >50 years. , jaw , and visual abnormalities character- ize GCA. Up to 50% of patients with GCA have PMR.2 (See “A trip to the eye doctor yields more than this patient bargained for” on page S7.) With both conditions, there are usually eleva- tions in the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, although the ESR in some cases can be normal.3 Offi ce-based primary care physicians are

Disclosure The authors reported no potential confl ict of interest Cross-section of a temporal artery specimen from a patient with giant relevant to this article.

Photo: Biophoto Associates / Science Source cell arteritis.

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R_CHPP_06.13_Rapport_v3.indd 5 5/29/13 10:25 AM often the fi rst to encounter these diseases. depends on clinical presentation and ruling out Symptoms can vary among patients and pre- other diagnoses. Serum ESR levels that sup- sentations can be vague, making the diagno- port a diagnosis of PMR typically are >40 to ses of PMR and GCA challenging. This article 50 mm/h.9 However, in up to 20% of patients, can assist you in recognizing the signs and ESR can be normal.10 Other lab fi ndings may symptoms of PMR and GCA, and in develop- include elevated CRP and normocytic anemia, ing and executing an appropriate plan of care. as well as negative results for antinuclear anti- body, rheumatoid factor, and anti-cyclic citrul- linated . Polymyalgia rheumatica Radiographs rarely aid in diagnosis, and The cause of PMR is unknown, and the disease magnetic resonance imaging (MRI) can detect is often self-limited.4 Average patient age at abnormalities but is usually not necessary for diagnosis is 70 years, though onset does occur diagnosis. in individuals in their 50s and 60s. PMR may arise abruptly, causing increasing pain and stiffness in the neck, , or pelvic girdle, Treat with which often lead to impairment of activities of While the mainstay of PMR treatment is oral daily living. Patients may complain of diffi culty glucocorticoids, data are limited on optimal lifting their arms above the shoulders, an inabil- dosing to achieve remission.11 There is no uni- ity to comb their hair, or trouble simply getting versally accepted approach for initiating, taper- in and out of a chair. Up to 40% of patients ing, or maintaining therapy. Available studies have associated fever, malaise, weight loss, suggest that be started at between depression, and joint swelling—most com- 10 and 20 mg/d.6,8,11 Symptoms should resolve monly in the hands.3,5 The myalgias and stiff- in a week.12 Most patients require up to Myalgias and ness are typically symmetrical; they tend to be 2 years of tapering glucocorticoid treatment, stiffness of worse in the morning and improve later in the and relapses occur in 23% to 29% of patients polymyalgia day. However, prolonged inactivity may cause using prednisone, prompting the need for a the stiffness to return. A duration of symptoms dose adjustment.11 In one study, 55% of PMR rheumatica lasting more than 2 weeks is part of the core patients taking relapsed.5 are typically inclusion criteria for diagnosis recommended A reasonable approach. A systematic symmetrical by the British Society for and review of the treatment of PMR found that and tend to the British Health Professionals in Rheumatol- prednisone given at 15 mg/d for 4 weeks is be worse in ogy (BSR-BHPR).6 most effective. After that, the suggested rate the morning Other diagnoses to consider. The dif- of tapering is 1 mg each month to reach a ferential diagnosis includes bacterial and viral dose of 8 to 10 mg/d. Further tapering should and improve , , malignancy, proceed by 1 mg every 2 months to discon- during the day. osteoarthritis, hypothyroidism, amyloidosis, tinuation. The review also noted that initiating vasculitis, infl ammatory myopathy, fi bromyal- prednisone doses at <10 mg/d and tapering at gia, iatrogenic causes, and, of course, GCA.7,8 a rate >1 mg/mo were associated with higher In many cases, patients live with their symp- relapse rates and a need for longer glucocorti- toms for weeks or longer, often attributing coid therapy.11 them to arthritis or just getting old, and do BSR-BHPR guidelines recommend initiating not seek medical attention until the symptoms prednisolone at 15 mg/d for 3 weeks, reduc- become signifi cant and debilitating. ing the dose to 12.5 mg/d for 3 weeks, then Physical exam clues. Limitation in a 10 mg/d for 4 to 6 weeks, and then reducing patient’s range of motion—eg, diffi culty the dose by 1 mg every 4 to 8 weeks until com- lifting arms or standing from a sitting posi- pletion.6 However, a lack of controlled studies tion—is attributable primarily to pain, not means no consistent evidence supports any muscular weakness. Hands may be swollen. advocated treatment plan. Rarely, with longer durations of illness, PMR Let the patient’s clinical course guide can cause muscle atrophy and proximal mus- you. Tailor the steroid regimen to a patient’s cle tenderness.2 regression of symptoms and normalization No pathognomonic test. Although of infl ammatory markers. Keep in mind that acute phase reactants are typically elevated in there is some benefi t in gradual tapers to PMR, a pathognomonic test for the disorder avoid relapses. Consider dose adjustments if does not exist. A diagnosis of PMR therefore symptoms resurface.6 Persistent or recurrent

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R_CHPP_06.13_Rapport_v3.indd 6 5/29/13 10:25 AM elevation of ESR or CRP may suggest an alter- nate diagnosis of malignancy or GCA. Also A TRIP TO THE EYE DOCTOR YIELDS MORE recommend regular exercise and, as needed, THAN THIS PATIENT BARGAINED FOR adequate intake of calcium, vitamin D, and visits his ophthalmologist because he had recently noticed blurry to prevent glucocorticoid- MJ vision in his right eye. While waiting to see the doctor, the 68-year- induced .6 old patient experiences chest pain and is immediately transported to the Treatments of unlikely or uncertain hospital. Cardiac catheterization reveals an occluded distal left anterior descend- benefi t. PMR studies have looked at differ- ing (LAD) artery, and the patient undergoes angioplasty. Other lesions of ent glucocorticoid routes of administration, concern involve the mid LAD and right circumfl ex arteries. MJ is considered -sparing drugs, and nonsteroidal a good candidate for further surgery, but he suddenly loses vision in his anti-infl ammatory drugs (NSAIDs). right eye. In addition, testing reveals decreased acuity in the Various glucocorticoids have been given left eye. You, along with his surgeon, decide that a stat biopsy of his right temporal artery is in order. The biospy results come back positive for giant intramuscularly, but oral glucocorticoid agents cell arteritis. have shown greater consistency in treatment effects and control of symptoms.11,13,14 Tipoffs to associated polymyalgia rheumatica As for corticosteroid-sparing drugs, metho- While talking with the patient, you learn that, for the past month, he’d trexate and anti-tumor necrosis factor (anti- been experiencing right-sided facial cramping when chewing food, left- sided , increasing pain with attempted shoulder movement, and TNF) agents have yielded mixed results.15 hip discomfort when getting out of bed in the morning. MJ says he thought Unfortunately, a lack of controlled studies and this was his arthritis acting up and indicates that he’d been taking ibuprofen long-term follow-up data make it diffi cult to to get some relief. safely recommend these agents.8,11,15 Metho- trexate used with prednisone has shown some Limited range of motion on examination A musculoskeletal examination reveals decreased range of motion in both promise in studies—less so in clinical prac- shoulders, with the left side more limited than the right. The patient’s hip tice—for reducing the duration of relapses and range of motion is decreased bilaterally and, due to the pain, he has diffi - the need for upward titration of prednisone, culty standing from the side of the bed. Palpation of the joints and muscles and for reducing prednisone-related adverse reveals no tenderness. effects such as osteoporosis.11 Lastly, adding Elevated lab values NSAIDs to glucocorticoid therapy has shown MJ’s erythrocyte sedimentation rate (ESR) is 78 mm/h; C-reactive protein no advantage over using glucocorticoids alone. level is 5 mg/dL; the level is mildly elevated at 134 U/L; And they increase the number of adverse and the complete blood count is within normal limits without evidence of effects. anemia or an altered count.

Treatment and follow-up You order IV methylprednisolone 1 g/d for 3 days, and then oral prednisone Following up the PMR-GCA connection 60 mg/d. After discharge, MJ’s ophthalmologist and rheumatologist moni- Given the strong clinical association between tor his progress. At 2 weeks, MJ’s ESR normalizes to 3 mm/h. PMR and GCA, even if a patient’s presentation After 1 month, there is neither improvement nor deterioration in either suggests isolated PMR, it might be prudent to visual fi eld—that is, the patient can’t see out of his right eye and his left eye remains blurry. The rheumatologist tapers the oral prednisone to consider a rheumatology consultation to rule 20 mg twice daily. The patient’s hip and shoulder pain resolve, with a return out the possibility of silent GCA. of full range of motion. He no longer has headaches or cramping with chew- ing. His chief complaint is his weight gain and Cushingoid appearance. He does well with a continued taper of the prednisone, and after 2.5 years is Giant cell arteritis down to 2.5 mg/d. The vision in his left eye returns to baseline acuity, and vision in his right eye improves enough to let him read large print and watch GCA, also known as temporal arteritis, is a television. that affects medium-size and large cranial arteries originating from the aortic arch. It tends to involve the extracranial branches of the carotid artery.16 disturbances. If appropriate treatment is not Visual disturbance is the most dire initiated at onset of symptoms, irreversible symptom. Presenting symptoms can vary visual loss may ensue. An important distinc- but classically include headache, tender- tion between PMR and GCA is that PMR alone ness/sensitivity, , and visual does not cause blindness.8,10 Less common changes. Nonvascular symptoms usually mimic manifestations of GCA are cough and other the vague symptoms of PMR: fever, malaise, upper-respiratory symptoms, arm claudication, aching joints, and weight loss.2,7 Due to the aneurysm, and .3,14 risk of abrupt visual loss with GCA, promptly First steps in the work-up. Physical exam evaluate any patient complaining of visual fi ndings are usually normal, but patients may

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R_CHPP_06.13_Rapport_v3.indd 7 5/29/13 10:25 AM have a large tender, nodular, or pulseless tem- of 1 to 2 mm.2 Positive histologic evidence poral artery.3 With a complaint of visual distur- reveals granulomatous lesions on multiple bances, conduct a visual acuity exam to assess levels, usually with giant cells and often in for monocular or binocular visual aberrations close proximity to disrupted, internal elastic and to identify any decrease in visual fi elds. lamina.17 Biopsy of the contralateral tempo- Additional physical exam fi ndings may be ral artery may increase yield, but it is seldom related to PMR.3 In up to 50% of GCA cases, necessary and not often done. Should biopsy PMR symptoms may be the presenting clinical results be negative on both sides, consider features.10,16 other diagnoses. However, 15.3% of GCA Lab fi ndings are nonspecifi c. The ESR is patients with a negative biopsy result meet usually >50 mm/h and is the most consistently other diagnostic criteria.17 elevated laboratory test in GCA. However, Exploration of other artery involvement a recent study showed that 25% of patients may be prudent. Consider involvement of who tested positive for GCA on biopsy had large vessels such as the and subclavian a normal ESR.10 Elevated CRP and alkaline- artery. MRI or angiography would be a study phosphatase levels and platelet count are often of choice, especially in cases where the patient noted.10 Normochromic or hypochromic ane- complains of arm claudication or other sys- mia is also a common fi nding, and it occurs in temic symptoms.3 PMR, as well.2 Other conditions to consider include and Takayasu arteritis. The Treat with oral prednisone temporal arteries are rarely abnormal on exam- In patients without risk of visual loss, an initial ination, and unaffected vision helps with the daily dose of oral prednisone, 40 to 60 mg, is differentiation.2 Takayasu arteritis is pathologi- suffi cient to suppress symptoms and normal- Hospitalize a cally similar to GCA but tends to target large ize infl ammatory factors.18 Continue at this patient with elastic arteries such as the aorta and its main dose until clinical and laboratory markers show suspected giant branches. And it occurs predominantly in indi- that the infl ammatory process has subsided. viduals younger than 40 years of age.10 Although systemic symptoms may reduce cell arteritis dramatically within 72 hours, it may take 2 to and visual 4 weeks for them to reach a level (in conjunc- disturbances, If vision is affected, tion with improving lab values) that allows ste- and start take immediate steps roid tapering to begin.2-4,10,16 high-dose IV There is no time to waste if you suspect GCA Associated manifestations such as head- glucocorticoid in a patient with visual disturbances. Hospital- ache, scalp tenderness, and jaw claudica- ize the patient and initiate high-dose intrave- tion may take longer to improve. As in the therapy nous (IV) glucocorticoid therapy immediately case of PMR, a slow gradual taper based on immediately to prevent permanent blindness. Normal vision the patient’s clinical response is prudent to to prevent returns in one-third of patients who receive IV reduce the risk of relapse. Do not be con- blindness. therapy within 24 hours.14 Treatment provides cerned if increased dose adjustments by 15 no benefi t if delayed for more than 48 hours to 25 mg/d are required before attempting after the onset of visual disturbances.16 further reductions. The disease course is gen- Give IV methylprednisolone 1 g/d for 3 to erally less than 2 years.2-4 However, relapses 5 days,10,16 then switch to oral prednisone start- occur in 30% to 50% of patients.4 It has ing at 60 mg/d and tapering the dose gradu- been recommended that patients receive ally as you would in PMR, according to the follow-up evaluation as long as 6 to 12 years patient’s clinical course.3,10,16 If treatment does after are withdrawn.2,4 not diminish the visual disturbance, it’s time to Steroid-sparing agents have not necessar- investigate other possible causes.10 ily shown benefi t in this group of patients, but newer agents are being investigated. Unless contraindicated, consider antiplate- No emergency? Consider biopsy let therapy with at 81 mg/d to reduce Unlike PMR, GCA can be diagnosed defi ni- the risk of visual loss, transient ischemic attack, tively, with a temporal artery biopsy. With or . As with PMR management, take suspicion of this diagnosis, immediately refer steps to prevent glucocorticoid-induced osteo- the patient to a surgeon for biopsy. Sliced seg- porosis, since corticosteroid therapy will con- ments of the artery are sampled at intervals tinue for at least 1 to 2 years. Up to 25% of

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R_CHPP_06.13_Rapport_v3.indd 8 5/29/13 10:25 AM patients with GCA have large-vessel involve- study. Ann Intern Med. 1982;97:672-680. 10. Weyand CM, Goronzy JJ. Giant cell arteritis, polymyal- ment, making it prudent to monitor for aor- gia rheumatica and Takayasu’s artertitis. In: Klippel JH, tic aneurysm, which is 17 times more likely in Stone JH, Croffore LJ, White PH, eds. Primer on the patients with GCA than among the general Rheumatic Diseases. 13th ed. New York, NY: Springer 3 Science+Business Media, LLC; 2008:398-406. population. 11. Hernandez-Rodriguez J, Cid MC, Lopez-Soto A, et al. Treatment of polymyalgia rheumatica: a systematic References review. Arch Intern Med. 2009;169:1839-1850. 1. Mercier LR. Practical Orthopedics. 4th ed. St. Louis, 12. Salvarani C, Cantini F, Boiardi L, et al. Polymyalgia MO: Mosby-Yearbook, Inc.; 1995:289. rheumatica and giant-cell arteritis. N Engl J Med. 2. Kumar R. Polymyagia rheumatica and temporal arte- 2002;347:261-271. ritis. In: Koopman KY, Boulware DW, Heudebert GR, 13. Salvarani C, Cantini F, Olivieri I, et al. Corticosteroid eds. Clinical Primer of Rheumatology. Philadelphia, injections in polymyalgia rheumatica: a double-blind, PA: Lippincott Williams and Wilkins; 2003:207-212. prospective, randomized, placebo controlled study. J 3. Hellman DB, Stone JH. Arthritis & musculoskeletal Rheumatol. 2000;27:1470-1476. disorders. In: Tierney LM, McPhee SJ, Papadakis MA. 14. Maksimowicz-McKinnon K. Giant cell arteritis: eds. 2007 Current & Treatment. diagnosing and managing urgent complications of 46th ed. New York, NY: McGraw-Hill; 2007:866-867. disease and therapy. UPMC Rheumatology Grand 4. Kennedy S. Polymyalgia rheumatica and giant cell Rounds. January 2011. Available at: http://www. arteritis: an in-depth look at diagnosis and treatment. upmcphysicianresources.com/fi les/dmfi le/fi nal_cxd_ J Am Acad Nurse Pract. 2012;24:277-285. S190-Rheumatology_GR_Jan_20111.pdf. Accessed 5. Cimmino MA, Parodi M, Montecucco C, et al. The cor- December 27, 2012. rect prednisone starting dose in polymyalgia rheumat- 15. Aikawa NE, Perreira RM, Lage L, et al. Anti-TNF ica is related to body weight but not to disease severity. therapy for polymyalgia rheumatica: report of 99 BMC Muskuloskelet Disord. 2011 May 14;12:94. cases and review of the literature. Clin Rheumatol. Available at: http://www.biomedcentral.com/1471- 2012;31:575-579. 2474/12/94. Accessed December 27, 2012. 16. Gonzalez-Gay MA, Vazquez-Rodriguez TR, Lopez- 6. Dasgupta B, Borg FA, Hassan N, et al. BSR and BHPR Diaz MJ, et al. Epidemiology of giant cell arteri- guidelines for the management of polymyalgia rheu- tis and polymyalgia rheumatica. Arthritis Rheum. matica. Rheumatology (Oxford). 2010;49:186-190. 2009;61:1454-1461. 7. van Hecke O. Polymyalgia rheumatica—diagnosis and 17. Klippel JH, Dieppe PA, Ferri F. Primary Care Rheuma- management. Aust Fam Physician. 2011;40:303-306. tology. London, England: Mosby; 1999:321-325. 8. Gonzalez-Gay M, Agudo M, Martinez-Dubois C, et 18. Sneller MC, Langford CA, Fauci AS. The vasculi- al. Medical management of polymyalgia rheumatica. tis syndromes. In: Kasper DL, Fauci AS, Longo DL, Expert Opin Pharmacother. 2010;11:1077-1087. Braunwald E, Hauser SL, Jameson JL, eds. Harrison’s 9. Chuang TY, Hunder GG, Ilstrup DM, et al. Polymyal- Principles of Internal Medicine. 16th ed. New York, gia rheumatica: a 10-year epidemiologic and clinical NY: McGraw-Hill; 2005:2009.

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R_CHPP_06.13_Rapport_v3.indd 9 5/29/13 10:25 AM FEATURE ARTICLE

What to do when pain and addiction coexist

A multidimensional approach to pain treatment will serve all patients with chronic pain well and is especially important for those who misuse alcohol, street drugs, or prescribed medications.

Seddon R. Savage, MD, MS Dartmouth Medical School Hanover, NH

hronic pain and addictive disorders are each distinct clinical conditions that can Cbe expressed in unique ways in differ- ent individuals. Similar to other chronic condi- tions such as , hypertension, or asthma, both pain and addictive disease often have bio- logical as well psychobehavioral contributors that may shape clinical expression.1 As with these other illnesses, it is helpful for clinicians to engage the patient in a consistent process of self-care and to provide long-term clinical care while at the same time coordinat- ing the care of other providers and special- ists.2,3 In some cases a defi nitive cure for pain may be possible, but more often, chronic pain, like addiction, is a persistent condition requir- ing treatment over many years. It will come as no surprise to learn that the convergence of pain and addiction can compli- cate recovery from both problems.4 Pain or its associated symptoms may prompt continuing

Disclosure The author reported no potential confl ict of interest

relevant to this article. Illustration: Steve Dininno

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CHPP_06.13_Savage_V4_R.indd 10 5/29/13 10:27 AM use of substances that provide transient relief, to conduct a thorough assessment of current but which sometimes perpetuate distress and and past use of alcohol, street drugs, tobacco, reduce quality of life. And addiction may drive and controlled prescription drugs in a nonjudg- the experience of pain and seem to justify use of mental manner. A number of validated screen- an addictive substance that the patient craves. ing tools are available that may help identify It is also important to recognize that pain substance abuse. and addiction frequently share a number of Consider using NIDA-Modifi ed ASSIST similar clinical features—including sleep and (http://www.drugabuse.gov/sites/default/fi les/ mood disturbances, substance use, decon- pdf/nmassist.pdf), an excellent assessment tool ditioning, functional losses, and high levels of for primary care providers that inventories sub- stress—such that the conditions can reinforce stance use and helps monitor it on an ongoing one another. Full evaluation and comprehensive basis. If the patient does not misuse substances, treatment of the biopsychosocial components the screen is very brief. If he or she misuses of both conditions can improve outcomes. them and acknowledges it, NIDA-Modifi ed The purpose of this article is to explore a ASSIST will provide a comprehensive picture of model of multidimensional care that will serve the nature of the problem. Other assessment all patients with chronic pain well, including tools—including those specifi cally geared to those with addiction disorders. opioid misuse11—are listed in the TABLE. If you are considering the use of opioids to treat a patient’s chronic pain, urine drug test- What drives substance use? ing can provide objective information regard- How common is it? ing current substance use and is especially Patients with chronic pain may use alcohol, important in patients with known addictive street drugs, or prescribed medications for disorders or substance misuse. diverse reasons. Many are self-medicating A 24-hour inventory of substance and Research pain, sleep diffi culties, mood fl uctuations, or medications use, identifying exactly when and suggests that painful, intrusive memories. Others use these for what symptoms each was used, can reveal there is a psychoactive agents as a form of recreation, important clinical information. It is not unusual, as a compulsive act due to addiction, or to for instance, to identify a pain patient using relatively high avoid withdrawal symptoms when physically alcohol at bedtime to induce sleep (although rate of chronic dependent. And still others use these agents alcohol actually disrupts sleep architecture) or pain among for diversion and profi t. using opioids for stress or anxiety even when individuals Sometimes only one motive drives their pain is not anticipated or present. with addiction behavior, but often several are present. As disorders. a physician, your goal is to identify the sub- stances being used and the motivators of use Multidimensional treatment approach (when possible) to better address the underly- Your goals in treating chronic pain include ing causes. reduction in pain and associated symptoms, The lifetime prevalence of addictive dis- enhanced functioning, and a return to a high orders among US adults is about 12.5% for quality of life with meaning and purpose. The alcohol dependence, 17.8% for alcohol abuse, goals of addiction or substance misuse recov- 2.6% for drug dependence, and 7.7% for ery usually include avoiding harmful use of drug abuse.5,6 substances and similarly achieving physical, Research also suggests that there is a rela- psychological, and spiritual well-being. These tively high rate of chronic pain among individu- goals are entirely compatible. als with addiction disorders.7 Many factors may Unless specifi c surgeries, procedures, or contribute to pain in people with addictions, other interventions are able to eliminate a including injuries8 and traumatic childhood patient’s pain, treatment usually must address experiences. The latter appears to increase the not only the pain, but also coexisting men- risk of developing addiction and/or chronic tal health or medical issues, as well as pain pain later in life.9,10 sequelae that may increase pain. An interdisci- plinary approach often offers the best oppor- tunity for success.12 Conducting a thorough assessment To effectively address substance misuse in In addition to a careful assessment of pain and the context of chronic pain requires an under- its consequences for the patient, it is important standing of what is driving the misuse and

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CHPP_06.13_Savage_V4_R.indd 11 5/29/13 10:27 AM TABLE Screens for addictive disorders

Instrument Screening target What’s involved

Addiction Behaviors Checklist Tracks behaviors of patients 20 observations http://dsibmeetings.westat.com/SBIRT/Wu%20addiction%20 who have been prescribed behaviors%20checklist.pdf opioids

CAGE-AID Alcohol, drugs 4 questions http://www.ncdhhs.gov/mhddsas/providers/DWI/dual diagnosis/CAGE-AID.pdf

Cyr Wartman screen Alcohol, drugs 2 questions http://www.ama-cmeonline.com/pain_mgmt/tables/table_ cage.htm

DAST (Drug Abuse Screening Test) Drugs 20 questions http://www.emcdda.europa.eu/attachements.cfm/ att_61480_EN_DAST%202008.pdf

DIRE (Diagnosis, Intractability, Risk, Effi cacy) Opioid risk specifi c Scoring of 4 factors http://www.google.com/url?sa=t&rct=j&q=&esrc=s&s ource=web&cd=5&ved=0CEgQFjAE&url=http%3A% 2F%2Fwww.fmdrl.org%2Findex.cfm%3Fevent%3Dc. getAttachment%26riid%3D6613&ei=vJ7lULDHFqKc 2AWCiIGwAQ&usg=AFQjCNECSYFnam9UATA-Xm_ JQ0cjm6Xdiw&bvm=bv.1355534169,d.b2I

NIDA-Modifi ed ASSIST Alcohol, tobacco, drugs Short to comprehensive, http://www.drugabuse.gov/sites/default/fi les/pdf/nmassist. depending on use pdf

ORT (Opioid Risk Tool) Opioid risk specifi c 5 questions http://www.partnersagainstpain.com/printouts/ Opioid_Risk_Tool.pdf

PMQ (Pain Medication Questionnaire) Opioid risk specifi c 26 questions http://download.journals.elsevierhealth.com/pdfs/ journals/0885-3924/PIIS0885392404001010.pdf

SOAPP (Screener and Opioid Assessment for Patients Opioid risk specifi c 3 versions: 24,14, with Pain) and 5 questions http://www.painedu.org/soapp.asp

Urine drug screening Objective information on drug/ Objective lab test medication use

again must address coexisting mental health support from pain or addiction providers. or other medical issues, as well as the sequelae The medical home can play important roles of the substance problem. A biopsychosocial in coordination of care, facilitation of self- approach to treatment of both pain and addic- management, and promotion of recovery from tion that actively engages the patient in self- both conditions.14 management is critical to recovery from both The structure of our health care system, chronic conditions.13 (See “Self-care options for however, favors payment for short clinic visits patients with chronic pain and addiction” on and procedures and may limit access to mental page S14.) health and substance services. It may be more Such treatment ideally involves the pri- expedient to prescribe a medication or refer for mary care physician, psychologist or counselor, a pain block than to explore things like stress, and physical or occupational therapist—with diet, exercise, sleep, mood, substance use, and

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CHPP_06.13_Savage_V4_R.indd 12 5/29/13 10:27 AM the ability to function at work and home. The not associated with old drug use patterns. “quick solution” approach often omits the They reframe negative thinking to gain a more development of a foundation of self-care that positive perspective that favors recovery and is important to long-term success. prevents relapse. “I can’t live without alcohol While patients without co-occurring sub- forever” becomes “I can enjoy today without stance use disorders may get by with this alcohol.” They also apply relaxation or medi- approach, patients with co-occurring addiction- tation skills to reduce stress, and they develop related disorders can be hurt by reliance on coping skills to address high-risk situations.17 medications and other passive therapies. Meditation-relaxation. Despite some sci- entifi c debate about the relative merits of dif- ferent relaxation approaches, such as hypnosis, Finding the best treatment approaches guided imagery, progressive muscle relaxation, Effective treatment of chronic pain may draw and meditation, there is clear evidence that from 4 broad categories: psychobehavioral, deep relaxation practices can play an impor- physical therapeutic, and interventionalist tant role in pain management. Recent studies approaches, as well as medications. have shown benefi t for mindfulness medita- Psychobehavioral and physical therapeutic tion in the treatment of pain.18 Other studies approaches can provide a foundation for recov- suggest various forms of meditation may help ery from chronic pain and a context in which patients recover from addiction.19 The physi- strategic use of interventionalist procedures and ologic basis of pain relief associated with medi- medications may be more effective. Fortunately, tation or deep relaxation has been variously many self-management strategies that have attributed to muscular relaxation, reduction in been shown to be effective in pain manage- sympathetic arousal, and changes in activity of ment are also effective in the treatment of addic- different brain centers that process pain and tion. Among these are: cognitive-behavioral pain inhibition. Effects on sleep enhancement There are therapy, meditation, emerging 12-step pro- and reduction in anxiety may also contribute to now 12-step grams for pain, and physical reconditioning. recovery from pain and substance abuse. programs for As you plan out each patient’s therapeutic One simple approach to meditation is for regimen, consider these options: the patient to sit comfortably for 10 to 20 min- chronic pain that Cognitive-behavioral therapy (CBT) utes while focusing awareness on the natural use the same aims to change behaviors and thought pat- fl ow of his or her breath going in and out. The basic strategies terns to help patients gain control over their patient is instructed to note thoughts, sounds, as Alcoholics condition. It has been shown to be effective in and sensations as they pass by and gently bring Anonymous improving outcomes in chronic pain and sub- attention back to the fl ow of breath. A word and Narcotics stance abuse treatment.15,16 In the treatment of or phrase can be silently thought on the out- chronic pain, patients often identify negative breath to enhance focus. Anonymous self-talk that is impeding their recovery—“My 12-step programs. Twelve-step pro- to engage in pain is killing me. I’ll never be able to work.” grams such as Alcoholics Anonymous (AA) the process They are encouraged to substitute more posi- and Narcotics Anonymous (NA) have been a of recovery. tive thoughts that favor recovery, eg, “My pain key element of self-management of recovery is hurtful but not harmful. My pain will lead me from addiction for at least 7 decades. AA and to new and more meaningful work.” similar meetings engage attendees in a process Patients also examine physical activi- of self-refl ection, reframing of perspectives, ties, stress, sleep challenges, and mood fl uc- interpersonal sharing, and acceptance that tuations that can increase pain and engage in for many are powerful supports for substance approaches such as activity pacing, stretching, abuse recovery.20 and relaxation that may mitigate their pain. 12-step programs for pain. Recently When CBT is used in addiction treatment, 12-step programs for chronic pain that use the patients similarly explore triggers for drug use same basic strategies and paradigm to engage (often people, places, and things), and they individuals in a process of recovery have begun substitute alternatives that support abstinence to proliferate; these meetings are open to and recovery. people both with pain alone and those with For example, patients may elect social pain and addiction.21 And when pain-specifi c opportunities with friends who do not get 12-step groups are not available, many patients high, participate in valued activities that don’t fi nd they can adapt the steps in an AA or NA involve alcohol or drugs, and frequent places meeting to address their pain.

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CHPP_06.13_Savage_V4_R.indd 13 5/29/13 10:27 AM SELF-CARE OPTIONS FOR PATIENTS WITH CHRONIC PAIN AND ADDICTION Consider suggesting that your patient: • Participate in a cognitive-behavioral therapy (CBT) pain and addiction recovery group to learn skills for pain and substance recovery. (Ideally, 8-10 sessions plus a periodic refresher.) Two resources for identifying CBT therapists are the Association for Behavioral and Cognitive Therapies (www.abct.org) and the National Association of Cognitive-Behavioral Therapists (www.nacbt.org).

• Practice deep relaxation/meditation one to 2 times daily on a regular basis. One widely available, evidence-based approach is mindfulness-based stress reduction (MBSR); certifi ed instructors can be found online.

• Engage in comfortable aerobic exercise on a regular basis, gently stretching before and after. Initial guidance from a physical therapist or trainer experienced with chronic pain may be helpful.

• Work with an addictions counselor to explore substance use and support recovery.

• Attend Chronic Pain Anonymous or another chronic pain peer-support group. Information on face-to-face, phone, and Internet groups can be found on the Web sites of the Ameri- can Chronic Pain Association (www.theacpa.org) and Chronic Pain Anonymous (www.chronicpain anonymous.org).

• Participate in a substance self-help group regularly. (Alcoholics Anonymous and Narcotics Anonymous are the most common. Alternative programs include Smart Recovery and Rational Recovery.) Meeting information for these groups can be found at: www.aa.org, www.na.org, www.smartrecov Some studies ery.org, and www.rational.org. suggest that exercise can • Identify a sponsor (a support person experienced in successful recovery in the 12-step world). improve Sponsors are usually identifi ed at self-help group meetings. outcomes • Engage in meaningful and/or pleasurable activities that focus attention away from pain. in addiction Activities can include things like art, crafts, gardening, outdoor activities, or volunteer work. treatment. Remember that chronic pain and addiction are chronic conditions, so it is important to check on self-care at each visit and revise the plan as helpful to the patient. Use selected treatments, such as targeted physical therapy, medications, procedures, or other approaches when appropriate.

The strengths of 12-step groups are that and reduce propensity for spasm. It is usu- they are free and widely available. Patients may ally important for a patient to initiate exercise need to try different groups, however, to fi nd under the guidance of a physical therapist. one at which they feel comfortable. Clinicians should advise patients with pain Physical reconditioning. The benefi ts of to exercise in a manner that is gentle, gradually exercise and movement therapies in chronic progressive, and avoids signifi cantly increas- pain management are well documented. Exer- ing the patient’s pain.22 Some studies suggest cise activates central endorphin release and exercise can improve outcomes in addiction descending pain inhibition. Aerobic exercise, treatment; it is speculated that enhanced self- such as cycling, using an elliptical machine, or esteem and the increase in endogenous endor- walking, may improve circulation and tissue phins may contribute.23 oxygenation, which in turn can improve heal- ing. Stretching can relieve muscular tension and normalize joint motion; however, stretches Adding active treatments must be tailored to the condition of the par- to the platform of self-care ticular patient. Improved posture and proper Selection of specifi c procedures and medica- biomechanics during movement reduce physi- tions for different pain problems is beyond cal stress. Similarly, toning or strengthening the scope of this article, but it is worth noting can provide support for spinal and other joints that engagement in a biobehavioral self-care

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CHPP_06.13_Savage_V4_R.indd 14 5/29/13 10:27 AM program provides a context that supports suc- reward (euphoria) when possible, as reward cessful use of procedures and medication. For can trigger misuse; and example, improved posture, muscular support • assuring that the setting of care can provide of the spine, and proper biomechanics may optimal care coordination.24 reduce disc stresses that can produce recur- For those with a history of opioid addiction, rent pain after a successful epidural injection the safest option for opioid therapy is engage- of steroids. Similarly, muscular trigger point ment in an addiction treatment paradigm of injections are more likely to result in protracted opioid therapy. This will mean either buprenor- muscular relaxation if a patient is engaged in phine/naloxone with a registered provider or regular stress management and stretching. methadone maintenance treatment through Similarly, when withdrawal-producing medi- a licensed clinic in which medications will be cations are eliminated, when stress, anxiety, tightly supervised and the patient engaged in and depression are addressed, and when the psychosocial addiction treatment. Both types patient is physically conditioned, he or she may of opioid agonist therapy may provide some respond better to nonopioid pain medications. pain relief while providing pharmacologic treatment of opioid addiction and minimizing the risk of misuse and associated harm (such Opioids for pain as overdose). in substance use disorders Opioids are rarely fi rst-line medications for chronic pain treatment but they can be valuable What’s your role? components of care for some who have not The key roles of the primary care physi- responded to self-management, intervention- cian in managing chronic pain and coexist- alist procedures, and nonopioid medications. ing substance use disorders are to (1) identify But use of opioids in chronic pain patients with the variables that contribute to the patient’s The process is addictive disorders requires exceptional care. experience of pain and use of substances, (2) often 2 steps As you might expect, the risk of opioid encourage and support the patient as he or forward, one misuse is higher in individuals with a prior his- she tries to develop a self-care program, (3) tory of substance use when compared with a strategically implement or refer for active treat- step back, so person without this history. But the relative risk ment of the various contributing factors, and clinicians and for people with different types of addiction (4) see the patient regularly to monitor engage- patients need is unknown. There’s the potential to become ment in both self-care and active treatments to celebrate addicted to opioids, for instance, when an indi- and to revise the plan as needed. small victories. vidual is in recovery from addiction to alcohol Coexisting pain and addiction are among or marijuana. However, observation suggests the most challenging scenarios encountered in the risk of addiction to prescribed opioids is primary care. Recovery is possible, but patience, more likely in patients with a past history of time, fl exibility, and consistent motivational opioid addiction than other addictions. Dura- support are critical. The process is often 2 tion of recovery is generally inversely related steps forward, one step back, so clinicians and to the risk of relapse, so longer term recovery patients need to celebrate small victories. presents less risk than recent recovery. Whenever possible, engage any patient References with a history of addiction in an active addic- 1. McLellan AT, Lewis DC, O’Brien CP, et al. Drug depen- dence, a chronic medical illness: implications for treat- tion recovery program and have him or her co- ment, insurance, and outcomes evaluation. JAMA. managed by an addiction specialist if you plan 2000;284:1689-1695. 2. Chelimsky TC, Fischer RL, Levin JB, et al. The primary to prescribe opioids. Patients in recovery from practice physician program for chronic pain (© 4PCP): nonopioid addiction who require opioids for outcomes of a primary physician specialist collabora- pain may benefi t from tightening the structure tion for community-based training and support. Clin J Pain. 2013 Mar 1. [Epub ahead of print]. of care. This may include: 3. Anderson D, Wang S, Zlateva I. Comprehensive • providing a smaller supply of medications at assessment of chronic pain management in primary more frequent intervals; care: a fi rst phase of a quality improvement initiative at a multisite Community Health Center. Qual Prim • increasing supports for recovery from pain, Care. 2012;20:421-433. addiction, and co-occurring disorders; 4. Pohl M, Smith L. Chronic pain and addiction: chal- • increasing supervision including offi ce vis- lenging co-occurring disorders. J Psychoactive Drugs. 2012;44:119-124. its, urine drug screens, and pill counts; 5. Hasin DS, Stinson FS, Ogburn E, et al. Prevalence, cor- • selecting treatments carefully to limit relates, disability, and comorbidity of DSM-IV alcohol

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CHPP_06.13_Savage_V4_R.indd 15 5/29/13 10:27 AM abuse and dependence in the United States: results 15. Morley S, Eccleston C, Williams A. Systematic review from the National Epidemiologic Survey on Alco- and meta-analysis of randomized controlled trials of hol and Related Conditions. Arch Gen Psychiatry. cognitive behaviour therapy and behaviour therapy 2007;64:830-842. for chronic pain in adults, excluding headache. Pain. 6. Compton WM, Thomas YF, Stinson FS, Grant BF. 1999;80:1-13. Prevalence, correlates, disability, and comorbidity of 16. McCracken LM, Turk DC. Behavioral and cognitive- DSM-IV drug abuse and dependence in the United behavioral treatment for chronic pain: outcome, States: results from the National Epidemiologic Survey predictors of outcome, and treatment process. Spine on Alcohol and Related Conditions. Arch Gen Psy- (Phila Pa 1976). 2002;27:2564-2573. chiatry. 2007;64:566-576. 17. SAMHSA/CSAT Treatment Improvement Protocols. 7. Clark MR, Stoller KB, Brooner RK. Assessment and Rockville, MD: Substance Abuse and Mental Health management of chronic pain in individuals seeking Services Administration; 1993-. Available at: http:// treatment for opioid dependence disorder. Can J Psy- www.ncbi.nlm.nih.gov/books/NBK82999/. Accessed chiatry. 2008;53:496-508. May 16, 2013. 8. West SL. Substance use among persons with trau- 18. Zeidan F, Grant JA, Brown CA, et al. Mindfulness matic brain injury: a review. NeuroRehabilitation. meditation-related pain relief: evidence for unique 2011;29:1-8. brain mechanisms in the regulation of pain. Neurosci 9. Khoury L, Tang YL, Bradley B, et al. Substance use, Lett. 2012;520:165-173. childhood traumatic experience, and posttraumatic 19. Dakwar E, Levin FR. The emerging role of medita- stress disorder in an urban civilian population. Depress tion in addressing psychiatric illness, with a focus Anxiety. 2010;27:1077-1086. on substance use disorders. Harv Rev Psychiatry. 10. Beck JG, Clapp JD. A different kind of co-morbidity: 2009;17:254-267. understanding posttraumatic stress disorder and 20. Kaskutas LA. Alcoholics anonymous effectiveness: chronic pain. Psychol Trauma. 2011;3:101-108. faith meets science. J Addict Dis. 2009;28:145-157. 11. Potter JS, Marino EN. How to avoid opioid misuse. 21. Colameco S. Chronic Pain: A Way Out. Comprehen- Chronic Pain Perspectives. 2013;62(3):S2-S7. sive Treatment & 12-Step Recovery Guide. Haddon- 12. Stanos S. Focused review of interdisciplinary pain fi eld, NJ: Stephen Colameco; 2012. rehabilitation programs for chronic pain manage- 22. Nijs J, Kosek E, Van Oosterwijck J, Meeus M. Dys- ment. Curr Pain Headache Rep. 2012;16:147-152. functional endogenous analgesia during exercise in 13. Cheatle MD, Gallagher RM. Chronic pain and comor- patients with chronic pain: to exercise or not to exer- bid mood and substance use disorders: a biopsy- cise? Pain Physician. 2012;15(3 suppl):ES205-ES213. chosocial treatment approach. Curr Psychiatry Rep. 23. Brown RA, Abrantes AM, Read JP, et al. A pilot 2006;8:371-376. study of aerobic exercise as an adjunctive treat- 14. Chouinard MC, Hudon C, Dubois MF, et al. Case ment for drug dependence. Ment Health Phys Act. management and self-management support for fre- 2010;3:27-34. quent users with chronic disease in primary care: a 24. Savage SR, Kirsch KL, Passik SD. Challenges in using pragmatic randomized controlled trial. BMC Health opioids to treat pain in persons with substance use Serv Res. 2013;13:49. disorders. Addict Sci Clin Pract. 2008;4:4-25.

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REFERENCES: 1. Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345(25):1809-1817. 2. Blot WJ, McLaughlin JK. Over the counter non-steroidal anti-inflammatory drugs and risk of gastrointestinal bleeding. J Epidemiol Biostat. 2000;5(2):137-142. 3. Prescott LF, Speirs GC, Critchley JA, Temple RM, Winney RJ. Paracetamol disposition and metabolite kinetics in patients with chronic renal failure. Eur J Clin Pharmacol. 1989;36(3): 291-297. 4. Martin U, Temple RM, Winney RJ, Prescott LF. The disposition of paracetamol and the accumulation of its glucuronide and sulphate conjugates during multiple dosing in patients with chronic renal failure. Eur J Clin Pharmacol. 1991;41(1):43-46. 5. Bugge JF. Renal effects and complications of NSAIDs for routine post-operative pain relief: increased awareness of a real problem is needed. Baillière’s Clinical Anaesthesiology. 1995;9(3):483-492. ©McNEIL-PPC, Inc. 2013 EST-877

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