Objectives Medicine • Describe and discuss tramadol as a novel , including risks and benefits • Describe and discuss the problem of opioid misuse and abuse. James R. Knight, MD • Discuss physician strategies for patient Clinical Assistant Professor of encounters influenced by opioid Internal Medicine & Pediatrics misuse/abuse Division of Hospital Medicine • Discuss new and coming legislation and The Ohio State University Wexner Medical Center regulation related to prescription .

Tramadol Opioids

• Centrally acting weak mu opioid receptor agonist • Also blocks reuptake of serotonin and norepinephrine (not fully reversible with naloxone) • Useful in neuropathic pain • Not a controlled substance • Seizure risk • Risk of serotonin syndrome with SSRIs or TCAs • Renal clearance

Image from Wikipedia Commons

1 Terminology Opioid Use • Americans make up 4.6% of the world’s • Opioid – chemical that binds to population yet use 80% of the global opioid receptors opioid supply, 99% of the global • Opiate – technically refers to a hydrocodone supply, and 2/3 of the world’s illegal dr ugs . natural alkaloid of the opium poppy (opiates are opioids). • Patients on long-term opioid use have been shown to increase the overall cost • Narcotic – a historically varied of healthcare, disability, rates of word with negative legal and surgery, and late opioid use. social connotations.

Manchikanti and Singh Pain Physician 2008; Opioid Special Issue: 11:S63-S88. http://www.justice.gov/dea/concern/narcotics.html Louise Joly, one half of AtelierJoly

Misuse and Abuse Opioid Abuse • Use, misuse, and abuse of prescription opioid analgesia has increased markedly since 1990. • In 1997, the American Society of Anaesthesiologists, the American Academy of Pain Medicine, and the American Pain Society all advocated for expanded opioid Opioids have been misused and abused for use in the management of chronic pain as long as they have been used to treat pain. when other treatments are inadequate after careful patient evaluation and counseling.

Anaesthesiology, 1997; 87:995-1004

2 Increased Use mg/person 1997-2006

• The degree of euphoria produced by a given • Morphine • 184% is likely related to ability to cross • Methadone • 1129% the blood brain barrier. • Euphoria may be related to • • 899% relative mu receptor subtype • Hydrocodone • 231% stimulation. • • 450% • Euphoria tolerance may be related to overdose potential.

Manchikanti and Singh Pain Physician 2008; Opioid Special Issue: 11:S63-S88.

circle=oxycodone 10, 20, 40 mg square=hydrocodone 15, 30, 45 mg triangle=hydromorphone 10, 17.5, 25 mg

Dose

White and Irvine, Addiction, 1999; 94(7), 961-972. Walsh et al. / Drug and Alcohol Dependence 98 (2008) 191–202.

3 Addicts and Prescription Opioids Informed Patients • In a Toronto study from 2003, 82% of patients presenting for enrollment in methadone Opioid abuse has entered the digital age. maintenance programs admitted prescription opioid use. Numerous forums are related to usage • 61% of those using prescription opioids reported obtaining them from a physician. patterns for prescription opioids. • 24% used prescription opioids only. forum.opiophile.org • 35% use dhd hero in fi rst and dth then prescri pti on opioids. www.bluelight.ru • 24% used prescription opioids first and later. • The majority of patients using prescription opioids starting to use them for pain control (86% of those only using prescription opioids and 62% of those who started with prescription opioids).

Brands, et al. Drug and Alcohol Depedence, 2004, 73:199-207.

A Sampling of Forum Thread Titles

“Finding a quack doctor...” “IF YOU HAD YER(sic) OWN RX PAD...” “Opiate Dosage Converter Program” “Surviving Acetaminophen (Tylenol) Poisoning” “State Monitoring Programs” “Cant(sic) feel 20mg dilaudid shot, help?”

cdc.gov

4 cdc.gov http://www.healthyohioprogram.org/vipp/data/rxdata.aspx

http://www.healthyohioprogram.org/vipp/data/rxdata.aspx http://www.healthyohioprogram.org/vipp/data/rxdata.aspx

5 Health Care Provider Obligations Keeping Patients Safe • “HCPs are obligated to act in the best • If the gut works, use it! interests of their patients.” – Use oral if the patient is able to • “This action may include the addition of opioid take oral intake. medication to the treatment plan of patients – Appropriate for long and short acting agents. whose symptoms include pain.” • SaSafetyfety ccheckshecks forfor tthehe roomsrooms ooff patpatientsients • “It is...a medical judgment that must be made suspected of altering the route of by a HCP in the context of the provider-patient administration of the medication or relationship based on knowledge of the surreptitiously taking other home medications patient, awareness of the patient's medical • Use urine drug screening on all chronic pain patients, patients admitted from the ED for and psychiatric conditions and on observation “uncontrollable pain” without a diagnosis, and of the patient's response to treatment.” outpatients in accordance with their pain A consensus document from the American Academy of Pain Medicine, the American Pain Society, and contracts. the American Society of Addiction Medicine. http://ampainsoc.org/advocacy/pdf/rights.pdf

Keeping Patients Safe http://www.ohiopmp.gov • Check an OARRS report (Ohio Automated Rx Reporting System) – In the literature, “doctor shopping” is usually defined as opioid prescriptions from 5 or more physicians in a year. • When to check OARRS – “If a pati ent i s exhibiti ng si gns of d rug ab use or diversion; – When you have a reason to believe the treatment of a patient with the above listed drugs will continue for twelve weeks or more; and – At least once a year for patients thereafter for patients receiving treatment with the above listed drugs for twelve weeks or more.” http://med.ohio.gov/pdf/rules/4731-11-11%20FAQs.pdf

6 Keeping Patients Safe Keeping Patients Safe

• Addicts, by definition, will be • Injection drug use often leads to manipulative and deceitful in efforts to infection. Patients with a documented obtain their desired drug. pattern of opioid abuse or directly observed dangerous behavior should be • Doing the “right” thing for the patient considered for facility placement for does not always mean prescribing prolonged courses of IV antibiotics via opioids. PICC line. • Patients should not be permitted to • Keep realistic expectations. Patients leave the floor while receiving IV with chronic pain are never going to be opioids. “pain free”.

Keeping Patients Safe Don’t Build a Bridge to Nowhere

• Chronic pain patients treated with chronic • What about the patient that has opioid therapy with a pain contract should not be prescribed their chronic pain “chronic pain,” an exceptional medications at discharge. inpatient opioid requirement, and no • A quick phone call to the patient’s pain outpatient prescribing physician for physician will often clarify any questions. their “chronic” opioids? • Quantity prescribed for opioid class – 5-7 day taper medications should be limited (They are – Methadone is to be avoided likely being prescribed for a limited acute condition).

7 Sentencing set for Doctor in The Prescription Opioid Problem in the News Ohio Pill Mill Case

http://www.wkbn.com/content/news/ohstate/story/Sentencing-set-for-doctor-in-Ohio-pill- mill-case/pjD6mpYsc0O3TQMRUhEUkQ.cspx

The Prescription Opioid Problem in the News The Prescription Opioid Problem in the News

8 Ohio’s New Law(s) Using Addiction Psychiatry Princinpals in Medical Practice • House Bill 93, Senate Bill 301 • Pain clinics must be physician owned • Pain clinics must be licensed • Limits regggarding the number of p ills that can be directly furnished to the patient Billy O. Barclay, MD • Pain clinic defined Medical Director • Primarily treating pain Addiction Medicine Services • Majority of patients receive controlled Department of Psychiatry substances for pain or tramadol The Ohio State University Wexner Medical Center

Objective A Substance Related Problem

•She reports severe panic attacks • To understand: •On Xanax 2 mg 3 X /day for her anxiety . screening, •Has taken Xanax for 12 years . management strategies, and •On her current dose for 7 years . referral, for patients with controlled •Her doctor just retired/she needs a new doctor substance prescriptions •Can’t imagine making it without the medication • As enlightened by the definition and neurobiology of addiction •Her other medical issues are routine

9 Evaluating a new patient

• She can not stop taking the alrazolam • If you don’t give it she will go elsewhere • You are concerned such a patient may be Is she an difficult t o manage addict ? • You run the risk of fostering her problems • Ethical responsibility to prescribe responsibly

Initial Screening Screening • Ask your patients about their substance use . How many alcoholic drinks do you have in a • Follow-up on any positive responses week? . CAGE questionnaire; a 4 question screener • Not, “Do you drink?” . MAST-Michigan Alcohol Screening Test . Tell me about you tobacco use. . More numerous and specific detail questions • And second hand smoke about drugs . What about marijuana? . DAST-Drug Abuse Screening Test . What other drugs do you use? . Enquire about prescriptions for opiates and . Tobacco . • Favorite cigarette of the day? • How often do you use more than prescribed? • How long until first cigarette of the day? • Do you give medications to others?

10 CAGE Brief MAST Questions • Only used for ETOH screening • 2 or more “yes” responses is a positive • Do you feel you are a normal drinker? screen • Do friends or relatives think you are a normal drinker? • C- Have you ever felt you ought to CUT • Have yygou ever attended a meeting of AA? down your drinking? • A- Have people ANNOYED you by • Have you ever lost friends or criticizing your drinking? girlfriends/boyfriends because of drinking? • G- Have you ever felt GUILTY about your • Have you ever gotten into trouble at work drinking? because of drinking? • E- Have you ever had a drink first thing in the morning (EYE OPENER) to steady your nerves or get rid of a hangover?

Brief Mast Continued Identification of • Have you ever neglected your obligations, • Warning signs/symptoms your family, or your work for 2 or more days . Biological in a row because you were drinking? • Weight loss, liver disease, GI • Have you ever had delirium tremens (DTs) conditions, loss of tooth enamel severe shaking, heard voices, or seen things . Psychological that weren’t th ere aft er h eavy d ri nki ng? • Anger, irr itabilit y, l eth argy, conf usi on • Have you ever gone to anyone for help . Social about your drinking? • Socializing with drug users, isolated • Have you ever been hospitalized because of from non-using friends, lack of family relationships, loss of job, arrests drinking? . Spiritual • Have you ever been arrested for driving drunk? • Loss of values, denial of morality

11 SCREENING Urine toxicology screening • Random urine toxicology screening is better than routine • You must understand the limitations of testing Consider utilizing point-of-care testing: • For example, with opiates: • Breath-alyzer, saliva, or urine testing for . Routine opiate screens do not detect alcohol meperidine, oxycodone, fentanyl, tramadol, • Urine (or hair) testing for drugs buprenorphine • Urine, saliva, or breath testing for tobacco . Heroin is excreted in urine as morphine (nicotine) . 6-monoacetyl morphine (6-MAM) detected for 12 hours – evidence of recent heroin use . Poppy seeds contain trace amounts of codeine and morphine and even small amounts of poppy seeds can give positive for morphine

Collateral/other information OARRS

• Concerned family members • Ohio Automated Rx Reporting System (OARRS) . Online tool to assist giving better treatment • Other physicians who are or have for while identifying illicit drug seeking behaviors treated the patient • Pharmacists who fill their . It lists prescriptions and prescribers prescribers for last prescriptions 12 months • May not show prescriptions written in last • Your office staff 1-2 weeks • May show multiple prescribers, in different • Electronic pharmacy records cities, similar or identical medications, often physicians in emergency departments

12 Substance Abuse (Addiction) Maladaptive pattern of substance use, characterized by 1 or more of following symptoms in a 12 month period: • A maladaptive pattern of use leading to clinically significant • Recurrent substance use resulting in failure to fulfill major role obligations impairment or distress, • RtbtRecurrent substance use iittiiin situations in whi hihitch it is physically hazardous characterized by at least 3 of 7 • Recurrent substance-related legal problems • Continued substance use despite having criteria within a one year persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of period the substance

* The symptoms have never met criteria for Substance Dependence for this class of substance

DSM 4 Criteria for Substance Dependence Tolerance Addiction . Need for more or diminished effect Withdrawal Addiction = “Substance Dependence” . Or taking the substance to avoid withdrawal symptoms “Addiction” is a non-specific term frequently Substance taken in larger amounts or over a longer period than intended used to refer to a variety of substance-related Persistent desire or unsuccessful efforts to cut down or problems control use

Great deal of time spent obtaining, using, or recovering from effects • Addiction is not just physical dependence

Important social, occupational, or recreational activities are – Physical dependence and a syndrome given up or reduced of substance dependence (DSM-IV) are Substance use continued despite knowledge of having importantly different persistent or recurrent physical or psychological problems due to use

13 Why Does Addiction Occur? Effects of Chronic Drug Use

• Drugs of abuse can release 5 to 10 times the • With repeated use, drugs cause profound amount of dopamine as natural rewards changes in neurons and brain circuitry • In some cases, this occurs almost immediately (as when drugs are smoked or injected), and the • These changes are associated with effects can last much longer than those “tolerance” produced by natural rewards • Decreased dopamine transporters result in • This creates a much stronger effect on the depression-like symptoms brain's reward circuit than those produced naturally (e.g., food, sex) • Drugs are needed to “return to baseline” • The effect of such a powerful reward strongly • Induces chronic changes & brain damage motivates people to take drugs again and again

Imaging Studies Patients who abuse substances

Structural abnormalities (MRI/MRS): If the patient is an addict: • Frontal cortex, prefrontal cortex, basal ganglia, and amygdala REFERRAL IS THE BEST COURSE, PARTICULARLY IF THE CASE IS Functional abnormalities (fMRI, PET, SPECT): COMPLEX. • Caudate nucleus, cingulate, and prefrontal cortex become activated during a drug “rush” • Nucleus accumbens becomes activated during periods of craving • Striatal dopamine spike associated with the pleasurable drug-related “high”

14 REFERRAL TO TREATMENT • Be familiar with options for treatment . Be able to provide information on AA/NA Meetings, On the other hand: smoking cessation options, etc. . Offer referral to outpatient addiction treatment ADDICTION EXISTS ON A CONTINUUM clinic OF SEVERITY & YOU MIGHT DECIDE TO . Suggest inpatient detoxification detoxification and/or long -term TAKE ON A MORE MANAGEABLE CASE residential treatment, if indicated • There continues to be a large “treatment gap” . In 2010, an estimated 23.1 million Americans (9.1 percent) needed treatment for a problem related to drugs or alcohol, but only about 2.6 million (1 percent) received treatment

Not an addict; you decide to treat In Conclusion her. Principals of treatment • Addiction is a serious, common, and • Treatment contract treatable condition that will be present in the patients you treat • Switch med? • Taper/long term treatment • As physicians – Fulfill ethical responsibility to patients • Dealing with lost prescriptions by prescribing responsibly • Check pharmacy record – Recognize and intervene with patients who have addiction, not just the physiological symptoms that may result from chronic substance use

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