Drug Testing & Office Based Detoxification

Drug Testing & Office Based Detoxification Laxmaiah Manchikanti, M.D. 1 DISCLAIMER Chief Executive Officer, ASIPP, SIPMS Medical Director, PMCP, ASC, PCS Associate Clinical Professor Anesthesiology and Perioperative Medicine University of Louisville, Kentucky Member: KBML, MCAC, CAC Publications: Over 200 journal articles and 3 books No outside funding, no Grants, no Industrial support Drug Testing: Some slides borrowed from Art Jordan, MD Office Based Detoxification : All slides borrowed from Roger S. Cicala, MD 2 1

Malprescribing 90.0% 82.8% 60.0% 44.1% 30.0% 30.2% 16.9% 0.0% Hypertension Depression Prescription drug abuse Illegal drug use Physician s very prepared to diagnose 1999 3 Opioid Use in Chronic Pain Over 90% of patients presenting to and in IPM centers are on opioids US Office based prescriptions All opioids o 8% in 1980 o 16% in 2000 Schedule II o 2% in 1980 o 9% in 2000 4 2

Chronic Pain 5 to 10 million persons may be misusing prescription drugs and/or using illicit drugs 44% of Methadone Maintainance patients said opioids were cause of their addiction Opioid abuse - 9% to 18% Illicit drug use - 14% to 32% 5 Prevalence of controlled prescription drug abuse Manchikanti et al, J KY Med Assoc 2003 6 3

Prevalence of illicit drug use in an interventional pain practice Group I (100) Third party Group II (100) Medicare with or without third party Group III (100) Medicare & Medicaid Group IV (100) Medicaid P Value Cocaine 7% 4% 6% 8% 0.684 Marijuana (THC) 11% 8% 20% b 34% a,b,c 0.0000 Methamphetamine/Amphetamine 3% 2% 4% 3% 0.876 Combined use of cocaine and marijuana 1% 2% 2% 3% 0.888 Total 17% 10% 24% b 39% a,b,c 0.0000 Totals may not correlate as some patients were in more than one category a: Indicates significant different with Group I b: Indicates significant different with Group II c: Indicates significant different with Group IIII Manchikanti et al, J KY Med Assoc 2005 7 Comparative evaluation of illicit drug use 2002 vs 2005 Third party Medicare w/wo third party Medicare & Medicaid Medicaid Total Marijuana Present study (192) 14%* (26) Previou s study (100) 11% (11) Present study (154) 5% (7) Previous study (100) 8% (8) Present study (85) 12%* (10) Previous study (100) 20% (20) Present study (69) 16%* # (11) Previou s study (100) 34% (34) Present study (500) 11% # (54) Previou s study (400) 18% (73) Cocaine 6%* (11) 7% (7) 1% (2) 4% (4) 8%* (7) 6% (6) 6% (4) 8% (8) 5% (24) 6% (25) Methamphetamine/ Amphetamine s 4% (8) 3% (3) 1% (1) 2% ( 2) 1% (1) 4% (4) 1% (2) 3% (3) 2% (11) 3% (12) Total Abuse 20%* (38) 17% (17) 6% (9) 10% (10) 21%* (18) 24% (24) 22%* # (15) 39% (39) 16% # (80) 22% (90) ( ) Number of patients * Indicates significant difference with Medicare with or without third party insurance # Indicates significant difference with previous study (within the same insurance group) Source: Manchikanti et al, Pain Physician 2006 8 4

Comparative evaluation of illicit drug use 2002 Vs 2005 Third party Medicare w/wo third party Medicare & Medicaid Medicaid Total Presen t study (192) Previo us study (100) Presen t study (154) Previo us study (100) Present study (85) Previou s study (100) Prese nt study (69) Previo us study (100) Presen t study (500) Previo us study (400) Marijuana 14%* (26) 11% (11) 5% (7) 8% (8) 12%* (10) 20% (20) 16%* # (11) 34% (34) 11% # (54) 18% (73) Cocaine 6%* (11) 7% (7) 1% (2) 4% (4) 8%* (7) 6% (6) 6% (4) 8% (8) 5% (24) 6% (25) Methamphetamine/ Amphetamines 4% (8) 3% (3) 1% (1) 2% ( 2) 1% (1) 4% (4) 1% (2) 3% (3) 2% (11) 3% (12) Total Abuse 20%* (38) 17% (17) 6% (9) 10% (10) 21%* (18) 24% (24) 22%* # (15) 39% (39) 16% # (80) 22% (90) ( ) Number of patients * Indicates significant difference with Medicare with or without third party insurance # Indicates significant difference with previous study (within the same insurance group) Manchikanti et al, Pain Physician 2006 9 Drug Testing Urine Drug Screening Specific drug analysis (blood) Hair Samples Saliva Testing 10 5

Drug Detection Periods in Various Matrices Source: E.J. Cone, Addiction Research Center 11 Gold Standard Easily obtained Relatively inexpensive Valid and reliable 12 6

Gold Standard What is the Purpose? Identify proper use and abuse Provide appropriate treatment Assist the patient in confronting addiction Identify denial 13 What Are Testing For? Is the patient taking the medications prescribed? Is the patient taking substances/drugs NOT prescribed? Is the patient using illicit drugs? 14 7

Drug Testing Results and Documentation of a drug depend on Dose size Frequency and proximity of use Metabolites Type of test used Characteristics of specific drug Cutoff levels 15 Source: Cone EJ. 16 8

Interpreting the results Know the characteristics of testing procedures, since many drugs are not routinely detected by all UDTs. Although no aberrant behavior is pathognomonic of abuse or addiction, such behavior should never be ignored. Reliance on aberrant behavior to trigger a UDT will miss more than 50% of those individuals using unprescribed or illicit drugs. 17 Typical screening and confirmation cutoff concentrations and detection times for drugs of abuse. Drug Screening cutoff concentrations ng/ml urine Analyte tested in confirmation Confirm ation cutoff concentr ations Urine detection time Amphetamine 1,000 Amphetamine 500 2-4 days Barbiturates 200 Amobarbital, secobarbital, other barbiturates 200 2-4 days for short acting; up to 30 days for long acting Benzodiazepines 200 Oxazepam, diazepam, other benzodiazepines 200 Up to 30 days Cocaine 300 Benzoylecgonine 150 1-3 days Codeine 300 Codeine, morphine 300; 300 1-3 days Heroin 300 Morphine, 6-acetylmorphine 300; 10 1-3 days Marijuana 100; 50; 20 Tetrahydrocannabinol 15 1-3 days for casual use; up to 30 days for chronic use Methadone 300 Methadone 300 2-4 days Methamphetami ne 1000 Methamphetamine, amphetamine 500; 200 2-4 days Phencyclidine 25 Phencyclidine 25 2-7 days for casual use; up to 30 days for chronic use Source: Cone EJ., Chemistry and Drug Metabolism Section 18 9

Metabolites of Opioids Opiate Morphine Meperidine Levorphanol Tartrate (Levo-Dromoran) Hydromorphone Oxycodone Codeine Hydrocodone Metabolites M3G and M6G Normorphine Normeperidine Long half-life Hydromorphone-3-glucuronide (H3G) Noroxycodone, oxymorphone, oxycodols, and their respective oxides. Norcodeine Morphine Normorphine Norhydrocodone Hydrocodol Hydromorphone hydromorphol Propoxyphene Pentazocine Norpropoxyphene Metabolized almost exclusively in the liver 19 Thin-layer chromatography (TLC) Relatively old technique, testing the migration of a drug on a plate or film, which is compared to a known control Gas chromatography: liquid and mass spectometry (CGMS) Most sensitive and specific tests Most reliable Labor intensive/costly oseveral days to know results oused to confirm results of other tests 20 10

Enzyme immunoassay Easy to perform/highly sensitive More sensitive than TLC Less expensive than GC/MS Common tests o EMIT (enzyme multiplied immunoassay test) o FPIA (fluorescent polarization immunoassay) o RIA (radioimmunoassay) Screen only one drug at a time Rapid drug screens Similar to other enzyme immunoassay tests May be more expensive 21 Sensitivity and Specificity The qualitative immunoassay drug panel reports each sample as either positive or negative for a particular drug or drug class, based on predetermined cutoff concentrations. In the ideal world, a UDT would be positive if the patient took the drug (true positive) and negative if the drug was not taken (true negative) 22 11

Sensitivity and Specificity False-positive or False-negative results can occur, so it is imperative to interpret the UDT results carefully. Sensitivity of a test is the ability to detect a class of drugs. Specificity is the ability to identify a particular drug. A highly specific test gives few false-positive results and identifies individual drugs and/or their metabolites. A highly sensitive test is due, in part, to its ability to detect both the parent drug and/or metabolite, combined, to reach the cutoff concentration for a positive report - may false-positive. 23 Interpretations of urine drug test results Patient has taken drug Patient has not taken drug Positive test result True positive False positive Negative test result False negative True Negative Wolff K et al. Addiction 1999;94;1279-1298 24 12

True-Positive Results With a Medical Explanation A positive UDT due to: Medication prescribed by another physician Use of OTC products Consumption of certain foodstuffs which result in a positive screen 25 False-positive results Technician or clerical error Due to cross-reactivity with other compounds found in the urine. GC/MS is not influenced by cross-reacting compounds. Review all positive results with the patient to explore possible explanations. Verify all unexpected results with the laboratory to ensure their accuracy. 26 13

True-negative Results UDT results positive for prescribed medications Negative for undisclosed licit and illicit drugs is ideal. 27 False-negative Results A false-negative result is technically defined as a negative finding in a sample known to contain the drug of interest. laboratory or clerical error tampering with the urine sample. o Adulteration and substitution should be suspected if the characteristics of the urine sample are inconsistent with normal human urine. Creatinine ph and other tests (eg, nitrite) are also useful. 28 14

Performance characteristics of different types of assays for drugs of abuse. Turnaround Assay Sensitivity Specificity Accuracy time Cost Onsite Moderate-high Moderate Qualitative* Minutes $4-25 EMIT, Moderate-high Moderate Low-high 1-4 hours $1-5 FPIA, RIA, KIMS TLC Low-high High Qualitative* 1-4 hours $1-4 GC High High High Days $5-20 GC/MS High High High Days $10-100 KEY: EMIT = enzyme-multiplied immunoassay technique; FPIA = fluorescent polarization immunoassay; RIA = radioimmunoassay; KIMS = kinetic interaction of microparticles in solution; TLC = thin layer chromatogra phy; GC = gas chromatography; GC/MS = GC/mass spectrometry. * = Results for onsite tests and TLC assays are generally expressed only in qualitative terms (i.e., positive/negative); consequently, accuracy may be difficult to assess. Source: Cone EJ 29 Urine Drug Test Methods Cocaine: Very specific Tests for cocaine react principally with cocaine and its primary metabolite, benzoylecgonine. These tests have low cross-reactivity with other substances Very specific in predicting cocaine use. 30 15

Urine Drug Test Methods Cocaine, a topical anesthetic, is clinically used in certain trauma, dental, ophthalmoscopic, and otolaryngologic procedures. A patient s urine may test positive for up to 2 to 3 days. There is no structural similarity between other caines and cocaine or benzoylecgonine. cross-reaction does not occur. A positive UDT result for the cocaine metabolite, in the absence of a medical explanation, should be interpreted as due to deliberate use. 31 Cocaine Myths Coca Tea There have been rare, but documented cases of cocaine ingestion by drinking tea made from coca leaves. The product containing cocaine and/or related metabolites is illegal under the US Drug Enforcement Administration and Food and Drug Administration regulations. Patients should be advised not to use hemp products or coca tea. 32 16

Urine Drug Test Methods THC: Marijuna: Moderate Specificity Reasonable reliability Positive result Marinol False-positive result Protonix Hemp products 33 Marijuana Myths Passive Inhalation In extreme conditions (eg, it is possible to blow enough smoke in an individual s face to cause them to become positive for marijuana). But, cannot occur without the patient s knowledge. Medical Marijuana Marinol for the control of nausea, vomiting and appetite stimulant. More specific testing would be required to distinguish between natural and synthetic THC. 34 17

Urine Drug Test Methods Amphetamines: Low Specificity Tests for amphetamine/methamphetamine are highly cross-reactive. They will detect other sympathomimetic amines such as ephedrine and pseudoephedrine Not very predictive for amphetamine/methamphetamine use. Further testing is required. 35 Amphetamines: Positive results can be challenging due to structural similarities of: Many prescription and OTC products, including diet agents, decongestants, and certain drugs used in the treatment of Parkinson s disease. Knowledge of potential sources of amphetamine and methamphetamine can prevent misinterpretation of results. 36 18

Urine Drug Test Methods Opioids: Pitfalls Tests for opiates are very responsive for morphine and Codeine Do not distinguish which is present. Show a low sensitivity for semisynthetic/synthetic opioids such as oxycodone. A negative response does not exclude oxycodone, methadone use. 37 Opiate immunoassays designed to detect morphine and codeine do not reliably detect synthetic or semisynthetic opioids. Cross-reacting compounds can also be structurally unrelated to the standardizing compound. Several quinolone antibiotics (eg, levofloxacin, ofloxacin) can potentially cause false-positive results for opiates by common immunoassays, despite no obvious structural similarity with morphine. Quinolones are not misinterpreted as opiates by GC/MS. 38 19

Cross-reactivity Detection of a particular drug by a drug-class specific immunoassay depends on: The structural similarity of that drug or its metabolites to the compound used for standardization The urine concentration of that drug/metabolite, compared with the standardizing compound The ability of opiate immunoassays to detect synthetic or semisynthetic opioids, such as methadone or oxycodone, varies among assays due to differing cross-reactivity patterns Methadone, although an opioid, does not trigger a positive opioid immunoassay result unless a specific methadone test is used. In the case of oxycodone, even large concentrations in the urine may not reliably be detected. 39 Not detected on routine tests Methadone Oxycodone Propoxyphene Meperidine Pentazocine Buprenorphine Tramadol 40 20

Source of opioid analgesics Natural (from Opium) Codeine Morphine Thebaine Semisynthetic # (derived from Opium) Hydrocodone Oxycodone Hydromorphone Oxymorphone Buprenorphine Synthetic # (man-made) Meperidine Fentanyl series Proproxyphene Methadone 41 Metabolism of codeine, heroin, & morphine 42 21

True-Positive Results Misleading Opiates: Indicative of heroin use A morphine-positive UDT may also result from codeine and morphine in foodstuffs (eg, poppy seeds in some breads/confectionery) A specimen that tests positive for morphine with the presence of 6-monoacetylmorphine (6-MAM), a heroin metabolite, is definitive proof of recent heroin use The window of detection for 6-MAM is only a few hours after heroin use due to its short half life 43 Opioid Results: Codeine and Morphine Codeine is metabolized to morphine, so both substances may occur in urine following codeine use: A prescription for codeine may explain the presence of both drugs in the urine. A prescription for codeine does not normally explain the presence of only morphine. This is most consistent with: Use of morphine or heroin. Prescribed morphine cannot account for the presence of codeine. Codeine metabolizes to morphine, but the reverse does not occur. Codeine alone is possible due to a small proportion of patients who lack the cytochrome P450 2D6 enzyme necessary to convert codeine to morphine. 44 22

Metabolism of hydrocodone 45 PRACTICAL STRATEGIES Select a testing laboratory or POC supplier. Establish a routine UDT panel. Recommended drugs/drug classes to screen for are: Cocaine Marijuana Amphetamines Opiates Oxycodone Methadone Benzodiazepines Additional tests may be added as needed. 46 23

Specimen collection: Random collection is preferred. Unobserved urine collection is usually acceptable. If tampering is suspected, check urine temperature, ph, and creatinine. 47 How to use UDT results? Consult with laboratory regarding ANY unexpected results. Schedule an appointment to discuss abnormal/unexpected results with the patient; discuss in a positive, supportive fashion to enhance readiness to change/motivational enhancement therapy (MET) opportunities. Use results to strengthen physician-patient relationship and support positive behavior change. Chart results and interpretation. 48 24

Point-of-care Testing POC UDTs typically use immunochromatographic methods that produce visually-read results. Most POC tests are based on competitive binding to antibodies by drug(s) present in the urine and a drug conjugate that is bound to a porous membrane. In the absence of drug in the sample, a limited number of dyeconjugated antibodies bind the immobilized drug conjugate, forming a colored line (negative result) in the test window. When the amount of drug in a urine sample is equal to or exceeds the cutoff concentration of a particular device, the drug saturates the antibody, preventing antibody binding the immobilized drug conjugate. So no line forms in the window (positive result). This is a counterintuitive response. 49 Point-of-care Testing POC devices advantages Rapid turn-around-time Portable Easy to perform requires little training to achieve proficiency Cost POC potential disadvantages the subjective nature of the qualitative assays Lack of adequate quality assurance and quality control (eg, the integrity of the test reagents following transportation and storage) Data management issues 50 25

9 Panel One Step icup - (COC,THC,OPI,AMP,METH,PCP,BZO,BAR,MTD) The icup Drug Screen Cup is the simplest, self-contained on-step drug test. Results are visible within minutes. A positive result is indicated with one line and a negative result with two. An additional bonus with the icup is that you may photocopy the results allowing you to maintain a visual record of the test. icup offers a completely closed system for total urine specimen integrity and easy collection. The clear construction gives optimum observation of urine specimen. The icup drug screen kit is a single unit with no dipping or pouring. Test results develop quickly in the sealed unit. The system remains closed until disposal of the device. The icup drug screen is zero exposure, leak-proof and tamper-proof. FDA Approved, 99% Accurate, Set to the SAMSHA Cut-off levels, Results are Ready in Minutes Have an 18 month shelf-life 51 Drug Identification GC/MS, or other chromatrographic, identification for all patients prescribed opioids. Specify no threshold testing to detect lowest concentrations. 52 26

Excuses I can t afford a drug screen I can t pee right now I am late for work, school, NA meeting.. You know I don t have a problem. I will come back in the morning I have been drinking lot of water,soft drinks,coffee I took a fluid pill I am gaining weight I haven t eaten for five hours 53 PASS YOUR DRUG TEST 54 27

55 56 28

http://www.ipassedmydrugtest.com/ 57 58 29

59 Economy Model Accept no substitute 60 30

61 Office Based Detoxification Why to do it? Who can do it? When to do it? How to do it? 62 31

What is the Scope of the Problem? Epidemiological surveys show the problem of opioid dependence to be rapidly growing in the United States: Currently: 810,000-1 million chronic opioid (heroin) users At least 6.4 million abusers of prescription narcotics 12-17 y.o.: 12%, 18-25 y.o. 22% report prescription opioid abuse 1994-2001 ED visits: 352% increase in oxycodone visits, 131% increase in hydrocodone visits Currently only 200,000± patients receiving methadone maintenance In 5 states, and in some counties in other states, public policy prohibits establishment of Opiate Treatment Programs Detoxification has been shown to be of limited long-term effectiveness Access to treatment restricted 63 New Role for Physicians Increase access to treatment Offer treatment to patients outside the traditional methadone clinic system Mainstream the treatment of opioid dependence by coordinating it with treatment of the other medical conditions 64 32

Who Can Perform Office Detoxification? To use schedule II opiates for detoxification from opiate addiction, a special registration is required: (21 Code of Federal Regulation 1306.07(a)). Drug Abuse Treatment Act of 2000 allows physicians to use schedule III agents to detoxify chemical dependent patients in an office setting, provided the physician qualifies for and obtains a waiver issued through the Substance Abuse and Mental Health Services (SAMHSA) and the DEA. ** ** State regulations may require further registration 65 Who Can Perform Office Detoxification? when it is necessary to discontinue a pain patient's opioid therapy by tapering or weaning doses, there are no restrictions with respect to the drugs that may be used. This is not considered "detoxification" as it is applied to addiction treatment. Patricia Good, Chief of Policy Section, Office of Diversion and Control 66 33

Who Can Perform Office Detoxification? Federal Guidelines allow for use of opioids for analgesia in persons with substance abuse disorder for legitimate medical reasons. Clear documentation of the pain problem is needed to demonstrate the physician without proper credentials is not attempting to detoxify an opiate abuser. State regulations in certain states do no allow for this, and consider prescribing opioids in known substance abusers malprescribing. 67 Pain Doctors Can Detox Any nonabuser who is opioid dependent from legitimate pain treatment and desires or needs to stop opioid therapy. A pain patient with substance abuse issues who has been on opioid therapy for legitimate medical reasons. ** Persons with substance abuse problems IF the physician has obtained SAMHSA and DEA waiver for office based detoxification. ** Detoxification of substance abuse without ongoing addiction treatment may present major liability issues to the physician. 68 34

REASONS FOR DETOX? All are controversial Opioid Holiday?? Inevitable end of opioid therapy Unacceptable tolerance or side effects Inability to control opioid use Preoperative requirement Employment requirement 69 Symptoms of Mild Withdrawal Opiate craving Sweating Rhinorrhea Dilated pupils Anxiety Dysphoria Piloerection Restlessness Yawning Muscle twitching Nervousness Fatigue Increased respiration Irritability Headache Anorexia 70 35

Symptoms of Severe Withdrawal Fever Tachycardia Cutaneous Hypersensitivity Hypertension Isomnia Hot/cold flashes Nausea Vomiting Bone pain Muscle Aches/spasms Abdominal Cramps Diarrhea 71 Standard Taper Simple reduction of dosage when other therapies provide relief. Most chronic pain patients in such situations will autotaper, often at a faster rate than we would suggest. If pain remains significant, tapering may still be successful, although pain levels will increase. Dose reduction of 30% to 50% every 10 days almost never results in withdrawal syndrome. Many persons will tolerate reductions as high as 50% every 4 to 5 days. 72 36

Methadone Taper Used in reliable patients - risk of overdose May taper quickly over 3 to 10 days, or as long as 21 days. May transition to Ultram or Darvocet if done rapidly. Secondary withdrawal may occur 7 to 10 days after completion. 73 Adjunctive Treatments Clonidine (may be used as primary agent) Benzodiazepines / Barbiturates Antiepileptics (Tegretol) Insomnia treatment or plan Vistaril Antidiarrheal / Antiemetic 74 37

Ultrarapid detoxification Usually under anesthesia / heavy sedation Intravenous Naltrexone or Naloxone administered Immediate, severe withdrawal symptoms Complete in 4 to 23 hours Expensive Some sudden deaths reported 75 Buprenorphine Detoxification High Mu affinity, weak agonist Kappa antagonist Cytochrome P 450 metabolized > 50% bioavailable sublingually Available parenteral, subingual, or sublingual combined with Naloxone. 76 38

Buprenorphine Detoxification Not appropriate for high dose opioids: majority of patients at 60 mg Methadone per day will have withdrawal symptoms. Usually begin after 12 hours abstinence - patient in mild withdrawal. Begin with 2 mg dose, repeated every 2 hours to maximum 8 mg first day. May use adjunctive medications if needed. 77 Buprenorphine Detoxification May increase to as much as 16 or even 32 mg per day. Once stable dose is reached it is usually continued for 2 to 3 days Patient is then tapered over 2 to 3 weeks. 78 39

Buprenorphine Detoxification from Long Acting Opiates Taper to methadone 30 mg / day equivalent 24 hrs after last dose, give buprenorphine 2 mg Withdrawal symptoms present? Yes Give buprenorphine 2 mg Withdrawal symptoms continue? Yes Repeat dose up to maximum 8 mg/24 hrs No No Daily dose established Withdrawal symptoms relieved? No Manage withdrawal symptomatically Daily Yes dose established Increase to 16 mg / day on day 2 Adapted from H. Heit, M. D.; www.asam.org 79 with Office Detoxification Important component of treatment Rules and expectations Deter continued use or abuse Further treatment objectives Confront addiction Identify denial Random testing Monitoring conditions Responding to positive results More intense referral Increase the dose or switch to another drug 80 40

Laxmaiah Manchikanti, MD Phone: (270) 554-8373 ext. 101 Phone (ASIPP): (270) 554-9412 E-mail: drm@apex.net 81 41