Utility of sweat patch testing for drug use monitoring in outpatient treatment for opiate dependence

We evaluated the utility of sweat testing for monitoring of drug use in outpatient clinical settings and compared sweat toxicology with urine toxicology and self-reported drug use during a randomized clinical trial of the efficacy of buprenorphine for treatment of opioid dependence in primary care settings. All study participants (N = 63) were opiate-dependent, treatment-seeking volunteers. The results based on toxicology tests obtained from 188 properly worn and unadulterated patches (out of 536 applied) show that the level of agreement between positive sweat test results and positive urine results was 33% for opiates and 92% for cocaine. The findings of this study, that there is a low acceptability of sweat patch testing by patients (only 54.3% were brought back attached to the skin) and that weekly sweat testing is less sensitive than weekly urine testing in detecting opiate use, suggest limited utility of sweat patch testing in outpatient clinical settings.     

Estimating the prevalence of opiates use by unlinked anonymous urine drug testing: a pilot study in Iran

In order to estimate the prevalence of opiate use and to cross-validate the current program of urine testing as the sole screening and detection method for finding opiate abusers in Iran, urine samples of 1120 men with a mean (+/- SD) age of 46.6 (+/- 16.5) years referring to a large clinical lab for diagnostic and screening purposes in Kerman (the center of the biggest province in Iran) were assayed by anonymous, unlinked testing for opioid metabolites during 2004. The specimens were analyzed by an immunoassay screening test and a thin-layer chromatography (TLC) confirmation test. The initial screening test was positive in 28.8% (95% CI: 26.1-31.5) of cases (322 individuals), half of whom were confirmed by TLC. As a whole, 14.4% (95% CI: 12.4-16.6) of urine samples were positive for opioid metabolites. Although individuals referring to clinical labs do not exactly represent the general population, according to relatively high figures achieved in this study we suggest revising the urine test as the sole screening and detection method for finding Iranians who use opiates for non-medical reasons. Research is needed to further pursue these findings.     

Detection of opiate use in a methadone maintenance treatment population with the CEDIA 6-acetylmorphine and CEDIA DAU opiate assays

Heroin, with a plasma half-life of approximately 5 min, is rapidly metabolized to 6-acetylmorphine (6-AM). 6-AM, a specific marker for heroin use, which also has a short half-life of only 0.6 h, is detected in urine for only a few hours after heroin exposure. Ingestion of poppy seeds and/or licit opiate analgesics can produce positive urine opiate tests. This has complicated the interpretation of positive opiate results and contributed to the decision to raise opiate cutoff concentrations and to require 6-AM confirmation in federally mandated workplace drug-testing programs. Microgenics Corp. has developed the CEDIA 6-AM assay, a homogeneous enzyme immunoassay for semiquantitative determination of 6-AM in human urine, in addition to its CEDIA DAU opiate assay. Urine specimens were collected 3 times per week from 27 participants enrolled in a clinical research trial evaluating a contingency management treatment program for heroin and cocaine abuse. Of the 1377 urine specimens screened, 261 (18.9%) were positive for opiates at > or = 300 ng/mL, 153 (11.1%) were positive for opiates at > or = 2000 ng/mL, and 55 (4.0%) were positive for 6-AM at > or = 10 ng/mL. For opiate-positive screens > or = 300 and > or = 2000 ng/mL, 91.3% and 80.8% confirmed positive for morphine or codeine at the respective gas chromatography-mass spectrometry (GC-MS) cutoffs. All specimens screening positive for 6-AM also confirmed positive by GC-MS at > or = 10 ng/mL. Increasing the opiate screening and confirmation cutoffs for the federal workplace drug-testing program resulted in 8% fewer opiate-positive tests; however, recent heroin use was not affected by this change.     

Estimating the Prevalence of Opiates Use by Unlinked Anonymous Urine Drug Testing: A Pilot Study in Iran

In order to estimate the prevalence of opiate use and to cross-validate the current program of urine testing as the sole screening and detection method for finding opiate abusers in Iran, urine samples of 1120 men with a mean (± SD) age of 46.6 (± 16.5) years referring to a large clinical lab for diagnostic and screening purposes in Kerman (the center of the biggest province in Iran) were assayed by anonymous, unlinked testing for opioid metabolites during 2004. The specimens were analyzed by an immunoassay screening test and a thin-layer chromatography (TLC) confirmation test. The initial screening test was positive in 28.8% (95% CI: 26.1–31.5) of cases (322 individuals), half of whom were confirmed by TLC. As a whole, 14.4% (95% CI: 12.4–16.6) of urine samples were positive for opioid metabolites. Although individuals referring to clinical labs do not exactly represent the general population, according to relatively high figures achieved in this study we suggest revising the urine test as the sole screening and detection method for finding Iranians who use opiates for non-medical reasons. Research is needed to further pursue these findings.     

Diffusion and Diversion of Suboxone: An Exploration of Illicit Street Opioid Selling

Interviews with fourteen opioid retail pill sellers provides an exploration into the diversion and diffusion of Suboxone to recreational (“week-end warriors”) drug users. The use of social media and electronic devices enables the diffusion of Suboxone to dependent and non-dependent opiate/opioid drug abusers. Overprescribing by physicians and prescribing in drug treatment settings fuels the diversion of Suboxone. The diversion and the diffusion of Suboxone have the potential to delay entrance into drug treatment and promote the misuse of the drug by both dependent opiate/opioid drug abusers and recreational users. The dilemma posed by Suboxone maintenance treatment will not be easily addressed or mitigated in the near future.     

Predictors of outcome after short-term stabilization with buprenorphine

Using buprenorphine as a medication to treat opioid dependence is becoming more prevalent as illicit opiate use increases. Identifying the characteristics of opiate dependent individuals best suited to benefit from buprenorphine would improve guidelines for its administration. This study evaluates baseline and treatment participation variables for predicting positive response to short-term stabilization with buprenorphine. Data include demographic, drug use, and other variables collected from participants undergoing stabilization over a 4-week period before being tapered off buprenorphine in a short-term detoxification process. Outcome variables include opioid use and retention. Logistic regression results indicate several characteristics associated with opioid use at the end of the stabilization period. These include being older, having no criminal history, and less opiate use. Criminal activity and opioid use in the last 30 days were significantly associated with shorter treatment stays. The benefits of identifying individual characteristics that may predict treatment response are discussed.     

Increasing opiate abstinence through voucher-based reinforcement therapy

Heroin dependence remains a serious and costly public health problem, even in patients receiving methadone maintenance treatment. This study used a within-subject reversal design to assess the effectiveness of voucher-based abstinence reinforcement in reducing opiate use in patients receiving methadone maintenance treatment in an inner-city program. Throughout the study subjects received standard methadone maintenance treatment involving methadone, counseling, and urine monitoring (three times per week). Thirteen patients who continued to use opiates regularly during a 5-week baseline period were exposed to a 12-week program in which they received a voucher for each opiate-free urine sample provided; the vouchers had monetary values that increased as the number of consecutive opiate-free urines increased. Subjects continued receiving standard methadone maintenance for 8 weeks after discontinuation of the voucher program (return-to-baseline). Tukey's posthoc contrasts showed that the percentage of urine specimens that were positive for opiates decreased significantly when the voucher program was instituted (P ≤ 0.01) and then increased significantly when the voucher program was discontinued during the return-to-baseline condition (P ≤ 0.01). Rates of opiate positive urines in the return-to-baseline condition remained significantly below the rates observed in the initial baseline period (P ≤ 0.01). Overall, the study shows that voucher-based reinforcement contingencies can decrease opiate use in heroin dependent patients receiving methadone maintenance treatment.     

Excretion profile of opiates in dependent patients in relation to route of administration and type of drug measured in urine with immunoassay

It is accepted that opiates are detectable in urine within three days from the last dose at a cut-off value of 300 ng/mL. In our clinical practice, some patients tested positive for morphine even after a week of detoxification. The present study evaluates the time course of opiate excretion in urine of dependent subjects (F11.25 according to ICD-10) in relation to route of administration and a kind of street heroin. The group comprised 71 men treated for opiate dependency: 33 of them used heroin exclusively by inhalation; 26 i.v.; 12 used i.v. homemade poppy straw decoctions. Opiate levels were measured once a day by fluorescence polarization immunoassay (TDx Abbott). Detection time ranged from 3 to 10 days for cut-off value 300 ng/mL and from less than one up to seven days for cut-off value 2000 ng/mL. The increases in urine drug concentration that result from changes in urinary output may be mistakenly interpreted as a new drug use. Normalization of drug excretion to urine creatinine concentration reduces the variability of drug measurement attributable to urine dilution. The time function of creatinine normalized opiate concentration has a log-linear character, and decreases at a rate of 2.5 per day on average. New "normalized" cut-off values were proposed: 225 ng/mg creatinine, 1500 ng/mg creatinine, and 3750 ng/mg creatinine that corresponds to 300 ng/mL urine, 2000 ng/mL urine, and 5000 ng/mL urine.     

Monitoring opiate use in substance abuse treatment patients with sweat and urine drug testing

Although urine testing remains the standard for drug use monitoring, sweat testing for drugs of abuse is increasing, especially in criminal justice programs. One reason for this increase is sweat testing may widen the detection window compared to urine testing. Drug metabolites are rapidly excreted in urine limiting the window of detection of a single use to a few days. In contrast, sweat collection devices can be worn for longer periods of time. This study was designed to compare the efficacy of sweat testing versus urine testing for detecting drug use. Paired sweat patches that were applied and removed weekly on Tuesdays were compared to 3-5 consecutive urine specimens collected Mondays, Wednesdays, and Fridays (355 matched sweat and urine specimen sets) from 44 patients in a methadone-maintenance outpatient treatment program. All patches (N = 925) were extracted in 2.5 mL of solvent and analyzed by ELISA immunoassay for opiates (cutoff concentration 10 ng/mL). A subset (N = 389) of patches was analyzed by gas chromatography-mass spectrometry (GC-MS). Urine specimens (N = 1886) were subjected to qualitative analysis by EMIT (cutoff 300 ng/mL). Results were evaluated to (1) determine the identity and relative amounts of opiates in sweat; (2) assess replicability in duplicate patches; (3) compare ELISA and GC-MS results for opiates in sweat; and (4) compare the detection of opiate use by sweat and urine testing. Opiates were detected in 38.5% of the sweat patches with the ELISA screen. GC-MS analysis confirmed 83.4% of the screen-positive sweat patches for heroin, 6-acetylmorphine, morphine, and/or codeine (cutoff concentration 5 ng/mL) and 90.2% of the screen-negative patches. The sensitivity, specificity, and efficiency of ELISA opiate results as compared to GC-MS results in sweat were 96.7%, 72.2%, and 89.5%, respectively. Heroin and/or 6-acetylmorphine were detected in 78.1% of the GC-MS-positive sweat patches. Median concentrations of heroin, 6-acetylmorphine, morphine, and codeine in the positive sweat samples were 10.5, 13.6, 15.9, and 13.0 ng/mL, respectively. Agreement in paired sweat patch test results was 90.6% by ELISA analysis. For the purposes of this comparison of ELISA sweat patch to EMIT urine screening for opiates, the more commonly used urine test was considered to be the reference method. The sensitivity, specificity, and efficiency of sweat patch results to urine results for opiates were 68.6%, 86.1%, and 78.6%, respectively. There were 13.5% false-negative and 7.9% false-positive sweat results as compared to urine tests. Analysis of sweat patches provides an alternate method for objectively monitoring drug use and provides an advantage over urine drug testing by extending drug detection times to one week or longer. In addition, identification of heroin and/or 6-acetylmorphine in sweat patches confirmed the use of heroin in 78.1% of the positive cases and differentiated illicit heroin use from possible ingestion of codeine or opiate-containing foods. However, the percentage of false-negative results, at least in this treatment population, indicates that weekly sweat testing may be less sensitive than thrice weekly urine testing in detecting opiate use.     

Positive predictive values of abused drug immunoassays on the Beckman Synchron in a veteran population

The pressure to reduce the cost of analytic testing makes it tempting to discontinue routine confirmation of urine specimens positive for drugs of abuse by immunoassay. Beyond the economic motivation, the requirement for confirmation should be driven by the positive predictive value of the screening tests. We have quantitated positive predictive values of our screening immunoassays in a large metropolitan Veterans Affairs Medical Center. We reviewed the confirmatory rate of urine specimens positive for drugs of abuse with Beckman Synchron reagents from June 1998 to June 1999 and tabulated the false-positive screening rate. There were 175 instances of false-positive screens during the 13 months we analyzed. Positive predictive values ranged from 0% (amphetamine) to 100% (THC). We determined that the low positive predictive value of the amphetamine assay in our laboratory was primarily due to the use of ranitidine (Zantac). Urine specimens containing greater than 43 microg/mL ranitidine were positive in our amphetamine assay. This concentration is routinely exceeded in our patients taking ranitidine. In our clinical and analytic setting, the Beckman THC assay did not require confirmation. The positive predictive values of the Beckman opiate, cocaine, barbiturate, propoxyphene, and methadone immunoassays dictate routine confirmatory testing in specimens that screen positive for these substances. Finally, because of its extreme sensitivity to ranitidine, the Beckman amphetamine assay has little utility in our laboratory setting.     

Experience with a urine opiate screening and confirmation cutoff of 2000 ng/mL.

Until recently, most laboratories used an opiate immunoassay screening and confirmation cutoff value of 300 ng/mL for codeine and morphine detection by gas chromatography-mass spectrometry (GC-MS). The cutoff value for opiates was increased to 2000 ng/mL or higher in various laboratories because of concerns that small doses of codeine and foods containing poppy seeds would give a positive opiate-screening result. Workplace drug-testing programs in the U.S. raised the opiate cutoff value to 2000 ng/mL on 30 November 1998. The objective of this study is to describe the results of opiate testing of 8600 urine specimens collected over 24 months with a 2000-ng/mL screening and confirmation (codeine and morphine) cutoff value. Specimens were screened by the EMITdau opiate assay using an in-house 2000-ng/mL morphine calibrator. Presumptive positive findings (N = 621) were analyzed quantitatively by GC-MS for codeine and morphine. One hundred and eighty six urine specimens were positive for codeine and morphine (> 2000 ng/mL), 298 specimens were positive for codeine only (> 2000 ng/mL) and 26 specimens were positive for morphine only (> 2000 ng/mL). All remaining specimens had codeine and morphine values < 2000 ng/mL. The codeine and morphine confirmation rate in this program reduced from 7.1% in 1994-1996 (300-ng/mL cutoff) to 2.1% in 1997-1998 with a 2000-ng/mL cutoff value. The codeine-only confirmation rate lowered from 6.6% (300-ng/mL cutoff) to 3.4% (2000-ng/mL cutoff). It was concluded that increasing opiate screening and codeine and morphine confirmation cutoff values led to > 300% reduction in the confirmed-positive rate for codeine and morphine and a 47% reduction in codeine-only confirmations in a urine drug-testing program where codeine was the major opiate used.     

Marijuana and Workplace Safety: An Examination of Urine Drug Tests

Although the decriminalization of recreational marijuana and medical marijuana laws provide a compassionate answer for treatment-related issues in patients’ lives, they leave questions open as to the impact on other realms of life, such as employment and safety. This is a case-control study comparing the proportion of marijuana positive urine specimens for post-accident verses random samples. The marijuana concentration of each sample underwent creatinine normalization to account for in vivo dilution. Any sample that tested positive for one or more substances other than marijuana was eliminated from the study. The prevalence of marijuana violations, the odds ratio and 95% confidence interval of accident involvement and the population attributable risk were calculated. A two-by-two table was created with the remaining data and the data were used to calculate the odds ratio, resulting in a value of 0.814 with a 95% confidence interval between 0.625 and 1.060. The Fisher exact probability test generated a 2-tailed P of .139. The subsequent population attributable risk was found to be –1.83%. These findings fail to reject the null hypothesis, and this study failed to demonstrate a statistically significant difference between the numbers of laboratory positive marijuana urine drug tests for a group of random drug tests compared with a group of post-accident drug tests.