Urine Drug Test Results Research Articles

They Don’t Know What They Don’t Know: Internal Medicine Residents’ Knowledge and Confidence in Urine Drug Test Interpretation for Patients with Chronic Pain

Urine drug testing (UDT) can help identify misuse or diversion of opioid medications among patients with chronic pain. However, misinterpreting results can lead to false reassurance or erroneous conclusions about drug use. To examine the relationship between resident physicians' knowledge about UDT interpretation and confidence in their ability to interpret UDT results. Cross-sectional survey. Internal medicine residents in a university health system in the Bronx, from 2010 to 2011. We assessed knowledge using a 7-item scale (UDT knowledge score), and confidence in UDT interpretation using a single statement ("I feel confident in my ability to interpret the results of urine drug tests"). We conducted chi-square tests, t-tests, and logistic regression to determine the association between knowledge and confidence, and in exploratory analyses to examine whether resident characteristics (gender, training level, and UDT use) moderated the relationship between knowledge and confidence. Among 99 residents, the mean UDT knowledge score was 3.0 out of 7 (SD 1.2). Although 55 (56 %) of residents felt confident in their ability to interpret UDT results, 40 (73 %) of confident residents had a knowledge score of 3 or lower. Knowledge score was not associated with confidence among the full sample or when stratified by training level or UDT use. The association between knowledge and confidence differed significantly by gender (interaction term p<0.01). Adjusting for training level and UDT use, knowledge was positively associated with confidence among females (AOR 1.79, 95 % CI: 1.06, 3.30), and negatively associated with confidence among males (AOR 0.47, 95 % CI: 0.23, 0.98). Despite poor knowledge about UDT interpretation, most resident physicians felt confident in their ability to interpret UDT results. Gender differences warrant further exploration, but even confident physicians who use UDT should evaluate their proficiency in interpreting UDT results. Educational initiatives should emphasize the complexities of UDT interpretation.

How Can the Clinical Picture Guide Appropriate Laboratory Drug Testing in the Treatment of Pain Clinic Patients with Opioid Analgesics?

It can be overwhelming when attempting to fully comprehend clinical scenarios associated with managing patients in pain clinics. Providers must correctly interpret multiple data sources in order to guide both patient treatment and management. Such data include details from the patient's clinic visit, social history, and urine drug testing (UDT) results. Substance abuse, in conjunction with aberrant behavior, can confound the clinical picture and has led some clinicians to marginalize lab results when considering treatment. Overlooking lab results or inappropriate use of the lab can multiply negative impacts associated with poor UDT interpretation skills. In such cases where clinicians fail to elucidate a clear clinical picture, outcomes due to inappropriate use of resources often lead to patient mismanagement and may lead to patient harm or death. Safe and clinically appropriate opioid prescribing requires a fundamental understanding of both pain management and laboratory testing. The challenge is to narrow information gaps between these two areas in order to improve patient management by diminishing overdose risk, drug abuse, aberrant behavior, and diversion. The need for evidence-based practice in terms of acceptable standards for lab use and interpreting UDTs has been expressed by opinion leaders in pain management who contend that UDTs are essential to assess and guide treatment. Pain management experts and laboratory medicine specialists agree that a UDT, like any lab test, can lead to negative patient impact unless an accurate result interpretation is made in the context of each case. Due to the likelihood of negative outcomes that accompany inappropriate result interpretation, the need for standardization is evident when treating and managing patients in pain clinics. While a universal treatment and management algorithm currently does not exist, elements of a standardization plan should be developed using guidelines requiring that practice is …

Medication and Illicit Substance Use Analyzed Using Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) in a Pain Population

Background: Patients on chronic opioid therapy are often closely monitored to identify prescribed or nonprescribed medications and/or illicit substances and to identify medication use that may lead to adverse events. Monitoring is typically performed using a combination of clinical tools and assessment methods that often include patient medication histories, risk assessments, and medication monitoring with urine testing. The chronic pain population may be prescribed an average of three to five medications for pain and associated symptoms. In addition to prescribed therapies, this patient population often takes non-prescribed medications and/or illicit substances. Medication monitoring with Urine Drug Testing (UDT), particularly when performed using mass spectrometry, provides accurate information about medications and illicit substances present in the urine. Purpose of the study: To use LC-MS/MS analyses to describe the variety of medications and metabolites observed in urine specimens from individuals on opioid therapy. Methods: Analytical procedures were developed using LC-MS/MS that could detect and differentiate between various opioids and their metabolites, other medications commonly prescribed for pain, and certain illicit substances. This retrospective analysis used approximately 340,000 de-identified specimens tested between November 2011 and February 2012 at Millennium Laboratories. Data was sorted to determine frequency of detection and concentrations of the excreted drugs and metabolites. Results: The most frequently observed medications were hydrocodone and oxycodone, and their metabolites. The next most frequently observed medication was the benzodiazepine class followed by gabapentin, buprenorphine, and morphine. Additionally, illicit substances were detected in 15% of specimens; the most common illicit substances were cannabinoids and cocaine. Conclusions: Urine drug testing, using LC-MS/MS technology with validated cutoff values for each analyte, provides objective data for providers to use when assessing medication use, potential drug-drug interactions, potential adverse events, and possible diversion. Specific identification of both the medication or substance and the associated metabolites allows for informed interpretation of UDT results. Understanding the medications and illicit substances found in UDT specimens from the pain population helps providers optimize medication monitoring for the best possible plan for pain management.

Double-blind placebo-controlled evaluation of the PROMETA™ protocol for methamphetamine dependence

To evaluate the efficacy and safety of the PROMETA™ Protocol for treating methamphetamine dependence. A double-blind, placebo-controlled 108-day study with random assignment to one of two study conditions: active medication with flumazenil (2 mg infusions on days 1, 2, 3, 22, 23), gabapentin (1200 mg to day 40) and hydroxazine (50 mg to day 10) versus placebo medication (with active hydroxazine only). Three substance abuse treatment clinics: two in-patient, one out-patient. Treatment-seeking, methamphetamine-dependent adults (n = 120). Primary outcome was percentage of urine samples testing negative for methamphetamine during the trial. No statistically significant between-group differences were detected in urine drug test results, craving, treatment retention or adverse events. The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving.

A Case of Psychosis After Use of a Detoxification Kit and a Review of Techniques, Risks, and Regulations Associated With the Subversion of Urine Drug Tests

The practice of drug testing in the workplace has been adopted for US federal government employees, and many state and local governments as well as private businesses have followed suit. However, a parallel industry dedicated to subverting the results of urine drug testing has emerged with little or no regulation. First, the case of a 19-year-old man who developed psychosis after the use of a detoxification kit is presented. Second, a review of the existing literature on the techniques, risks, and regulations associated with the use of drug tampering kits is provided. PubMed, Cochrane Database, and Google Scholar were searched using the keywords UDS, urine toxicology, pass the drug test, and clean UA, with no restrictions on publication date. Case reports, letters to the editor, and original research and review articles in multiple languages were reviewed, as were federal regulations and acts on the topic. The search yielded 4,082 results, of which 49 articles were selected for relevance. Some articles were later omitted as they had cited the original article and had nothing new to offer. Three commonly used tampering techniques are in vivo adulteration, urine substitution, and in vitro adulteration. Review of the literature regarding the risks involved with use of tampering kits yielded no results. In 1986, an executive order was issued requiring all federal employees to refrain from illicit drug use, and the 1988 Drug-Free Workplace Act precipitated the Substance Abuse and Mental Health Services Administration guidelines and their subsequent revisions. Recently, many states have made regulatory efforts to bring drug test defrauding under the ambit of law. Clinicians need to be aware of the tampering techniques and the possibility of false-negative urine drug tests. Cognizance of inherent risks involved with using these techniques including psychiatric and/or medical complications is also warranted. The manufacture, sale, and use of these products have little or no regulation by state or federal authorities, making them potentially dangerous and imposing new challenges in testing for abused drugs. The extent of use of these products and techniques is not known at this time and is an area that warrants further research.

Comparative Evaluation of the Accuracy of Benzodiazepine Testing in Chronic Pain Patients Utilizing Immunoassay with Liquid Chromatography Tandem Mass Spectrometry (LC/ MS/MS) of Urine Drug Testing

Background: Eradicating or appreciably limiting controlled prescription drug abuse, such as opioids and benzodiazepines, continues to be a challenge for clinicians, while providing needed, proper treatment. Detection of misuse and abuse is facilitated with urine drug testing (UDT). However, there are those who dispute UDT’s diagnostic accuracy when done in the office (immunoassay) and claim that laboratory confirmation using liquid chromatography tandem mass spectrometry (LC/MS/MS) is required in each and every examination. Study Design: A diagnostic accuracy study of UDT. Study Setting: The study was conducted in a tertiary referral center and interventional pain management practice in the United States. Objective: Comparing UDT results of in-office immunoassay testing (the index test) with LC/MS/ MS (the reference test). Methods: A total of 1,000 consecutive patients were recruited to be participants. Along with demographic information, a urine sample was obtained from them. A nurse conducted the immunoassay testing at the interventional pain management practice location; a laboratory conducted the LC/MS/ MS. All index test results were compared with the reference test results. The index test’s efficiency (agreement) was calculated as were calculations for sensitivity, specificity, false-positive, and false-negative rates. Results: Approximately 36% of the specimens required confirmation. The index test’s efficiency for prescribed benzodiazepines was 78.4%. Reference testing improved accuracy to 83.2%, a 19.6% increase, and 8.9% of participants were found to be taking non-prescribed benzodiazepines. The index test’s false-positive rate for benzodiazepines use was 10.5% in patients receiving benzodiazepines. Limitations: This study was limited by its single-site location, its use of a single type of point of care (POC) kit, and reference testing being conducted by a single laboratory, as well as technical sponsorship. Conclusion: Clinicians should feel comfortable conducting in-office UDT immunoassay testing. The present study shows that it is reliable, expedient, and fiscally sound for all involved. In-office immunoassay testing compares favorably with laboratory testing for benzodiazepines, offering both high specificity and agreement. However, clinicians should be vigilant and wary when interpreting results, weighing all factors involved in their decision. Key words: Controlled substances, benzodiazepines, opioids, illicit drugs, abuse, liquid chromatography tandem mass spectrometry, immunoassay, urine drug testing

Can clinicians accurately predict which patients are misusing their medications?

Identifying patients on chronic opioid therapy who may be abusing or misusing their medications remains difficult despite the numerous risk assessment tools available. In this study, clinicians were asked to identify patients who they thought were at risk for medication misuse and those that weren't based on risk assessment methods used in their practice. In addition, a third group was identified as a random sample where no risk assessments were performed. Urine drug testing results were then compared with these assessments. For the purposes of this study, urine drug testing results were considered abnormal if illicits were present or if the prescribed medications were absent from the urine sample. A total of 549 samples were received from 62 clinicians in 50 practices. Clinician assessments of patients who were thought to potentially be misusing their medications (N= 173) were correct 72% of the time. In patients they thought were not at risk for misuse of medications (N=204) they were only correct in 40% of patients, with 60% of this group, who were thought to be compliant, having urine drug tests showing illicits, missing prescribed medication or both. The third random group (N=172) showed 61% of samples were normal and 30% abnormal. Overall, the ability of clinicians to correctly categorize patients into the two groups was only slightly better than by chance alone. Accuracy was greater in the group thought to be misusing, but in the group thought to be compliant, clinicians missed 60% of patients who had an abnormal urine drug test. This study reinforces that all patients on chronic opioid therapy need to have urine drug monitoring in order to identify those patients who may be misusing their medications as risk assessment methods utilized in practice settings may miss a significant portion of these patients.

Collaborative Care of Opioid-Addicted Patients in Primary Care Using Buprenorphine

Opioid addiction is a chronic disease treatable in primary care settings with buprenorphine hydrochloride, but this treatment remains underused. We describe a collaborative care model for managing opioid addiction with buprenorphine hydrochloride-naloxone hydrochloride dihydrate sublingual tablets. Ours is a cohort study of patients treated for opioid addiction using collaborative care between nurse care managers and generalist physicians in an urban academic primary care practice during a 5-year period. We examine patient characteristics, 12-month treatment success (ie, retention or taper after 6 months), and predictors of successful outcomes. From September 1, 2003, through September 30, 2008, 408 patients with opioid addiction were treated with buprenorphine. Twenty-six patients were excluded from analysis because they left treatment owing to preexisting legal or medical conditions or a need to transfer to another buprenorphine program. At 1 year, 196 of 382 patients (51.3%) underwent successful treatment. Of patients remaining in treatment at 12 months, 154 of 169 (91.1%) were no longer using illicit opioids or cocaine based on urine drug test results. On admission, patients who were older, were employed, and used illicit buprenorphine had significantly higher odds of treatment success; those of African American or Hispanic/Latino race had significantly lower odds of treatment success. These outcomes were achieved with a model that facilitated physician involvement. Collaborative care with nurse care managers in an urban primary care practice is an alternative and successful treatment method for most patients with opioid addiction that makes effective use of time for physicians who prescribe buprenorphine.

Comparative Evaluation of the Accuracy of Immunoassay with Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS) of Urine Drug Testing (UDT) Opioids and Illicit Drugs in Chronic Pain Patients

Background: The challenge for physicians in treating chronic pain with opioids is to eliminate or significantly curtail abuse of controlled prescription drugs while assuring proper treatment when indicated. Urine drug testing (UDT) has been shown to be a useful approach in identifying patterns of compliance, misuse, and abuse. However, significant controversy surrounds the diagnostic accuracy of UDT performed in the office (immunoassay) and the requirement for laboratory confirmation with liquid chromatography tandem mass spectrometry (LC/MS/MS). Study Design: A diagnostic accuracy study of urine drug testing. Study Setting: The study was performed in an interventional pain management practice, a tertiary referral center, in the United States. Objective: The objective of this study was to compare the results of UDT of immunoassay inoffice testing (index test) to LC/MS/MS (reference test). Methods: One-thousand participants were recruited from an interventional pain management program. Urine sample was collected from all the consecutive patients with demographic information. Immunoassay testing was performed by a nurse at the location, laboratory assessment was performed with LC/MS/MS. Results of the index test were compared to the reference test in all patients. The sensitivity, specificity, false-positive, and false-negative rates, and index test efficiency (agreement) were calculated. Results: Overall, results showed that confirmation was required in 32.9% of the specimens. Agreement for prescribed opioids was high with the index test (80.4%). The reference test of opioids improved the accuracy by 8.9% from 80.4% to 89.3%. Non-prescribed opioids were used by 5.3% of patients. The index test provided false-positive results for non-opioid use in 44% or 83 of 120 patients. For illicit drugs, the false-positive rate by index test was 0% for cocaine, whereas it was 2% for marijuana, 0.9% for amphetamines, and 1.2% for methamphetamines. Limitations: The limitations include a single site study utilizing a single POC kit and a single laboratory, as well as technical sponsorship. Conclusion: The UDT with immunoassay in an office setting is appropriate, convenient, and cost-effective. Compared with laboratory testing for opioids and illicit drugs, immunoassay inoffice testing had high specificity and agreement, demonstrating the value of immunoassay drug testing. Because of variable sensitivity, clinicians would be well-advised to take a cautious approach when interpreting the results. Key words: Controlled substances, opioids, illicit drugs, abuse, liquid chromatography tandem mass spectrometry, immunoassay, urine drug testing

Association Between Urine Drug Test Results and Treatment Outcome in High-Risk Chronic Pain Patients on Opioids

: How to best use urine drug test (UDT) results in the management of opioid pharmacotherapy has not been elucidated. The purpose of this study was to describe how the results of UDTs gathered from a group of chronic pain patients in a high-risk monitored opioid pharmacotherapy program apply to treatment outcome. : Retrospective review of the medical records of 335 primary care patients on chronic opioids more than 22 months. : Patients with a UDT containing unprescribed opioids were more likely to demonstrate resolution of aberrant behavior (P = 0.02) and less likely to be discharged from treatment (P = 0.04). Patients with cocaine, alone or in combination, in the UDT were less likely to resolve aberrant behavior (P = 0.007 and 0.001), and were more likely to be electively or administratively discharged from treatment (P = 0.012 and 0.001). : In this group of high-risk pain patients on chronic opioids, information gained from UDT results can be used to predict treatment outcomes and inform appropriate interventions. Patients on chronic opioids who have a UDT positive for an illicit opioid or unprescribed opioids alone are more likely to respond to monitored opioid pharmacotherapy. Patients with a UDT positive for cocaine, alone or in combination, are less likely to resolve aberrant behavior within the structure of a monitored opioid pharmacotherapy program and are more likely to be discharged electively or administratively from the program without significant transition to addiction treatment. Further studies are needed to investigate which patient responded best to structured opioid pharmacotherapy programs and how to appropriately handle abnormal UDT results to improve the management and engagement in appropriate treatment for this population.

Clinic-Based Treatment of Opioid-Dependent HIV-Infected Patients Versus Referral to an Opioid Treatment Program

Opioid dependence is common in HIV clinics. Buprenorphine-naloxone (BUP) is an effective treatment of opioid dependence that may be used in routine medical settings. To compare clinic-based treatment with BUP (clinic-based BUP) with case management and referral to an opioid treatment program (referred treatment). Single-center, 12-month randomized trial. Participants and investigators were aware of treatment assignments. (ClinicalTrials.gov registration number: NCT00130819) HIV clinic in Baltimore, Maryland. 93 HIV-infected, opioid-dependent participants who were not receiving opioid agonist therapy and were not dependent on alcohol or benzodiazepines. Clinic-based BUP included BUP induction and dose titration, urine drug testing, and individual counseling. Referred treatment included case management and referral to an opioid-treatment program. Initiation and long-term receipt of opioid agonist therapy, urine drug test results, visit attendance with primary HIV care providers, use of antiretroviral therapy, and changes in HIV RNA levels and CD4 cell counts. The average estimated participation in opioid agonist therapy was 74% (95% CI, 61% to 84%) for clinic-based BUP and 41% (CI, 29% to 53%) for referred treatment (P < 0.001). Positive test results for opioids and cocaine were significantly less frequent in clinic-based BUP than in referred treatment, and study participants receiving clinic-based BUP attended significantly more HIV primary care visits than those receiving referred treatment. Use of antiretroviral therapy and changes in HIV RNA levels and CD4 cell counts did not differ between the 2 groups. This was a small single-center study, follow-up was only moderate, and the study groups were unbalanced in terms of recent drug injections at baseline. Management of HIV-infected, opioid-dependent patients with a clinic-based BUP strategy facilitates access to opioid agonist therapy and improves outcomes of substance abuse treatment. Health Resources and Services Administration Special Projects of National Significance program.

Unexpected Urine Drug Testing Results in a Hospice Patient on High-Dose Morphine Therapy

A 41-year-old African-American woman was admitted to an inpatient hospice facility with advanced, inoperable cervical cancer. The patient was experiencing severe pain secondary to extensive local tumor invasion, osseous pelvic metastases, and sacral decubitus ulcers. Her pain was treated with an escalating-dose schedule of morphine sulfate until satisfactory analgesia was achieved with stable doses of a combination of controlled-release morphine sulfate (MSContin®, Purdue Pharma LP) 400 mg orally every 8 h, and immediate-release morphine sulfate (MSIR®, Purdue Pharma LP), 180 mg orally every 4 h, as needed for breakthrough pain (average 2 to 3 doses per day). The patient experienced several episodes of life-threatening vaginal bleeding for which she was hospitalized for red blood cell transfusions and bilateral hypogastric artery embolizations. She spent the final 12 weeks of her life exclusively on the inpatient hospice unit. Approximately 3 weeks before her death, the patient underwent urine specimen collection and analysis of morphine and metabolites. GC-MS analysis revealed the presence of morphine as well as small quantities of hydromorphone. During the past 2 decades, chronic opioid analgesic therapy (COAT) for chronic nonmalignant pain has gained increasing clinical acceptance. An unintended consequence of more liberal opioid prescription practices has been a dramatic increase in the abuse and diversion of these drugs. According the most recent National Survey on Drug Abuse and Health (1), the number of new, past-year abusers of prescription opioids was 2 147 000—more than the number of new abusers of any other single class …

‘False-Positive’ and ‘False-Negative’ Test Results in Clinical Urine Drug Testing

The terms 'false-positive' and 'false-negative' are widely used in discussions of urine drug test (UDT) results. These terms are inadequate because they are used in different ways by physicians and laboratory professionals and they are too narrow to encompass the larger universe of potentially misleading, inappropriate and unexpected drug test results. This larger universe, while not solely comprised of technically 'true' or 'false' positive or negative test results, presents comparable interpretive challenges with corresponding clinical implications. In this review, we propose the terms 'potentially inappropriate' positive or negative test results in reference to UDT results that are ambiguous or unexpected and subject to misinterpretation. Causes of potentially inappropriate positive UDT results include in vivo metabolic conversions of a drug, exposure to nonillicit sources of a drug and laboratory error. Causes of potentially inappropriate negative UDT results include limited assay specificity, absence of drug in the urine, presence of drug in the urine, but below established assay cutoff, specimen manipulation and laboratory error. Clinical UDT interpretation is a complicated task requiring knowledge of recent prescription, over-the-counter and herbal drug administration, drug metabolism and analytical sensitivities and specificities.

Substance use and quality of life over 12 months among buprenorphine maintenance-treated and methadone maintenance-treated heroin-addicted patients

The purpose of this study was to investigate the effects of methadone treatment and buprenorphine treatment on retention in treatment, urine drug testing results, psychiatric status, social adjustment, and quality of life among patients involved in long-term treatment with the cited medications. Two hundred thirteen patients (106 on buprenorphine treatment and 107 on methadone treatment) were enrolled in this open study at the 3rd month of their treatment and followed up until the 12th month; those who left the program before the end of the 3rd month of their treatment were not included in the study sample. The results of this study show statistically significant improvements in opioid use, psychiatric status, and quality of life between the 3rd and 12th months for both medications. This study suggests the long-term efficacy of methadone treatment and buprenorphine treatment on symptoms of opioid addiction and quality of life.

Urinary Pharmacokinetics of Methamphetamine and Its Metabolite, Amphetamine Following Controlled Oral Administration to Humans

Methamphetamine is widely abused for its euphoric effects. Our objectives were to characterize the urinary pharmacokinetics of methamphetamine and amphetamine after controlled methamphetamine administration to humans and to improve the interpretation of urine drug test results. Participants (n = 8) received 4 daily 10-mg (low) oral doses of sustained-release (d)-methamphetamine hydrochloride within 7 days. After 4 weeks, 5 participants received 4 daily 20-mg (high) oral doses. All urine specimens were collected during the study. Methamphetamine and amphetamine were measured by GC-MS/PCI. Maximum excretion rates ranged from 403 to 4919 microg/h for methamphetamine and 59 to 735 microg/h for amphetamine with no relationship between dose and excretion rate. The mean molar percentage of dose in the urine as total methamphetamine and amphetamine were 57.5 +/- 21.7% (low dose) and 40.9 +/- 8.5% (high dose). Mean urinary terminal elimination half-lives across doses were 23.6 +/- 6.6 hours for methamphetamine and 20.7 +/- 7.3 hours for amphetamine. Methamphetamine renal clearance across doses was 175 +/- 102 mL/min. The mean amphetamine/methamphetamine percentage ratio based on the area under the urinary excretion-time curve increased over time from 13.4 +/- 6.5% to 35.7 +/- 26.6%. Slow urinary excretion results in drug accumulation and increases in detection time windows. Our findings also support the presence of an active renal excretion mechanism for methamphetamine.

Hospitalization of patients with cocaine and amphetamine use disorders from a psychiatric emergency service.

Among the illicit stimulants, cocaine and amphetamines are the most widely abused. Although these drugs have similar psychoactive properties and routes of administration, their duration of action and mechanism of action are different, as are the psychiatric problems that accompany their use. The authors explored whether these differences and results of urine drug testing were associated with differences in use of psychiatric inpatient services. The records of 2,357 patients admitted to a large county psychiatric emergency service were examined to determine whether patients admitted for amphetamine-related or cocaine-related disorders differed in rates of transfer to an inpatient psychiatric ward or in length of stay on the ward after transfer. The authors also examined whether positive or negative results of urine drug screens predicted transfer or length of stay. Patients with amphetamine-related disorders were more than a third more likely than patients with cocaine-related disorders to be transferred to the inpatient ward. Patients with negative urine screens were a third more likely than those with positive screens to be transferred and stayed slightly longer on the ward after transfer. Patients with cocaine-related disorders stayed slightly longer on the ward than patients with amphetamine-related disorders. Patients with amphetamine-related disorders have higher rates of psychiatric hospitalization than patients with cocaine-related disorders. Diagnostic uncertainty and other factors may also influence transfer rates and subsequent length of stay.

A screening trial of amantadine as a medication for cocaine dependence

This screening trial evaluated whether amantadine hydrochloride (100 mg bid) demonstrated sufficient clinical efficacy compared to placebo to recommend development as a pharmacotherapy for cocaine dependence. Participants were randomized to amantadine ( n=34) or placebo ( n=35) conditions in a 16-week, placebo-controlled, double blind trial with three times per week group counseling. Amantadine-treated participants were retained significantly longer than placebo. Based on results of a joint probability index for urine drug testing results (i.e. the proportion of cocaine-metabolite free urine samples divided by the number of participants assigned to the condition), participants assigned to amantadine were found to be significantly more likely to be cocaine abstinent on the last day of 8-weeks of treatment than participants assigned to placebo. Results at the end of 16 weeks of treatment were similar. Standard measures of urine drug testing consistently favored the amantadine condition over placebo, although not at levels of statistical significance. There was no statistical significance infrequency or severity of reported adverse events by treatment condition. Participants assigned to amantadine exhibited greater reductions in global staff ratings of cocaine dependence severity from baseline to termination compared with placebo. There were no significant differences in frequency or severity of reported adverse events by treatment condition. These results provide moderate support for further study of amantadine for the treatment of cocaine dependence.

A gas chromatography-mass spectrometry method for the quantitation of clobenzorex.

Drugs metabolized to amphetamine or methamphetamine are potentially significant concerns in the interpretation of amphetamine-positive urine drug-testing results. One of these compounds, clobenzorex, is an anorectic drug that is available in many countries. Clobenzorex (2-chlorobenzylamphetamine) is metabolized to amphetamine by the body and excreted in the urine. Following administration, the parent compound was detectable for a shorter time than the metabolite amphetamine, which could be detected for days. Because of the potential complication posed to the interpretation of amphetamin-positive drug tests following administration of this drug, the viability of a current amphetamine procedure using liquid-liquid extraction and conversion to the heptafluorobutyryl derivative followed by gas chromatography-mass spectrometry (GC-MS) analysis was evaluated for identification and quantitation of clobenzorex. Qualitative identification of the drug was relatively straightforward. Quantitative analysis proved to be a far more challenging process. Several compounds were evaluated for use as the internal standard in this method, including methamphetamine-d11, fenfluramine, benzphetamine, and diphenylamine. Results using these compounds proved to be less than satisfactory because of poor reproducibility of the quantitative values. Because of its similar chromatographic properties to the parent drug, the compound 3-chlorobenzylamphetamine (3-Cl-clobenzorex) was evaluated in this study as the internal standard for the quantitation of clobenzorex. Precision studies showed 3-Cl-clobenzorex to produce accurate and reliable quantitative results (within-run relative standard deviations [RSDs] < 6.1%, between-run RSDs < 6.0%). The limits of detection and quantitation for this assay were determined to be 1 ng/mL for clobenzorex.

Detection of amphetamine and methamphetamine following administration of benzphetamine.

Interpretation of urine drug-testing results is a challenging endeavor for several reasons. Effects of pH, dilution, legitimate and illicit sources of the drugs, and, perhaps the most challenging, the possibility of the methamphetamine and/or amphetamine being the result of the use of some other drug. Although it is known that 14 different compounds are metabolized to methamphetamine or amphetamine or both, there is little information on the metabolic profile of many of these compounds, making interpretation of results difficult. Benzphetamine, administered as a single Didrex tablet, was given to 10 subjects (7 male and 3 female) and urine samples collected for the next 7 days. Gas chromatography-mass spectrometry results showed 3 of the 10 subjects did not have a single urine sample that exceeded a 500-ng/mL cutoff for amphetamine or methamphetamine. The other subjects had between one and six samples that tested positive at or above that level. Two subjects excreted more methamphetamine than amphetamine, whereas the other eight excreted greater amounts of amphetamine than methamphetamine. The observed ratio between amphetamine and methamphetamine was significantly different than what would be expected from the use of methamphetamine. Results of this study indicate the metabolism of benzphetamine to desmethylbenzphetamine is a major pathway in the metabolism of the drug. Enantiomer analysis of the methamphetamine and amphetamine revealed only the d-enantiomer. Results of this study add significant information useful to interpret the possibility of benzphetamine as the origin of methamphetamine and amphetamine in urine samples.

Efficacy of two commercial products for altering urine drug test results.

We have become aware of several commercial products that, when orally ingested, will purportedly not only eliminate "toxins" from a person's system, but will also correct any urinary imbalances caused by excessive water consumption. Unblinded study of one volunteer subject, tested weekly x 4 for 24-hour urine elimination of test drug under conditions of control, control plus 1200 mL water, Quick Flush', and Eliminator. Each of the treatment protocols studied caused reductions of drug or metabolite concentrations as measured by gas chromatography-mass spectrometry in urine specimens collected up to 24 hours after ingestion of amphetamine, 9-carboxy-11-nor-delta-9-THC, benzoylecgonine, or codeine, yet the radioimmunoassay screening results demonstrated very little effect. Water alone was approximately as effective as the two commercial products in reducing the metabolite level. None of the treatment protocols employed in this study altered urinary pH, specific gravity, or creatinine concentration outside the normally accepted physiological range. Attempts to conceal drug abuse by water dilution are most likely to play a substantial role when concentrations are at or near the detection threshold for a particular assay such as the terminal stages of drug eliminations.