Total antioxidant capacity is significantly lower in cocaine-dependent and methamphetamine-dependent patients relative to normal controls: results from a preliminary study.

BACKGROUND: Oxidative stress can result in damage to the brain and other organs. To protect from oxidative damage, the human body possesses molecular defense systems, based on the activity of antioxidants, and enzymatic defense systems, including the enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Although pre-clinical research has shown that stimulant use is associated with oxidative damage, oxidative stress and the antioxidant defense systems have not been evaluated in clinical samples of stimulant-dependent patients. OBJECTIVES: This study aimed to investigate the link between stimulant dependence and oxidative stress. METHODS: Peripheral blood samples from 174 methamphetamine (n = 48) and/or cocaine-dependent (n = 126) participants as well as 30 normal control participants were analyzed for the enzyme activities of CAT, SOD, and GSH-Px in the erythrocytes and the total antioxidant capacity and the malondialdehyde concentration in the plasma. RESULTS: We could show an association of stimulant dependence with a depletion of total antioxidant capacity to 54.6 ± 4.7%, which correlates with a reduced activity of the SOD to 71.3 ± 0.03% compared with healthy control participants (100%). CONCLUSION: Stimulant-dependent patients had significantly lower antioxidant capacity relative to controls, suggesting that they may be at greater risk for oxidative damage to the brain and other organs.

Preliminary evaluation of a model of stimulant use, oxidative damage and executive dysfunction.

BACKGROUND: Illicit stimulant use increases oxidative stress and oxidative stress has been found to be associated with deficits in memory, attention and problem-solving. OBJECTIVE: To test a model of the association among oxidative DNA damage, a severe form of oxidative stress, and stimulant use, executive function and stimulant-use outcomes. METHODS: Six sites evaluating 12-step facilitation for stimulant abusers obtained peripheral blood samples from methamphetamine-dependent (n = 45) and cocaine-dependent (n = 120) participants. The blood samples were submitted to a comet assay to assess oxidative DNA damage. Executive Dysfunction was assessed with the Frontal Systems Behavior Scale (FrSBe), which is a reliable and valid self-report assessment of executive dysfunction, disinhibition and apathy. Stimulant-use measures included self-reported stimulant use and stimulant urine drug screens (UDS). RESULTS: While more recent cocaine use (<30 days abstinence) was associated with greater oxidative DNA damage (W = 2.4, p < 0.05, d = 0.36), the results did not support the hypothesized relationship between oxidative DNA damage, executive dysfunction and stimulant use outcomes for cocaine-dependent patients. Support for the model was found for methamphetamine-dependent patients, with oxidative DNA damage significantly greater in methamphetamine-dependent patients with executive dysfunction (W = 2.2, p < 0.05, d = 0.64) and with executive dysfunction being a significant mediator of oxidative DNA damage and stimulant use during active treatment (ab = 0.089, p < 0.05). As predicted, neither disinhibition nor apathy were significant mediators of oxidative damage and future stimulant use. CONCLUSION: These findings provide preliminary support for a model in which oxidative damage resulting from methamphetamine use results in executive dysfunction, which in turn increases vulnerability to future stimulant use.

Characteristics of Northern Plains American Indians seeking substance abuse treatment in an urban, non-tribal clinic: a descriptive study.

Because few data exist on substance abuse rates in American Indian (AI) communities, the Methamphetamine and Other Drug project was developed and implemented by five nodes within the National Institute on Drug Abuse Clinical Trials Network (NIDA CTN). This article presents findings from AI clients in a Northern Plains urban non-Native substance abuse treatment setting. Alcohol and marijuana were used earlier, longer, and by more clients, followed by stimulants and prescription opioids. Most regularly smoked tobacco. Differences in substance use patterns were associated with age of onset and victimization. Age of onset was correlated with victimization, gender, cognitive impairment, and suicidal behavior. Despite considerable health and economic disparities, most clients found support for recovery in relationships and elements of Native culture.

Prescription drug abuse as a public health problem in Ohio: a case report.

Prescription drug overdose is the leading cause of injury death in Ohio, as well as in 16 other states. Responding to the prescription drug epidemic is particularly challenging given the fragmentation of the health care system and that the consequences of addiction span across systems that have not historically collaborated. This case study reports on how Ohio is responding to the prescription drug epidemic by developing cross-system collaboration from local public health nurses to the Governor's office. In summary, legal and regulatory policies can be implemented relatively quickly whereas changing the substance abuse treatment infrastructure requires significant financial investments.

Power of automated algorithms for combining time-line follow-back and urine drug screening test results in stimulant-abuse clinical trials.

BACKGROUND: In clinical trials of treatment for stimulant abuse, researchers commonly record both Time-Line Follow-Back (TLFB) self-reports and urine drug screen (UDS) results. OBJECTIVES: To compare the power of self-report, qualitative (use vs. no use) UDS assessment, and various algorithms to generate self-report-UDS composite measures to detect treatment differences via t-test in simulated clinical trial data. METHODS: We performed Monte Carlo simulations patterned in part on real data to model self-report reliability, UDS errors, dropout, informatively missing UDS reports, incomplete adherence to a urine donation schedule, temporal correlation of drug use, number of days in the study period, number of patients per arm, and distribution of drug-use probabilities. Investigated algorithms include maximum likelihood and Bayesian estimates, self-report alone, UDS alone, and several simple modifications of self-report (referred to here as ELCON algorithms) which eliminate perceived contradictions between it and UDS. RESULTS: Among the algorithms investigated, simple ELCON algorithms gave rise to the most powerful t-tests to detect mean group differences in stimulant drug use. CONCLUSIONS: Further investigation is needed to determine if simple, naïve procedures such as the ELCON algorithms are optimal for comparing clinical study treatment arms. But researchers who currently require an automated algorithm in scenarios similar to those simulated for combining TLFB and UDS to test group differences in stimulant use should consider one of the ELCON algorithms. SCIENTIFIC SIGNIFICANCE: This analysis continues a line of inquiry which could determine how best to measure outpatient stimulant use in clinical trials (NIDA. NIDA Monograph-57: Self-Report Methods of Estimating Drug Abuse: Meeting Current Challenges to Validity. NTIS PB 88248083. Bethesda, MD: National Institutes of Health, 1985; NIDA. NIDA Research Monograph 73: Urine Testing for Drugs of Abuse. NTIS PB 89151971. Bethesda, MD: National Institutes of Health, 1987; NIDA. NIDA Research Monograph 167: The Validity of Self-Reported Drug Use: Improving the Accuracy of Survey Estimates. NTIS PB 97175889. GPO 017-024-01607-1. Bethesda, MD: National Institutes of Health, 1997).

Determining the primary endpoint for a stimulant abuse trial: lessons learned from STRIDE (CTN 0037).

BACKGROUND: No consensus is available for identifying the best primary outcome for substance use disorder trials, making interpretation across trials difficult. Abstinence is the most desirable treatment outcome although a wide variety of other endpoints have been used. OBJECTIVES: This report provides a framework for determining an optimal primary endpoint and the relevant measurement approach for substance use disorder treatment trials. The framework was developed based on a trial for stimulant abuse using exercise as an augmentation treatment, delivered within the NIDA Clinical Trials Network. The use of a common endpoint across trials will facilitate comparisons of treatment efficacy. METHODS: Primary endpoint options in existing substance abuse studies were evaluated. This evaluation included surveys of the literature for endpoints and measurement approaches, followed by assessment of endpoint choices against study design issues, population characteristics, tests of sensitivity, and tests of clinical meaningfulness. CONCLUSION: We concluded that the best current choice for a primary endpoint is percent days abstinent, as measured by the Time Line Follow Back interview conducted three times a week with recall aided by a take-home Substance Use Diary. To improve the accuracy of the self-reported drug use, the results of qualitative urine drug screens will be used in conjunction with the Time Line Follow Back results. SCIENTIFIC SIGNIFICANCE: There is a need for a standardized endpoint in this field to allow for comparison across treatment studies, and we suggest that the recommended candidate endpoint be considered. However, the study design and goals ultimately must guide the final decision.

Increasing prenatal care and healthy behaviors in pregnant substance users.

Evidence suggests that prenatal care, healthy behaviors such as exercise and nutrition, and general stress level are associated with fetal and maternal health but there is a relative dearth of research on interventions to improve these factors in pregnant substance users. Two hundred pregnant substance users entering outpatient substance abuse treatment were randomized to receive either three individual sessions of Motivational Enhancement Therapy for pregnant substance users (MET-PS) or the first three individual sessions normally provided by the program. The present study evaluated the relative efficacy of MET-PS, compared to treatment as usual, on modifiable healthy behaviors and the impact of treatment when the groups were pooled. The results suggest that MET-PS was not more effective than treatment as usual in improving modifiable healthy behaviors. When the treatment groups were pooled, the results suggest that there were significant increases in prenatal care utilization and prenatal/multi-vitamin and water consumption, and a significant decrease in stress. Limitations and recommendations for further research are discussed.

The SRPHK1 outcome measure for cocaine-dependence trials combines self-report, urine benzoylecgonine levels, and the concordance between the two to determine a cocaine-use status for each study day.

BACKGROUND: There is currently no FDA-approved medication for cocaine dependence and no standard primary outcome measure for reduction of cocaine use in cocaine-dependence trials. The ability to detect a significant medication effect will depend, in part, on the primary outcome measure utilized. The goal of the present paper is to compare self-report or either of two urine toxicology measures used alone to a relatively new measure -- the SRPHK1 -- which combines self-report, quantitative urine benzoylecgonine levels, and an estimate of the concordance between the two to determine the cocaine-use status of each study day. METHOD: Datasets from two separate randomized, placebo-controlled cocaine-dependence trials were used to compare four cocaine-use outcome measures. RESULTS: The two data sets yielded very similar findings and suggest that the combined measure is associated with significantly fewer missing data than urine toxicology and that estimated cocaine use varied significantly depending on which measure was used, with the lowest use estimate being yielded by self-report, the highest by the two urine toxicology measures evaluated, and an intermediate value obtained using the combined measure. The results also suggest that the concordance between self-report and urine toxicology is around 90% at the beginning of the clinical trial but decreases to around 75% by the end of the trial. CONCLUSION: By combining the objectivity of urine toxicology with the reduced incidence of missing data characteristic of self-report, the SRPHK1 may provide advantages over self-report or urine toxicology measures used alone. In any case, the SRPHK1 provides an interesting complement to these other outcome measures and may warrant further evaluation.

The effect of multiple doses of peginterferon alfa-2b on the steady-state pharmacokinetics of methadone in patients with chronic hepatitis C undergoing methadone maintenance therapy.

This multicenter, open-label study evaluated the effects of multiple doses of peginterferon alfa-2b on the steadystate pharmacokinetics of methadone in 20 adults with hepatitis C virus infection who were enrolled in a methadone maintenance program. All subjects received peginterferon alfa-2b 1.5 mug/kg/wk for 4 weeks and maintained their normal methadone regimen. Serial blood samples were collected immediately before the first and after the fourth peginterferon alfa-2b dose (day 23). At day 23, exposure to the active methadone R-enantiomer increased by approximately 15% following administration of peginterferon alfa-2b, with 90% confidence intervals just outside the bioequivalence criteria (range, 80%-125%). Similar increases in exposure (C(max), AUC(0-24), and AUC(last)) were observed with S-methadone and total methadone. Peginterferon alfa-2b was well tolerated. Peginterferon alfa-2b is associated with minor increases in exposure to methadone in individuals with hepatitis C virus infection; however, these increases are unlikely to be clinically meaningful and are not associated with any safety concerns.

A double-blind, placebo-controlled trial of tiagabine for the treatment of cocaine dependence.

BACKGROUND: The potential efficacy of tiagabine for treating cocaine dependence is suggested by both pre-clinical research and two small clinical trials. METHOD: One hundred and forty one participants who met DSM-IV criteria for cocaine dependence were enrolled into this 12-week, double blind, placebo controlled outpatient trial. Participants received either tiagabine (20 mg/day) or matching placebo. All participants received 1h of manualized individual cognitive behavioral therapy on a weekly basis. Outcome measures included cocaine use as determined by self-report confirmed with urine benzoylecgonine (BE) results, and qualitative and quantitative urine toxicology measures. Safety measures included adverse events, EKGs, vital signs, and laboratory tests. RESULTS: Seventy-nine participants (i.e., 56%) completed the 12-week trial. The safety results suggest that tiagabine was safe and generally well tolerated by the participants. Participants in both groups improved significantly on cocaine craving and global functioning, with no significant differences between the groups. There were no significant changes in cocaine use as measured by self-report confirmed by urine BE or by quantitative urine toxicology results. Qualitative urine toxicology results suggest a possible weak effect for tiagabine in reducing cocaine use. CONCLUSION: These results suggest that tiagabine, at a dose of 20 mg/day, did not have a robust effect in decreasing cocaine use.

A double-blind, placebo-controlled trial of reserpine for the treatment of cocaine dependence.

BACKGROUND: Cocaine's increase of dopamine is strongly associated with its reinforcing properties and, thus, agents that reduce dopamine have received much attention as candidate cocaine-dependence treatments. The potential efficacy of reserpine, a dopamine depletor, for treating cocaine dependence is suggested by both pre-clinical research and a small clinical trial. METHOD: One hundred and nineteen participants who met DSM-IV criteria for cocaine dependence were enrolled into this 12-week, double-blind, placebo-controlled outpatient trial. Participants received either reserpine (0.5 mg/day) or matching placebo. All participants received 1h of manualized individual cognitive behavioral therapy on a weekly basis. Outcome measures included cocaine use as determined by self-report confirmed with urine benzoylecgonine results, cocaine craving, addiction severity index scores, and clinical global impression scores. Safety measures included adverse events, EKGs, vital signs, laboratory tests, and the Hamilton Depression Inventory. RESULTS: Seventy-nine participants (i.e., 66%) completed the 12-week trial. The safety results suggest that reserpine was safe and well tolerated by the participants. The efficacy measures indicated no significant differences between reserpine and placebo. CONCLUSION: These results do not support the efficacy of reserpine as a cocaine-dependence treatment.

Pharmacokinetics and pharmacodynamics of multiple sublingual buprenorphine tablets in dose-escalation trials.

In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combination with naloxone. Peak concentration (Cmax) and area under the concentration-time curves (AUCs) increased for both buprenorphine and naloxone with escalating doses. Significant differences were found across the range of doses administered for dose-adjusted Cmax for both tablet formulations and for the dose-adjusted AUCs for the buprenorphine-naloxone tablets. For both formulations, the maximal buprenorphine-induced decreases in respiratory rate and pupil diameter did not vary significantly across doses. Several of the subjective effects of buprenorphine did not increase as the dose of buprenorphine administered was increased. These findings are consistent with the ceiling effect associated with the partial agonist actions of buprenorphine. They also indicate a lack of dose proportionality for buprenorphine sublingual tablets, at least during the times at which levels of this agent are highest.

Methylphenidate and cocaine: a placebo-controlled drug interaction study.

Up to thirty percent of cocaine addicted individuals may meet diagnostic criteria for Attention-Deficit/Hyperactivity Disorder (ADHD). Methylphenidate (MPH) is a highly effective and commonly used treatment for ADHD but, like cocaine, is a cardiovascular and central nervous system stimulant with the potential to cause toxicity at high doses. The present study was undertaken to investigate the likelihood of a toxic reaction in individuals who use cocaine while concurrently taking MPH. Seven non-treatment seeking cocaine-dependent individuals completed this placebo-controlled, crossover study with two factors: Medication (placebo, 60 mg MPH, 90 mg MPH) and Infusion (saline, 20 mg cocaine, 40 mg cocaine). Physiological measures included vital signs, adverse events, and electrocardiogram. Subjective response was measured with visual analog scale (VAS) ratings of craving and drug effect. Cocaine pharmacokinetic parameters were calculated for each participant at each drug combination, using a non-compartmental model. MPH was well tolerated, did not have a clinically significant impact on cocaine's physiological effects, and decreased some of the positive subjective effects of cocaine. MPH did not significantly alter the pharmacokinetics of cocaine. The study results suggest that MPH at the doses studied can likely be used safely in an outpatient setting with active cocaine users.

Major Depressive Disorder and Dysthymia at the Intersection of Nativity and Racial-Ethnic Origins.

Immigrants often have lower rates of depression than US-natives, but longitudinal assessments across multiple racial-ethnic groups are limited. This study examined the rates of prevalent, acquired, and persisting major depression and dysthymia by nativity and racial-ethnic origin while considering levels of acculturation, stress, and social ties. Data from the National Epidemiologic Survey on Alcohol and Related Conditions were used to model prevalence and 3-year incidence/persistence of major depression and dysthymia (DSM-IV diagnoses) using logistic regression. Substantive factors were assessed using standardized measures. The rates of major depression were lower for most immigrants, but differences were noted by race-ethnicity and outcome. Furthermore, immigrants had higher prevalence but not incidence of dysthymia. The associations between substantive factors and outcomes were mixed. This study describes and begins to explain immigrant trajectories of major depression and dysthymia over a 3-year period. The continuing research challenges and future directions are discussed.

A medication screening trial evaluation of reserpine, gabapentin and lamotrigine pharmacotherapy of cocaine dependence.

AIMS: To conduct a preliminary evaluation of the safety and efficacy of reserpine, gabapentin or lamotrigine versus an unmatched placebo control as a treatment for cocaine dependence. DESIGN: A 10-week out-patient study using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design. SETTING: The study was conducted at the Cincinnati Medication Development Research Unit (MDRU). PARTICIPANTS: Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty participants were enrolled, with 50 participants completing the final study measures. INTERVENTION: The targeted daily doses of medication were reserpine 0.5 mg, gabapentin 1800 mg and lamotrigine 150 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis. MEASUREMENTS: Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression scale--observer and self-report of cocaine use. Safety measures included adverse events, electrocardiograms (ECGs), vital signs and laboratory tests. FINDINGS: Subjective measures of cocaine dependence indicated significant improvement for all study groups. Urine BE results indicated a significant improvement for the reserpine group (P < 0.05) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. The medications appeared to be tolerated well. CONCLUSIONS: The present findings suggest that reserpine may be worthy of further study as a cocaine dependence treatment.

A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments.

AIMS: To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence. DESIGN: A 10-week out-patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design. SETTING: This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio. PARTICIPANTS: Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty-seven participants were enrolled with 55 completing final study measures. INTERVENTION: The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis. MEASUREMENTS: Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale-Observer and self-report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests. FINDINGS: Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5-8 (P = 0.10) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. CONCLUSIONS: The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment.

Retrospective analyses of pooled data from CREST I and CREST II trials for treatment of cocaine dependence.

AIM: To analyze pooled data from the Cocaine Rapid Evaluation Screening Trial (CREST). Pooling data from these small pilot trials into four major drug classes permitted data exploration for treatment and covariate effects with increased sample size. DESIGN: Small pilot trials were conducted to screen fifteen medications as prospective treatments for cocaine dependence. Studies included a flexible 2-week to 4-week screening/baseline period followed by an 8-week randomized treatment condition. Participants were randomized equally to one of up to three active medications or placebo. SETTING: Five Medications Development Research Units at the five academic centers of University of Cincinnati, New York University, University of Pennsylvania, University of California Los Angeles and Boston University. PARTICIPANTS: The pooled data set consisted of 357 total subjects. Standardized inclusion and exclusion criteria were employed in subject selection to enhance consistency of cocaine-dependent study participants across all sites (see reports on individual trials in this supplement for details). All participants provided at least two urine samples that were positive for cocaine metabolite during a two-week period prior to being randomized. INTERVENTION: All subjects in these trials, those randomized to placebo and active medications, received active treatment in the form of evidence-based cognitive behavioral therapy. MEASURES: Quantitative urine benzoylecgonine (BE), self-report of cocaine use, and total Brief Substance Craving Scale (BSCS) scores were compared between each class of medication and its matched-placebo group. FINDINGS: Regression analysis of pooled data did not identify any statistically significant differences between treatment and matched-placebo for any of the four classes. Exploration of the effects of baseline covariates indicated that gender and African American status were associated significantly with outcome. Female gender was consistently associated with poorer outcomes for medication and placebo groups, while the direction of association between African American status and outcome differed by treatment groups. Retention was also examined: dropout rates may have been somewhat higher for placebo than treatment groups during the early active-treatment period. Classification trees were used to identify characteristics of subjects who were abstinent for at least two weeks during the eight-week trial; only 4.0% of females while 17.9% of males achieved this criterion. CONCLUSIONS: Results presented here may prove useful for planning future clinical trials for therapies targeting cocaine dependence.

Cocaine Rapid Efficacy Screening Trials (CREST): lessons learned.

AIMS: The Cocaine Rapid Efficacy Screening Trials (CREST) were designed by the National Institute on Drug Abuse Division of Treatment Research and Development (NIDA, DT R&D) to rapidly screen a number of medications potentially useful for the treatment of cocaine dependence. DESIGN: Each CREST trial was designed to compare several medications in a single trial against an unmatched placebo. The placebo group was included in each trial to avoid the nearly universal positive response to medications seen in open-label trials. In addition, a common set of procedures and outcome measures were employed throughout to increase comparability of results obtained from different trials and from different times. PARTICIPANTS: In all, 18 medications were screened in seven different trials, conducted in four different sites throughout the United States involving 398 cocaine-dependent patients. FINDINGS: Three medications were found to be promising enough to include in subsequent larger trials. Common statistical procedures for evaluating medications were developed to facilitate comparisons across sites and across time. A portion of the data were pooled and analyzed, which yielded some useful insights into cocaine dependence and its treatment. Finally, a review of individual trials together with the pooled analysis revealed several potential improvements for future screening trials. CONCLUSIONS: Overall, the CREST trials proved to be useful for rapidly screening medications for treatment of cocaine dependence, but several modifications in design should be made before this framework is applied further.

Measuring outcome in cocaine clinical trials: a comparison of sweat patches with urine toxicology and participant self-report.

AIMS: To evaluate the advantages of using a sweat patch (PharmCheck) for detecting cocaine abuse in cocaine-dependent patients participating in a clinical trial. The utility of the sweat patch was assessed from the following perspectives: the reliability and validity of quantitative sweat patch results, the possible degradation of cocaine to benzoylecgonine (BE) as a function of the length of time that a patch is worn, the completeness of the dataset yielded by thrice-weekly urine toxicology compared with thrice-weekly and weekly sweat patches, and the relative costs associated with sweat patch versus urine measures. DESIGN: Data were collected during a 10-week out-patient clinical trial in which participants wore two sweat patches, one applied every visit and one applied weekly. Urine samples were collected thrice weekly, as were self-reports of substance use. SETTING: A multi-site clinical trial conducted in Boston, Cincinnati and New York, USA. PARTICIPANTS: Twenty-seven participants with comorbid diagnoses of cocaine dependence and adult attention deficit disorder completed the study. MEASUREMENTS: Sweat patch and urine samples were analyzed by standard methods for cocaine and cocaine metabolites. FINDINGS: Quantitative sweat patch measures had good reliability in that the correlation between the weekly and per-visit patches was 0.96 (P < 0.0001). The concurrent validity, as judged by the correlation between quantitative urine BE levels and either weekly (0.76, P < 0.0001) or per-visit (0.73, P < 0.0001) cocaine sweat patch levels was reasonable. The correlation between the self-report of cocaine use and these same two patches, however, was lower (0.40, P < 0.05 and 0.30, P < 0.05, respectively). The results revealed no significant degradation of cocaine to BE associated with wearing the patch for a longer time. Finally, the per-visit patch provided cocaine use data on 80.5% of all study days (a total of 70), while urine toxicology and the weekly patch provided 77.4% and 76.1%, respectively. CONCLUSIONS: The present findings suggest that the PharmCheck patch might be an attractive alternative to urine toxicology for use as an outcome measure in cocaine clinical trials.

The Feasibility of Using the Spanish PHQ-9 to Screen for Depression in Primary Care in Honduras.

BACKGROUND: The Patient Health Questionnaire depression module (PHQ-9) is a brief (10 items) screening and monitoring measure designed for use in primary care settings that operationalizes most of the DSM-IV and ICD-9 diagnostic criteria for major depression. In the United States, the PHQ-9 has become the recommended depression measure in primary care settings. However, there are no published reports of its use in developing countries and no reports of the feasibility of using the Spanish version of the PHQ-9 to screen for depression. METHOD: During a medical brigade in October 2001, we tested the feasibility of using the Spanish PHQ-9 to screen for major depression in primary care clinics. A team of U.S. and Honduran physicians and medical students assessed 199 mothers of children under 10 years of age as part of a depression prevalence study in 5 rural sites. RESULTS: The PHQ-9 proved easy to administer to this population of poor, rural, young, and mostly illiterate Honduran women who had never participated in research before. Rater training required about 30 minutes of instruction for this group of physicians and medical students, plus occasional questions on the first day of use. Duration of administration of the PHQ-9 by interview ranged from 3 to 15 minutes. No items required major modification for cultural differences. The PHQ-9 identified a rate of 15% for major depression in this sample, and the PHQ-9 results showed a sensitivity of 77% and a specificity of 100% compared with the Structured Clinical Interview for DSM-IV mood disorders module. CONCLUSION: Like the English PHQ-9, the Spanish PHQ-9 is an efficient and reliable screening measure for major depression in primary care. It is useful as a research measure for estimating the prevalence of major depression and as an aid to the primary care clinician in rural Honduras.