Christopher Cargile

Randomized, double blind, placebo-controlled trial of disulfiram for the treatment of cocaine dependence in methadone-stabilized patients.

UNLABELLED This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants. DESIGN One hundred and sixty-one cocaine- and opioid-dependent volunteers were entered into a 14-week, double blind, randomized, placebo-controlled clinical trial at two sites. METHODS Participants were stabilized on methadone during weeks 1-2 and received disulfiram at 0, 62.5, 125 or 250 mg/day during weeks 3-14. All participants also received weekly cognitive behavioral therapy. Thrice-weekly urine samples and weekly self-reported drug use assessments were obtained. RESULTS Baseline subject characteristics, retention and drug use did not differ across groups. Outcome analyses were performed on those who participated beyond week 2. Opioid-positive urine samples and self-reported opioid use did not differ by treatment group. The prevalence of alcohol use was low prior to and during the trial and did not differ by treatment group. Cocaine-positive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over time in the 250 mg disulfiram and placebo groups (p < 0.0001). Self-reported cocaine use increased in the 125 mg disulfiram group relative to the other three treatment groups (p = 0.04). CONCLUSIONS Disulfiram may be contraindicated for cocaine dependence at doses <250 mg/day. Whether disulfiram at higher doses is efficacious in reducing cocaine use in dually cocaine and opioid dependent individuals needs to be determined.

Open Label Pilot Study of Modafinil for Methamphetamine Dependence

Methamphetamine has become a major public health issue globally, particularly in the United States. Despite this, no effective pharmacotherapy for methamphetamine abuse has been developed to date. This 6-week, open-label pilot clinical trial examined the safety and tolerability of modafinil up to 400 mg/d in 8 methamphetamine-dependent individuals. Subjects were inducted onto modafinil at 400 mg/d for more than 3 days and remained on 400 mg/d for 4.5 weeks. Participants received weekly blister packs and underwent weekly individual cognitive behavioral therapy. Adjunctive contingency management procedures were used to enhance retention. Vital signs and supervised urine samples were obtained thrice weekly, and self-reported drug use and Hamilton anxiety and depression ratings were completed once weekly. Eight subjects (50% female, 100% white, aged 35-52 years) were enrolled. Four completed the 6-week study, 3 completed a portion, and 1 withdrew consent before completing intake. Results showed that systolic blood pressure (t = 1.09, P = 0.28), diastolic blood pressure, (t = 1.18, P = 0.24), and heart rate (t = 1.55, P = 0.13) did not change over time. Scores on the modafinil side effects checklist (t = −2.63, P = 0.01), Hamilton anxiety scale (t = −2.50, P = 0.018), and Hamilton depression scale (t = −3.25, P = 0.003) all decreased over time. The proportion of urine positive for amphetamines did not change over time (t = −0.52, P = 0.61), whereas self-reported methamphetamine use did (t = −2.86, P < 0.005). These results suggest that modafinil at 400 mg/d is safe and tolerable for methamphetamine-dependent individuals.

Prolactin levels and erectile function in patients treated with risperidone

Abstract: Treatment with risperidone is associated with prolactin (PRL) elevation, and PRL elevations are associated with erectile dysfunction (ED). We evaluated whether the PRL elevations caused by risperidone treatment of subjects with schizophrenia are associated with objective measures of erectile function. Subjects were hospitalized for 2 nights, and serum measurements of PRL, total testosterone, and free and weakly bound testosterone were performed in the morning and afternoon of each day. Risperidone levels, parent compound, and 9-hydroxy metabolite levels were drawn on the first day. Erectile function assessments, using the RigiScan, an instrument that measures nocturnal penile tumescence and rigidity, were performed on both nights. Consistent with previous reports, the correlation between total risperidone level and PRL was very high (r = 0.92, df = 12, P < 0.0001), but risperidone did not appear to affect either testosterone (r = 0.29, df = 5, P = 0.51) or free and weakly bound testosterone (r = −0.11, df = 10, P = 0.72). Contrary to expectations, PRL levels from the second night were positively correlated with erectile function (r = 0.68, df = 9, P = 0.022). Using objective measures, we were unable to confirm a detrimental association between PRL levels and male erectile function. These results are tentative given the small sample.

Clinical efficacy of sertraline alone and augmented with gabapentin in recently abstinent cocaine-dependent patients with depressive symptoms.

Background Cocaine dependence is a major public health problem with no available robustly effective pharmacotherapy. This study’s aim was to determine if treatment with sertraline (SERT) or SERT plus gabapentin (GBP) improved treatment retention, depressive symptoms, and/or cocaine use. Methods Depressed cocaine-dependent patients (N = 99) were enrolled in a 12-week, double-blind, randomized, placebo (PLA)-controlled, clinical trial and placed in research beds at a residential treatment facility (Recovery Centers of Arkansas). They were randomized by depressive symptom severity and inducted onto 1 of the following while residing at the Recovery Centers of Arkansas: SERT (200 mg/d), SERT (200 mg/d) plus GBP (1200 mg/d), or PLA. Participants transferred to outpatient treatment at the start of their third week, continued receiving study medications or PLA (weeks 3–12), and participated in weekly individual cognitive behavioral therapy. Compliance was facilitated through the use of contingency management procedures. Supervised urine samples were obtained thrice weekly and self-reported mood weekly. At the end of 12 weeks, participants were tapered off the study medication over 5 days and referred to a local treatment program. Results Sertraline, but not SERT plus GBP, showed a significantly lower overall percentage of cocaine-positive urine samples compared with that of PLA. A significantly greater percentage of participants experienced relapse in the PLA group (88.9%) compared with that of the SERT group (65.2%). Hamilton depression ratings decreased significantly over time regardless of the treatment group. Retention in treatment did not differ significantly between the treatment groups. Conclusions Sertraline plus GBP may not be superior to SERT alone in delaying relapse among abstinent cocaine-dependent individuals undergoing cognitive behavioral therapy.

Red blood cell transfusion: Impact of an education program and a clinical guideline on transfusion practice

BACKGROUND Red blood cell (RBC) transfusion guidelines have been developed by professional societies. These guidelines recommend a restrictive RBC transfusion practice for most clinical populations. Despite the consistency of guidelines and limited evidence for RBC transfusion efficacy, there is variability in RBC transfusion practice. METHODS A program was initiated in a tertiary medical center to align RBC transfusion practice with best-practice RBC transfusion guidelines. The program included an educational program, followed after 6 months by RBC transfusion decision support that included the approval of a best-practice RBC transfusion guideline by the hospital medical board and an RBC transfusion order form that included the guideline recommendations. RBC transfusion practice was followed over an 18-month period and compared with transfusion practice over the prior 18 months. The primary outcome variables were adult inpatient RBC units transfused, RBC units per admission, and RBC units per 100 patient-days. RESULTS The mean RBC units transfused decreased with initiation of each component of the program: from 923 ± 68 units to 852 ± 40 (P = 0.025) with education and further to 690 ± 52 (P < 0.0001) with the RBC transfusion decision support. Similarly, RBC transfusions per 100 patient-days fell from 10.56 ± 0.80 to 9.69 ± 0.49 (P = 0.02) and to 7.68 ± 0.63 (P = 0.0001) during the 3 time periods. CONCLUSION An education program coupled with institutional adoption of a best-practice RBC transfusion guideline and RBC transfusion order set resulted in a reduction in total RBC units transfused.

Identifying Areas for Curricular Program Improvement Based on Perceptions of Skills, Competencies, and Performance

ObjectiveEducational program evaluation and program improvement are processes that can be enhanced by involving multiple stakeholders and measurement tools. The purpose of this study was to compare faculty and resident physician perceptions of both teaching quality and resident competence for 13 core psychiatric skills and the six Accreditation Council for Graduate Medical Education general competencies. Additionally, resident performance as assessed by portfolios was descriptively examined relative to these perceptions of skills and competencies. Using this combination of data, the authors propose a useful approach for identifying areas for improvement within a medical residency’s program curriculum.MethodsTen teaching faculty members (100%) and 18 residents (82%) within a psychiatry department completed parallel surveys. Trained raters scored resident-completed portfolio entries. Nonparametric and descriptive analyses were used to compare the various data sources.ResultsIn general, faculty and residents showed congruence in their perceptions about resident performance. They agreed on the quality of teaching skills and general competencies. General competency scores from the portfolios were congruent with this perspective. However, there were mismatches in perceptions and performance on portfolios for some areas. Of the 13 core psychiatric skills examined, only one area, neuropsychiatry, was rated below average by both faculty and residents, while the median portfolio performance score was below competent for four skills, including neuropsychiatry. Faculty rated resident competence significantly higher than residents rated themselves for biopsychosocial formulation and medical psychiatry.ConclusionThis study describes and highlights the usefulness of a multidimensional approach that includes resident and faculty perspectives and externally rated performance measures to assist in identifying potential target areas for curriculum improvement.