This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants.Design-One hundred 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. Cocainepositive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-Disulfiram may be contraindicated for cocaine dependence at doses less than 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. NIH Public Access

Methamphetamine has become a major public health issue in both the US and globally. 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 400mg/day in eight methamphetamine dependent individuals. Subjects were inducted onto modafinil at 400 mg/day over three days and remained on 400 mg/day 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% Caucasian, aged 35-52 yrs) were enrolled. Four completed the 6-wk study, 3 completed a portion and one 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/day is safe and tolerable for methamphetamine dependent individuals.

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.

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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.