Drugs of Abuse.

Drug abuse and its consequences remain a significant public health issue. An increasing number of individuals are present in the emergency room with life-threatening drug intoxication. It is imperative that emergency room physicians are cognizant of the signs, symptoms, and treatment to improve the chances of early recognition and treatment. As a result, the proportion of lives saved will increase significantly. In this article, we present some of the most prevalent life-threatening drugs that lead to emergency room admission. The signs, symptoms, and treatment modalities are discussed.

Socio-demographic Characteristics of Individuals with History of Crack Cocaine Use in the US General Population.

This study explores socio-demographic characteristics of individuals with history of crack cocaine use. Data from the 29th Round of General Social Survey was used. Respondents with history of crack cocaine use were compared to respondents without such history. T test was applied to identify differences between groups. Approximately 6 % of respondents reported lifetime history of crack cocaine use. Groups with and without history of crack cocaine use differed significantly in gender, marital status, education, income distribution, employment, health perception, family and financial satisfaction, criminal history, happiness, sexual history, history of injection drug use, and HIV testing. There were no significant differences for race. The study provides insights that could improve identification and prevention of substance use disorders.

Alcohol use in Polish 9/11 responders: implications for cross-cultural treatment.

More than 35,000 individuals are estimated to have responded to the World Trade Center (WTC) site following the terrorist attacks of September 11, 2001. The federally funded WTC Medical Monitoring and Treatment Program (WTCMMTP) provides medical monitoring and occupational medicine treatment as well as counseling regarding entitlements and benefits to the workers and volunteers who participated in the WTC response. A major component of the WTCMMTP is the WTC Mental Health Program (WTCMHP), which offers annual mental health assessments and ongoing treatment for those found to have 9/11 associated mental health problems. In the program's 9.5 years of evaluating and treating mental health problems in thousands of Ground Zero responders, diversity in multiple domains (e.g., gender, family, profession and employment status, state of physical health, cultural identity, and immigration status) has been a hallmark of the population served by the program. To illustrate the types of issues that arise in treating this diverse patient population, the authors first present a representative case involving a Polish asbestos worker with an alcohol use disorder. They then discuss how accepted alcohol treatment modalities can and often must be modified in providing psychiatric treatment to Polish responders, in particular, and to foreign-born patients in general. Treatment modalities discussed include cognitive and behavioral therapy, relapse prevention strategies, psychodynamic therapy, motivational approaches, family therapy, group peer support, and pharmacotherapy. Implications for the practice of addiction psychiatry, cultural psychiatry, and disaster psychiatry are discussed.

Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis.

OBJECTIVES: The objective of this investigation was to characterize the pharmacokinetic profile of lofexidine. Lofexidine is an orally bioavailable alpha 2-adrenergic receptor agonist analogue of clonidine that acts centrally to suppress opiate withdrawal symptoms. METHODS: During the detoxification period of a phase 3 placebo-controlled, randomized, double-blind trial, six subjects were entered in this preliminary pharmacokinetic study. RESULTS: Pharmacokinetic analysis of plasma samples collected during study day 7 indicated that C(max) was 3242 +/- 917 ng/L. The mean trough levels between the study days were not significantly different (p > .05), suggesting that the subjects were at steady-state. CONCLUSIONS: Although preliminary due to the limited number of subjects, these findings are the first to document lofexidine clinical pharmacokinetics in opiate addicts using a highly sensitive liquid chromatography tandem mass spectrometric analysis.

A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal.

CONTEXT: Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine. OBJECTIVE: To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo. DESIGN: An inpatient, Phase 3, placebo-controlled, double-blind, randomized multi-site trial with three phases: (1) opioid agonist stabilization phase (days 1-3), (2) detoxification/medication or placebo phase (days 4-8), and (3) post detoxification/medication phase (days 9-11). SUBJECTS: Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo. MAIN OUTCOME MEASURE: Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (second opioid detoxification treatment day). RESULTS: Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (least squares means 19.5+/-2.1 versus 30.9+/-2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). CONCLUSIONS: Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification.

Dextromethorphan and quinidine combination for heroin detoxification.

Dextromethorphan (DM) is a low-affinity, non-competitive NMDA receptor antagonist that has shown promise in preclinical and preliminary clinical studies for the reduction of opioid withdrawal symptoms, but when used at higher doses, it is associated with deleterious side effects attributed to its metabolite, dextrorphan. A clinical trial was therefore conducted to test the withdrawal-suppressant effect of a combination of dextromethorphan with quinidine (DM/Q). Quinidine inhibits the metabolism of dextromethorphan, reducing dextrorphan levels. Opioid-dependent patients were admitted to an inpatient unit, stabilized for three days on morphine (25 mg, sc, every six hours), and randomly assigned on day 2 to DM/Q (30 mg/30 mg, twice a day) (n = 22) or matching placebo (n = 9) prior to the discontinuation of morphine on day 4. Withdrawal symptoms, measured with the Modified Himmelsbach Opioid Withdrawal Scale (MHOWS), increased significantly on days 4 and 5 (Z = 3.70, p = .0002), and by day 6, 90% of the sample (28/31) had dropped out of the study. There were no differences between treatment groups on either outcome measure. The combination of dextromethorphan and quinidine appears ineffective as a primary treatment for opioid withdrawal. Future studies should examine dextromethorphan as an adjunct to other anti-withdrawal medications and focus more on the relationship between dextrorphan levels and withdrawal suppression.

Management of relapse in naltrexone maintenance for heroin dependence.

UNLABELLED: Opioid dependence is a growing public health problem. Maintenance on the antagonist naltrexone for clinic- or office-based treatment of opioid dependence is plagued by high rates of relapse. This paper identifies critical determinants of lapses to opioid use during naltrexone maintenance. Time retained in treatment was examined as a function of whether lapses to opioid use occurred while adherent to naltrexone (blocked use), or after having missed naltrexone doses (unblocked). METHOD: Participants (N=83) met DSM-IV criteria for opioid dependence and identified a significant other willing to participate in their treatment. Following inpatient detoxification, participants were enrolled in a 26-week outpatient course of therapy and naltrexone maintenance. RESULTS: Patients with unblocked use had a very high rate of dropout (10% retained at 6 months), dropout usually occurring within 2 weeks after unblocked use. Patients with only blocked use had less dropout (33% retained at 6 months). However, episodes of blocked use were often followed by unblocked use and dropout. CONCLUSIONS: During naltrexone maintenance for opioid dependence unblocked opioid use calls for immediate intervention, such as detoxification or switching to the partial agonist buprenorphine. Episodes of blocked use warrant increased clinical attention, such as direct observation of naltrexone ingestion, increased dose, or increased intensity of treatment contact. Maintenance on oral naltrexone is a fragile treatment because it is so easily undermined by episodes of opioid use while non-compliant. New long-acting injectable or implantable formulations of naltrexone may address this limitation and should be investigated for treatment of opioid dependence.

Comparison of olanzapine to risperidone in substance-abusing individuals with schizophrenia.

A 14-week double blind study compared the efficacy of olanzapine to risperidone in reducing marijuana/cocaine craving and use in individuals with schizophrenia. The study consisted of three phases: a two-week assessment phase, a two-week cross-taper phase onto olanzapine/risperidone, and a ten-week period of maintenance on olanzapine/risperidone. The proportion of cocaine-positive urines decreases over time for both groups with a trend for a greater reduction for the olanzapine group compared to risperidone group. In the last six weeks, marijuana craving was more likely for the risperidone group compared to the olanzapine group, although there was no group difference in the proportion of negative marijuana urines. The data suggest some potential for the utility of olanzapine for the treatment of cocaine dependence in individuals with schizophrenia.

Pharmacotherapy for marijuana dependence: a double-blind, placebo-controlled pilot study of divalproex sodium.

There is a noticeable lack of targeted treatment options for marijuana dependence, in particular pharmacologic approaches. This is the first study evaluating a targeted pharmacologic approach for marijuana dependence. The goals of the study were to determine if such patients would seek pharmacologic treatment, whether these patients could be retained in treatment using a design previously developed for cocaine-dependent patients, and especially whether divalproex sodium showed promise as a treatment agent for marijuana dependence. We found that marijuana-dependent patients will seek treatment, and such patients can be adequately maintained in a pharmacologic trial. Regardless of treatment group, patients reported a significant reduction in their frequency and amount of marijuana use as well as a reduction in irritability. Given the lack of proven effective treatments for marijuana dependence, pharmacotherapies should be sought. The design of a preliminary clinical trial should include a psychosocial/behavioral intervention emphasizing motivation and medication compliance and a placebo control group.

Effects of HIV triple therapy on methadone levels.

There is a belief among methadone patients that triple therapy for HIV reduces methadone potency. This cross-sectional study compared the rate of methadone metabolism (peak-trough blood levels) in two groups of methadone-maintained patients, AIDS patients receiving triple therapy (N = 17), and HIV patients without triple therapy (N = 19). These preliminary findings suggest that triple therapy may increase the rate of methadone metabolism, though further studies are warranted.

Substance abuse among patients with schizophrenia.

Substance use in the general population is a significant public health problem. Problems associated with substance use are aggravated by concomitant psychiatric illness, particularly schizophrenia and schizoaffective disorder. Although there is a general agreement on the need to address this problem, a wide range of opinions exists on exactly what is the best modality. In this article, we provide a brief overview of the etiology and consequences of substance use in individuals with schizophrenia, followed by a more detailed review of pharmacological and psychotherapeutic trends in the treatment of this population. Research studies indicate that, while some evidence supports the self-medication hypothesis, individuals with schizophrenia or schizoaffective disorder frequently use substances for the same reasons and in the same manner as the general population. In the pharmacotherapy section, we briefly discuss the rationale for current medication strategies, their efficacy, and directions for future research. This is followed by an assessment of current psychotherapeutic interventions, their limitations, and potential modifications to improve treatment outcome. The research literature suggests that integrated treatment and well-tailored interventions that take into account psychosocial factors and motivation offer the most promise for the future. More controlled trials are necessary to validate this hypothesis.