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Carbamazepine for cocaine dependence.

BACKGROUND: Cocaine dependence has become a substantial public health problem, developing a significant number of medical, psychological and social problems, including the spread of infectious diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. Although there is no consensus regarding how to treat cocaine dependence, effective pharmacotherapy has a potentially major role to play as part of a broader treatment milieu. The anti-convulsant carbamazepine, a tricyclic medication that is widely used to treat a variety of neurological and psychiatric disorder, has also been used for treatment of cocaine dependence, although its effectiveness has not been established. OBJECTIVES: To determine whether carbamazapine (CBZ) is effective on the treatment of cocaine dependence. SEARCH STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT, Biological Abstracts and LILACS; scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of carbamazepine drugs versus placebo on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and Odds Ratios, weighted mean difference and number needed to treat were estimated. Qualitative assessments of the methodology of eligible studies were carried out using validated checklists. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Where possible analysis was carried out according to the "intention to treat" principles. MAIN RESULTS: 5 studies were included in the review, with 455 people randomised. No differences were found regarding positive urine sample for cocaine metabolites. Scores on Spielberg State Anxiety Inventory slightly favoured carbamazepine, but didn't reach statistical significance. Dropouts were high in both groups up to 70% in the placebo group. Less dropout occurred in the Carbamazepine group (RR 0.87 95%CI 0.71-1.06). When no retention in treatment was due to side effects no differences were found. The number of participants presenting at least one side effect, reported in Kranzler (1995), was higher in the carbamazepine group (RR 4.33 95% CI 1.45-12.91). REVIEWER'S CONCLUSIONS: There is no current evidence supporting the clinical use of CBZ in the treatment of cocaine dependence. Larger randomised investigation must be considered taking into account that these time-consuming efforts should be reserved for medications showing more relevant and promising evidence.

Anticonvulsants↗

Dopamine agonists for cocaine dependence.

BACKGROUND: Cocaine is a major drug of abuse. Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. There is a wide and well documented range of consequences associated to chronic use of this drug, such as medical, psychological and social problems, including the spread of infectious diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. Therapeutic management of the cocaine addicts includes an initial period of abstinence from the drug. During this phase the subjects may experience, besides the intense craving for cocaine, symptoms such as depression, fatigue, irritability, anorexia, and sleep disturbances. It was demonstrated that the acute use of cocaine may enhance dopamine transmission and chronically it decreases dopamine concentrations in the brain. Pharmacological treatment that affects dopamine could theoretically reduce these symptoms and contribute to a more successful therapeutic approach. OBJECTIVES: To evaluate the efficacy and acceptability of dopamine agonists for treating cocaine dependence. SEARCH STRATEGY: We searched: The Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of dopamine agonists on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. MAIN RESULTS: Twelve studies were included, with 587 participants randomised. Amantadine and Bromocriptine were compared to placebo in most of trials. In two studies amantadine was directly compared to bromocriptine, while amantadine was compared to desipramine, an antidepressant in three. The main efficacy outcome presented was positive urine sample for cocaine metabolites, with no significant differences between interventions. When retention in treatment was assessed as an acceptability measure, it was found a similar rate of patients remaining in treatment in both placebo and active drugs. There were no significant differences in trials where participants had primary cocaine dependence or had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. REVIEWER'S CONCLUSIONS: Current evidence does not support the clinical use of dopamine agonists in the treatment of cocaine dependence. Given the high rate of dropouts in this population, clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.

Amantadine↗

A comparison of drugs versus placebo for the treatment of dysthymia.

OBJECTIVES: Dysthymia is a depressive disorder of chronic nature but of less severity than major depression, which depressive symptoms are more or less continuous for at least two years. The aim of this review was to conduct a systematic review of all RCTs comparing drugs and placebo for dysthymia. SEARCH STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT, Biological Abstracts and LILACS; reference searching; personal communication; conference abstracts; unpublished trials from the pharmaceutical industry; book chapters on the treatment of depression. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of drugs versus placebo for dysthymic patients. Exclusion criteria were: non randomised, mixed major depression/ dysthymia (trials not providing separate data) and depression secondary to other disorders (e.g. substance abuse). DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently. In order to achieve an intention-to-treat analysis, when trials failed to report it was assumed that people who died or dropped out had no improvement. Authors of relevant trials were contacted for additional and missing data. Absence of treatment response as defined by authors was the main measure of outcome used. Relative Risks (RR) and 95% confidence intervals (CI) of dichotomous data were calculated with the Random Effects Model. Where possible, number needed to treat (NNT) and number needed to harm (NNH) were estimated, taking the reciprocal of the absolute risk reduction. MAIN RESULTS: Currently the review includes 15 trials. Similar results were obtained in terms of efficacy for different groups of drugs, such as tricyclic (TCA), selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAOI) and other drugs (sulpiride, amineptine, and ritanserin). The pooled RR for absence of treatment response was 0. 68 (95% CI 0.59-0.78) for TCA and the NNT was 4.3 (95% CI 3.2-6.5). SSRIs showed similar RR for this outcome: 0.64 (95% CI 0.55-0.74), the NNT being 4.7 (95% CI 3.5-6.9). Concerning MAOIs, the RR was 0. 59 (95% CI 0.48-0.71) and the NNT was 2.9 (95% CI 2.2-4.3). Other drugs (amisulpride, amineptine and ritanserin) showed similar results in terms of absence of treatment response. Using more stringent criteria for improvement - full remission - the results were unchanged. Patients treated on TCA were more likely to report adverse events, compared with placebo. REVIEWER'S CONCLUSIONS: Drugs are effective in the treatment of dysthymia with no differences between and within class of drugs. Tricyclic antidepressants are more likely to cause adverse events and dropouts. As dysthymia is a chronic condition, there remains little information on quality of life and medium or long-term outcome.

Antidepressive Agents↗

Antidepressants for cocaine dependence.

BACKGROUND: Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. The past decade has witnessed a sustained search for an effective pharmacotherapeutic agent for the treatment of cocaine dependence. While administration of cocaine acutely increases intercellular dopamine, serotonin, and norepinephrine levels by blocking their presynaptic reuptake, chronic cocaine abuse leads to down-regulation of monoamine systems. Post-cocaine use depression and cocaine craving may be linked to this down-regulation. Antidepressant pharmacotherapy, by augmenting monoamine levels, may alleviate cocaine abstinence symptomatology, as well as relieving dysphoria and associated craving by general antidepressant action. OBJECTIVES: To conduct a systematic review of all RCTs on the use of antidepressants for treating cocaine dependence. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Other searches:reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of antidepressants on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. MAIN RESULTS: 18 studies were included in the review, with 1177 people randomised. Positive urine sample for cocaine metabolites was the main efficacy outcome, with no significant results obtained regardless the type of antidepressant. Compared to other drugs, desipramine performed better but showing just a non significant trend with heterogeneity present as revealed by the chi-square test (8.6, df=3; p=0.04). One single trial showed imipramine performed better than placebo in terms of clinical response according to patient's self-report. A similar rate of patients remaining in treatment was found for both patients taking desipramine or placebo. Results from one single trial suggest fluoxetine patients on SSRIs are less likely to dropout. Similar results were obtained for trials where patients had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. REVIEWER'S CONCLUSIONS: There is no current evidence supporting the clinical use of antidepressants in the treatment of cocaine dependence. Given the high rate of dropouts in this population, clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.

Antidepressive Agents↗

Textual decay.

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Academies and Institutes↗

Accident versus near miss causation: a critical review of the literature, an empirical test in the UK railway domain, and their implications for other sectors.

An essential assumption for the usefulness of basing accident prevention measures on minor incidents is the common cause hypothesis: that causal pathways of near misses are similar to those of actual accidents (such as injuries and damages). The idea of a common cause hypothesis was originally proposed by Heinrich in his seminal book "Industrial Accident Prevention" [McGraw-Hill, New York]. In this paper, it is argued that the hypothesis of similarity of causes for major and minor accidents has become confounded with the interdependence of the ratio relationship between severity and frequency. This confounded view of the hypothesis has led to invalid tests of the hypothesis and erroneous conclusions. The evidence from various studies is examined and it is concluded that the hypothesis has not been properly understood or tested. Consequently, such a proper test was carried out using data from the UK railways which were analysed using the confidential incident reporting and analysis system (CIRAS) 21 cause taxonomy. The results provide qualified support for the common cause hypothesis with only three out of the 21 types of causes having significantly different proportions for the three consequence levels investigated: 'injury & fatality', 'damage' and 'near miss'.

Accidents, Occupational↗

Occupationally related hydrogen sulfide deaths in the United States from 1984 to 1994.

Alice Hamilton described fatal work injuries from acute hydrogen sulfide poisonings in 1925 in her book Industrial Poisons in the United States. There is no unique code for H2S poisoning in the International Classification of Diseases, 9th Revision; therefore, these deaths cannot be identified easily from vital records. We reviewed US Occupational Safety and Health Administration (OSHA) investigation records for the period 1984 to 1994 for mention of hazardous substance 1480 (hydrogen sulfide). There were 80 fatalities from hydrogen sulfide in 57 incidents, with 19 fatalities and 36 injuries among coworkers attempting to rescue fallen workers. Only 17% of the deaths were at workplaces covered by collective bargaining agreements. OSHA issued citations for violation of respiratory protection and confined space standards in 60% of the fatalities. The use of hydrogen sulfide detection equipment, air-supplied respirators, and confined space safety training would have prevented most of the fatalities.

Adolescent↗

Current status of biomedical book reviewing: Part IV. Major American and British biomedical book publishers.

This is the fourth part of a comprehensive, quantitative study of biomedical book reviews. The data base of the total project was built from statistics of 3,347 reviews of 2,067 biomedical books taken from all 1970 issues of fifty-four reviewing journals. This part of the study identifies the major American and British biomedical book publishers in terms of their quantitative production of book titles reviewed, and determines the relationships among these publishers. It is found that Williams & Wilkins, Charles C Thomas, Academic Press, and Springer Verlag are the most productive biomedical book publishers in terms of books reviewed in 1970. These four publishers accounted for 32% of the 1,674 books available in the United States and reviewed in the reviewing media in 1970. Williams & Wilkins is especially significant by virtue of reprint activity. The present study also explores the price trend of biomedical books. It is found that the mean price for 1,077 books studied was $16.20 per volume, with a standard deviation of $9.42.

Biology↗