Drug Impairment Reviews: Opiates and Minor Tranquilizers

STUDY: Gordon, N.B. Reaction Times of Methadone-Treated Heroin Addicts. Psychopharmacologia, 16:337-344. 1970. Site: Rockefeller University and Yeshiva University, New York City, New York. Subjects: The subjects were divided into six groups. Groups 1 and 3 both had been maintained for at least 1 year on methadone for the treatment of heroin addiction. Group 1 had 18 males whose average age was 32.5 years; group 3 had 9 females whose average age was 33.5 years. Group 2 consisted of 20 unpaid male volunteers who did not use drugs; they averaged 32.5 years. The participants in groups 4 and 5 had recently withdrawn from narcotic drugs. The 20 males in group 4 averaged 31.5 years and had withdrawn 14 days earlier. The 19 males in group 5 averaged 30 years and had withdrawn 4 days earlier. Group 6 consisted of 9 females whose average age was 23 years. They were paid volunteers from the nonprofessional hospital staff, and did not use drugs. Method: Measurements were taken under controlled laboratory conditions; urines were tested (details were not given) for drugs to assure conformity to group. Variations of reaction time were tested in a button-pressing situation: (a) simple reaction time (one of six stimuli); (b) Read more […]

Sedatives

An assessment of the relationship between sedatives and driving accidents requires the survey of literature dealing with: (1) the effects of sedatives on actual driving behaviors, (2) the epidemiological studies of sedatives and traffic accidents, and (3) the physiological, psychological, and behavioral effects of sedatives on factors related to driving. Only a few studies have tested the effects of sedatives either in a simulator or in the field. Loomis and West () tested eight subjects in a driving simulator from 1 to 6 hours after they were given various drugs. The simulator consisted of an automobile steering wheel and brake accelerator pedals arranged as in a standard automobile. The steering wheel operated a model car placed on a moving belt 150 ft. long and 30 in. wide with an opaque l-in. strip running down it lengthwise, which simulated the road bed. The strip was shifted randomly, moving smoothly from side to side as the belt advanced. Accelerator and brake pedals actuated and controlled the rate of belt movement, and the steering wheel controlled the position of the model car. A light source placed 14 in. above the car was capable of producing an amber, red, or green light. The subject was required to Read more […]

General Tranquilizers

Current methodology for determining plasma levels of diazepam and its active metabolites employs electron-capture gas chromatography and can measure 1- to 10-ng quantities (). When a group of people are administered diazepam at a particular dose, there is a wide range of plasma concentrations of diazepam (). This range, in 13 subjects administered 15 mg of oral diazepam daily for a week or more, is 16 to 400 ng/ml (). Garattini et al. () found a range of 10 to 250 ng/ml in 27 subjects given a single 15-mg oral dose. A half-life of 38 to 92 minutes has been measured by this group in five female subjects. Kleijn et al. () calculated a half-life of 20 to 42 hours after 10 mg three times a day, about 0.5 mg/kg/day orally in five subjects. This great variability in plasma concentration is a major problem in interpreting drug effects on human performance. Perhaps the factors that influence plasma concentration curves can be identified and controlled. With seven subjects, Linnoila et al. () showed that ingestion of food increases plasma levels of diazepam 6, 7, and 8 hours after intravenous administration of 0.3 mg of diazepam per kg. They suggest that enterohepatic recycling of diazepam is occurring. Kleijn et al. () Read more […]

Outpatient Treatment and Outcome of Prescription Drug Abuse

Forty-six consecutive patients who voluntarily sought outpatient treatment for abuse of one or more prescription drugs were studied. Barbiturates, amphetamines, and diazepam were the most common drugs abused. Desired treatments by patients included counseling, medical withdrawal, or medical maintenance with the drug of abuse or a chemically related drug. Twenty-two (47.8 percent) patients left treatment and relapsed within one month; another eight (17.4 percent) patients relapsed between one and three months after entering treatment. Only 13 (28.3 percent) reported abstinence 90 days after entering treatment. This experience suggests that a wide range of medical, social, and psychologic resources are required to treat prescription drug abuse, and that long-term drug abstinence is difficult to achieve with all patients. Treatment of prescription drug abuse has dealt primarily with drug complications such as overdose, toxic reactions, and techniques for medical withdrawal. Other reports describe behavior patterns of prescription drug abuse and often refer to it as poly-drug abuse, since many persons frequently abuse more than one drug. Some reports emphasize the clinical complexity of poly-drug abuse and particularly Read more […]

Longterm Treatment with Anxiolytic Drugs: Possibilities of Pharmacodependence

Since the introduction of meprobamate as an anxiolytic or ataraxic substance, the possibility of drug dependence has been discussed. The reason is that these substances, both meprobamate and benzodiazepines, could be included in the broad classification of sedatives, since the prototype of sedatives is still the barbiturate group. This article presents a more or less critical analysis of this problem, comparing our data with those in the literature. Patients and methods The Out-Patient Clinic of the Post-Graduate Course at the Institute of Psychiatry has, since 1972, determined in patients with anxiety states the possibility of drug dependence induced by anxiolytics. Furthermore, it was also of interest to compare the therapeutic efficacy of various anxiolytics. Patients who were pregnant or concomitantly presented neurological disorders, glaucoma and/or prostatic disorders were excluded from the study. On this basis, 600 patients (65.8% women) participated in several double-blind studies. All previously treated patients went on a 10-day washout programme. The selected patient was then randomly put into either the treated or the placebo group. In comparative studies, they were randomly put in one or the other drug Read more […]

Sedative-, Hypnotic-, and Anxiolytic-Related Disorders

Abuse and Dependence Sedative-hypnotic and alcohol intoxications are similar in symptoms and complications. Because sedative-hypnotic use is so frequent in hospitalized patients, the detection of sedative abuse can be difficult. Abuse rarely starts as a result of treatment of acute anxiety or insomnia in a hospitalized patient. The risk of sedative abuse in chronically medically ill outpatients is far greater. There are three major classes of benzodiazepine abusers: polysubstance abusers, pure sedative abusers, and therapeutic users who have lost control. Individuals prone to polysubstance abuse tend to use sedatives for their calming effects (i.e., to come down after use of a stimulant such as cocaine) and for their ability to decrease dysphoric affects, including anxiety, or to potentiate euphoric effects of other drug classes (e.g., benzodiazepines in combination with methadone to boost euphoria). Pure sedative abusers usually have significant underlying psychopathological conditions, and relapse is common. In a long-term follow-up study involving subjects with primary sedative-hypnotic dependence, 46% of the subjects continued to abuse drugs after in-hospital rehabilitation treatment. Anyone can develop physiological Read more […]

Treatment of Alcoholism

Apparently because of the lack of knowledge of the physiological basis for what is now known as the acute alcohol withdrawal syndrome, there has been an enormous variety of therapies advocated and employed in their treatment. All workers know of, and probably many have used: alcohol itself, in tapering-off doses, paraldehyde, adrenal extract, thiamine, insulin, oxygen, nicotinic acid, magnesium sulphate, intravenous fluids, dehydration, etc. In the mid-1950s, reserpine, and then the phenothiazines, were hailed as the drugs of choice in the treatment of the alcohol withdrawal states. Although early reports were enthusiastic, controlled studies subsequently found these agents less than ideal in this indication. Reserpine, in the large doses required, added to the gastro-intestinal woes of these patients, and often also led to serious hypotensive episodes. Fortunately, it rather quickly lost favour; I have seen no recent references to its use in alcohol withdrawal. The phenothiazines as a group have been found to lower the convulsive threshold, a severe handicap in the treatment of a condition in which the convulsive threshold is already low. That this is not merely an interesting theoretical consideration is evidenced Read more […]

Benzodiazepines and Depression

The use of anxiety-reducing drugs in the treatment of anxiety syndromes accompanied by depression or of depressive illness with an anxiety component has been extensively debated in recent times. Many workers in this field have written about the efficacy of treatment of patients with symptoms of neurosis characterized by anxiety and depression. According to some of these authors, neither the anxiety-reducing drugs nor the hypnosedatives have been very successful in the treatment of depression-anxiety syndromes. On the other hand, it has been shown that these drugs can lead to the development of acquired tolerance and habit formation, a problem involving the barbiturates especially and, to a lesser degree, the minor tranquillizers. Emphasis has been placed on the fact that anxiety and depression tend to occur simultaneously in an anxiety-depression syndrome. Taking this frequent coincidence of anxiety and depression as our base, we will discuss the advantages and drawbacks of using tranquillizers when depression is seen in an anxious patient. Before proceeding with this, however, we would like to establish some basic concepts to provide a better understanding of this complex matter. Concept of depression According Read more […]

Human Experiments On Provoking Physical Dependence

The classical experiment is that of Hollister and his co-workers. They gave chlordiazepoxide 100-600 mg daily to 36 hospitalized psychotics for periods of between 1 and 7 months. Eleven of these patients were abruptly changed to placebo on a single blind basis and ten of them developed subjective or objective signs interpreted as those of withdrawal (depression in six, aggravation of the psychoses in five, insomnia and agitation in five, anorexia in four, twitching in one and convulsions in three). These symptoms appeared mainly between the 4th and 8th day and disappeared by the 10th day, coinciding with the half-life data and are considered to be evidence of dependence. It is relevant to note that while this study has been very extensively quoted as evidence for clinical dependence on benzodiazepines, Hollister has subsequently been critical about its relevance to normal clinical use. Thus in 1973 ‘. . . the relative lack of tolerance to the drug and long duration of action makes it a poor candidate for production of physical dependence. Although I was able to show many years ago that physical dependence to chlordiazepoxide could occur, it has generally been overlooked that it took extremes of dose and duration Read more […]

Ex Cathedra Statements

Ex cathedra statements abound in the medical literature on the dependence liability risks of the benzodiazepines and as is often the case the number of cautionary statements is exceeded by the number of statements extolling the absence of abuse liability. Such statements and comments typically contain no evidence or negligible evidence, and it is clear that many are based solely on a misinterpretation of the significance of the Hollister study. Hollister has himself subsequently cast doubt on the clinical signilicance of this finding. A few typical statements are quoted below from acknowledged national and international authorities in the field. ‘Physical dependence on diazepam is unusual and rarely documented. Such cases as are described are mostly in the context of multiple drug use. Psychologic dependence is seen in some patients who simply do not want to stop taking the drug or who fear being caught without a supply on hand. Great emphasis was placed on not prescribing the drug in large quantities or for long periods in vulnerable patients. However, it was extremely difficult to detect the addiction-prone individual except on the basis of past or current history of abuse of alcohol and a variety of other Read more […]