Archive for category Benzodiazepines'

Benzodiazepines in the Treatment of Alcoholism

This post comprises three sections that cover the main aspects of benzodiazepines and alcohol: (1) the basic pharmacology of benzodiazepines; (2) use of benzodiazepines in the treatment of withdrawal; and (3) the use of benzodiazepines in treating alcoholics. The basic studies suggest that a major site of action of alcohol may be the GABA/benzodiazepine receptor complex and that compensatory alterations in this complex may underly withdrawal. In the section on alcohol withdrawal, interactions between the GABA/benzodiazepine receptor complex, sympathetic nervous system, and hypothalamic-pituitary-adrenal axis are discussed. Use of benzodiazepines in the treatment of the alcohol withdrawal syndrome are reviewed, including the possibility that the benzodiazepines may prevent withdrawal-induced “kindling”. Lastly, we review indications for, and efficacy of, benzodiazepines in long-term treatment of patients with alcoholism. Benzodiazepines are not indicated for the treatment of alcoholism. Furthermore, they have very few indications in alcoholics and their dependency-producing potency has to be appreciated when they are used in patients with alcoholism. The benzodiazepines () are a group of compounds that were first Read more […]

Alcohol and Panic Attacks

Panic attacks with and without agoraphobia are more common among alcoholics than the rest of the population. The simplest explanation may be that certain patients with panic attacks drink alcohol to alleviate anticipatory anxiety. The relationship between panic attacks and alcoholism may, however, be complex. Both alcohol withdrawal and panic attacks have been demonstrated to be associated with noradrenergic overactivity. Furthermore, tolerance to alcohol seems to be partly conditioned, at least in experimental animals, and it involves physiological changes compatible with sympathetic activation. Tolerance is not maintained in experimental animals with central noradrenergic lesions. Thus, noradrenergic activation may play an important role both in conditioning tolerance and panic attacks. Another phenomenon pertinent to alcohol withdrawal, with implications for panic attacks, is kindling. Repeated alcohol withdrawals may lead to kindling. This was first postulated based on a retrospective chart review of patients with alcohol dependence which showed that repeated withdrawals became progressively more severe. More recently, it was demonstrated that blunted responsiveness of noradrenergic a2-autore-ceptors was positively Read more […]

Benzodiazepines in the Treatment of Alcoholism: Future Directions

The above treatment recommendations emphasize that minimal signs and symptoms of ethanol withdrawal can generally be treated without pharmacotherapy. The repeated experience of untreated ethanol withdrawals, however, may produce a “kindling” effect over time. Kindling is the “progressive increase in neural responsivity produced by spaced and repeated epileptogenic stimulation of certain brain structures.” The kindling hypothesis suggests that each additional episode of withdrawal will elicit increasingly severe signs and symptoms. Preclinical studies in which the severity of the ethanol withdrawal syndrome increased in rats subjected to repeated episodes of ethanol withdrawal or following kindling induced by electroshock, metrazol injections, or amygdaloid stimulation indicate that such a process may take place. In addition, a retrospective study in alcoholics reported that periods of heavy drinking and dependence on ethanol were associated with an exacerbation of agoraphobia and social phobias, and that subsequent periods of abstinence were associated with substantial improvements in these phobic anxiety states. A recent study demonstrated that patients with panic disorder and alcohol dependence do not distinguish Read more […]

Benzodiazepine Treatment of the Ethanol Withdrawal Syndrome

The objective of drug treatment in ethanol withdrawal is the relief of subjective symptoms, the prevention or treatment of more serious complications such as seizures or delirium tremens, and the preparation for long-term rehabilitation with minimal hazard of new dependence problems or direct toxicity related to drug treatment. The ideal drug for alcohol withdrawal should have a rapid onset and long duration of action, wide margin of safety, metabolism not dependent on liver function, and absence of abuse potential. The various benzodiazepines offer many of these advantages; the selection of the most appropriate benzodiazepine will depend on the clinical situation. Withdrawal severity can be quickly and reliably determined upon admission by measuring breath alcohol concentration and administering an objective rating scale, such as the CIWA-A (Clinical Institute Withdrawal Assessment of Alcohol). Patients in mild ethanol withdrawal (CIWA-A<20) and without a prior history of withdrawal seizures can generally be treated conservatively (fluids, multivitamins, reassurance, antacids, thiamine). Treatment without medication offers the patient an opportunity to exercise nonpharmacological control over his or her life 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 […]

Treatment of Alcoholism: Experience with Benzodiazepines

The treatment of alcoholism depends on the phase of the disease which the physician is called on to treat: acute intoxication, acute withdrawal, or chronic alcoholism. When should anti-anxiety drugs be used? Almost never for intoxication, almost always during withdrawal, and sometimes during the treatment of chronic alcoholism. Acute intoxication First, acute intoxication, excluding pathological intoxication, but including stupor and coma, should never be treated with any depressant drug. Potentiation of the CNS depression due to the high level of blood alcohol would inevitably lead to a worsening of the condition. Alcohol plus sedative drugs are often a lethal combination. The intoxicated individual should simply be allowed to sleep it off, preferably in the protective environment of his own home. Alcoholic coma may require haemodialysis, although providing a clear airway, fluids, vasopressor drugs, steroids and meticulous nursing care usually will suffice. The one exception which requires sedative treatment is pathological intoxication. This condition of wild excitement in which the patient is a danger to himself and others probably represents an idiosyncratic reaction to a relatively small amount of alcohol. Read more […]

Alcohol withdrawal

Many reports of studies in alcoholism suffer a credibility gap in their failure to differentiate among the various alcohol-related syndromes, which are then treated together, leading to meaningless analyses of a mixed salad of numbers of cases improved, unimproved, worse or dead. The several states associated with excessive use of alcohol may have different aetiologies, courses, signs and symptoms. Some of the therapeutic agents employed in such studies may be contra-indicated in some of the disparate syndromes of the subjects treated. The results of such a ‘mixed bag’ can provide no real clues as to the comparative merits of the drugs under study. The acute alcohol withdrawal states result from the discontinuation, or reduction of intake, of alcohol after a prolonged bout of drinking. Although still not universally accepted, several experimental studies have provided scientific proof of the validity of the thesis that abstinence is the cause of these syndromes. Isbell et al? maintained ten human subjects in a chronic state of alcohol intoxication over prolonged periods. Four of these volunteers suffered severe symptoms following discontinuance of alcohol, consisting mainly of nausea, insomnia, excessive perspiration 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 in Masked Depressions

Depressive illness is gradually becoming the pathology-symbol of our era of crisis, showing ever-growing epidemic proportions in its several forms and clinical manifestations: endogenous (MDP and involutional melancholia), reactive (depressive reactive psychosis), neurotic (neurotic depressions), symptomatic (in other psychiatric disturbances) and many organic diseases. In 1977, in Sao Paulo, Brazil, the prevalence of depressive illness was considered by all the physicians (more than 7000, mostly non-psychiatrists) interviewed by our group, to have increased by 83 %. In the past decades, besides an increase in the prevalence of depressive illness, a kind of ‘mutation’ has been noted in depressive symptomatology translated as a more frequent phenomenon of ‘depressive somatization’. This brings patients to seek repeated somatic examination, searching in vain for physical changes that lead to expensive and varied clinical and surgical treatments. Although thymopathic masking can appear in different forms (obsessions, aggressiveness, alcoholism, toxicomania, etc.), the term ‘masked depression’ usually refers to a depressive illness in which classic psychopathological symptoms of depression do exist, but are masked 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 […]