Something old, something new: a successful case of meprobamate withdrawal.

Meprobamate, a benzodiazepine-like drug, was commonly prescribed for anxiety in the 1960s and 1970s, but fell out of favour, at least in part, due to the risk of dependence, for which there is little published evidence to guide clinical management. We discuss a 70-year-old man with a 45-year history of meprobamate dependency and multiple failed previous withdrawal attempts who was successfully withdrawn from meprobamate using diazepam during a 2-week inpatient stay on a specialist Addictions ward. An appropriate diazepam dose was established using the Clinical Institute Withdrawal Assessment scale for benzodiazepines (CIWA-B). This dose was then slowly reduced over 12 days. Multidisciplinary input, especially psychological therapy tackling his underlying anxiety disorder during his admission, was thought to be particularly helpful.

Acute hand ischemia after intra-arterial injection of meprobamate powder.

BACKGROUND: Meprobamate tablets contain microcrystalline cellulose, a potent embolic agent that has been shown to cause gangrene in animal studies. Microvascular embolization caused by microcrystalline cellulose can contribute to the ischemic process. OBJECTIVE: We report a case of acute hand ischemia after accidental intra-arterial injection of crushed meprobamate powder in a 23-year-old male drug abuser. CASE REPORT: The distal tips of the patient's right thumb, index finger, ring finger, and little finger continued to develop gangrene despite medical therapy with heparinization, low molecular-weight dextran infusion, corticosteroid administration, and hyperbaric oxygen therapy. CONCLUSION: We believe this is the first case of acute limb ischemia caused by intra-arterial injection of meprobamate powder documented in humans. Emergency physicians should be aware that accidental intra-arterial injection of crushed oral drug formulations is potentially limb threatening and prompt recognition of similar clinical scenarios is of vital importance.

[Unsuspected danger of a medicinal preparation]. / Danger inattendu d'une préparation magistrale.

INTRODUCTION: Inhaled foreign bodies are commonly reported in childhood but less so among adults. We report the case of a patient who inhaled a medicinal preparation containing meprobamate and quinine sulfate. The consequence of this was caustic damage to the airways. CASE REPORT: A 64-year-old woman came to the emergency room because of dyspnea, oropharyngeal pain and sialorrhea. She reported that she had inhaled a capsule containing meprobamate and quinine sulfate the previous day. Flexible bronchoscopy showed evidence of caustic damage to the larynx and lower airways. The patient was treated by fasting, corticoids and intravenous broad-spectrum antibiotics. All the lesions recovered and she was discharged from the hospital 15 days after the event. CONCLUSIONS: Inhalation of drugs mostly leads to airway obstruction. Risk of harm is influenced by neurological status, the motility of the digestive system and the properties of the drug. To the best of our knowledge, this is the first time that caustic airway disease has been described following inhalation of a medicinal preparation containing meprobamate and quinine. It highlights the need to be familiar with the chemical properties of medications when prescribing them to patients who are at risk of aspiration.

Psycho-pharmacotherapy for anxiety and obsessive-compulsive disorder: the issue of prolonged barbiturate retention.

The authors report the case of a 32-year-old man who had been treated for anxiety and obsessive-compulsive disorder and had received 800 mg methylphenobarbital (MPB). After switching to a barbiturate-free schedule, his condition continued to be unstable for more than 21 MPB half-lives (approx. 30 days) and did not stabilize until MPB-metabolites dropped below their urinary detection limit. Considering that this article provides findings from a single patient, the authors use this experience to discuss and emphasize the importance of clinical control of barbiturates in psychiatry.

Sleep complaints: Whenever possible, avoid the use of sleeping pills.

(1) Most sleep complaints involve difficulties in getting to sleep or staying asleep, or not feeling refreshed on awakening. Misconceptions and worrying over the lack of sleep and its consequences can contribute to reinforcing these disorders; (2) How can patients who complain of poor-quality sleep be helped, without resorting to treatments that can have adverse effects? To answer this question, we conducted a systematic review of the literature based on the standard Prescrire procedure; (3) One effective approach is to explain the basic physiology of sleep, to discuss misconceptions, and to adopt a strategy of "stimulus control". This method has a similar efficacy to prescribing a benzodiazepine. and the effect is longer lasting; (4) Moderate, regular physical exercise, especially in the morning, seems to help some patients, but the evidence is weak; (5) Some clinical trials of phytotherapy have shown a positive risk-benefit balance of weak aqueous or hydroalcoholic valerian extracts. Efficacy is limited, however; (6) A meta-analysis of placebo-controlled trials showed that benzodiazepines and related drugs increase the duration of sleep and help patients to fall asleep sooner. However, none of these trials provides comparative data spanning periods of more than two weeks. Efficacy is uncertain in the longer term, as patients quickly develop a tolerance to the hypnotic effects of benzodiazepines; (7) The adverse effects of benzodiazepines include frequent memory disorders, daytime drowsiness, falls, fractures and road accidents, and a withdrawal syndrome after treatment cessation. Related drugs such as zolpidem and zopiclone provoke similar adverse effects; (8) Sedative antihistamines have not been as well-evaluated as benzodiazepines in this setting. Small comparative trials of doxylamine and diphenhydramine showed no major difference in efficacy versus benzodiazepines and related drugs. The main adverse effects of sedative antihistamines are daytime drowsiness and altered vigilance, and atropinic effects; (9) Case-control studies showed a statistical link between benzodiazepine use in early pregnancy and birth defects such as cleft lip. In contrast, data on the use of doxylamine during pregnancy are reassuring; (10) Other sedative psychotropics have not been adequately tested in this setting or have been shown to have a negative risk-benefit balance; (11) In practice, patients who complain of poor-quality sleep should be given appropriate information on the mechanisms of normal sleep and related misconceptions, on the best methods for getting to sleep, and on the dangers of sedative psychotropics (dependence, withdrawal syndrome). When prescribing or dispensing a benzodiazepine to a woman of child-bearing age, the risk of birth defects, although not clearly demonstrated, must be mentioned.

Carisoprodol use and abuse in Norway: a pharmacoepidemiological study.

AIM: Carisoprodol was developed to create a drug with less potential for abuse than meprobamate. However, case reports have established carisoprodol as a drug of abuse. This paper explores the extent of potential abuse of this drug in Norway. METHODS: The Norwegian Prescription Database contains information on prescription drugs dispensed to individuals in Norway. Patients can be followed over time. High levels of carisoprodol use could indicate use for pleasurable effects or development of tolerance. Concomitant use of other potential drugs of abuse was also studied. We studied drug-seeking behaviour by looking at patients who received carisoprodol from many different pharmacies and doctors or from high-prescribing doctors. Carisoprodol was compared with a series of other medicinal drugs with or without known potential for abuse. RESULTS: Some 53,889 Norwegian women (2.4%) and 29,824 men (1.3%) > or =18 years old received carisoprodol at least once in 2004. Prescribing of carisoprodol was skewed. As many as 32% of the patients received more than 15 defined daily doses (DDDs) of carisoprodol and >11,000 patients (15%) received > or =75 DDDs in 2004. High users of carisoprodol also received more benzodiazepines and opioids. Few patients used three or more doctors for prescriptions, but carisoprodol-abusing patients more often received their prescription from high-prescribing doctors. CONCLUSIONS: Carisoprodol was widely used and the skewedness in use indicated that it is a potential drug of abuse. A large number of patients used more carisoprodol than recommended in the guidelines. The high level of use and abuse of carisoprodol should be of concern in Norway.

[Gender differences in suicidal behavior]. / Nemi különbségek a szuicid viselkedésben.

Gender-specific differences in suicidal behaviour have been analysed in a number of recent studies. According to these, several socioeconomic, demographic, psychiatric, familial, help-seeking differences can be identified in protective and risk factors between males and females. Gender is one of the most replicated predictors for suicide. In the framework of the WHO/EURO Multicentre Study on Suicidal Behaviour, more than fifty thousand suicide attempts have been registered so far. Until now data on more than 1200 monitored suicidal events have been collected in Pecs centre. In most countries male suicid rates are higher. In contrast to suicides, rates of suicide attempts are usually higher in females. Concerning the differences in methods, it is a recognised fact that males use violent methods of both suicide and attempted suicide more often than females. The summarised clinical impression suggests that compliance of male patients is poorer than that of females. According to our data, a typical male attempter is characterised as follows: unemployed, never married, lives alone. He tends to use violent methods; if he takes drugs, it is mostly meprobamate or carbamazepine. A lot of male attempters have alcohol problems or dependence. As for the females, we found high odds ratios in the following cases: divorced or widowed, economically inactive, depressive state in the anamnesis. Female attempters are mainly repeaters using the method of self-poisoning, mostly with benzodiazepines. As suicide is a multicausal phenomenon, its therapy and prevention should also be complex and gender differences should be taken into account in building up our helping strategies.

[Characteristics of the choice of psychotropic drugs in suicide attempts]. / A pszichofarmakonválasztás jellemzöi öngyilkossági kísérletekben.

UNLABELLED: Review of results of Pecs centre in WHO/EURO Multicentre Study on Suicidal Behaviour. OBJECTIVE: Studies concerning the choice of methods and psychotropics in the suicidal acts have a great importance because the outcome of suicides is decisively determined by the potential lethality of the method. In the sample of patients who attempted suicides, the features of overdoses have been investigated as well as their relations to the age, sex and repetition. METHOD: Within the framework of the WHO/EURO Multicentre Study on Suicidal Behaviour data, 1158 cases with suicide attempts were collected from 1997 to 2001. RESULTS: Among methods of suicide attempts the most frequents were overdoses, while cutting, and hanging were more rarely, and alcohol consumption associated with 15% of attempts. Psychotropics were found in three-quarters of overdoses. A more detailed analysis of the methods used by suicidal patients shows that benzodiazepines represented almost two-thirds of all the drugs taken followed by meprobamate, carbamazepine and antidepressants. Repeaters used frequently antidepressants, antipsychotics, carbamazepine, while benzodiazepines and meprobamate poisoning were rather typical of first-ever group. CONCLUSION: Considerable differences in the use of psychotropics for parasuicide related to gender, age and repetition were found. The results suggest, that the features of overdoses may be in connection with the availability of drugs and the special national characteristics of drug-prescribing. The differences of repeaters may reflect the insufficiency of the mental health care system. The authors emphasize the importance of these facts among the possibilities of prevention.

Risks of non-Hodgkin's lymphoma, multiple myeloma, and leukemia associated with common medications.

We utilized data from two Kaiser Permanente medical care programs to evaluate risks of hematopoietic and lymphoproliferative (HLP) malignancies after use of 14 common medications. The subjects were adult cases of non-Hodgkin's lymphoma (NHL) (N = 94), multiple myeloma (N = 159), and leukemia (N = 257) and individually matched controls (N = 695). Abstractors reviewed medical records and recorded medication notations. Using a minimum 5-year exposure lag between first notation and malignancy diagnosis, the risk of NHL was greater among plan members who were prescribed amphetamines [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.1-4.8], lidocaine (OR = 2.6; 95% CI = 1.2-5.5), and meprobamate (OR = 2.1; 95% CI = 1.03-4.3). The risk of NHL rose with increasing number of medical record notations for amphetamines; however, there was no association with number of notations for lidocaine or meprobamate. The odds ratio for total leukemia was decreased among patients who took chloramphenicol (OR = 0.4; 95% CI = 0.2-0.97).

Pharmacological studies on meprobamate incorporation in human beard hair.

The time course of appearance of meprobamate in beard hair after single oral administration (400, 800, or 1200 mg) was monitored in 3 groups of 4 subjects by GC/MS. Meprobamate appeared in beard hair approximately 4-5 days after administration and peaked during the 7-9th day. Drug levels in beard hair appeared to be dose-related.

Different effects of psychotropic drugs on delayed hypersensitivity responses in mice.

The influence of certain psychotropic drugs on the delayed-type hypersensitivity (DTH) response to sheep red blood cells in BALB/c mice was studied. The effects on the overall response and the induction and elicitation phases were evaluated, using two alternative dosage schedules for each agent. It was found that diazepam had no effect on the DTH reaction but the administration of imipramine, haloperidol, chlorpromazine or meprobramate all resulted in depression of the response, impairing both the induction or elicitation phases. The results indicate that psychotropic drugs may produce in vivo depression of cell-mediated immunity by different mechanisms.

The pharmacokinetics of meprobamate following its oral and rectal administration as a series of combinations with diphenhydramine, acetylsalicylic acid, codeine and pentaerythritol tetranitrate.

Studies in human volunteers of the pharmacokinetics of the active drugs in the formulations Visano-mini (meprobamate and diphenhydramine HCl), DoloVisano (meprobamate, diphenhydramine HCl, acetylsalicylic acid and codeine phosphate) and VisanoCor (meprobamate, diphenhydramine HCl and pentaerythritol tetranitrate (PETN], have demonstrated systemic absorption of each of the drugs from all of the formulations. Bioequivalence of meprobamate is indicated despite the drug combinations involved. Some differences in diphenhydramine pharmacokinetics are, however, apparent. The bioavailability of meprobamate administered rectally to human volunteers as the marketed preparations DoloVisano Suppositories and Dolo-Visano Suppositories sine codeino, is similar to that observed following oral administration.

[Regulation of oxidative phosphorylation as a possible method of normalizing cerebral metabolism]. / Reguliatsiia okislitel'nogo fosforilirovaniia kak odin iz vozmozhnykh putei normalizatsii metabolizma mozga.

Experiments were performed to study the effect of chronic emotional painful stress on oxidative phosphorylation in different structures of rat brain at varying times of the development as well as after pretreatment with psychotropic agents. During the stage of excess catabolism, stress was demonstrated to dramatically inhibit and dissociate oxidative phosphorylation. This led to the impairment of macroerg synthesis and to the reduction of the brain macroerg content. Prophylactic administration of the derivatives of nicotinic acid and GABA markedly stimulated oxidative phosphorylation making it return to the initial level. Mebicar and meprobamate were less powerful. Chlorodiazepoxide aggravated stressful effects on tissue respiration and oxidative phosphorylation. It has been demonstrated that energy metabolism of the brain may return to normal at the expense of stimulation of oxidative phosphorylation.

Dissolution of meprobamate from various tablet formulations.

The effect of some formulation variables on the release of meprobamate from compressed tablets has been investigated. Possible interaction among the various variables was also studied. As a diluent, lactose produced a better dissolution rate than did starch. Tablets made with starch paste as the binder produced a faster release of meprobamate than those made with gelatin solution. Acacia proved to be the best disintegrating agent when compared to microcrystalline cellulose or starch, especially when the formulation already contained starch as the diluent. Under these conditions, microcrystalline cellulose was a better disintegrating agent than starch. Magnesium stearate or talc when used as a lubricant did not reduce the rate of release of meprobamate. Formulations containing a large proportion of starch (about 50%) did not produce a fast release of meprobamate.

[The use of a sedative neuroleptic agent, sultopride, in posttraumatic Korsakoff syndrome in a young adult]. / Utilisation d'un neuroleptique sédatif, le sultopride, dans le cadre d'un syndrome de korsakoff post-traumatique chez un adulte jeune.

In a young woman with a post-traumatic Korsakoff syndrome exhibiting agitation and anxiety, sedative drugs were difficult to use as they either exacerbated confusion or generated ataxia. Administration of meprobamate with oral sultopride in a high dosage (2 g per day) was promptly followed by an improvement in the patient's condition. Doses were therefore rapidly tapered (over approximately a month and a half). Complete recovery, which is the well-known outcome, thus took place in favorable conditions, as anxiety and agitation no longer hindered the patient's relationships with others.