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We have conducted in two nursing homes a survey to study the impact of meprobamate's withdrawal, at the beginning of 2012, in terms of extent of prescribing to others psychotropic drugs and occurrence of adverse events. After meprobamate's withdrawal, 65 % of residents did not receive alternative medication and within three months after meprobamate stopping, adverse events (drowsiness, falls and hospitalization) decreased while agitation did not increase., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

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with a 45-year history of meprobamate dependency and multiple failed previous withdrawal attempts who was successfully withdrawn from meprobamate using diazepam during a 2-week inpatient stay on a specialist Addictions ward.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., (2016 BMJ Publishing Group Ltd.)

Meprobamate is usually a safe drug prescribed for anxiety disorders. Fixed drug eruption (FDE) is an exceptional cutaneous adverse effect of this drug. We report a case of FDE induced by meprobamate with positive patch test. A 22-year-old woman was prescribed for depression meprobamate, aceprometazine, valpromide and lorazepam. On the second day of treatment, the patient presented red erythematous and pruriginous plaques in the limbs and the face. After stopping the previous treatment, the patient's lesions resolved completely within 3 weeks with residual pigmentation. One month later, patch tests were performed and were positive to meprobamate. Exceptional cases of FDE were reported in literature with meprobamate. None has reported the use of patch test to confirm the diagnosis.

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

(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.

Objective: Carisoprodol, a drug used for acute lower back pain, may cause psychomotor impairment. We wanted to investigate if patients using carisoprodol had increased risk of being involved in a traffic accident., Methods: Data were retrieved from three population-based registries for the period April 2004-September 2005. The Norwegian Prescription Database contained individual information on all dispensed drugs at all pharmacies outside hospitals. The Norwegian Road Accident Registry contained information on all drivers involved in motor vehicle accidents with person injury. The Norwegian Central Population Registry was used to control for emigration or death. The accident incidence among carisoprodol exposed and unexposed subjects was compared by standardized incidence ratio., Results: Having a prescription for carisoprodol dispensed increased the standardized incidence ratio for being involved in an accident with person injury to 3.7 (95% CI 2.9-4.8) the first week after the date of dispensing. This was similar to diazepam (2.8; 2.2-3.6), but higher than for salbutamol (1.1; 0.6-1.8)., Conclusions: Patients receiving carisoprodol seem to have an increased risk of being involved in traffic accidents involving person injury. The study gives support to earlier work published on the impairing effects of carisoprodol.

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.

Aim: To discuss, through a retrospective study, the epidemiological and clinical aspects and the causative agents of fixed drug eruption., Methods: Thirteen cases were collected retrospectively during 11 years. There were 10 females and 3 males with a mean age of 44 years., Results: The lesions correspond to erythematous plaques which fade to leave slate-brawn macules in all cases. The most frequent localizations were limbs (12 cases), trunk (6 cases), face (3 cases) ans external genitals (3 cases). Sulfonamides were the most frequent responsible drugs in our series (7 cases)., Conclusion: Fixed drug eruption is characterized by one or more erythematous plaques which recur in the same places after challenge. Sulfonamides are actually the most frequent causative drugs in the different series.

This paper considers the pharmacology of the centrally acting muscle relaxant carisoprodol, and its metabolite meprobamate, which is also administered as an anxiolytic in its own right. Literature implicating these drugs in impaired driving is also reviewed. A series of 104 incidents in which these drugs were detected in the blood of drivers involved in accidents or arrested for impaired driving was considered, with respect to the analytical toxicology results, patterns of drug use in these subjects, the driving behaviors exhibited, and the symptoms observed in the drivers. Symptomatology and driving impairment were consistent with other CNS depressants, most notably alcohol. Reported driving behaviors included erratic lane travel, weaving, driving slowly, swerving, stopping in traffic, and hitting parked cars and other stationary objects. Drivers on contact by the police displayed poor balance and coordination, horizontal gaze nystagmus, bloodshot eyes, unsteadiness, slurred speech, slow responses, tendency to doze off or fall asleep, difficulty standing, walking or exiting their vehicles, and disorientation. Many of these cases had alcohol or other centrally acting drugs present also, making difficult the attribution of the documented impairment specifically to carisoprodol and meprobamate. In 21 cases, however, no other drugs were detected, and similar symptoms were present. Impairment appeared to be possible at any concentration of these two drugs; however, the most severe driving impairment and most overt symptoms of intoxication were noted when the combined concentration exceeded 10 mg/L, a level still within the normal therapeutic range.

Misuse of prescription drugs in the elderly can be a serious problem that is difficult to manage. Prescriptions for non-narcotic central nervous system (CNS) depressants (e.g., anxiolytics and sedative-hypnotics) are commonly written, and their use is associated with severe intoxication and withdrawal effects. The presence of comorbid psychiatric conditions (e.g., depression or panic disorder), for which these agents are prescribed frequently, complicates the clinical picture. This paper, using case examples of meprobamate abuse, describes how physicians can recognize, manage, and treat a patient who is abusing a non-narcotic CNS depressant.

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).

A case is reported of a 49 years-old man who presented with cutaneous and muscular manifestations revealing periarteritis nodosa. Two years after detection of this disease occured a preleukemic condition and four years later a chronic lymphocytic leukaemia is discovered. In clinical course appeared a tuberous infiltration of the face and a sudden bilateral deafness. Regression of these two abnormalities is obtained after administration of prednisolone. The patient died of generalized infectious process postoperatively. From these clinical and pathological findings relations between periarteritis and CLL, occurence of deafness and cutaneous lesions are discussed. The relationship between the development of CLL and the immunosuppressive treatment is considered.

A 36-year-old female was treated successfully by hemoperfusion over Amberlite XAD-4 resin after ingestion of 40 gm of meprobamate. Hemoperfusion was started five hours after the ingestion. At that time the patient was in deep coma. The patient was treated by hemoperfusion for five hours, at the end of which time she was awake. Meprobamate clearance over the resin was about 290 mg/min. There were no bleeding complications. It is concluded that hemoperfusion over amberlite XAD-4 resin is a highly effective method in the treatment of severe cases of meprobamate intoxication.

A case report revealing two previously unreported adverse side effects of meprobamate and tridihexethyl chloride (Milpath) drug therapy for a spastic colon is presented. The two previously unreported adverse effects are a diffuse loss of color discrimination and an increased time course to complete dark adaptation.

An investigation of the following psychoactive drugs: barbiturate, benzodiazepine, meprobamate, methaqualone and phenothiazine, was performed on all automobile occupants killed in accidents in southern Sweden during 1977 and 1978. Of 122 drivers and 55 passengers analysed, low concentrations of these drugs were found in nine drivers and in five passengers. Thus, 7.3% of the drivers were driving under the influence of drugs and, of these, two drivers (1.6% of all analysed drivers) were also inebriated. Twenty-three per cent of the drivers were inebriated only. According to the circumstances in the accidents and the number of drivers whose analyses proved positive, drug influence seldom seems to be the cause of fatal traffic accidents.

A 52 year old man admitted to hospital in a toxic state, was found to have agranulocytosis, which recovered when an analgesic containing meprobamate was stopped. The patient was known to have had similar symptoms 9 months previously when the drug was first used, thereby demonstrating an idiosyncratic reaction to meprobamate.

Withdrawal syndromes after discontinuation of benzodiazepine or meprobamate administration are rarely observed, in spite of the large number of prescriptions given. Similar manifestations are noted as after barbiturate withdrawal, and appear 1 to 10 days after sudden interruption of prolonged treatment at high doses. The 6 cases reported include 4 patients with withdrawal syndromes after benzodiazepines (diazepam, oxazepam, lorazepam) and 2 after meprobamate. No evidence of epilepsy was found in the patients, who were hospitalized for treatment after suicidal attempts, or medication overdosage (phenothiazine) in one case. Withdrawal symptoms appeared between the 2nd and 7th day with confusion and/or generalized convulsions and paroxystic changes with slow spike-wave type on EEG tracings. In such cases, precise information must be obtained about previous medication in order that it may be readministered and the diagnosis of epilepsy avoided in patients with withdrawal symptoms.

If the abuse potential of tranquilizers, and particularly benzodiazepines, is examined by their administration as a therapeutic agent to persons dependent on alcohol, alcohol and drugs, or drugs alone, these substances are found to be potentially dependence producing with similar mechanisms to those of other hypnotics and sedatives. However, their abuse potential varies from one substance to another, and on the whole is relatively small. At all events, with constant medical supervision, patients who were previously dependent on a drug of barbiturate type do not independently increase their intake so as to become dependent on the tranquilizers. These experiments on persons with an inherent susceptibility to dependency show that tranquilizers must represent only a very small risk to the general population. The view that benzodiazepines are not potentially dependence producing has no more scientific foundation than the exaggerated fears of this potential. Important is that the uncontrolled supply of highly potent tranquilizers, and above all those with a strong sedative component, leads to dependence in a considerable percentage of cases in the treatment of mixed abuse. No conclusions in absolute terms on the risk presented by tranquilizers (and above all benzodiazepines) may be drawn from observations made in the uncontrolled administration of these substances in case of polytoxicomania. It follows that tranquilizers, which, as far as their therapeutic effect is concerned, are a valuable aid in the treatment of drug abuse, can be safely given when there is constant medical supervision combined with psychotherapy. The basic principle to be followed in the use of tranquilizers for the treatment of drug-dependent persons, is, therefore, their periodic administration in limited doses with constant medical supervision. In principle, however, because of the abuse potential which is nevertheless present, the same mode of administration is also to be recommended for other patient groups. Uncontrolled long-term administration is to be rejected in all circumstances, and supply should be strictly on prescription only in order to prevent uncontrolled acquisition. The various experiments carried out by us on the administration of benzodiazepines to patients with simple or mixed drug dependence show that the habit forming potential of benzodiazepines must, on the whole, be considered as being relatively small; at all events, this group of substances is the least hazardous of all known sedatives. This is of considerable importance, since the neuroleptics and antidepressants (which in themselves present no risk of abuse) are generally poorly tolerated and refused by patients with an inherent tendency towards drug dependence.

Meprobamate use was studied in an ambulatory elderly population in Dunedin, Florida. All participants taking this medication were mailed a questionnaire concerning their pattern of use. From 2,278 subjects, 30 (1.3%) reported the use of this drug. The average age of participants using this drug was 81.3 years. Five participants began using the drug over 27 years ago and over one-half of the respondents reported using the drug on a regular basis for over 10 years. With this type of history of meprobamate use, one might expect to encounter a large number of patients in the future who, in a similar manner, have been using benzodiazepines for many decades.