Meprobamate dependence

Williams H, Oyefeso A, Ghodse AH Benzodiazepine misuse and dependence among opiate addicts in treatment. It J Psychol Med 13 62-64, 1996 Wiseman SM, Spencer-Peet J Prescribing for alcoholics a survey of drugs taken prior to admission to an alcoholism unit. Practitioner 229 88—89, 1985 Wolf B, Grohmann R, Biber D, et al Benzodiazepine abuse and dependence in psychiatric inpatients. Pharmacopsychiatry 22 54—60, 1989 Wood MR, Kim JJ, Han W, et al Benzodiazepines as potent and selective bradykinin B1 antagonists. J Med Chem 46 1803—1806, 2003 Zawertailo LA, Busto UE, Kaplan HL, et al Comparative abuse liability and pharmacological effects of meprobamate, triazolam, and butabarbital. J Clin Psycho-pharmacol 23 269-280, 2003... 

I particularly recalled my clinical work in 1958 and early 1959, when my assignment was to care for hospitalized soldiers and their dependents. We had few drugs to work with in those days. We relied mainly on Thorazine in the treatment of psychotic patients. It was the first major tranquilizer and preceded by decades the wonder drugs used today. For less severely disturbed patients we used meprobamate (Equanil) which has all but disappeared from today s pharmacies. In fact, the value of lithium, for mood swings, was just beginning to be accepted. 

Geriatric Considerations - Summary Because meprobamate has a low therapeutic window, rapid development of folerance, and great potential for abuse and dependence, these agents are not recommended for use in older adulfs. 

Gelfand EW, Dosch HM, Hastings B, et al Lithium a modulator of cyclic AMP-dependent events in lymphocytes. Science 203 365-367, 1979 Geller 1, Seifter J The effects of meprobamate, d-amphetamine and promazine on experimentally induced conflict in the rat. Psychopharmacologia 1 482-492, 1967... 

Schedule IV - This class represents medications considered to be of low abuse potential with the possibility of limited dependence especially when compared to the previous schedules. Examples are phenobarbital, chloral hydrate, the benzodiazepine tranquilizers, propoxyphene and meprobamate (all are sedatives). 

Schedule IV. These drugs supposedly have a lower potential for abuse than schedule III drugs, with only a limited possibility of physical dependence, psychologic dependence, or both. Examples include certain antianxiety drugs (meprobamate), certain barbiturates (barbital, phenobarbital), and a variety of other depressants and stimulants. 

Long term or excessive use of these medications may also cause tolerance and physical dependence.14,31 In particular, carisoprodol should be used cautiously because this drug is metabolized in the body to form meprobamate, which is a controlled substance (see Chapter 1) that has sedative/anxiolytic properties but is not used extensively because it has strong potential for abuse.13,73 Hence, use of cariso-... 

Meprobamate (Miltown, Equanil) was introduced in the 1950s. It had the effect of relieving anxiety without producing sleep. However, regular use produced psychological and physical dependence. 

The drugs in Schedule IV have a relatively low abuse potential and risk for psychological or physical dependence relative to those listed in Schedule in and include such drugs as barbital, phenobarbital, methylphe-nobarbital, chloral betaine (Beta Chlor), chloral hydrate, ethchlorvynol (Placidyl), ethinamate (Valmid), meprobamate (Equanil, Miltown), paraldehyde, methohexital, fenfluramine, diethyipropion, phentermine, chlor-diazepoxide (Librium), diazepam (Valium), oxazepam (Serax), clorazepate (Tranxene), flurazepam (Dalmane), clonazepam (Clonopin), prazepam (Verstran), lorazepam (Ativan), mebutamate, and dextropropoxyphene (Dar-von). 

The barbiturates and meprobamate have been entirely superseded by the benzodiazepines and because of their low benefit-to-risk ratio (dependence producing, lethality in overdose, potent sedative effects) they should never be used as anxiolytics. Despite their popularity as short-term sedatives, antihistamines are ineffective anxiolytics, while the use of sedative antidepressants such as amitriptyline should be limited to the treatment of patients with symptoms of both anxiety and depression due to their limited efficacy and the poor patient compliance associated with their adverse effects. However, patients with panic disorder do appear to show a beneficial response to antidepressants (see Chapter 6). A similar argument... 

Because of its relation to benzodiazepines, dependence on carisoprodol can be a problem. Among patients who had taken carisoprodol for 3 months or more, up to 40% had used it in amounts larger than prescribed, and up to 30% had used it for an effect other than that for which it was prescribed (2). A significant percentage of physicians were unaware of the potential of carisoprodol for abuse and of its metabolism to meprobamate. Patients with carisoprodol withdrawal can present with agitation, restlessness, hallucinations, seizures, anorexia, and vomiting. 

Meprobamate causes physical dependence similar to that seen with barbiturate dependence. No physical dependence on buspirone administration has been... 

The treatment of anxiety throughout human history has involved a variety of natural agents which were administered to relieve tension and induce a state of altered consciousness, with ethanol in its various forms the most widely used [4]. Within the last century, general CNS depressants such as barbiturates, bromide salts, and ethanol surrogates such as chloral hydrate and paraldehyde have been employed to treat anxiety. Because of side-effects of the other drugs, barbiturates were used predominantly in the first half of this century as anxiolytics, but their clinical utility was limited by tolerance and dependence liability. Propanediolcarbamates such as meprobamate were also used to treat anxiety but displayed many of the barbiturate side-effects. 

Meprobamate is widely used. Its action in man is altogether similar to that of a weak sedative. In this respect, it behaves like the barbiturates. It can be substituted for the barbiturates with modest success. Although many claims have been made for unusual effects of the drug, and animal data are interesting, so far the experienced clinician has not been convinced that this drug has any unusual merits (13). Certainly, physical dependence develops and blood dyscrasias have been observed (17). 

The abuse of meprobamate has continued despite a substantial decrease in the clinical use of the drug. Carisoprodol (soma), a skeletal muscle relaxant whose active metabolite is meprobamate, also has abuse potential and has become a popular street drug. Meprobamate is preferred to the benzodiazepines by subjects with a history of drug abuse. After long-term medication, abrupt discontinuation evokes a withdrawal syndrome usually characterized by anxiety, insomnia, tremors, and, frequently, hallucinations generalized seizures occur in about 10% of cases. The intensity of symptoms depends on the dosage ingested. 

Acute and chronic administration of alcohol can inhibit the biotransformation or detoxification of many drugs, such as barbiturates, meprobamate, and amphetamines by liver enzymes. The effect can occur in two opposite ways. Alcohol and cannabinoids effects are additive. Both are CNS depressants. Animal studies indicate that simultaneous administration of alcohol and tetrahydrocannabinol (THC), the psychoactive component of marijuana, increased the tolerance and physical dependence to alcohol. Human studies show that alcohol and THC combination enhanced the impairment of physical and mental performance only, and there is no evidence of any interaction between both drugs. With barbiturates. 

Both meprobamate and alcohol are CNS depressants, which appear to have additive effects. There is also some evidence that alcohol may inhibit or increase meprobamate metabolism, depending on whether it is taken acutely or chronically, but the contribution of this to the enhanced CNS depression is uncertain. Meprobamate does not appear to increase blood alcohol levels. ... 

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