Benzodiazepine alcohol withdrawal

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

Antipsychotics are not indicated for the treatment of withdrawal, except when hallucinations or severe agitation are present (Naranjo and Sellers 1986), in which case they should be added to a benzodiazepine. In addition to their potential to produce extrapyramidal side effects, antipsychotics lower the threshold for seizures, which is particularly problematic during alcohol withdrawal. 

Benzodiazepines and other anxiolytics. Although benzodiazepines are widely used in the treatment of acute alcohol withdrawal, most nonmedical personnel involved in the treatment of alcoholism are opposed to the use of medications that can induce any variety of dependence to treat the anxiety, depression, and sleep disturbances that can persist for months following withdrawal. Researchers have debated the pros and cons of the use of benzodiazepines for the management of anxiety or insomnia in alcoholic patients and other substance abuse patients during the postwithdrawal period (Ciraulo and Nace 2000 Posternak and Mueller 2001). 

In general, with the exception of the central role that benzodiazepines play in the treatment of alcohol withdrawal, the use of medications that have been approved for alcoholism rehabilitation remains very limited. A survey of nearly 1,400 addiction physicians showed that they prescribed disulfiram to only 9% of their alcoholic patients and that naltrexone was prescribed for only slightly higher proportion of patients (13%) (Market al. 2003). These tesults contrast with findings for antidepressants, which were prescribed to 44% of alcoholic patients. Although neatly all of these physicians had heatd of both disulfiram and naltrexone, their self-reported level of knowledge of these medications was much lowet than that of antidepressants. 

Iwata N, Cowley DS, Radel M, et al Relationship between a GABA alpha g Pro385Ser substitution and benzodiazepine sensitivity. Am] Psychiatry 156 1447—1449,1999 Jacobson AF, Dominguez RA, Goldstein B, et al Comparison of buspirone and diazepam in generalized anxiety disorder. Pharmacotherapy 5 290—296, 1985 Jaffe JH, Ciraulo DA, Nies A, et al Abuse potential of halazepam and diazepam in patients recently treated for acute alcohol withdrawal. Clin Pharmacol Ther 34 623-630, 1983... 

Lejoyeux et al. 1998). Similar to opioid-dependent persons, these patients reported that they use benzodiazepines to self-medicate anxiety, insomnia, and alcohol withdrawal and, less commonly, to enhance the effects of ethanol. Approximately l6%-25% of patients presenting for treatment of anxiety disorders abuse alcohol (Kushner et al. 1990 Otto et al. 1992). Controversy exists concerning appropriate benzodiazepine prescribing in this population (Cir-aulo and Nace 2000 Posternak and Mueller 2001). 

Benzodiazepines are the evidence-based treatment of choice for uncomplicated alcohol withdrawal.17 Barbiturates are not recommended because of their low therapeutic index due to respiratory depression. Some of the anticonvulsants have also been used to treat uncomplicated withdrawal (particularly car-bamazepine and sodium valproate). Although anticonvulsants provide an alternative to benzodiazepines, they are not as well studied and are less commonly used. The most commonly employed benzodiazepines are chlordiazepoxide, diazepam, lorazepam, and oxazepam. They differ in three major ways (1) their pharmacokinetic properties, (2) the available routes for their administration, and (3) the rapidity of their onset of action due to the rate of gastrointestinal absorption and rate of crossing the blood-brain barrier. 

Secobarbital exhibits the same pharmacologic properties as other members of the barbiturate class. Most nonmedical use is with short-acting barbiturates, such as secobarbital. Although there may be considerable tolerance to the sedative and intoxicating effects of the drug, the lethal dose is not much greater in addicted than in normal persons. Tolerance does not develop to the respiratory effect. The combination of alcohol and barbiturates may lead to fatalities because of their combined respiratory depressive effects. Similar outcomes may occur with the benzodiazepines. Severe withdrawal symptoms in epileptic patients may include grand mal seizures and delirium. 

Benzodiazepines. The benzodiazepines were developed in the 1950s and introduced into the U.S. market in the 1960s. They have found a variety of uses including the treatment of several anxiety disorders, insomnia, seizure disorders, alcohol withdrawal, surgical anesthesia, and others. The benzodiazepines have also been used to calm agitated patients and are therefore useful during the acute treatment phase of bipolar mania. 

Benzodiazepines have a wide array of clinical uses. In addition to relieving anxiety, they can be used to treat epilepsy, alcohol withdrawal, insomnia, agitation, and perhaps impulsivity. They can also be used as muscle relaxants or to produce conscious sedation during certain medical procedures such as cardiac catheterization and colonoscopy. 

Historically, the treatment of alcohol use disorders with medication has focused on the management of withdrawal from the alcohol. In recent years, medication has also been used in an attempt to prevent relapse in alcohol-dependent patients. The treatment of alcohol withdrawal, known as detoxification, by definition uses replacement medications that, like alcohol, act on the GABA receptor. These medications (i.e., barbiturates and benzodiazepines) are cross-tolerant with alcohol and therefore are useful for detoxification. By contrast, a wide variety of theoretical approaches have been used to reduce the likelihood of relapse. This includes aversion therapy and anticraving therapies using reward substitutes and interference approaches. Finally, medications to treat comorbid psychiatric illness, in particular, depression, have also been used in attempts to reduce the likelihood of relapse. 

Barbiturates. The first barbiturate, barbital, was introduced at the turn of the 20th century. Hundreds of others, including phenobarbital and pentobarbital, were later developed. The barbiturates were a highly successful class of medications as it became clear that they treated not only alcohol withdrawal but seizure disorders, anxiety, and insomnia as well. By the 1960s, however, the barbiturates were largely surpassed by the benzodiazepines. The newer benzodiazepines act in a similar fashion and provide much the same therapeutic benefit but are significantly safer and easier to tolerate. 

Benzodiazepines. Like the barbiturates, benzodiazepines bind to the GABA receptor and are therefore cross-tolerant with alcohol. As a result, they also make suitable replacement medications for alcohol and are widely used for alcohol detoxification. Theoretically, any benzodiazepine can be used to treat alcohol withdrawal. However, short-acting benzodiazepines such as alprazolam (Xanax) are often avoided because breakthrough withdrawal may occur between doses. Intermediate to long-acting benzodiazepines including chlordiazepoxide (Librium), diazepam (Valium), oxazepam (Serax), lorazepam (Ativan), and clonazepam (Klonopin) are more commonly utilized. 

Side effects of benzodiazepines include drowsiness and reduced respiratory function. In patients who are severely medically ill, especially those with lung disease, this side effect can be problematic. However, benzodiazepines are much safer in this regard than their predecessors, the barbiturates, and untreated delirium tremens, the most severe form of alcohol withdrawal, can be fatal. 

Benzodiazepines. Safer than the barbiturates but acting in a similar manner, the benzodiazepines have largely replaced barbiturates since their introduction in the 1960s. Other uses of benzodiazepines include treatment for epilepsy, alcohol withdrawal, several anxiety disorders, agitation, and impulsivity, as muscle relaxants, and as conscious sedation during certain medical procedures. 

All benzodiazepines are indicated in obsessive compulsive disorders. Diazepam and lorazepam are effective in status epilepticus, whereas chlordiazepoxide is indicated in alcohol withdrawal. 

Gustatory, olfactory - benzodiazepine or alcohol withdrawal, drug-induced psychotic states... 

Ntais C, Pakos E, Kyzas P, loannidis JPA. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev 2005. 

There is no evidence from randomized trials that general strategies to prevent delirium are successful. Benzodiazepines are significantly better than placebo in preventing delirium and seizures due to alcohol withdrawal, and long-acting benzodiazepines (such as diazepam) are more effective than... 

Benzodiazepines are also used for several other conditions that are related to, but not actually termed, anxiety. For example, benzodiazepines are commonly given as soporific or hypnotic drugs (drugs that help people sleep). One of the benzodiazepines, flurazepam, is the most frequently prescribed hypnotic drug in the United States. Benzodiazepines also are administered as muscle relaxants, and can even reduce the occurrence of seizures or convulsions. Another common use of benzodiazepines is in alcohol withdrawal. Someone who is trying to stop drinking alcohol is usually given a heavy dose of... 

Benzodiazepines (BZDs) may be given to patients with moderate agitation. These agents also are the treatment of choice in alcohol withdrawal states, characterized by agitation, tremors, or change in vital signs (see also the section The Alcoholic Patient in Chapter 14) (156). 

Other sedative-hypnotics (e.g., benzodiazepines) are also capable of producing a phenomenologically similar syndrome during the withdrawal phase of addiction, but the mechanisms responsible are not well understood. The possibility that common mechanisms are involved is supported by the fact that a depression induced by one class of sedative-hypnotics can be reversed by another class. For example, benzodiazepines can reverse the syndrome induced by alcohol withdrawal. 

Overstreet DH, Kralic JE, Morrow AL, Ma ZZ, Zhang YW, Lee DY. 2003. NPI-031G (puerarin) reduces anxiogenic effects of alcohol withdrawal or benzodiazepine inverse or 5-HT2C agonists. Pharmacol Biochem Behav 75 619-625. 

Significant progress has been made in establishing safe and effective medications for alcohol withdrawal. Pharmacotherapy with a benzodiazepine is the treatment of choice for the prevention and treatment of the signs and symptoms of alcohol withdrawal. Many patients detoxify from alcohol without specific treatment or medications. However, it is difficult to determine accurately which patients require medication for alcohol withdrawal. Patients in good physical condition with uncomplicated, mild to moderate alcohol withdrawal symptoms usually can be treated as outpatients. 

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