Benzodiazepines for Alcohol Withdrawal

Clinical Question

Are benzodiazepines safe and effective for the treatment of alcohol withdrawal?

Evidence-Based Answer

Benzodiazepines are safe and effective for the treatment of alcohol withdrawal, particularly for the prevention of withdrawal seizures, although their superiority to anticonvulsants has not been demonstrated convincingly. There is no clear benefit of one benzodiazepine over another or of symptom-triggered versus fixed-dose scheduling.

Practice Pointers

Benzodiazepines are used widely for the treatment of alcohol withdrawal, with the goals of reducing the severity of withdrawal, preventing delirium, and reducing the incidence of seizures. This systematic review identified 57 relevant randomized controlled trials with a total of 4,275 participants. The quality of the included studies, many of which date from the 1970s and 1980s, was fair, and most were small. Only nine studies clearly concealed allocation of patients to treatment or control groups, and only 21 adequately described the randomization procedures, although all but three were double-blinded.

Not surprisingly, the authors found that benzodiazepines were much more effective than placebo at preventing alcohol withdrawal seizures (relative risk 0.16; 95% confidence interval, 0.04 to 0.69). However, there was no significant difference in prevention of seizure between benzodiazepines and antiseizure drugs. There also was no difference in control of symptoms (as measured by standard scales) among benzodiazepines and other drugs such as clonidine (Catapres) or carbamazepine (Tegretol). There were trends in favor of benzodiazepines, particularly longer-acting drugs, for prevention of delirium. Thirteen studies, with a total of 571 patients, compared different benzodiazepines but found no differences in effectiveness among them. Only three studies, with a total of 262 patients, compared fixed-dose with symptom-triggered dosing schedules, and no clear conclusions could be drawn.

An evidence-based guideline from the American Society of Addiction Medicine1 recommends benzodiazepines as a first-line agent for the treatment of alcohol withdrawal. The guideline notes that although agents with a longer duration of action may provide fewer breakthrough symptoms, those with a shorter duration of action, such as lorazepam (Ativan), may be preferred when there is concern about prolonged sedation (e.g., in patients with significant comorbidities or liver disease).1

Inhaled Beta Agonists for Chronic, Nonspecific Cough in Children?

Clinical Question

Are inhaled beta agonists effective for the treatment of chronic, nonspecific cough in children?

Evidence-Based Answer

The single clinical trial on this topic found that inhaled beta agonists do not reduce cough frequency or improve symptoms in children with chronic, nonspecific cough.

Practice Pointers

Cough lasting more than three weeks in children often is caused by asthma, postnasal drip, gastroesophageal reflux disease, or chronic exposure to irritants such as tobacco smoke or allergens; it also may be attributed to overestimation of symptoms by parents. Rarely, it is caused by a serious problem such as cystic fibrosis or tuberculosis. When these causes have been excluded, chronic, nonspecific cough, sometimes called “cough variant asthma,” often is diagnosed.

The authors of this systematic review identified only one study that compared an inhaled beta agonist with placebo in a randomized, double-blind trial. This study compared inhaled albuterol (Proventil) in a dosage of 200 mcg twice daily via metered dose inhaler with placebo in 42 children who had chronic, nonspecific cough.1 At the end of the one-week study, the researchers found no differences between groups regarding cough frequency, symptom score, airway responsiveness, or sensitivity of cough receptors to capsaicin. The study was small, and although it was powered to detect a 70 percent difference in cough frequency between groups, it might have missed a small but clinically significant benefit with inhaled beta agonists. The authors note that observational studies and examination of the symptoms of children in placebo groups suggest that cough tends to improve over time.

Another Cochrane review2 performed in 2005 by the same group of researchers found a possible benefit from high-dose inhaled corticosteroids in two studies with a total of 123 children; however, children in the placebo group also improved, and the clinical impact was of uncertain significance. An evidence-based guideline from the Finnish Medical Society3 recommends that treatment with inhaled corticosteroids be considered in children with cough-predominant asthma if pulmonary function testing is abnormal. For younger children who cannot cooperate adequately with pulmonary function testing, an empiric trial of inhaled corticosteroids should be considered.