Treatment of the acute alcohol withdrawal state: a comparison of four drugs.
T seriousness of alcohol withdrawal and its widespread occur­ rence in the 166 Veterans Administration hospitals in the 1960’s was the principal reason this pivotal study was conducted. The important work by Kaim and colleagues has endured over the years, because alcohol withdrawal still is common, potentially life threatening, and often not recognized and treated promptly and effectively. Kaim and colleagues studied the ef­ ficacy of four drugs—chlordiazepoxide (a benzodiazepine), chlorpromazine ( a n e u r o l e p t i c o r a n t i p s y c h o t i c agent), hydroxyzine (a sedating anti­ histamine), and thiamine (a vitamin)— commonly used at that time to treat alcohol withdrawal symptoms, specifi­ cally the more serious symptoms of delirium tremens and convulsions. These researchers’ results help estab­ lish the benzodiazepines as drugs of choice in treating alcohol withdrawal. To fully understand the context in which Kaim and colleagues conducted their study, it is useful to consider the state of pharmacological treatment of withdrawal at that time. D u r i n g t h e 1 9 5 0 ’ s a n d e a r l y to mid­1960’s, several initial studies suggested that promazine and chlorpro­ mazine (both antipsychotic medica­ tions) were effective in treating alcohol withdrawal. Later studies did not con­ firm these findings. Moreover, several subsequent studies suggested that the incidence of serious withdrawal symp­ toms, such as seizures and delirium, might actually be higher after adminis­ tration of these two agents (Sereny and Kalant 1965). Pharmacologically, based on today’s knowledge, compli­ cations such as confusion and delirium would be expected. These tranquilizing agents decrease the seizure threshold by making the brain more susceptible to spontaneous cellular electrical activ­ ity. The agents also have properties (i.e., anticholinergic) that disrupt cellu­ l ar commu nic atio n, re su l t i ng i n changes in body function (e.g. gas­ trointestinal disorders). C hlo rd i az ep o xid e w as a no th er medication studied by Kaim and col­ leag ues in thei r article. Chlordia­ zepoxide was marketed in 1961. It is interesting to note that in that same year, Kaim and Rostenstein (1961) opined that based on clinical evidence,