SCIENTIFIC ARTICLE Anxiolytic activity of chloral hydrate and hydroxyzine

The combination of chloral hydrate and hydroxyzine is given frequently to anxious pediatric dental patients. In order to observe and quantify the anxiolytic effects of these drugs given alone and in combination, highly explorative male C57/black mice were tested using the light~dark test box after injecting subhypnotic doses for increased transitions between the light and dark side of the test box. Fifty-one mice were subjected individually to a l O-min test in the box for dose responses following the i.p. administration of 32-, 64-, and 132-mg/kg doses of chloral hydrate; 1-, 4-, 7-, and lO-mg/kg doses of hydroxyzine; or a combination of each of these doses of hydroxyzine and chloral hydrate. The automated test box recorded the number of times a mouse crossed between the two chambers. Doses of chloral hydrate 132 mg/kg and hydroxyzine I mg/kg resulted in significantly increased transitions. None of the combinations studied produced significantly increased transitions when compared with the effective doses identified for each individual drug. The paradigm did not support the hypothesis that the anxiolytic effects of chloral hydrate and hydroxyzine are additive or synergistic. (Pediatr Dent 16:183-89, 1994) Introduction and literature review Antianxiety drugs are referred to by many terms 1 including "anxiolytic," which refers to drugs that have more specific anxiety reduction properties than CNS depression properties. Anxiolytics allow a patient to maintain near-normal motor function while sedatives (or sedative doses) severely impede motor and cognitive function. Dentists have long sought a single, safe, orally administered drug that would reliably reduce anxiety in children and adults when administered prior to dental treatment. No single drug has all the effects desired by many dental practitioners, therefore there is considerable use of combinations of orally administered sedative agents. 2-~ Some combinations were initially used on an empirical basis. Few basic animal studies were done on these combinations prior to their use in dentistry. One notable animal study was done by Pruhs, 6 who investigated the effects of adding nitrous oxide to chloral hydrate. Pruhs’ study, like this one, attempted to provide a basic understanding of some narrow part of the activity of a popular combination used in pediatric dentistry. There are a few animal studies of the sedative and antianxiety effects of chloral hydrate and hydroxyzine as single agents. Stuphel7 studied the effect of hydroxyzine on aggressiveness of mice and Lenegre8 used mice to find that amnesia induction was not a property of subhypnotic doses of hydroxyzine. Pollard9 reviewed studies of pigeons and rats that tested the effects of many drugs, including chloral hydrate, on punished responses. Most of the antianxiety studies of the currently popular dental combinations like chloral hydrate and hydroxyzine were done approximately 20 years ago and used a more aversive test than the one utilized in this study. Many of the modern benzodiazepine-type anxiolytic agents were tested prior to clinical use in the light/dark test box utilized in this study. 1° No readily available reports evaluate the antianxiety effects of hydroxyzine hydrochloride and chloral hydrate in a modern mouse anxiety paradigm. Many physiologic and behavioral clinical studies have appeared in the pediatric dental literature, but clinical use and research have not clearly established the anxiolytic effectiveness of the combination. Justifiably or not, anxiety reduction is often alluded to in clinical studies, texts, lectures, and case reports on the use of combinations. There appears to be a collective opinion among pediatric dentists who have studied anxiolytic agents that an effective agent for uncooperative dental patients would have a primary effect against anxiety21