diazepam (10–15mg/day), lorazepam (1–6mg/day), and clorazepate (30mg/day) in directly comparative randomized controlled trials. Alpidem has also been directly compared with buspirone (20–30mg/day) for generalized anxiety disorder. Relative to buspirone, it was found to produce more rapid improvement, to have significantly greater effectiveness, and to have fewer side effects and a lower discontinuation rate. The recommended dose of alpidem was 75 to 150mg total per day, given in single doses of 25 to 75mg two to three times per day. Available forms Alpidem was provided in the form of 50-mg oral tablets. Side effects Alpidem is described as well-tolerated. Side effects include sedation (6–8%; dose-dependent), fatigue (3–4%), dizziness (3–4%), and headache (2–3%), among others. It is reported to have minimal sedative effects and to have virtually no negative effects on cognition, memory, and psychomotor function at therapeutic doses. However, some impairment of vigilance and psychomotor function has been reported at high doses (100–200mg). In addition, driving ability has been studied with alpidem and has been found to be impaired. The central side effects of alpidem were found to be no worse in elderly people than in young adults. Alpidem does not alter sleep architecture as measured by electroencephalography. In laboratory tests, 0.9% of patients treated with alpidem showed alterations. No adverse effects on cardiovascular or respiratory function were seen in clinical trials. No rebound anxiety or withdrawal symptoms have been observed with alpidem after abrupt discontinuation following 4weeks to 6–12months of treatment. Conversely, substantial withdrawal symptoms, including rebound anxiety, were observed with lorazepam. The side effects of alpidem are described as quite different from those of benzodiazepines. In directly comparative trials, alpidem produced similar anxiolytic effects with less fatigue, asthenia, depressive mood, and psychomotor impairment than benzodiazepines, while rates of somnolence and drowsiness were comparable to benzodiazepines but described as milder in severity. Whereas benzodiazepines commonly produce dizziness, muscle weakness, fatigue, and sleepiness as side effects, these are not prominent adverse effects with doses of alpidem that have similar anxiolytic effectiveness. The lack of withdrawal or rebound symptoms with alpidem upon discontinuation is also in contrast to benzodiazepines. In addition, alpidem significantly antagonized the amnestic effects of lorazepam and showed similar trends for other cognitive measures in a clinical study in which the two drugs were combined and assessed for interaction. Following marketing authorization in France, several cases of severe liver toxicity were reported in people taking alpidem. This resulted in