Alpidem, sold under the brand name Ananxyl, is a nonbenzodiazepine anxiolytic medication which was briefly used to treat anxiety disorders but is no longer marketed. It was previously marketed in France, but was discontinued due to liver toxicity. Alpidem is taken by mouth.
Side effects of alpidem include sedation, fatigue, dizziness, and headache, among others. It has much less to no impact on cognition, memory, and psychomotor function relative to benzodiazepines. Similarly, no rebound anxiety or withdrawal symptoms have been observed with alpidem. Rarely, alpidem can cause serious liver toxicity, including liver failure and death. Alpidem is a nonbenzodiazepine of the imidazopyridine family, structurally related to the Z-drug zolpidem, and acts as a GABAA receptor positive allosteric modulator of the benzodiazepine site of the receptor complex. In contrast to zolpidem however, alpidem has anxiolytic effects rather than sedative or hypnotic effects at normal therapeutic doses.
Alpidem was first described by 1982 and was introduced for medical use in France in 1991. It was also under development for use in other countries in the 1990s, but development was discontinued and the drug was never marketed in any other country. Alpidem was withdrawn from the market in France in 1993 due to liver toxicity.
Medical uses
Alpidem was approved for the treatment of generalized anxiety disorder and possibly also other anxiety problems. By 1990, 17clinical studies including more than 1,500patients had been conducted in Europe studying alpidem for the treatment of anxiety. In clinical trials, alpidem demonstrated effectiveness in the treatment of chronic and situational anxiety, including stress-related anxiety, generalized anxiety, and adjustment disorder (situational depression) with anxiety. It also showed preliminary effectiveness in institutionalized individuals with chronic psychosis and high anxiety levels. The effectiveness of alpidem for panic disorder, on the other hand, is understudied and uncertain.
The anxiolytic effects of alpidem are described as rapid, robust, and maintained in the long-term. For situational anxiety, the anxiolytic effects of alpidem onset within 1.5 to 2hours, whereas for chronic anxiety disorders the effects onset within 3 to 5days in most cases. No indications of tolerance to its anxiolytic effects or need for dose increases have been observed. In people with anxiety taking alpidem, improvement in mood and sleep have also been found.
The anxiolytic effectiveness of alpidem, for example measured by reductions on the Hamilton Anxiety Rating Scale (HAM-A), was superior to placebo and comparable or equivalent to that of benzodiazepines including 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.