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Benzodiazepine withdrawal syndrome (BZD withdrawal) is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines as prescribed develops a physical dependence on them and then reduces the dose or stops taking them without a safe taper schedule.
Tofisopam [3] (Emandaxin, Grandaxin, Sériel) is an anxiolytic that is marketed in several European countries. [4] Chemically, it is a 2,3-benzodiazepine. Unlike other anxiolytic benzodiazepines (which are generally 1,4- or 1,5-substituted) however, tofisopam does not have anticonvulsant, sedative, [5] skeletal muscle relaxant, motor skill-impairing or amnestic [6] properties.
For withdrawal purposes, stabilisation with a long-acting agent such as diazepam is recommended before commencing withdrawal. Chlordiazepoxide (Librium), a long-acting benzodiazepine, is gaining attention as an alternative to diazepam in substance abusers dependent on benzodiazepines due to its decreased abuse potential. [16]
Post-acute withdrawal syndrome (PAWS) is a hypothesized set of persistent impairments that occur after withdrawal from alcohol, [1] [2] opiates, benzodiazepines, barbiturates, and other substances. [ 3 ] [ 4 ] [ 5 ] Infants born to mothers who used substances of dependence during pregnancy may also experience a PAWS.
This was demonstrated by the ability to avoid the withdrawal syndrome by the administration of AMPA antagonists. It is believed that different glutamate subreceptors, e.g., NMDA and AMPA, are responsible for different stages/time points of the withdrawal syndrome. NMDA receptors are upregulated in the brain as a result of benzodiazepine tolerance.
The changes are most notable with long acting benzodiazepines as these are prone to significant accumulation in such individuals and can lead to withdrawal symptoms. [citation needed] For example, the equivalent dose of diazepam in an elderly individual on lorazepam may be half of what would be expected in a younger individual.