Benzodiazepines (BDZ) are the most commonly used drugs for anxiety disorders, because of their anxiolytic, hypnotic, muscle relaxant and anticonvulsant properties. Through the receptorial binding with the GABA A receptor (Fig. 1), benzodiazepines seem to enhance the g-aminobutyric acid neurotransmission (GABA), which in turn has an inhibitory effect on other neurotransmitter systems involved in anxiety disorders, in particular noradrenergic and serotonergic pathways. Among the pharmacokinetic properties of benzodiazepines, absorption and metabolism are the most important as they influence the rapidity of action and the duration of the pharmacological effects of these drugs. Once in blood circulation, the benzodiazepines extensively bind to plasma proteins, showing strong lipophilic properties, which facilitate the passage through biological membranes, especially those included in the Central Nervous System (CNS). When benzodiazepines are administered as a single dose, the duration of their pharmacological action depends on the speed and degree of tissues distribution, in consideration of the hepatic metabolism and presence of active metabolites.
With reference to the metabolism processes, the benzodiazepines can be divided in:
- long-acting benzodiazepines (half-life > 48 h);
- benzodiazepines with intermediate duration of action (halflife 24-48 h);
- short-acting benzodiazepines (half-life < 24 h);
- benzodiazepines with shorter duration of action (half-life 1-7 h) (Table I).
Because of this variety of available molecules, it is possible to suite the treatment to the individual needs of patients. Indeed, molecules such as bromazepam are widely used as a minor tranquilizer, anticonvulsant, sedative, muscle relaxant, because of its rapid absorption and consequent rapid tissues distribution after oral administration, which together describe the optimal risk-benefit ratio of this molecule.
Consequently, after 50 years of benzodiazepines clinical use, there are lots of scientific evidences that allow us to provide sufficient details for an appropriate prescription of benzodiazepines, in order to optimize the relationship between efficacy and safety.
However, it is still necessary to follow some general rules, such as to use the minimum effective dose, to provide a specific therapy related to the features of clinical status (such as an intermittent treatment for anxious symptoms and/or resistant insomnia) as well as a gradual withdrawal from treatment, to know properly the different pharmacological properties of the molecules employed, in order to determine the possibility of the reaffirmation of this class of drugs, which are still fundamental and probably irreplaceable for the treatment of several conditions, such as anxiety disorder and insomnia, both primary and associated with other psychiatric disorders.