Understanding the pharmacokinetics of anxiolytic drugs

Anxiety disorders are considered the most common mental disorders and they can increase the risk for comorbid mood and substance use disorders, significantly contributing to the global burden of disease. For this reason, anxiolytics are the most prescribed psychoactive drugs, particularly in the Western world.

This review aims to analyze pharmacokinetic profile, plasma level variations so as the metabolism, interactions and possible relation to clinical effect of several drugs which are used primarily as anxiolytics. The drugs analyzed include benzodiazepines, anticonvulsants (pregabalin, gabapentin), buspirone, β-blockers and antihistamines (hydroxyzine). Regarding the most frequently used anxiolytic benzodiazepines, data on alprazolam, bromazepam, chlordesmethyldiazepam, chlordiazepoxide, clotiazepam, diazepam, etizolam, lorazepam, oxazepam, prazepam and clonazepam have been detailed.

There is a need for a more balanced assessment of the benefits and risks associated with benzodiazepine use, particularly considering pharmacokinetic profile of the drugs to ensure that patients, who would truly benefit from these agents, are not denied appropriate treatment. An optimal pharmacological approach involving an integrative pharmacokinetic and pharmacodynamic optimization strategy would ensure better treatment and personalization of anxiety disorders. So it would be desirable for the development of new anxiolytic drug(s) that are more selective, fast acting and free from the unwanted effects associated with the traditional benzodiazepines as tolerance or dependence.