19.03.4 Benzodiazepines

Benzodiazepines are allosteric modulators of the GABAA receptors. GABAA receptors are ligand-gated ion channels, gated by the amino acid transmitter, GABA. When activated, they conduct chloride ions, the net effect being a reduction in membrane excitability and inhibition of cell firing.

These receptors are found in many brain regions such as the amygdala (including central nucleus), hippocampus, bed nucleus of the stria terminalis, striatum (dorsal and ventral), hypothalamus and prefrontal cortex. When GABA is bound, benzodiazepines increase the frequency of ion channel opening, thus increasing chloride conductance and the potency of GABA.

Examples of benzodiazepines include diazepam, midazolam and temazepam.  These drugs are similar in their mechanism of action, however differ in their pharmacokinetics, such that some are much shorter-acting (e.g. midazolam) and some are much longer-acting (e.g. diazepam,). Shorter acting drugs may be useful for inducing or maintaining sleep, while longer acting are preferred for treatment of anxiety disorders.

Benzodiazepines have the advantage of being rapid in onset (within hours) and are therefore very useful in treating acute anxiety states, such as panic disorder and phobias, and they are also useful in generalised anxiety disorder. Unfortunately, while being very effective anxiolytics, benzodiazepines have some unwanted side effects, including sedation, memory loss (amnesia) and dependence liability (they are addictive). Their tendency to cause drowsiness and confusion in elderly patients also negates their use in this demographic.

Benzodiazepines interact with other depressants such as alcohol, making their use in combination dangerous as this enhances sedation, memory loss, and respiratory depression. Since they are potentially addictive, benzodiazepines are recommended for acute use, usually two weeks at a time, although in some cases chronic use is justified. The withdrawal syndrome from benzodiazepines can be quite severe, therefore gradual weaning is required.