Benzodiazepines efficacy

Clobazam is not available in the USA but is marketed in most countries and is widely used in a variety of seizure types. It is a 1,5-benzodiazepine (other marketed benzodiazepines are 1,4-benzodiazepines) and reportedly has less sedative potential than benzodiazepines marketed in the USA. Whether the drug has significant clinical advantages is not clear. It has a half-life of 18 hours and is effective at dosages of 0.5-1 mg/kg/d. It does interact with some other antiseizure drugs and causes adverse effects typical of the benzodiazepines efficacy, in some patients, is limited by the development of tolerance. 

A class of sedative/hypnotic type drug that exert their effects through the benzodiazepine binding site on GABAa receptors. The class consists both of molecules that contain the benzodiazepine moiety, for example diazepam, lorazepam and flunitrazepam, and the newer, non-benzodiazepine compounds such as zolpidem, zopiclone, indiplon and zaleplon. BzRAs are primarily used for the treatment of anxiety, insomnia and to elicit varying levels of sedation. The wide selection of compounds currently available affords the prescribing clinician extensive options in terms of relative efficacies and durations of action. 

Braestrup C, Nielsen M, HonoreT, etal Benzodiazepine receptor ligands with positive and negative efficacy. Neuropharmacology 22 1451—1457, 1983... 

Otto MW, Pollack MH, Sachs GS, et al Discontinuation of benzodiazepine treatment efficacy of cognitive-behavioral therapy for patients with panic disorder. Am J... 

Silberstein SD, McCrory DC Butalbital in the treatment of headache history, pharmacology, and efficacy. Headache 41 953-967, 2001 Smith DE, Wesson DR Benzodiazepine dependency syndromes. J Psychoactive Drugs 15 85-95, 1983... 

Psychopharmacology (Bed) 141 30-36, 1999 Mullins ME, Fitzmaurice SC Lack of efficacy of benzodiazepines in treating gamma hydroxybutyrate withdrawal. J Emerg Med 20 418 20, 2001 Mycyk MB, Wilemon C, Aks SE Two cases of withdrawal from 1,4-butanediol use. Ann Emerg Med 38 345-346, 2001... 

The undisputed efficacy of benzodiazepines in relief of anxiety led to the question of whether this disorder could arise from abnormal concentrations in the brain of an endogenous ligand or a malfunction of the benzodiazepine/GABA receptor system. An important study, aimed at distinguishing between these possibilities, has been carried out in humans (Nutt et al. 1990) and was based on the premise that anxiety could be caused by either ... 

Dysfunction of the GABAa receptor complex such that the effects of all benzodiazepine receptor ligands are shifted in the direction of inverse agonism. In this case, fiumazenil (which normally has zero efficacy) should induce anxiety in anxious patients but have no effects in healthy subjects because they have normal receptors. 

A series of 2-phenyl [ 1,2,3 triazolo[l,2-tf][l,2,4]bcnzotriazin-l,5(6//)-diones display submicromolar/nanomolar potency at the central benzodiazepine receptor. The most potent compound 687 (Kj= 2.8 nM) with enhanced affinity is a full agonist at al and aZ receptor subtypes, and has an antagonist efficacy at a5 receptors <2005JME2936>. 

Oxazepam and other benzodiazepines have been used to treat anxiety, agitation, and aggression, but they generally show inferior efficacy compared with antipsychotics. They can also worsen cognition, cause disinhi-bition, and increase the risk of falls. 

Marketed compounds display well-known efficacy in inducing sleep onset, but many fail in the maintenance of sleep throughout the night due to short half-lives. On the other hand, longer acting compounds, such as the benzodiazepines, elicited significant next-day adverse effects. Therefore, the balance between sustained efficacy and adequate pharmacokinetic profile remains to be solved. 

A therapeutic alternative for treatment of anxiety and depression is the use of 5-HT1A agonists. Azapirones comprise the major class of 5-HT1A agonists of which buspirone (Buspar [4]) is the only FDA-approved 5-HT1A selective agonist (relative to the other 13 serotonin receptor subtypes) for anxiety currently on the US market (Scheme 19.1). Buspirone has shown efficacy in randomized controlled trials of GAD for which it was approved [5-7]. Unlike benzodiazepines, buspirone is not addictive... 

Some studies found kava to be effective using only 2 acute doses (preoperatively), while others found benefit after chronic doses (Bhate et al. 1989 Lehmann et al. 1989 Volz and Kieser 1997). Another interesting study found kavain to be equivalent in efficacy to the benzodiazepine oxazepam on standard measures of anxiety (Anxiety Status Inventoiy and Zung s Self-Rating Anxiety Scale) (Lindenberg and Pitule-Schodel 1990). There were no serious side effects reported in the clinical studies reviewed by Pittler and Ernst (2000). 

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