Benzodiazepine sedative-hypnotics

Compared to the benzodiazepine sedative-hypnotics, secobarbital is more lethal in overdosage, has a higher tendency for abuse and addiction, and is more likely to cause drug interactions via induction of hepatic microsomal enzymes few advan-fages if any in safety or efficacy over benzodiazepines... 

The benzodiazepine sedative-hypnotic estazolam added to an antipsychotic reduced auditory hallucinations in selected chronic schizophrenics (191)... 

Insomnia is a common comorbid condition with depression, and frequently is made worse by antidepressants, particularly the SSRIs. When insomnia persists despite adequate evaluation and attempts to reduce it by other approaches, it is often necessary to use a concomitant sedative-hypnotic, especially a short-acting nonbenzodiazepine with rapid onset such as zaleplon or zolpidem. At times a benzodiazepine sedative hypnotic such as triazolam or temazepam may be necessary. If anxiety persists during the day and cannot be otherwise managed, it may be necessary to add an anxiolytic benzodiazepine such as alprazolam or clonazepam. Use of sedative-hypnotics and anxiolytics should be short-term whenever possible. 

The nonbenzodiazepine sedative-hypnotics zaleplon, zolpidem, and zopiclone are replacing benzodiazepine sedative-hypnotics as first-line treatments for insomnia. Some antidepressants, such as sedating tricyclic antidepressants and trazodone, are also used as sedative-hypnotic agents for the treatment of insomnia. 

The therapeutic profile and adverse effects of the non-benzodiazepine sedative-hypnotics... 

From the published clinical studies, it would appear that the partial agonists bretazenil and abercamil are less likely to cause physiological dependence, have lower reinforcing effects and a lower incidence of subjective effects associated with abuse liability than the conventional 1,4-benzodiazepine sedative-hypnotics. It is presently unclear whether the full agonists for the GABA-A receptor, zolpidem and zopiclone, offer a real advance in the treatment of insomnia although their adverse effect profiles and abuse liability may be lower than that of the conventional benzodiazepines. 

In quick succession, two heterocyclic non-benzodiazepine sedative/hypnotics were launched in 1985 by Rhone-Poulenc as zopi-clone and 1 88 by Synthelabo as zolpidem. In 1999, Wyeth Ayerst launched another heterocyclic non-benzodiazepine sedative/hyp-notic, zaleplon. 

The Second Phase. The second phase of the development of heterocyclic sedative-hypnotics was initiated after the development and launch of the benzodiazepine sedative-hypnotics. Although the 1,4-benzodiazepines are safe and effective drugs, they too have produced certain undesirable side effects. This compelled some companies to develop non-benzodiazepine sedative-hypnotic drugs. 

Numerous CNS drugs including narcotics, analgesics, general anesthetics, antihistamines, phenothiazines, barbiturates, benzodiazepines, sedative-hypnotics, tricyclic antidepressants, alcohol, and muscle relaxants, potentiate the respiratory and CNS depression, sedation, and hypotensive effects of levorphanol. 

Benzodiazepine sedative-hypnotic widely used in anxiety states, selectivity for panic attacks and phobias possible antidepressant actions. Tox psychologic and physiologic dependence, additive effects with other CNS depressants. 

Section II Benzodiazepines Sedative-Hypnotic Agents Peter Wald MD, MPH... 

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. 

Benzodiazepines have found wide therapeutic applications as anxiolytics, sedatives, hypnotics, anticonvulsants, and central muscle relaxants. 

Benzodiazepines and similar agents occupy a position of intermediate abuse potential, compared with most other sedative-hypnotics (Griffiths and Weerts 1997). Animal models of abuse habihty indicate that the reinforcing effects of benzodiazepines are less pronounced than are those of the barbiturates, opioids, and stimulants. Differences in abuse potential within the class have not been consistently demonstrated however, most chnicians agree that benzodiazepines with a rapid onset and short duration of action pose the greatest risk in susceptible individuals. 

Sporadic use (e.g., for the induction of sleep after a psychostimulant binge) does not require specific detoxification. Sustained use can be treated as described in the previous sections on detoxification from therapeutic or high dosages but with added caution. In mixed opioid and benzodiazepine abuse, the patient should be stabilized with methadone (some clinicians use other oral preparations of opioids) and a benzodiazepine. Buprenorphine should not be administered with benzodiazepines, because a pharmacodynamic interaction is possible (Ibrahim et al. 2000 Kilicarslan and Sellers 2000) and fatalities have been reported with the combination (Reynaud et al. 1998). Sedative-hypnotic withdrawal is the more medically serious procedure, and we usually... 

In subjects with sedative-hypnotic dependence who underwent detoxification in an addictions treatment unit, a significant association was not found between abstinence rate and either gender or psychiatric status (Charney et al. 2000). Patients dependent on benzodiazepines reported decreased anxiety during follow-up, even though their use of these agents had decreased. 

Cantopher T, Olivieri S, Cleave N, et al Chronic benzodiazepine dependence a comparative smdy of abrupt withdrawal under propranolol cover versus gradual withdrawal. Br J Psychiatry 156 406-411, 1990 Caplan RD, Andrews FM, Conway TL, et al Social effects of diazepam use a longitudinal field study. Soc Sci Med 21 887—898, 1985 Charney DA, Paraherakis AM, Gill KJ The treatment of sedative-hypnotic dependence evaluating clinical predictors of outcome. J Clin Psychiatry 61 190—195, 2000... 

Taper off antipsychotics, benzodiazepines or sedative-hypnotic agents if possible... 

A number of medications have been associated with an increased risk of falling, including drugs affecting mental status such as antipsychotics, benzodiazepines, tricyclic antidepressants, sedative-hypnotics, anticholinergics, and corticosteroids. Some cardiovascular and antihypertensive drugs also can contribute to falls, especially those causing orthostatic hypotension.9... 

For testing sedative hypnotic drugs of the triazolam type the preparation was undertaken of 8-chloro-6-(o-chlorophenyl)-4ff-.y-triazolo[4,3-a][l,4]benzodiazepin-1 -valeric acid methyl ester as an intermediate, with subsequent cyclization and amida-... 

Barbiturate The family name for a group of drugs with anticonvulsant, anaesthetic and sedative-hypnotic properties. Examples include amylobarbitone and pheno-barbitone. The problem of dependence and the introduction of safer benzodiazepine alternatives has resulted in a marked reduction in their clinical use. 

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