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PubMed2001

Hypnotic action of N3-substituted arabinofuranosyluracils on mice.

Methyl (2), ethyl (3), propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p-xylyl (8-10), and alpha-phenylethyl (11) derivatives of arabinofuranosyluracil (1) were synthesized and their pharmacological effects in mice were examined by using hypnotic activity and synergism with pentobarbital as indices for the CNS depressant effects. At a dose of 2.0 micromol/mouse by intracerebroventricular injection, the values of mean sleeping time induced by 7-11 were 144, 154, 117, 33, and 34 min, respectively, whereas the alkyl (2-6) derivatives did not cause any hypnotic activity. N3-o-Xylylarabinofuranosyluracil (8) displayed the most potent hypnotic activity among the derivatives tested. Certain derivatives (6-11) significantly prolonged the pentobarbital-induced sleeping time compared to control. The present study indicated that substitution with benzyl and/or related groups on the N3-position of arabinofuranosyluracil produced CNS depressant effects.

Animals↗
PubMed1992

[Syntheses and central depressant activity in mice of uracil derivatives. Studies on development of new sedative-hypnotics. II].

Fifteen kinds of uracil derivatives, which were substituted with functional groups such as benzyl (Bn), methoxymethyl (MOM), n-propyl (Pr) or allyl (A) group at the N1 and/or N3 position of uracil, were synthesized. Sedative-hypnotic activity, pentobarbital (PB)-induced sleep prolongation and acute toxicity as indices of their pharmacological activities were evaluated using mice. Spontaneous activities of mice treated with N1-benzyluracil (N1-BnU, 7), N3-benzyluracil (N3-BnU, 8), N1,N3-dibenzyluracil (DBnU, 9), N1-benzyl-N3-allyluracil (BnAU, 14) and N1-allyl-N3-benzyluracil (ABnU, 15) were measured. Ten kinds of uracil derivatives showed hypnotic activity. ED50's values of ABnU (15) and N1-propyl-N3-benzyluracil (PrBnU, 13) were 155 and 172 mg/kg, i.p., respectively. Those effects were more potent than that of barbital (179 mg/kg, i.p.) Ten kinds of uracil derivatives tested significantly prolonged the PB-induced sleeping time. N3-BnU (8) increased the spontaneous activity of mice at a dose of 80 mg/kg, i.p., while ABnU (15) depressed the spontaneous activity at a dose of 160 mg/kg, i.p. The other compounds did not show any significant effect on the spontaneous activity of mice. LD50's values of ABnU (15), PrBnU (13) and N1-methoxy-methyl-N3-benzyluracil (MOMBnU, 11) were 199, 229 and 363 mg/kg, i.p., respectively. LD50's values of the other derivatives were more than 480 mg/kg, i.p. These results indicate that the benzyl group at the N3 position of uracil is important for exhibiting sedative-hypnotic activity of uracil derivatives, and that ABnU (15) has the most potent central depressant activity among the uracil derivatives tested.

Animals↗
PubMed2006

An oral hypnotic medication does not improve continuous positive airway pressure compliance in men with obstructive sleep apnea.

BACKGROUND: Compliance with continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) is highly variable. Recent studies suggest that the initial experience with CPAP may determine long-term success. We hypothesized that administration of a hypnotic medication to new CPAP users would facilitate acclimation and increase usage. METHODS: Seventy-two male OSA patients referred for CPAP treatment were randomized to also receive an oral hypnotic agent (zolpidem), placebo pill, or neither (standard care) for the first 14 days of CPAP treatment. CPAP usage (effective mask pressure [hours per day]) was recorded by an internal data chip. Patient symptoms were assessed with the Epworth sleepiness scale (ESS) and functional outcomes of sleep questionnaire (FOSQ). Treatment groups were matched for age, body mass index, and baseline ESS and FOSQ scores. Despite randomization, the standard care group had a higher apnea/hypopnea index than either the zolpidem or placebo pill groups (54.75 +/- 28.02 vs 32.61 +/- 25.12 vs 38.09 +/- 25.65, p = 0.012) [mean +/- SD]. Compared to placebo pill and standard care groups, the zolpidem group did not show greater CPAP usage in terms of total days used (zolpidem, 20.58 +/- 7.40 days; placebo pill, 17.83 +/- 9.33 days; standard care, 22.92 +/- 6.95 days; p = 0.198) or average time used per night (4.43 +/- 1.16 h vs 4.23 +/- 2.14 h vs 4.94 +/- 1.44 h, p = 0.361). All groups showed significant symptom improvements on both the ESS (p < 0.001) and FOSQ (p < 0.05). CONCLUSION: Administration of an oral hypnotic agent did not improve initial CPAP compliance in men with OSA.

Administration, Oral↗
PubMed2005

Extrasynaptic GABAA receptors of thalamocortical neurons: a molecular target for hypnotics.

Among hypnotic agents that enhance GABAA receptor function, etomidate is unusual because it is selective for beta2/beta3 compared with beta1 subunit-containing GABAA receptors. Mice incorporating an etomidate-insensitive beta2 subunit (beta(2N265S)) revealed that beta2 subunit-containing receptors mediate the enhancement of slow-wave activity (SWA) by etomidate, are required for the sedative, and contribute to the hypnotic actions of this anesthetic. Although the anatomical location of the beta2-containing receptors that mediate these actions is unknown, the thalamus is implicated. We have characterized GABAA receptor-mediated neurotransmission in thalamic nucleus reticularis (nRT) and ventrobasalis complex (VB) neurons of wild-type, beta2(-/-), and beta(2N265S) mice. VB but not nRT neurons exhibit a large GABA-mediated tonic conductance that contributes approximately 80% of the total GABAA receptor-mediated transmission. Consequently, although etomidate enhances inhibition in both neuronal types, the effect of this anesthetic on the tonic conductance of VB neurons is dominant. The GABA-enhancing actions of etomidate in VB but not nRT neurons are greatly suppressed by the beta(2N265S) mutation. The hypnotic THIP (Gaboxadol) induces SWA and at low, clinically relevant concentrations (30 nM to 3 microM) increases the tonic conductance of VB neurons, with no effect on VB or nRT miniature IPSCs (mIPSCs) or on the holding current of nRT neurons. Zolpidem, which has no effect on SWA, prolongs VB mIPSCs but is ineffective on the phasic and tonic conductance of nRT and VB neurons, respectively. Collectively, these findings suggest that enhancement of extrasynaptic inhibition in the thalamus may contribute to the distinct sleep EEG profiles of etomidate and THIP compared with zolpidem.

Animals↗
PubMed2006

Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate.

A fundamental objective of anesthesia research is to identify the receptors and brain regions that mediate the various behavioral components of the anesthetic state, including amnesia, immobility, and unconsciousness. Using complementary in vivo and in vitro approaches, we found that GABAA receptors that contain the alpha5 subunit (alpha5GABAARs) play a critical role in amnesia caused by the prototypic intravenous anesthetic etomidate. Whole-cell recordings from hippocampal pyramidal neurons showed that etomidate markedly increased a tonic inhibitory conductance generated by alpha5GABAARs, whereas synaptic transmission was only slightly enhanced. Long-term potentiation (LTP) of field EPSPs recorded in CA1 stratum radiatum was reduced by etomidate in wild-type (WT) but not alpha5 null mutant (alpha5-/-) mice. In addition, etomidate impaired memory performance of WT but not alpha5-/- mice for spatial and nonspatial hippocampal-dependent learning tasks. The brain concentration of etomidate associated with memory impairment in vivo was comparable with that which increased the tonic inhibitory conductance and blocked LTP in vitro. The alpha5-/- mice did not exhibit a generalized resistance to etomidate, in that the sedative-hypnotic effects measured with the rotarod, loss of righting reflex, and spontaneous motor activity were similar in WT and alpha5-/- mice. Deletion of the alpha5 subunit of the GABAARs reduced the amnestic but not the sedative-hypnotic properties of etomidate. Thus, the amnestic and sedative-hypnotic properties of etomidate can be dissociated on the basis of GABAAR subtype pharmacology.

Action Potentials↗
PubMedDate not supplied

Zopiclone. A review of its pharmacological properties and therapeutic efficacy as an hypnotic.

Zopiclone is a cyclopyrrolone which is chemically unrelated to the benzodiazepines and is thought to act on the GABAA receptor complex at a site distinct from, but closely related to, the benzodiazepine binding site. The hypnotic efficacy of zopiclone administered as single oral doses has been demonstrated in patients undergoing next-day surgery and in patients with insomnia, and these studies have established an optimal dose of 7.5mg for elderly patients. Using this dose, clinical studies have shown that zopiclone improved sleep in elderly patients to a similar extent as triazolam 0.125 to 0.5mg, flurazepam 15mg, and nitrazepam 5mg. Studies that also included younger patients have shown that zopiclone 7.5mg is at least as effective as triazolam 0.25 or 0.5mg, and on most sleep parameters is comparable to temazepam 20mg, nitrazepam 5mg, flunitrazepam 2mg, and flurazepam 20mg. Zopiclone causes minimal impairment to psychomotor performance and mental alertness the morning after night-time administration. The drug is generally well tolerated by patients of all ages; the most frequently reported adverse effects being bitter taste and dry mouth. Treatment withdrawal due to adverse effects is seldom required and reports of rebound insomnia after zopiclone withdrawal are rare. While symptoms of physical dependence have not been observed in clinical studies, there have been isolated reports of physical dependence in patients with a history of substance abuse. Although the latter finding should be kept in mind, it appears that zopiclone has a low dependence liability. Thus, with its short duration of action and good tolerability profile, zopiclone is a well established alternative to the benzodiazepine hypnotics and may be particularly beneficial in those patients unable or unwilling to tolerate the residual effects associated with many other hypnotic agents.

Aged↗
PubMed1981

Temazepam: a review of its pharmacological properties and therapeutic efficacy as an hypnotic.

Temazepam is a benzodiazepine drug which is a minor metabolite of diazepam. In clinical studies using subjective evaluation methods it was effective for maintaining sleep and increasing total sleep time. However, sleep laboratory studies did not show a significant effect on some sleep parameters, especially sleep induction. Temazepam has a relatively short half-life (about 5 to 11 hours, longer in some subjects and in the elderly), and no active metabolites of clinical importance, and thus may be considered more suitable for use as an hypnotic than longer acting drugs such as diazepam, nitrazepam or flurazepam when residual sedative effects the next day are not desirable. Indeed, few residual effects on morning performance appear to occur with usual single doses of temazepam, although at the upper end of the recommended dosage range (30 mg or more) some evidence of impaired psychomoter and cognitive function in the morning has been reported. Whether or not temazepam is likely to produce "hangover" with repeated night-time administration needs further clarification. While a call for a large number of controlled trials may not be justifiable in evaluating a new hypnotic, a few well designed additional comparative studies in insomniac subjects are needed to assess adequately the relative merits of temazepam (particularly with regard to sleep onset) compared with other benzodiazepine hypnotics, especially those which are short- or intermediate-acting.

Animals↗
PubMed1986

Zopiclone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy as an hypnotic.

Zopiclone is the first of the cyclopyrrolones, a new class of psychotherapeutic agents possessing a pharmacological profile of high efficacy and low toxicity similar to that of the benzodiazepines. Binding is thought to occur to the benzodiazepine receptor complex, or to a site closely linked to this complex. Although zopiclone exhibits anticonvulsant, muscle relaxant and anxiolytic properties in animals, it finds better use as an hypnotic because of marked sedating effects. In clinical trials, zopiclone (usually 7.5 mg) improved sleep in chronic insomniacs similarly to nitrazepam 5 mg, flurazepam 15 to 30 mg, triazolam 0.5 mg and temazepam 20 mg, but in a single study was slightly less effective than flunitrazepam 2 mg in some evaluation criteria. Sleep induction before surgical procedures in hospitalised patients is satisfactory with zopiclone, but when the drugs are administered a few hours before surgery, diazepam appears to be more effective in alleviating preoperative anxiety. Minimal impairment of psychomotor skills and mental acuity occurs in the morning after a bedtime dose of zopiclone, which has a short half-life of about 5 hours and no long acting metabolites. No serious side effects have been reported in the relatively small number of patients studied to date; the development of 'bitter taste' does not deter patients from continuing therapy. Thus, with its short duration of action zopiclone is a useful alternative to other hypnotics, especially in patients intolerant of residual effects the morning after taking an hypnotic.

Anti-Anxiety Agents↗
PubMed2000

Prevalence of sleep disturbance and hypnotic medication use in relation to sociodemographic factors in the general Japanese adult population.

This study was the first nationwide population-based study to estimate the prevalence rates of sleep disturbance and hypnotic medication use in the general Japanese adult population. In 1997, 2,800 Japanese adults aged 20 years and over were randomly selected from the 1995 Census and 1,871 were examined using the Pittsburgh Sleep Quality Index. The respective estimated overall prevalences of insomnia (INS), difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), poor perceived quality of sleep (PQS) and hypnotic medication use (HMU) were 17.3%, 8.6%, 12.9%, 17.8%, and 3.5% in males and 21.5%, 12.6%, 16.2%, 20.2% and 5.4% in females. Among males, DIS (OR = 2.76) and PQS (OR = 2.12) were associated with never having married. DMS was associated with being 60 years and older (OR = 2.68) or divorced/separated (OR = 3.74). Among females, DMS was associated with being widowed (OR = 1.65), unemployed (OR = 1.60), 40 to 59 years old (OR = 0.57) or never having married (OR = 0.39). DIS was associated with being widowed (OR = 1.67) or unemployed (OR = 1.58). HMU was associated with advancing age (OR = 8.26-10.7), being widowed (OR = 2.12) or never having married (OR = 2.84). PQS was associated with advancing age (OR = 0.63-0.50). Our study showed sleep disturbance and hypnotic medication use were prevalent among Japanese adults and some sociodemographic factors contributed to them.

Adult↗
PubMed1996

Self-reported depressive symptoms following treatment with corticosteroids and sedative-hypnotics.

OBJECTIVE: To evaluate associations between exposure to corticosteroids or sedative-hypnotic medications and incident self-reported depressive symptoms in medical inpatients. METHOD: The study utilized a prospective cohort design, focusing on acute depressive symptoms developing soon after medication exposure. The incidence of self-reported depressive symptoms was evaluated using a modified version of the Center for Epidemiological Studies Depression Rating Scale (CES-D). The incidence of depressive symptoms in subjects newly exposed to corticosteroids and sedative-hypnotics was compared to that of a nonexposed comparison cohort. RESULTS: The incidence of self-reported depressive symptoms was elevated in subjects newly exposed to corticosteroids (Risk Ratio = 3.10), although the association did not attain statistical significance (p = .07). The risk ratio for sedative-hypnotic exposure was 4.18, a statistically significant finding (p = .02). As expected, incident self-reported depressive symptoms were also associated with several psychosocial variables. However, the data did not suggest that the observed associations between drug exposures and depressive symptoms were due to confounding by psychosocial or illness-related variables.

Adrenal Cortex Hormones↗
PubMedDate not supplied

[Impacts of the new flunitrazepam regulations on the consumption of hypnotics].

The frequent misuse of flunitrazepam has led the French drug agency (AFSSAPS [Agence française de sécurité sanitaire des produits de santé]) to subject this agent to the regulatory regime for drugs known to produce dependency; this drug may now be prescribed for no more than 14 days, is available only on an "ordonnance sécurisée" (prescribing and dispensing subject to stupefacient regulations), and pharmacists must dispense no more than 7 days' supply. We identified, in a French medical-care database, 738 patients who had received at least one flunitrazepam prescription in January 2001, and monitored the hypnotics delivered to this cohort over a period of 8 months. Sixty-nine percent of the patients had replaced flunitrazepam by another hypnotic without any further change. The most surprising result of our survey was the discovery that nearly half of the selected patients stopped using hypnotics during the review period. Although many hypotheses can be offered to account for this phenomenon, it seems that many consumers halted their consumption of flunitrazepam as a result of the new regulatory regime.

Adult↗
PubMed1997

General practitioners' prescribing patterns of benzodiazepine hypnotics: are elderly patients at particular risk for overprescribing? A report from the Møre & Romsdal Prescription Study.

OBJECTIVE: To compare general practitioners' (GPs) prescribing patterns of benzodiazepine hypnotics with current recommendations. DESIGN: Observational, cross-sectional study. SETTING: The Norwegian county Møre and Romsdal. SUBJECTS: 3452 prescriptions for benzodiazepine hypnotics prescribed by GPs for patients aged 20 years and older during two months. MAIN OUTCOME MEASURES: Prescriptions (strength of tablets, amount prescribed given in Defined and Prescribed Daily Doses: DDDs and PDDs, directions for use); initial or repeat, patients (age, sex); kind of GP-patient contact during prescribing. RESULTS: 68.4% of the prescriptions for benzodiazepine hypnotics were for women; 52.7% were for patients aged 65 or older (65+); 59.9% were issued during indirect contacts; 81.9% were repeat prescriptions. The amount of drug per prescription increased with patients' age: 65+ received on average 69.9 DDDs (76.9 PDDs) per prescription compared with 34.4 DDDs (37.1 PDDs) for young adults (20-29 years). About four of five prescriptions were for the "strong" (i.e. 1 tablet = 1 DDD) sleeping pills irrespective of patients' age and type of prescription (initial or repeat). Written directions for use were: "to be taken daily" in 55.1%, and "only if required" in 38.0% of the prescriptions. Written information on duration of "cure" was only found in one case. CONCLUSIONS: GPs' prescribing patterns are not in accordance with recommended dosage and duration of treatment; this pattern is most pronounced for elderly patients.

Adult↗
PubMed1993

Phenobarbital versus clonazepam for sedative-hypnotic taper in chronic pain patients. A pilot study.

A randomized, double-blind controlled trial is reported comparing phenobarbital and clonazepam for the purpose of sedative-hypnotic taper in inpatients with chronic, nonmalignant pain. After receiving the Minnesota Multiphasic Personality Inventory (MMPI) and a standardized psychiatric diagnostic interview, patients' baseline sedative-hypnotic use was assessed over 48 hours. Baseline use was converted into phenobarbital or clonazepam equivalents and administered in four doses daily using a blinded liquid pain cocktail. Baseline dose was maintained for two days and then tapered by 10% per day. Over the first week of taper, differences in mean and maximum Beck Anxiety and Benzodiazepine Withdrawal scores were not significant. However, when scales 1, 3, or 8 of the MMPI were taken as covariates, differences on the Withdrawal Scale only increased to a trend level for mean scores and to a significant level for maximum scores. These findings support the superiority of benzodiazepines over barbiturates for sedative-hypnotic taper for symptoms of withdrawal but not of recurrent or rebound anxiety.

Adult↗
PubMed2004

Newer hypnotic drugs for the short-term management of insomnia: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical and cost-effectiveness of zaleplon, zolpidem and zopiclone (Z-drugs) compared with benzodiazepines. DATA SOURCES: Electronic databases, reference lists of retrieved articles and pharmaceutical company submissions. REVIEW METHODS: Randomised controlled trials (RCTs) that compared either benzodiazepines to the Z-drugs or any two of the non-benzodiazepine drugs in patients with insomnia were included in the review. Data on the following outcome measures were considered: sleep onset latency, total sleep duration, number of awakenings, quality of sleep, adverse effects and rebound insomnia. A search was also undertaken for any study designs that evaluated issues related to adverse events (e.g. dependency and withdrawal symptoms). Full economic evaluations that compared two or more options and considered both costs and consequences including cost-effectiveness, cost-utility analysis or cost-benefit analysis undertaken in the context of high-quality RCTs were considered for inclusion in the review. RESULTS: Twenty-four studies, involving a total study population of 3909 patients, met the inclusion criteria. These included 17 studies comparing a Z-drug with a benzodiazepine and seven comparing a Z-drug with another Z-drug. The diversity of possible comparisons and the range of outcome measures in the review may be confusing. Outcomes were rarely standardised and, even when reported, differed in interpretation. In addition, variations in assessment and variety in the level of information provided make study comparisons difficult. As a result, meta-analysis has been possible on only a small number of outcomes. However, some broad conclusions might be reached based on the limited data provided. The existing published economic literature in this area is very limited. No relevant economic evaluations were identified for inclusion in the review. The industry submissions did not include detailed evidence of cost-effectiveness. Given the lack of robust clinical evidence, no economic model describing the costs and benefits of the newer hypnotic drugs for insomnia was developed. The systematic review provided in this report suggests that an agnostic approach to cost-effectiveness is required at this stage. In the short-term, no systematic evidence is available concerning significant outcome variations between either the different classes of drugs or between individual drugs within each class. Within this short-term horizon, the one element that does vary significantly is the acquisition cost of the individual drugs. CONCLUSIONS: The short-acting drugs seem equally effective and safe with minor differences that may lead a prescriber to favour one over another in different patients. There is no evidence that one is more cost-effective than any other. Analysis of the additional costs to the NHS, depending on the rate of change from benzodiazepine prescriptions to Z-drug prescriptions, at current levels of hypnotic prescribing, range from GBP2 million to GBP17 million per year. There are clear research needs in this area; in particular, none of the existing trials adequately compare these medications. It is suggested that further consideration should be given to a formal trial to allow head-to-head comparison of some of the key drugs in a double-blind RCT lasting at least 2 weeks, and of sufficient size to draw reasonable conclusions. We would also recommend that any such trial should include a placebo arm. It should also collect good-quality data around sleep outcomes and in particular quality of life and daytime drowsiness. We do not believe that any formal study of risk of dependency is feasible at present. Finally, the management of long-term insomnia is suggested for further investigation: considering the frequency of this symptom and its recurring course, the short-term trial of medication and lack of long-term follow-up undermine attempts to develop evidence-based guidelines for the use of hypnotics in this condition, or indeed for its whole management.

Adult↗
PubMed2004

[Studies of time-course changes in human body balance after ingestion of long-acting hypnotics].

Falling accidents are a serious nocosomial problem, with balance disorders after the ingestion of hypnotics said to be a cause. Based on the results of animal studies, it was postulated that this problem involves the muscle relaxation that is a pharmacological effect of benzodiazepines (BZP). No reports have, to our knowledge, been made of time-course changes in human body balance after ingestion of hypnotics. Accordingly, we used quazepam (Doral), a long-acting hypnotic considered to show comparatively weak muscle relaxation, to study static balance after drug ingestion in human volunteers. Briefly, informed consent was obtained from 8 healthy adults, then a gait analytic system (Gangas) was used to test static balance after drug ingestion (Mann and Romberg tests). We also measured circulating drug concentration over time. Our results showed that balance disorders occurred after quazepam ingestion with an unstable posture particularly striking. Given the function of quazepam receptors, it is difficult to surmise that balance disorders after drug ingestion were due to the drug's muscle relaxation. We surmised that inhibition from the central nervous system in connection with nerves awakening was involved. We found a strong correlation between the manifestation of balance disorders after drug ingestion and circulating drug concentration.

Accidental Falls↗
PubMed1992

An attempt to influence hypnotic and sedative drug use.

OBJECTIVE: To assess the impact of a hospital based educational campaign on the prescription and use of hypnotic and sedative drugs. DESIGN: Two three-month cross-sectional surveys were performed. The first was to obtain a baseline evaluation of hypnotic and sedative drug use within the hospital, and the second was to evaluate the success of an educational intervention designed to promote more rational prescribing and use of these drugs. SETTING: St Vincent's Hospital, Sydney, a tertiary referral hospital. PATIENTS: Five patients were randomly selected each day from the hospital's admission list (only psychiatric patients were excluded); 296 patients were interviewed for the first survey and 299 for the second. A minimum six-day admission was necessary for inclusion in the study. Early discharges resulted in 214 patients remaining in each survey group. INTERVENTION: Campaigns were developed for hospital staff and for patients. A booklet and video were produced. The intervention commenced several months after the initial survey and continued throughout the second. MAIN OUTCOME MEASURE: A change in the prescription, administration and use of hypnosedatives. RESULTS: The education of staff had a considerable impact on the administration of these drugs by nursing staff and their prescribing by medical staff. The education of patients resulted in an increase in drug knowledge but had little impact on the use of hypnosedatives in hospital. However, a postal survey conducted three months after discharge from hospital showed a significant reduction (P less than 0.005) in hypnotic and sedative drug use among patients exposed to the educational campaign. CONCLUSION: The importance of continuing education in promoting more rational drug use is highlighted by the study. But the question of the best time and place for an intervention to achieve maximum impact has yet to be answered.

Adolescent↗
PubMed1999

[Methods of sleep induction for EEG recordings: comparison between three hypnotics and natural sleep].

We compared the effects of three oral hypnotics, monosodium trichloroethyl phosphate (MTP), chloral hydrate (CH), and pentobarbital calcium (PTB), to those of non-medication on wake-sleep states and sleep activation of epileptic seizure discharges. The subjects consisted of 410 epileptics and 171 non-epileptic outpatients (mean age: 12.5 years) of the Department of Pediatrics, Nagoya City University Hospital. Complete EEG records including awake and sleep states were obtained in 230/241 (95%) of patients with MTP, 20/22 (91%) of those with CH, 72/85 (85%) of those with PTB, and 225/233 (97%) of those without any hypnotics. There were no statistically significant differences in the effect of sleep induction among the four groups. Sleep activation effects were observed in 25% of patients with natural sleep and 35% of those with induced sleep. There was no statistical difference (p > 0.05). These results suggested MTP, CH, and PTB are useful hypnotics for sleep EEG recordings.

Adolescent↗
PubMed2000

The need for flexibility in dosing of hypnotic agents.

Although a variety of medical and psychiatric disorders are known to cause insomnia, there are many patients for which a cause cannot be determined. When the etiology is unknown, treatment of insomnia must be symptomatic. Epidemiologic studies suggest that insomnia does not occur on a regular basis in most people. In addition, the presentation of insomnia relative to the time of night is often variable, with waking in the middle of the night and initiating sleep upon going to bed being the most common. The intermittent occurrence of most insomnia suggests that treatment is best accomplished by using hypnotics on an "as needed" basis when difficulties with sleep occur. When pharmacological treatment of insomnia is warranted, benzodiazepine receptor agonists (BzRAs) are often the preferred class of agents. Agents with a shorter duration of action and rapid onset of action are preferred for flexible administration, providing an option for middle of the night dosing if this is when insomnia occurs. Of the available hypnotic agents in the BzRA class, triazolam, zolpidem, and zaleplon have rapid onsets of action and short half-lives. However, with a half-life of 1 hour, only zaleplon appears to be suited for middle of the night administration. Other important factors that affect selection of an agent for the treatment of intermittent insomnia include psychomotor or cognitive impairment and rebound insomnia after discontinuation of therapy. In one placebo-controlled trial, residual sedation was seen after flurazepam, but not with zaleplon, following middle-of-the-night administration. In addition, rebound insomnia was not apparent in a 4-week, placebo-controlled trial of zaleplon. In this same study, transient rebound insomnia was apparent with zolpidem compared to placebo. More data are needed on long-term therapy with hypnotic agents given intermittently on nights during which insomnia occurs.

Chronic Disease↗