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PubMed1983

Sedative-hypnotic drug use and ageing.

Behavioural disadvantages associated with the use of sedative-hypnotic drugs in the elderly are considered in relation to four aspects of drug usage reported in the epidemiological literature between 1960 and 1982, viz. (1) the prevalence of drug usage; (2) the type of drug, and the dose used; (3) the typical duration of usage; and (4) the typical frequency of usage. Demographic characteristics of elderly hypnotic users are also examined. The pattern and prevalence of usage over the past 20 yr show many consistent features. In particular, the prevalence of drug usage among the elderly has remained relatively high, especially within institutional settings. Sex differences in the prevalence of sleeping drug usage, frequently reported for elderly populations, appear to be related to bereavement, health status, and age. The advanced age of hypnotic drug users, however, does not appear to influence the choice of hypnotic drug prescribed. Moreover, drugs and dosages typically prescribed, and the duration and frequency of use typically reported, do not reflect a consistent approach to the problem of minimizing some of the adverse behavioural consequences associated with sedative-hypnotic drug use in the elderly.

Aged↗
PubMedDate not supplied

Subarachnoid bupivacaine blockade decreases midazolam and thiopental hypnotic requirements.

STUDY OBJECTIVE: To test the hypothesis that subarachnoid bupivacaine blockade decreases hypnotic requirements for thiopental sodium and midazolam. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Teaching hospital. PATIENTS: 53 nonpremedicated ASA physical status I and II adult male patients scheduled for elective lower abdominal, pelvic, or lower limb surgery. INTERVENTIONS: Intravenous injections of midazolam or thiopental were administered with or without subarachnoid bupivacaine blockade (12.5 mg) at the L3-L4 level. Thiopental or midazolam hypnotic requirements were determined using loss of ability to open eyes in response to verbal command as an endpoint. The thiopental requirements were determined by titration; the midazolam requirements were determined from dose-response curves obtained with bolus injections of predetermined doses of the drug. MEASUREMENTS AND MAIN RESULTS: Subarachnoid bupivacaine blockade decreased the hypnotic dose of thiopental from 3.40 +/- 0.68 mg/kg (mean +/- SD) with a dose range of 2.3 to 4.5 mg/kg (intramuscular saline) to 2.17 +/- 0.48 mg/kg with a dose range of 1.3 to 2.8 mg/kg (p < 0.005 for the difference). The ED50 value of midazolam decreased with the bupivacaine blockade, from 0.23 mg/kg (95% confidence limits: 0.08 to 0.38 mg/kg) to 0.06 mg/kg (0.01 to 0.14 mg/kg), with p < 0.0001 for the difference. CONCLUSION: Subarachoid bupivacaine blockade decreases hypnotic requirements for both thiopental and midazolam. The results suggest that the reduction in hypnotic requirements is due to the decrease in afferent input induced by spinal anesthesia.

Adult↗
PubMed1996

The impact of sedative-hypnotic use on sleep symptoms in elderly nursing home residents.

OBJECTIVE: To determine the frequency of sleep-related complaints among institutionalized elderly subjects and to assess the relationship between perceived sleep quality and the use of sedative-hypnotic agents and other psychoactive medications. METHODS: In 12 nursing homes in Massachusetts, we conducted observational, cross-sectional, and longitudinal studies of 145 institutionalized elderly subjects (average age, 83.0 years; age range, 65 to 105 years). We recorded the patients' demographic characteristics and all medication use (both scheduled and as needed) during a 1-month baseline period. A research assistant who was blinded to diagnoses and medication use performed detailed neuropsychologic testing and administered a series of standardized questions concerning difficulty sleeping, early morning awakening, and time spent awake in bed. Medication use and patient assessments were repeated after a 6-month interval. RESULTS: One or more sleep-related complaints were present at baseline in 94 (65%) of the residents studied. Using logistic regression to adjust for potential confounding, we found no relationship in the baseline month between use of sedative-hypnotic agents and the presence or absence of sleep complaints. After 6 months of follow-up, 27 (19%) of the residents had decreased their use of sedative-hypnotic agents and 23 (16%) had increased their use. However, there was no relationship between decreased use of sedative-hypnotic agents and worsened sleep (p > 0.20) or between their increased use and improved sleep reports (p > 0.10). Improvement in functional status was significantly associated with improved sleep at follow-up (p < 0.005). CONCLUSIONS: Sleep complaints occur in the majority of institutionalized elderly persons. Neither cross-sectional nor longitudinal analyses showed a relationship between patterns of sedative-hypnotic use and the presence, absence, or change in sleep complaints.

Aged↗
PubMed2003

The challenge of chronic insomnia: is non-nightly hypnotic treatment a feasible alternative?

The adverse effects of insomnia on health and quality of life are matters receiving increasing attention. Yet, surveys have consistently shown that most people suffering from insomnia do not seek medical help, perhaps, in part, because of a concern of becoming dependent on hypnotic medication. The treatment of chronic insomnia poses a particular dilemma in that continuous hypnotic treatment is restricted in many countries to a maximum of 4 weeks, and behavioural treatment is not readily available. Non-nightly hypnotic treatment of chronic insomnia offers a promising alternative option for the many patients whose symptoms do not necessitate nightly drug intake, allaying fears of psychological dependence on medication and respecting regulatory constraints on hypnotic use while providing patients with adequate symptom relief. The practical feasibility and efficacy of this approach has been demonstrated with zolpidem using various treatment regimens and study designs. So far, six clinical trials have been completed on over 4000 patients. Published results show effective treatment of insomnia without any evidence of either adverse event associated with a discontinuous regimen or increased hypnotic use over the treatment period.

Humans↗
PubMed1999

Independent sleep EEG slow-wave and spindle band dynamics associated with 4 weeks of continuous application of short-half-life hypnotics in healthy subjects.

OBJECTIVES: Habituation and adverse withdrawal reactions after prolonged medication with benzodiazepine (BZ) hypnotics are believed to play a role in dose escalation and the development of dependence. METHODS: In the current sleep EEG study in 43 healthy male subjects, the known property of BZ- and similar hypnotics to change the NREM sleep EEG spectrum is utilized for a detailed quantitative analysis across 4 weeks of continuous medication and a subsequent two-week withdrawal period. The BZ hypnotic triazolam and the non-BZ hypnotics zopiclone and zolpidem, differing in pharmacological properties and reported adverse effects, were examined in parallel to a placebo group. RESULTS: Reliably occurring spectral effects in the sleep stage 2 EEG were found in the 3 frequency bands 0.8-5 Hz, 5-10 Hz and 10-15 Hz. All 3 hypnotics showed the typical 'benzodiazepine signature', a 10-15 Hz increase and lower-frequency (<10 Hz) suppression relative to the preceding drug-free night. However, these effects developed differently across the first medication night, across the 4 medication weeks and after withdrawal: While the 5-10 Hz effect covaried with the blood presence of the drugs as estimated from the known plasma half-lifes, showed habituation and a rebound after withdrawal, the 10-15 Hz power increased across medication days and showed no rebound. Effects in the 0.8-5 Hz band in the first medication night correlated with the decrease of sleep efficiency at later withdrawal for triazolam and zolpidem.

Adult↗
PubMed2000

Use of an anesthesia information management system (AIMS) to evaluate the physiologic effects of hypnotic agents used to induce anesthesia.

OBJECTIVE: The aim of this study was to utilize an anesthesia information management system (AIMS) in investigating the effects of hypnotic agents used to induce anesthesia on blood pressure, heart rate and arterial oxygen saturation. The characteristics of these agents, known from previous studies, were compared to the effects documented in this study during routine clinical use. METHODS: During the years 1997 and 1998, all relevant data from anesthetic procedures were recorded online using the automated anesthesia information system NarkoData. The data from 8,078 general anesthesia procedures using endotracheal intubation were exported via "structured query language" (SQL) from the AIMS database into a statistics program after excluding children (age < 14), patients who received atropine during induction and procedures with use of extracorporeal circulation. The effects of drug administration on systolic, diastolic and mean arterial blood pressure (SBP, DBP, MBP), heart rate (HR) and arterial oxygen saturation (SpO2) were analyzed prior to induction and at 5, 10 and 15 minutes following bolus administration of the hypnotic agent. The data were classified into three groups based on the induction agent used: thiopental, etomidate or propofol and further separated into two groups based on ASA status (ASA < or = II and ASA > II). The mean and standard deviations were calculated for each parameter at each point in time. Statistical comparisons were performed to determine whether the results for each time point differed from the previous time point. RESULTS: There was a significant decrease in blood pressure (MAP, SBP, DBP) after bolus administration of all three hypnotics in all of the 8,078 procedures analyzed. The decrease was greater in patients of ASA class > II than in those of ASA class < or = II. Propofol caused the greatest drop in blood pressure whereas etomidate caused the least. During the observation period the HR also fell in each group, except for thiopental where an initial rise of the HR could be observed. An initial rise of SpO2 was recorded in each group with no differences observed between the individual hypnotics. CONCLUSIONS: The effects of the induction hypnotic agents thiopental, etomidate and propofol on blood pressure and heart rate as documented by an AIMS corresponded to those found in clinical studies. An AIMS with the corresponding documentation, software and database structure is suitable for collecting and evaluating data for dinical investigations.

Adult↗
PubMed2001

High-dose flumazenil potentiates the hypnotic activity of propofol, but not that of thiopental, in ddY mice.

BACKGROUND: Flumazenil is a specific benzodiazepine agonist, which is reported to have a partial benzodiazepine agonist-like effect at a high dose. This study investigated the effects of flumazenil and midazolam on the hypnotic dose of propofol and thiopental in ddY mice, using a behavioral model. METHODS: Mice were given either propofol or thiopental intravenously to induce hypnosis, which was defined as a loss of the righting reflex. The mice were pre-treated with flumazenil (0.05, 0.1, or 0.2 mg kg(-1)) or midazolam (0.1 or 0.2 mg kg(-1)), and given propofol or thiopental after a 30-s delay. RESULTS: Pre-treatment with flumazenil (0.1 or 0.2 mg kg(-1)) significantly decreased the hypnotic dose of propofol compared to the control group (9.3+/-0.39 [8.5-10.0] or 9.0+/-0.28 [8.5-9.6] vs. 10.8+/-0.42 [9.9-11.6] mg kg(-1) (ED50+/-SEM and [95% confidence interval]) P<0.05), but not that of thiopental (9.1+/-0.30 [8.5-9.7] with 0.2 mg kg(-1) flumazenil vs. 9.3+/-0.42 [8.4-10.1] mg kg(-1) with saline). Midazolam reduced the hypnotic dose of both propofol and thiopental. Flumazenil antagonized the potentiating effect of midazolam (0.2 mg kg(-1)) on the hypnotic activity of propofol. CONCLUSIONS: These results suggest that the hypnotic activity of propofol is potentiated by the partial agonist activity of flumazenil in ddY mice.

Anesthetics, Intravenous↗
PubMed1998

Survival analytic approach to long-term prescription of benzodiazepine hypnotics.

Eight hundred and sixty-two patients who visited the department of neuropsychiatry and who were prescribed benzodiazepine (BZ) hypnotics were investigated to evaluate the actual state of their use, in terms of age, gender, diagnostic categories according to ICD-9, duration of prescription and dose equivalent to diazepam prescribed. The frequency of prescriptions in subjects were surveyed using Kaplan-Meier survival analysis at every 3 months. Mean survival time to discontinuation was 8.5 months. A total of 60% of the subjects did not receive BZ hypnotics at the end of the third month, but 20% remained to be prescribed after 1 year. Moreover, 7.9% of the subjects were prescribed BZ hypnotics even after 3 years. The results indicated that 20% of patients who had started prescriptions for BZ hypnotics had the potential to induce dependence. The following variables were found in the long-term prescription: male patients; aged patients over 60; and affective psychoses (which mainly consisted of depression) including neurotic depression, in the present study. A low dose was considered to be associated with an ability to be free from BZ hypnotics in an early period.

Adult↗
PubMed2002

Hypnotic prescriptions in a university hospital: Analysis of data from the computer-ordering system.

The computer-ordering system (COS) database was used to investigate hypnotic prescriptions issued to outpatients at various medical departments at the Dokkyo University School of Medicine. Hypnotics were prescribed for 3428 patients (1613 men, 1815 women), with a mean age of 56 years (range 8-91 years). The number of prescriptions was 3.5% of the total number of prescriptions (123 518). Although hypnotics were prescribed most often to patients in their 60s, generally, the incidence was higher for younger-aged patients. Physicians in all specialty areas tended to prescribe short-acting benzodiazepine hypnotics. The issuance of hypnotic prescriptions should be investigated to determine the prevalence of insomnia in various medical specialties.

Adolescent↗
PubMed1998

Use of anxiolytics and hypnotics in gynecological, surgical and medical departments of general hospitals.

While several surveys have shown that patients in nonpsychiatric hospital departments frequently receive anxiolytics or hypnotics during hospitalization, and also receive discharge prescriptions for these drugs, as yet none has investigated the start of intake of these drugs during hospitalization in conjunction with an assessment of all types of psychiatric disorders. Therefore, we studied 728 patients in medical, gynecological, and surgical departments of two non-university general hospitals in Austria for the prevalence of anxiolytic and hypnotic drug use during hospitalization as compared to discharge prescriptions for such drugs. Altogether, 50.4% of all admitted patients were treated with anxiolytics or hypnotics during their stay in hospital, and 42.8% of those who had not taken such drugs before admission. Of the patients using these medications during hospitalization, 26.1% also received discharge prescriptions. The significant associations between psychiatric variables and both drug use during hospitalization and prescriptions at discharge, suggest that anxiolytic and hypnotic drugs are used aptly. However, considering that about half of the patients suffering from substance abuse disorders received discharge prescriptions, the risk of continued substance abuse must not be neglected. Overall, fewer patients received anxiolytics or hypnotics at discharge than had used them before admission.

Aged↗
PubMed1982

Hypnotic usage in residential homes for the elderly: a prevalence and longitudinal analysis.

The usage of hypnotic drugs in 23 local authority homes for the elderly was recorded in a one-day point-prevalence survey. Residents were under the care of their own general practitioners. From a total population of 1122 residents, 382 (34.0%) received hypnotics both on the night of the survey, and on the preceding night. The proportion of residents receiving hypnotics within each home varied from 2.3% to 56.5%. No preference was shown for prescribing short half-life hypnotics. The most frequently used hypnotic was nitrazepam, which accounted for 33.2% of total usage. These data were then compared with information similarly recorded from the same local authority homes six months earlier. The pattern and prevalence of drug usage showed little variation between the two surveys.

Adolescent↗
PubMed2007

A comparison of hypnotic and analgesic based sedation in a general intensive care unit.

BACKGROUND: Sedation of the critically ill patient has several components including hypnosis and analgesia. Hypnotic-based sedation (HBS), where midazolam and/or propofol are used, with morphine or another analgesic added as needed has been common. The advent of remifentanil has allowed greater use of analgesia-based sedation (ABS) where relief of discomfort from the tracheal tube or pain are the important objectives, and hypnosis is given as necessary. Method. We compared HBS and ABS (remifentanil-based sedation) within a general intensive care unit (ICU). During the first study period of 12 weeks, 111 patients received HBS. After the development of new guidelines for the use of remifentanil in the ICU, a second 12 week study period used an analgesia-based regimen, with hypnotics added only if needed. RESULTS: Ninety-six patients received ABS, and 79 received remifentanil. It was possible to manage 29 (37%) of the patients receiving remifentanil without the use of supplementary hypnotic agents. In the remaining 63% the use of remifentanil was associated with a reduction in the amount and duration of propofol used. Significantly more patients receiving ABS had satisfactory levels of sedation during synchronized intermittent mandatory ventilation (19 [2,55] vs 50 [14,83], P<0.001). CONCLUSIONS: The use of ABS allowed patients to be managed more comfortably, either without a hypnotic drug or with less hypnotic drug, than using conventional HBS.

Adolescent↗
PubMed2002

Diagnostic codes associated with hypnotic medications during outpatient physician-patient encounters in the United States from 1990-1998.

STUDY OBJECTIVES: This investigation tabulates the most common diagnostic codes associated with use of hypnotic medications during physician-patient encounters in the U.S. DESIGN: Estimates were derived from the National Ambulatory Medical Care Survey (NAMCS) from 1990 through 1998. Diagnoses were coded according to the International Classification of Disease-Clinical Modification-9th Edition (ICD-9-CM). SETTING: The NAMCS collects outpatient visit data from nonfederal physicians of all specialties, except anesthesiology, pathology, and radiology. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Hypnotic medications were more commonly associated with psychiatric codes than with the symptom of insomnia. Primary insomnia did not appear among the codes most commonly associated with a hypnotic prescription. CONCLUSIONS: Hypnotics were more commonly associated with psychiatric codes than with insomnia codes, but it is unknown whether the coding accurately reflects the true diagnoses. Still, since there is minimal data on the efficacy and safety of hypnotics in persons with psychiatric disorders, these findings may signal a critical knowledge gap in the treatment of insomnia.

Drug Administration Schedule↗
PubMed2004

A postmarketing study of relative abuse liability of hypnotic sedative drugs.

AIMS: To demonstrate the utility of postmarketing studies using in-treatment drug and alcohol abusers as informants for assessing the relative abuse liability of sedative-hypnotic drugs. DESIGN: A survey was conducted that ascertained exposure to a variety of drugs with hypnotic/sedative properties and elicited subjective evaluations indicative of abuse liability. METHODS: Complete data were obtained from 297 admissions (78% male) to three addiction treatment sites in the United Kingdom. Subjects were asked 15 questions about 12 different drugs, including five benzodiazepines, three antidepressants, two non-benzodiazepine hypnotics and two antihistamines (plus one fictitious drug). Three of the benzodiazepines (diazepam, nitrazipam, temazepam) emerged as having substantially more abuse liability than any of the other drugs tested, as revealed by higher scores on abuse liability items (purchased on street, taken to get high, like drug, potential for addiction to drug). The antihistamines (chlorpheniramine, diphenhydramine) had lowest abuse liability profiles, while the antidepressants (amitriptyline, fluoxetine, trazadone) and non-benzodiazepine hypnotics (zolpidem, zopiclone) had similar profiles. CONCLUSION: This pilot study suggests that postmarketing information on hypnotic drug use obtained from drug addicts entering treatment produces data consistent with other measures of abuse liability. The data suggest that the risk of misuse of newer non-benzodiazepine hypnotics may be less than that of benzodiazepine drugs, and similar to that of sedating antidepressants. The new methodology may serve to clarify or validate premarketing abuse liability data, and may help to inform the regulatory process and physician practice.

Cluster Analysis↗
PubMed2007

Use of a computer-based reminder to improve sedative-hypnotic prescribing in older hospitalized patients.

OBJECTIVES: To develop a feasible, inexpensive, point-of-care computerized reminder to improve sedative-hypnotic prescribing in hospitalized older people. DESIGN: Pre-postintervention with a computer-based reminder. SETTING: Academic medical center. PARTICIPANTS: Hospitalized patients aged 65 and older. INTERVENTION: Computer-based reminder directing clinicians to prescribe a nonpharmacological sleep protocol, to minimize the potential for harm with diphenhydramine and diazepam use by choosing an alternative medication (trazodone or lorazepam), or both. MEASUREMENTS: Frequency of prescription of four sedative-hypnotic drugs (diphenhydramine, diazepam, lorazepam, and trazodone) during the 12 months before (n=12,356 patients) and after (n=12,153) the reminder was instituted. RESULTS: Prescribing of sedative-hypnotics decreased from 2,208 per 12,356 (18%) patients preintervention to 1,832 per 12,153 (15%) postintervention (odds ratio for the intervention=0.82, 95% confidence interval=0.76-0.87), an 18% risk reduction. Combined prescription rates for all four drugs fell consistently throughout the postintervention period. Diphenhydramine, diazepam, and lorazepam orders declined overall, with lorazepam prescriptions decreasing 39% during the intervention. Ninety-five percent of patients were successfully directed to a safer sedative-hypnotic drug or a nonpharmacological sleep protocol. CONCLUSION: Using real-time computer-based reminders could lead to improved sedative-hypnotic prescribing for older persons in acute care. This study highlights the potential to address patient safety concerns, and the quality of medication prescribing in particular, in vulnerable hospitalized patients.

Academic Medical Centers↗
PubMed1986

Hypnotics: clinical value of pharmaco-EEG methods.

The central effects of sedative-hypnotic drugs were defined through the use of electroencephalographic (EEG) techniques in two species (rat and cat). In immobilized rats, spectral and visual electrocorticogram analysis provides a means of studying and comparing different profiles of sedative-hypnotic drugs. As with spectral analysis, Hjorth's descriptors allow one to detect the sedative effects of drugs and to study drug interactions in acute preparations. We have evaluated the action of hypnotics on the sleep-wakefulness cycle in freely implanted rats during their maximally active period because it is easier to estimate the duration of the sedative effect. We have also examined the action of sedative-hypnotic agents in rats and cats because of the different species reactivity to drugs such as benzodiazepines. These EEG methods are of value in the development of new hypnotic agents.

Animals↗
PubMed1996

Antisense technology reveals the alpha2A adrenoceptor to be the subtype mediating the hypnotic response to the highly selective agonist, dexmedetomidine, in the locus coeruleus of the rat.

Alpha2 adrenergic agonists are used in the anesthetic management of the surgical patient for their sedative/hypnotic properties although the alpha2 adrenoceptor subtype responsible for these anesthetic effects is not known. Using a gene-targeting strategy, it is possible to specifically reduce the expression of the individual adrenoceptors expressed in the central nervous system and to thereby determine their role in hypnotic action. Stably transfected cell lines (PC 124D for rat alpha2A; NIH3T3 for rat alpha2C adrenoceptors) were exposed to 5 microM antisense oligodeoxynucleotides (ODNs) for alpha2A and alpha2C adrenergic receptor subtypes for 3 d. Individual receptor subtype expression, as determined by radiolabeled ligand binding, was selectively decreased only by the appropriate antisense ODNs and not by the "scrambled" ODNs. These antisense ODNs were then administered three times, on alternate days, into the locus coeruleus of chronically cannulated rats and their hypnotic response to dexmedetomidine (an alpha2 agonist) was determined. Only the alpha2A antisense ODNs significantly change the hypnotic response causing both an increase in latency to, and a decrease in duration of, the loss of righting reflex following dexmedetomidine; hypnotic response had normalized 8 d after stopping the ODNs. Therefore, the alpha2A adrenoceptor subtype is responsible for the hypnotic response to dexmedetomidine in the locus coeruleus of the rat.

Adrenergic alpha-Agonists↗
PubMed1987

Hypnotics in infusion anaesthesia--with particular reference to thiopentone.

Hypnotics are a group of drugs whose primary action is to produce unconsciousness. This contrasts to the opioids whose primary action is to reduce the sensation of pain and the tranquillisers whose primary action is to calm and to attenuate psychotic disease. Hypnotics of interest to the anaesthetist are the inhalational agents and intravenously administered drugs, including the barbiturates thiopentone and methohexitone, chlormethiazole, etomidate and propofol. Knowledge of the use of hypnotics to maintain anaesthesia is largely confined to the volatile anaesthetic agents, while knowledge of the use of the intravenous hypnotics is largely restricted to their use as intravenous induction agents and as sedative for regional procedures. The use of intravenous hypnotics to maintain anaesthesia requires careful control of infusion rates based on pharmacokinetic predictions. Once techniques are established, favourable operating conditions can be achieved, as well as acceptably short recovery times. With such techniques, the benefits of freedom from many of the adverse aspects of inhalational anaesthesia can be realised.

Anesthesia, Intravenous↗