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At least 19 recordsLinked to original sources
PubMed1985

Non-convulsive status epilepticus after abrupt withdrawal of hypnotic-sedative drugs.

Four patients with severe addiction to sedative-hypnotics and with acute withdrawal symptoms of these drugs are described. They developed latent confusional states with characteristic EEG patterns (bilateral slow and sharp waves of high amplitude). Following small doses of benzodiazepines the EEG became normal together with a reduction in the clinical symptoms. It is suggested that the confusional states were of an epileptic nature.

Adult↗
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↗
PubMed2002

Pharmacological properties and SAR of new 1,4-disubstituted piperazine derivatives with hypnotic-sedative activity.

Preparation, pharmacological properties and structure-activity relationships of new pyrimidyl-piperazine derivatives, exhibiting sedative and hypnotic activity in mice, are reported. The hypnotic activity of the compounds was comparable with that of zopiclone (the known hypnotic-sedative agent), their interaction with ethanol, however, being much lower. The obtained results suggested that zopiclone and pyrimidylpiperazines 2, 4 and 5 exerted their pharmacological activity through a different mechanism - zopiclone through the interaction with benzodiazepine receptors and compounds 2, 4 and 5 through an unidentified molecular target. The pharmacological properties of compound 3 could be the result of a mixed mechanism of action, combining the properties of zopiclone and those of compounds 2, 4 and 5. A common feature of zopiclone and compounds 2 and 3 was that, after their systemic administration, independently of mechanism of action, together with the hypnotic effect a reduction of the 5-HT turnover in the mouse brain was observed. Minimum structural requirements for the hypnotic activity were formulated. Structural considerations have shown that removing the alpha-carbonyl group did not influence the drug's ability to inhibit the locomotor activity. However, it did influence its ability to disturb motor coordination or abolish the righting reflex within non-lethal doses.

Animals↗
PubMed1980

The quantitative measurement of changes in EEG frequency spectra produced in the cat by sedative-hypnotics and neuroleptics.

The sedative-hypnotic secobarbital and the sedative-anti-anxiety agent, chlordiazepoxide and two neuroleptics, chlorpromazine and halopridol, were treated for effects on the EEG of the cat using broad-band frequency analysis of 6 brain sites. Dose-related, 'drug-=specific' effects were abstracted from the data by the use of multivariate statistical techniques. These demonstrated that the two neuroleptic agents produced very similar alterations in the EEG frequency spectrum which were distinctly different from those resulting from the administration of the sedative-hypnotic and the sedative-anti-anxiety agent. The time-course of the central activity of the 4 compounds was also depicted.

Animals↗
PubMed1991

Has the New York State triplicate benzodiazepine prescription regulation influenced sedative-hypnotic overdoses?

A retrospective analysis of sedative-hypnotic overdoses reported to the New York City Poison Control Center (NYCPCC) for the years 1988 and 1989 was performed to evaluate the effects of the triplicate benzodiazepine (BZ) prescription program on the incidence and severity of sedative hypnotic overdoses. Although total BZ overdoses fell slightly, from 1,294 in 1988 to 1,265 in 1989, a statistically significant increase in non-benzodiazepine (NBZ) sedative-hypnotic overdoses, from 111 in 1988 to 144 in 1989, was noted. No difference in clinical outcomes between the two years could be demonstrated. These results suggest that the restriction of BZ failed to reduce the incidence or severity of sedative-hypnotic overdose, largely because of the substitution of similar nonrestricted agents.

Anti-Anxiety Agents↗
PubMed2005

Behavioral effects of photothrombotic ischemic cortical injury in aged rats treated with the sedative-hypnotic GABAergic drug zopiclone.

Sedative-hypnotic drugs commonly used in the elderly may affect functional recovery following cerebrovascular events. Previous research has shown that prolonged exposure to diazepam can interfere with recovery of function and exaggerate tissue loss after brain injury. The present study evaluated the effect of zopiclone, a widely used hypnotic drug, on functional and histological outcome after cortical photothrombosis in aged rats, which might be particularly vulnerable to brain insults and inhibitory sedative-hypnotic drugs. Aged Wistar rats were treated with zopiclone at a dose of 3 mg/kg (i.p., once a day) beginning 4 days before ischemia induction and continuing for 23 days. Sensorimotor recovery was assessed by a new ledged beam-walking test and spatial learning by the Morris water-maze. After a 7-day washout period all rats were administered a single dose of zopiclone (3 mg/kg, i.p.) and retested. Infarct volumes were measured from nitroblue tetrazolium-stained sections at the end of the experiment. Beam-walking data showed that ischemic rats treated with zopiclone were not more impaired than untreated rats. Indeed, they showed fewer faults with the impaired hindlimb than ischemic controls on post-operative day 16. Water-maze performance was not affected by zopiclone. After the washout period a single dose of zopiclone did not worsen forelimb or hindlimb function, but seemed to improve performance in the water-maze test. Cortical infarct volumes were similar in ischemic controls and ischemic rats treated with zopiclone. In conclusion, zopiclone was not detrimental and even seemed to improve behavioral outcome without affecting ischemic damage in aged rats subjected to cortical photothrombosis.

Aging↗
PubMed1989

Sedative-hypnotics: pharmacology and use.

The quest for an ideal sedative-hypnotic drug has been fraught with failure. The goals of the perfect sedative-hypnotic drug are to: (1) produce a transient reduction in the level of consciousness for the purpose of sedation, calmness, and tranquility without lingering aftereffects; (2) produce sleep without the potential to arrest respirations and without aftereffects on sensorium and mood; and (3) produce no abuse, addiction, tolerance, or dependence. Nonetheless, clinical conditions have required the use of sedative-hypnotic drugs in spite of the inherent difficulties with them. The history of sedative-hypnotic drugs is replete with attempts to produce a safe and effective drug. The introduction of one sedative-hypnotic drug for another has been heralded by unguarded optimism and misguided claims. History has repeated itself with each new drug. Toxicities, abuse, addiction, and development of tolerance and dependence have remained in force for each drug that has appeared on the market. Only minor variations on a theme have differentiated one drug from another as the essential features have remained in force.

Drug Interactions↗
PubMed1997

Sedative-hypnotic use by the elderly: effects on hospital length of stay and costs.

Sedative-hypnotic medications are often used to treat anxiety and sleep disorders, although they may not be used appropriately. Relationships between hospital length of stay (LOS), costs, and levels of sedative-hypnotic use were examined. Charts of 856 elderly patients were reviewed for sedative hypnotic use and categorized into three groups: those whose use exceeded Health Care Financing Administration (HCFA) guidelines, those who used sedative-hypnotic medications but did not exceed HCFA guidelines, and those who did not receive any sedative-hypnotic medications. Patients whose sedative-hypnotic use exceeded guidelines had longer LOS (21.5 exceeding guidelines vs. 12.3 within guidelines vs. 6.7 no use, p < or = .001) and higher costs ($29,245 exceeding guidelines vs. $15,219 within guidelines vs. $7,516 no use, p < = or .001.) Even after controlling for severity of illness and comorbid conditions, differences in LOS and costs persisted. This study indicates that sedative-hypnotic medications are frequently prescribed to elderly patients, often in doses exceeding proposed guidelines, and are associated with longer hospital stays and higher hospital costs.

Age Factors↗
PubMed2002

The prevalence and clinical course of sedative-hypnotic abuse and dependence in a large cohort.

Relatively little is known about the prevalence and clinical characteristics of dependence on sedative-hypnotics, and almost nothing has been published regarding abuse. This report relates information on Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IIIR) sedative-hypnotic use disorders among subjects from the Collaborative Study on the Genetics of Alcoholism (COGA). A standardized interview was used to generate data on 407 men and women in Group 1 with sedative-hypnotic dependence (4.4% of the COGA sample), 34 in Group 2 with abuse (0.4%), and 3,426 comparison subjects in Group 3 with alcohol dependence in the absence of a sedative-hypnotic use disorder (36.7%). The remaining COGA subjects (48.5%) were not included as they had neither alcohol nor sedative-hypnotic dependence or abuse. Those with sedative-hypnotic abuse or dependence were more likely to be Caucasian individuals with abuse or dependence on marijuana, cocaine, amphetamines, or opioids. Subjects in Groups 1 and 2 were also more likely to have histories of independent major depressive and panic disorders, as well as substance-induced mood disorders. Those with dependence, compared to abuse, were likely to be women, reported staying intoxicated for a day or more, but noted less abuse of opioids or amphetamines, although Group 2 members also had high rates of difficulties with sedative-hypnotics. These results highlight notable rates of sedative-hypnotic dependence in the COGA families, and indicate that while sedative-hypnotic abuse does occur, and while the clinical course can involve relatively serious problems, it is less common than dependence.

Adult↗
PubMedDate not supplied

Prescribing of selective serotonin reuptake inhibitors, anxiolytics, and sedative-hypnotics by general practitioners in The Netherlands: a multivariate analysis.

A study of the prescribing of anxiolytics and sedative-hypnotics and the occurrence of anxiety or sleep disorders before and after the initiation of selective serotonin reuptake inhibitor (SSRI) therapy may provide insight into differences in individual SSRIs. The purpose of our study was to evaluate whether and in what way the likelihood of being prescribed an anxiolytic or sedative-hypnotic or receiving a diagnosis of an anxiety or sleep disorder differed in patients prescribed either fluoxetine or paroxetine by a general practitioner (GP) in the Netherlands, where these two agents are the most commonly prescribed SSRIs. Episodes of SSRI treatment were constructed from a recently available GP database in the Netherlands. Logistic regression analysis was used to determine whether, after controlling for other observable factors, the receipt of paroxetine or fluoxetine was a statistically significant determinant for receipt of an anxiolytic or sedative-hypnotic or a diagnosis of an anxiety or sleep disorder. We found that patients who were prescribed fluoxetine as their index drug were less likely to receive a concomitant sedative-hypnotic on their index date compared with patients receiving paroxetine. After controlling for other observable factors, such as use of anxiolytics and sedative-hypnotics before SSRI therapy or on the index date or the existence of comorbid anxiety or sleep disorders, patients starting fluoxetine therapy were no more likely than patients starting paroxetine therapy to receive an anxiolytic or sedative-hypnotic or a diagnosis of an anxiety or sleep disorder during the 60-day post period. The likelihood of a patient's being diagnosed with or receiving a prescription for an anxiety or sleep disorder does not appear to be a differentiating factor between the prescribing of fluoxetine or paroxetine by GPs in the Netherlands.

Aged↗
PubMed1990

Abuse liability of barbiturates and other sedative-hypnotics.

The principal action of the sedative-hypnotic drugs, of whom the barbiturates are the most widely known and utilized, is to produce drowsiness and promote sleep. At one time these were also the only drugs available to calm seriously anxious or disturbed people. Unfortunately, in addition to their clinical applications these drugs manifest a very high abuse potential. Experienced drug abusers report feelings of well-being and euphoria while under the influence of these drugs. Self-administration experiments conducted in animals have shown that the barbiturates are potent reinforcing agents. In controlled studies in humans, former drug abusers express a preference for barbiturates over benzodiazepines and will "work" to receive barbiturates. Long term consumption of the sedative-hypnotics, particularly barbiturates, leads to dependence characterized by a severe, potentially life-threatening abstinence syndrome following the abrupt withdrawal of the drug. Withdrawal manifestations include delirium and grand mal seizures. Because of the high abuse potential of these drugs, their manufacture and distribution has been greatly curtailed, and for most clinical applications they have been largely replaced by drugs, e.g., the benzodiazepines, which appear to have much less abuse liability.

Animals↗
PubMed1991

Sedative-hypnotic drug use in Canada.

Although many studies of sedative-hypnotic drug use have been performed in Canada, there has been no national study of the use of these drugs. We have attempted to correct this deficit in our knowledge by using data from an international survey of health care utilization performed in 1968-9 and from the Canada Health Survey (1978-9), the Health Promotion Survey (1985) and the National Alcohol and Other Drugs Survey (1989) to examine sedative-hypnotic use among individuals aged 15 or more. The results suggest that the use of these drugs in Canada is about average for an industrialized society. Several socioeconomic and health care correlates of sedative-hypnotic use were found. The rate of use of these drugs was higher among women, the elderly, separated, divorced or widowed individuals, those who had a secondary school education or less, individuals with a low family income, the retired, and the unemployed. Among women, higher rates of use were reported by those whose main activity was keeping house (as compared with those who were employed outside the home) and by those who lived alone. Higher rates of use were also found for individuals who had consulted a physician or been hospitalized recently, individuals taking multiple drugs, those who scored highly on an anxiety scale, persons in whom negative feelings predominated, and those who had experienced a high frequency of psycho-physiological symptoms of anxiety and depression. From a regional point of view, the highest rates of use for women were consistently reported from Quebec, while the lowest were consistently found in the Prairie provinces. No consistent pattern was found for men.

Adolescent↗
PubMed1985

Paradoxical excitement to sedative-hypnotics in mentally retarded clients.

The relationships among "paradoxical" excitement to sedative--hypnotic medication, self-injurious behavior, and perinatal trauma were evaluated. Mentally retarded patients were classified as either paradoxical or normal responders to sedative-hypnotics. Paradoxical responders to these medications have a lower MA, a history of perinatal trauma, self-injurious behavior (SIB), and aggressive behavior when compared to normal responders. These findings confirmed and extended previous reports that a type of SIB may be indexed by paradoxical response to sedative-hypnotics. Results also suggested that perinatal trauma may be of etiological importance in the development of SIB. Because perinatal trauma or fetal distress results in excessive levels of B-endorphin, in utero, an impaired endogenous opiate system may be a critical factor maintaining a syndrome of SIB. Thus, these data may indicate psychopharmacological markers of SIB that may have both treatment and etiological significance.

Adolescent↗
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↗
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↗
PubMed2004

Characterization of the interaction of indiplon, a novel pyrazolopyrimidine sedative-hypnotic, with the GABAA receptor.

Clinically used benzodiazepine and nonbenzodiazepine sedative-hypnotic agents for the treatment of insomnia produce their therapeutic effects through allosteric enhancement of the effects of the inhibitory neurotransmitter GABA at the GABA(A) receptor. Indiplon is a novel pyrazolopyrimidine sedative-hypnotic agent, currently in development for insomnia. Using radioligand binding studies, indiplon inhibited the binding of [(3)H]Ro 15-1788 (flumazenil) to rat cerebellar and cerebral cortex membranes with high affinity (K(i) values of 0.55 and 0.45 nM, respectively). [(3)H]Indiplon binding to rat cerebellar and cerebral cortex membranes was reversible and of high affinity, with K(D) values of 1.01 and 0.45 nM, respectively, with a pharmacological specificity consistent with preferential labeling of GABA(A) receptors containing alpha1 subunits. In "GABA shift" experiments and in measurements of GABA-induced chloride conductance in rat cortical neurons in culture, indiplon behaved as an efficacious potentiator of GABA(A) receptor function. In both the radioligand binding and electrophysiological experiments, indiplon had a higher affinity than zolpidem or zaleplon. These in vitro properties are consistent with the in vivo properties of indiplon as an effective sedative-hypnotic acting through allosteric potentiation of the GABA(A) receptor.

Acetamides↗
PubMed1998

A randomized controlled trial of a drug use review intervention for sedative hypnotic medications.

OBJECTIVES: Drug use review is used by both the public and private sector to influence prescribing behavior and patient drug use. Past interventions mailed to prescribers have had mixed results. The objective was to evaluate the effect of a one-time, mailed intervention on subsequent use of sedative hypnotic medication. METHODS: An experimental design was used. The intervention contained guidelines for the use of sedative hypnotics, a prescriber profile detailing sedative hypnotic prescribing, and a patient profile. Clustering of patients and their shared prescribers was done to avoid contamination bias and statistical problems associated with a lack of independence of observations. Subjects were 189 Washington State Medicaid recipients who had received at least one tablet per day of a sedative hypnotic medication for 1 year and their prescribing physicians or (when information about the physician was lacking) the dispensing pharmacy. RESULTS: A significant reduction in the use of targeted sedative hypnotic medications was measured in the intervention group (-27.6%) versus the control group (-8.5%). In the intervention group, 9.4% of patients began a new prescription for a benzodiazepine not targeted by the drug use review, whereas no control patients had new use of nontarget benzodiazepines. CONCLUSIONS: The intervention achieved a statistically significant decrease in targeted drug use, and the amount of reduction is likely to have decreased the risk of fractures associated with benzodiazepine use. This study adds to the recent evidence that mailed drug use review interventions can have a desirable impact on patient drug use.

Adult↗