Sedative-hypnotic Medications Research Articles

Treatment of insomnia in hospitalized patients.

To provide recommendations for the short-term management of insomnia in hospitalized patients and review patient assessment, nonpharmacologic treatment modalities, and selection of hypnotic medications. Review articles and primary literature representative of current knowledge regarding the treatment of insomnia were identified by MEDLINE search (1966-January 2001). Search terms included insomnia (sleep initiation and maintenance disorders), benzodiazepines, zaleplon, zolpidem, and trazodone. Literature regarding the management of insomnia in hospitalized patients is limited; therefore, data pertinent to the treatment of ambulatory patients must be extrapolated to the inpatient setting. When evaluating insomnia in hospitalized patients, it seems reasonable to obtain a thorough history and physical examination to identify potential underlying etiologies. Treatment of these underlying etiologies should be considered. When the use of a sedative-hypnotic agent is necessary, medication and dose selection should be based on the pharmacokinetic and adverse effect profiles of each agent. Patent-specific characteristics should also be considered to provide effective treatment while minimizing adverse effects. Nonpharmacologic approaches to the treatment of insomnia should be considered for hospitalized patients. When sedative-hypnotic medications must be administered, the pharmacokinetic profile of intermediate-acting benzodiazepines (e.g., lorazepam, temazepam) makes them good first-line agents. Zaleplon and zolpidem are also attractive hypnotic agents; however, they are typically reserved for second-line therapy due to cost. Trazodone may be an alternative for patients unable to take benzodiazepines.

Delirium in psychiatric inpatients: a case-control study.

To investigate the clinical and pharmacoepidemiological determinants of delirium in a psychiatric inpatient population. A case-control study design was used. Potential cases and potential controls were identified using hospital discharge data. The clinical record of each subject was reviewed using a validated protocol to confirm case and control status. Subsequently, exposure data were recorded from clinical records. Subjects admitted to hospital with delirium tended to be older, to have pre-existing cognitive deficits, and to have diagnoses of substance use disorders. Subjects who developed delirium after their admission to hospital were older than control subjects, more likely to have a history of cognitive impairment, and were significantly more likely to be treated during the hospitalization with lithium or anticholinergic antiparkinsonian medications. Antipsychotic medication exposures were also associated with delirium, but only at standard or above-standard dosage levels. Antidepressant and sedative-hypnotic medications were not associated with delirium. These findings indicate that using conservative dosages of antipsychotic medications and minimizing the use of anticholinergic medications for parkinsonian symptoms may help to prevent delirium in psychiatric inpatients. Anticonvulsant mood stabilizers may convey less delirium risk than lithium. Antidepressant medications and sedative-hypnotics were not important determinants of delirium in this population.

Sleep Disorders in the Elderly.

Sleep disturbances in the elderly may not be a result of the aging process per se, but rather are likely caused by many factors that are amenable to treatment. These factors include medical and psychiatric problems, medications, and circadian rhythm changes, all of which can cause difficulties during sleep at night, and can lead to complaints of insomnia. Other factors that cause disturbances include a high prevalence of specific sleep disorders such as sleep disordered breathing (SDB), periodic limb movements during sleep (PLMS) and rapid eye movement (REM) sleep behavior disorder (RBD). Although these disorders are more prevalent in the older than younger population, they are not exclusive to this age group, and treatment options that are applicable to young adults are also applicable to older adults. On the other hand, dementia and Parkinson's disease are two neurologic disorders that are almost exclusive to the elderly and most often involve sleep disturbances. Because there are many causes of sleep complaints, when considering treatment options one must identify the underlying problem. If caused by illness, effective treatment of a specific medical or psychiatric problem should help alleviate the sleep problem as well. Changes in the timing of drug administration may improve sleep. For the treatment of chronic insomnia, behavior techniques should always be used in combination with pharmacologic therapy, and sedative-hypnotic medications should be considered when appropriate. The treatment of choice for obstructive sleep apnea is continuous positive airway pressure (CPAP). For PLMS, dopaminergic agents are most effective. For RBD, clonazepam effectively controls the aversive sleep behaviors. Sleep disturbances secondary to dementia and Parkinson's disease are usually problematic for the patient as well as the caregiver, whether in the home or in the nursing home. Proper management of these disturbances is beneficial in terms of delaying institutionalization and reducing nursing care costs, as well as improving the quality of life for both patient and caregiver.

Improving evidence-based practice in the treatment of chronic insomnia: a commentary for Sleep Medicine Reviews on “Chronic hypnotic use: deadly risks, doubtful benefits” (Daniel F. Kripke)

The view on chronic hypnotic use by Professor Daniel F. Kripke underscores a scandalous public health issue, namely, the lack of scientific and clinical evidence to support the prevalent clinical practice of chronic sedative hypnotic prescription for patients with chronic insomnia. Not only is there a lack of controlled data to support this practice, there is also reason to think that it may be ultimately harmful to the health and wellbeing of some, if not many, patients, as argued in this review. This state of affairs leads compellingly to the research agenda recommended by Kripke for randomized, placebo-controlled maintenance clinical trials of sedative hypnotics to assess definitively the benefits and risks of these medications in the long-term clinical management of a chronic relapsing condition. Pending the collection of such data, Kripke recommends that maintenance treatment with sedative hypnotics be withdrawn and that cognitive behavioral therapy [1] be offered. While agreeing with Professor Kripke’s research agenda, I believe that it does not go far enough. I also think that there may be a role for support by the pharmaceutical industry, in tandem with federal sponsorship. In my opinion, we definitely need placebo-controlled evaluation of the efficacy of maintenance sedative hypnotic medication for the long-term management of chronic primary insomnia. The data reviewed by Kripke raise the distinct possibility that placebo may be at least as effective, if not more effective, and safer than sleeping pills. Since the highest currency both scientific and ethical between doctor and patient is derived from placebo-controlled evaluation, that standard should be applied to this prevalent clinical practice. However, I also believe that this is too narrow a research agenda and would not adequately inform clinical practice. Patients with chronic insomnia also frequently

Headache medication-use among primary care headache patients in a health maintenance organization.

Medication-use among headache patients 2 and 5 years after a primary care headache visit is assessed, and the pattern of medication-use compared before and after the introduction of subcutaneous sumatriptan among migraineurs. The study was carried out among headache patients visiting a primary care physician at the Group Health Cooperative of Puget Sound in 1989-90. We report medication-use patterns 2 and 5 years later for the 530 subjects completing both a 2-year (1991-92) and a 5-year (1994-95) follow-up interview. Medication-use was determined by self-report for the month prior to the interview. Medication-use to control or prevent headache is shown for all headache patients and for those meeting International Headache Society criteria for migraine at the 2-year and the 5-year follow-up. The overall pattern of medication-use was similar at the 2-year and the 5-year follow-up, before and after the introduction of subcutaneous sumatriptan (March, 1993). There was a modest but statistically significant decline in the use of opioid and sedative-hypnotic medications, and in the use of ergotamine. At 5 years, 11% of migraineurs reported use of sumatriptan in the prior month. The large majority of study patients used symptomatic medications, usually non-prescription analgesics, sedative-hypnotics, and opiates. Only one-fifth of the migraineurs reported use of a prophylactic medication for headache. Continuing use of symptomatic headache medications was characteristic of patients with migraine and other common forms of headache. The introduction of subcutaneous sumatriptan was not associated with notable change in this pattern, although a modest reduction in use of sedative-hypnotics and opiates was observed. Overall, the pattern of use of headache medications was similar before and after the introduction of subcutaneous sumatriptan.

Informal caregivers and the intention to hasten AIDS-related death.

To determine the extent to which homosexual men dying of the acquired immunodeficiency syndrome (AIDS) receive medication intended to hasten death. To assess the impact on caregivers of administering medications intended to hasten death. In a prospective study of caregiving partners of men with AIDS (n = 140), characteristics of the ill partner, the caregiver, and the relationship were assessed at baseline and 1 month before the ill partner's death. Three months after the death, caregivers were asked if they had increased their partner's narcotic and/or sedative-hypnotic medication dose and if so, what had been the objective of the increase, and their comfort with their medication decisions. Of 140 ill partners who died of AIDS, 17 (12.1%) received an increase in the use of medications immediately before death intended to hasten death. Diagnoses and care needs of ill partners who received increases in the use of medications to hasten death did not differ from those of ill partners receiving medication for symptoms. Fourteen increases (10%) in use of medications were administered by caregivers. These caregivers did not differ from those administering medication for symptom control in level of distress, caregiving burden, relationship characteristics, or comfort with the medication decision, but they reported more social support and positive meaning in caregiving. The decision to hasten death is not a rare event in this group of men. There is no evidence that it is the result of caregiver distress, poor relationship quality, or intolerable caregiving burden; and it does not cause excessive discomfort in the surviving partner. This study, although small, has implications for the policy debate on assisted suicide.

Addiction to benzodiazepines.

Benzodiazepines are sedative hypnotic medications that can induce a state of dependence. Dependence however is not the same as addiction. The development of dependence is a predictable phenomenon, influenced by dose, duration of treatment, and a number of other factors including individual characteristics of the benzodiazepine user. It is unclear whether there are meaningful differences among benzodiazepines in producing a state of dependence. Benzodiazepine dependence is also characterized by a predictable discontinuation syndrome. Benzodiazepines are rarely abused by non-substance abusers. The regulation of benzodiazepines although the legitimate therapeutic use has been significantly reduced.

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.

Physician responses to an educational intervention on improving their long-term prescribing of sedatives

The current study examined response forms returned by physicians in response to a Medicaid retrospective therapeutic intervention on the long-term use of sedatives. The educational intervention was designed to notify physicians about their patients' long-term use of sedatives and suggest that they reevaluate the patient's need for sedative hypnotic medication and decrease or discontinue prescribing the medication and/or suggest non-pharmacological alternatives if deemed appropriate. Forty=seven percent of physicians responded to the educational intervention. Nineteen percent of responding physicians planned to change the patient's medication in some way. The most common planned change was to decrease the dose. Physicians also stated that they would recommend one or more non-pharmacological alternatives to 17% of patients. Thirty-eight percent of physicians planned to monitor and/or counsel the patient. Over 40% of physicians reported planning no action after receiving the intervention. Twenty-six percent of physicians planned no action because of patient demand for the sedatives. The study concludes that physicians need to be better trained on how to: (1) discuss non-pharmacological treatments with patients and (2) deal with and respond to patients who demand controlled substances.

Behavioral measures of anxiety during opiate withdrawal

Heightened anxiety is a major component of the withdrawal syndromes associated with ethanol and sedative hypnotic medications. Because of similarities between the opiate and sedative-hypnotic withdrawal syndromes as well as data implicating heightened noradrenergic tone with opiate withdrawal, we investigated changes in anxiety measures identified by plus-maze and social interaction testing during opiate withdrawal. Because Sprague Dawley rats had very low levels of entry into plus-maze open arms, further studies were conducted using the Long-Evans strain. Long-Evans rats received continuous infusions of morphine sulfate at 44 mg/kg per day delivered by osmotic pump over 7 days while control animals received inert implants. During the first 3 days of withdrawal, the number and time of entries into open and closed arms of a plus-maze was recorded. Both social and aggressive behaviors were scored during pairings of groups of two socially naive animals. Body weight was significantly reduced in morphine-treated animals prior to and during withdrawal. Both the number of entries into open plus-maze arms and the time spent in open areas increased over the 3 days of testing. However, no difference in plus-maze activity was detected between morphine-treated and control subjects. On the third day of withdrawal, social interaction time was greater in pairs of withdrawn and control subjects compared to pairs of two control subjects. In conclusion, behavioral measures of anxiety are not increased during opiate withdrawal.

A ten-year review of the effect of OBRA-87 on psychotropic prescribing practices in an academic nursing home.

The Omnibus Budget Reconciliation Act of 1987 (OBRA-87) included provisions for regulating the use of psychotropic medication, particularly antipsychotics, in long-term-care facilities. The study examined the effect of OBRA-87 on patterns of prescribing of psychotropic medication in a 514-bed nursing home affiliated with a large medical school. Computerized pharmacy records for the ten-year period from March 1984 through July 1994 were retrospectively reviewed to identify orders written for psychotropic medications and to determine the percentage of nursing home residents who received prescriptions for those agents and the average daily dose of the most frequently prescribed agents. During the period before implementation of the regulations, the percentages of residents who received antidepressants, anxiolytic and sedative-hypnotic medications, and antipsychotic medications were stable. After implementation, prescription of antidepressants increased significantly, coinciding with a reduction in prescription of anxiolytics and sedative-hypnotics and a substantial decrease in prescription of antipsychotics. The total number of residents who received any type of psychotropic medication decreased, and over time a trend toward prescription of agents recommended for geriatric use, such as short-acting benzodiazepines and tertiary tricyclic antidepressants, emerged. The changes that resulted from the OBRA-87 regulations reffect both the restrictions placed on classes of medication and the prevalence of psychiatric disorders in the nursing home. In this facility, OBRA-87 appears to have served as an impetus for clinical review and change in practice style.

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

To evaluate associations between exposure to corticosteroids or sedative-hypnotic medications and incident self-reported depressive symptoms in medical inpatients. 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. 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.

Clinical practice guidelines for chronic non-malignant pain syndrome patients

The current paper provides specific guidelines for treating chronic non-malignant pain syndrome patients. The guidelines were developed from an extensive review of existing literature on practice guidelines, the research literature, and common clinical practice across major pain treatment facilities in the USA. They are intended for application to all chronic pain syndrome patients (other than cancer pain) regardless of specific site or etiology of pain. They advocate goal directed treatment to reduce medication misuse and invasive medical procedures, maximize and maintain physical activity, return to productive activity, increase the patient's ability to manage pain, reduce subjective pain intensity, reduce or eliminate the use of healthcare services for primary pain complaint, provide useful information for case settlement, and minimize treatment cost without sacrificing quality. The guidelines recommend interdisciplinary integrated evaluation and treatment on a time limit basis with a focus on conservative medical, psychological behavioral, physical, and vocational interventions based upon the patient's needs. There is emphasis on increasing the patient's level of function and ability to manage pain and related problems. Outpatient care is strongly recommended, with specific upper limits regarding treatment intensity and the use of trigger point injections and nerve blocks delineated. The guidelines also recommend that the long term use of opioid or sedative-hypnotic medications, surgery, implantable spinal devices, or brain stimulation techniques be avoided with chronic pain syndrome patients. These guidelines are intended to serve as a starting point to effectively extend and complement those released by the Agency for Health Care Policy and Research for other types of pain problems such as cancer and acute low back pain.

The chronic pain coping inventory: development and preliminary validation

This paper describes the development and validation of a measure of strategies used by patients to cope with chronic pain, the Chronic Pain Coping Inventory (CPCI). A 104-item measure of pain coping responses and 3 measures of functioning were completed by 176 chronic pain patients. Two-week retest data were provided by 111 of these patients. Item and scale analyses resulted in a 65-item measure that assessed 11 pain coping dimensions. This inventory was then cross-validated in a second sample of chronic pain patients (n = 78), who also completed a measure of pain-related distress. The significant others (typically, spouses) of patients in the second sample rated patients on a significant-other version of the CPCI and on other measures of patient functioning. The results support the reliability of the CPCI scales. Four scales (Guarding, Resting, Asking for Assistance, and Task Persistence) predicted patient- and significant other-reported patient adjustment. Eight scales (Guarding, Opioid Medication Use, NSAID Use, Sedative-Hypnotic Medication Use, Resting, Asking for Assistance, and Exercise/ Stretch) demonstrated moderate-to-strong relationships between patient and significant-other versions, further supporting their validity.

Postoperative Myocardial Ischemia

Recent data suggest that postbypass and postoperative myocardial ischemia are related to adverse cardiac outcome following myocardial revascularization. Therapeutic trials to suppress postoperative ischemia are warranted. Because anesthetics can suppress a variety of physiologic responses to stress as well as myocardial ischemia intraoperatively, we examined whether use of intensive analgesia in the stressful postoperative period could decrease postoperative ischemia. In 106 patients undergoing elective myocardial revascularization, we standardized the anesthetic prior to bypass (sufentanil 5-10 micrograms/kg [induction] and 4.2-6.0 micrograms.kg-1.h-1 [infusion] supplemented with up to 0.5 mg/kg of diazepam). During bypass, patients were randomly assigned to receive either morphine sulfate (group M, n = 54, up to 2 mg/kg) or sufentanil (group S, n = 52, 1 microgram/kg and 1 microgram.kg-1.h-1). In the intensive care unit (ICU), group M received low-dose analgesia (morphine sulfate 1-10 mg intravenously every 30 min, average dose = 2.2 +/- 2.1 mg/h), while group S continued to receive intensive analgesia (infusion of sufentanil at 1 microgram.kg-1.h-1). Both groups received supplemental midazolam in the ICU (group M = 1.1 +/- 1.1 mg/h; group S = 0.6 +/- 0.6 mg/h; P = 0.01). All analgesic and sedative-hypnotic medications were discontinued at 18 hours following myocardial revascularization. Using continuous two-channel electrocardiographic (ECG) monitoring (CC5 and CM5), we documented and characterized ECG changes consistent with ischemia during the preoperative, intraoperative (pre- and postbypass), and postoperative (on- and off-treatment) periods. The total ECG monitoring time was 8,486 h, averaging 81 h per patient. During the prebypass (anesthetic control) period, groups M and S had a similar incidence, but group S episodes were more severe: maximum ST-segment change (median), S versus M: -1.8 mm versus -1.4 mm (P = 0.04). During the postbypass period, both groups had a similar incidence of ischemia, but episodes in group S were less severe: maximum ST-segment change, S versus M: -1.8 mm versus -2.7 mm (P = 0.0005). During the ICU-on-therapy period, the incidence of ischemic episodes was less in group S patients, and the severity was less: area-under-the-ST-time curve, S versus M: -21 mm.min versus -161 mm.min (P = 0.05). After discontinuation of the drug regimen in the ICU, the incidence and severity of ischemic episodes was similar. The incidence of hypotension, hypertension, and tachycardia was similar in both groups in both the intraoperative and ICU periods.(ABSTRACT TRUNCATED AT 400 WORDS)

Factors related to sleep quality in healthy elderly women.

Elderly women in subjectively good health--free of acute illness and major sleep pathologies--who were self-identified as good (n = 22) and poor (n = 16) sleepers were compared on measures of physical health, psychological symptoms, psychosocial status, and life-style. Poor sleepers reported longer sleep latencies, less total sleep time, more nonrestorative sleep, and more daytime fatigue than did good sleepers. Sleep recordings confirmed subjective reports, with shorter total sleep times and trends for lower sleep efficiency, longer sleep latencies, and more wake-after-sleep onset among women with subjective poor sleep. Poor sleepers also were more frequent users of sedative-hypnotic medications in the past. Current medication use, alcohol and caffeine use, daytime napping, and exercise were equivalent in both groups. Psychosocial status failed to discriminate groups. Poor sleepers reported significantly more psychological symptoms than did good sleepers. The levels of both psychological symptoms and sleep disturbance were mild.

Expenditures for psychotropic medications in the United States in 1985

Psychotropic medications have seldom been included in estimates of the costs of mental health services. In the infrequent case that these costs have been assessed, they have been estimated by using national surveys of consumers of health services. The objective of this study was to estimate the costs of prescriptions for psychotropic medications in the United States in 1985 and to assess the difference with the most recent cost estimate from a health services survey (1977). Study data were based on retail costs of psychotropic medications reported to the Pharmaceutical Data Service Alpha National Prescription and Sales Audit. The data come from a computerized survey panel of 2,250 pharmacies representative of the more than 14,000 pharmacies nationwide. The database includes all medication prescriptions filled, whether paid with cash or Medicaid or reimbursed by third-party payment. Analyses were limited to psychotropic medication prescriptions. In 1985, $1.45 billion was spent on outpatient psychotropic medications. Nearly $868 million (60% of the total) was spent on antianxiety and sedative-hypnotic medications, while approximately $263 million (18%) was spent on antipsychotic medications, $240 million (17%) on antidepressants, and $84 million (5%) on combination psychotropic medications. These expenditures were much higher than would have been expected given the most recent health services estimate of $513 million. These results demonstrate the substantial cost of psychotropic medications in 1985. The finding that the cost of psychotropic medications was so high, in contrast to the lower estimate from the 1977 survey, demonstrates the importance of obtaining more frequent cost estimates and basing future estimates on medication databases.

Pain behavior and pain coping strategies in low back pain and myofascial pain dysfunction syndrome patients

Pain behavior and pain coping strategies were systematically measured in a group of 32 chronic low back pain (LBP) and 32 myofascial pain dysfunction (MPD) syndrome patients. Both groups reported high levels of psychological distress on the SCL-90R. The LBP patients were significantly less active, took more narcotic and sedative-hypnotic medications, and showed higher levels of motor pain behavior (guarding, rubbing, and bracing) than the MPD patients. The LBP patients used attention diversion, and praying or hoping as pain coping skills to a much greater extent than the MPD patients. The relationship of these findings to prior research is described, and future research needs in this area are identified.

Short-term stimulus control treatment of insomnia in older adults

A 4-week stimulus control treatment was administered in small groups to 16 ambulatory, noninstitutionalized older adults with sleep onset insomnia. Nine subjects received immediate treatment, and 7 received delayed treatment. Subjective sleep onset latency was collected at baseline, at termination of treatment, and at a 6-week follow-up. Results showed a strong treatment effect which was replicated with the delayed treatment group; both groups maintained their gains through the 6-week follow-up period. The effectiveness of these procedures with the older insomniac is especially encouraging, since it is a much safer intervention than sedative-hypnotic medications.