Doris A. Chernik

Validity and Reliability of the Observer??s: Assessment of Alertness/Sedation Scale

The Observers Assessment of Alertness/Sedation (OAA/S) Scale was developed to measure the level of alertness in subjects who are sedated. This scale was tested in 18 subjects in a three-period crossover study to assess its reliability and its criterion, behavioral, and construct validity. After receiving either placebo or a titrated dose of midazolam to produce light or heavy sedation, each subject was administered two sedation scales (OAA/S Scale and a Visual Analogue Scale) and two performances tests (Digit Symbol Substitution Test and Serial Sevens Subtraction). Two raters individually evaluated the subjects level of alertness on each of the two sedation scales. The results obtained on the OAA/S Scale were reliable and valid as measured by high correlations between the two raters and high correlations between the OAA/S Scale and two of the three standard tests used in this study. The OAA/S Scale was sensitive to the level of midazolam administered; all pairwise comparisons were significant (p < 0.05) for all three treatment levels at both test periods.

Sedative-hypnotics and human performance

In 52 studies, performance data were obtained the next day following bedtime ingestion of a sedative-hypnotic or a placebo. Only eight of these studies used insomniac patients. Most studies used young adult males. Benzodiazepine hypnotics were most frequently administered and psychomotor performance was most often measured. Little consistent data are available on cognitive functioning and more complex behavior. Durg-related improvement in performance was not found, and, in comparing active drug to placebo, it is clear that all hypnotics, at some doses, produce decrements in performance the next day. Higher doses consistently showed a decrement, and this decrement was usually persistent over the entire day. Although long-acting drugs generally showed more performance decrement, half-life data were not consistent.

Efficacy without tolerance or rebound insomnia for midazolam and temazepam after use for one to three months

Midazolam (15 mg) was compared with temazepam (30 mg) in a randomized, double‐blind, parallel group study. An initial screening period was followed by 3 days of placebo baseline, 4 to 12 weeks of nightly oral use of the medication and a 4‐day placebo withdrawal period. One hundred seventy‐five patients with chronic insomnia participated in this multicenter outpatient study. Because the elimination half‐life of midazolam, a new trizolobenzodiazepine hypnotic, is short (1.3‐2.2 hr) compared to temazepams (12–16 hr), more problems with tolerance and rebound insomnia were expected to occur. Hypnotic efficacy (increased total sleep time, decreased wake time, and decreased sleep latency) was demonstrated for both medications over the entire 3‐month period without the development of tolerance, In fact, if anything, efficacy increased with time on medication, suggesting possible facilitation or “inverse tolerance” effect. On withdrawal, sleep was improved compared with baseline, suggesting partial resolution of the insomniac condition rather than rebound insomnia. These effects were both statistically and clinically significant for midazolam, with 16% to 50% improvement in sleep measures. The results of this study suggest that patients with chronic insomnia may benefit from 30 to 90 days of treatment. A three‐factor model that separates pharmacologic from behavioral and psychologic effects of hypnotics was proposed to explain these results in part.

Illness impact and adjustment to Parkinson's disease: before and after treatment with tolcapone.

Research on the impact of disease and treatment on health status and quality of life in patients with movement disorders is limited. We studied quality of life in 46 patients with Parkinsons disease (PD) to determine whether the impact of illness and psychosocial adjustment to illness were improved by 42 days of adjunctive therapy with tolcapone (50 mg, 200 mg, or 400 mg three times a day). This study was conducted in parallel with a double‐blind, placebo‐controlled, dose‐response study of the safety and efficacy of tolcapone in combination with levodopa/carbidopa therapy. Only a subset of individuals from the larger study participated. In the quality of life study, illness impact and adjustment to illness were measured subjectively by the Sickness Impact Profile (SIP) and the Psychosocial Adjustment to Illness Scale‐Self‐Report (PAIS‐SR). Patient ratings of total illness impact (p = 0.003), physical illness impact (p = 0.05), and psychosocial illness impact (p = 0.007) improved significantly in individuals receiving tolcapone compared with those receiving placebo. There was no statistically significant difference in adjustment to illness when the tolcapone and placebo groups were compared; however, 17 of 21 adjustment to illness indicators showed improvement.

Validity and Reliability of the Neurobehavioral Assessment Scale

The Neurobehavioral Assessment Scale (NAS) was developed to measure the full range of behavioral functioning from fully alert to deep coma. This investigator-rated scale was evaluated in 60 patients undergoing conscious sedation for maxillofacial procedures. The results obtained on the NAS were reliable, as evidenced by high correlations between the rating of the two raters. The scale is also valid as determined by high correlations between the NAS and a standard scale, the Glasgow Coma Scale (criterion validity) and between the NAS and the Digit Symbol Substitution Test (behavioral validity). The NAS clearly distinguished between two levels of sedation (heavy and light). Furthermore, the NAS appears to be better able to discriminate among the different degrees of sedation in lightly sedated patients than the Glasgow Coma Scale.

Sleep, Performance, and Plasma Levels in Chronic: Insomniacs during 14-Day Use of Flurazepam and

Methods are described for a five-center study of flurazepam and midazolam, in which 107 patients with histories of benzodiazepine use for chronic insomnia were enrolled. Data were available for 99 of these patients. Staff and patient manuals and a behavior-based computer system were specially designed to measure and delineate clearly the study procedures and parameters. Patients were carefully followed and supported during a 20-day washout period and underwent extensive training on psychomotor performance tasks. They received placebo for 2 nights and were then randomly assigned to one of four study treatments--flurazepam 15 or 30 mg, midazolam 15 mg, or placebo--for 14 consecutive nights. All-night sleep electroencephalographic recordings were obtained on study nights--1 and 0 (placebo) and 1, 2, 7, 13, and 14 (treatment nights). Results of four computer-generated psychomotor performance tasks and three cognitive tasks, plus subjective evaluations of sleep, performance, and mood, were recorded in the morning after each night spent in the sleep laboratory. Blood and urine samples were analyzed for drug concentrations in plasma and for compliance with the protocol. A pilot study, using a high (nonclinical) dose of flurazepam (45 mg), preceded the multi-center study and was designed to evaluate tests in healthy volunteers and to familiarize staff with equipment and tests.