Comparison of the daytime sleep and performance effects of zolpidem versus triazolam.

Fifty healthy male subjects were administered zolpidem (5, 10, or 20 mg), triazolam (0.5 mg) or placebo, then attempted to sleep in a non-sleep-conducive environment. Subjects were awakened at 90 min post-drug (near peak blood concentration for both drugs) and tested on several cognitive tasks, including Two Column Addition, Logical Reasoning, and a Simulated Escape Task. This was followed by a second, 3.5-h sleep period. Hypnotic efficacy of the 20 mg zolpidem (Z-20) dose was similar to that of the 0.5 mg triazolam (TRIAZ) dose, as indicated by comparably shortened sleep latencies and lengthened total sleep times. Though accuracy on most performance measures was not affected by either drug, a reduction in speed of responding on logical reasoning and addition tasks was evident for the TRIAZ group at 90 min post-drug (Ps less than 0.05). On the simulated escape task, only triazolam significantly increased the mean number of errors, and interfered with subsequent memory of the task. Thus, zolpidem had milder effects on performance than triazolam. However, 60% of the Z-20 subjects experienced mild, adverse physical reactions. Performance differences between somnogenically comparable doses of zolpidem and triazolam may be due to their differential affinities for the BZ1 and BZ2 receptor subtypes.

Administration of triazolam prior to recovery sleep: effects on sleep architecture, subsequent alertness and performance.

The effects of triazolam (0.125, 0.25, and 0.5 mg) versus placebo on recovery sleep staging, subsequent alertness and psychomotor performance were evaluated in humans. Forty-five healthy male subjects were deprived of sleep for 24 h, then administered a single dose of triazolam or placebo using a double-blind procedure. Subjects then attempted to obtain recovery sleep under non-sleep-conducive conditions (sitting upright in a well-lit, crowded chamber) for the next 6 h, followed by 18 more hours of sleep deprivation. During all sleep deprivation periods subjects were tested bihourly on a performance assessment battery which included symbol digit modalities tests (SDMT), four-letter search (FLS), logical reasoning (LR), time estimation (TE), visual vigilance (VV), and short term memory (STM) tasks. Sleepiness levels were measured objectively with multiple sleep latency tests (MSLT) and subjectively with the Stanford Sleepiness Scale (SSS). Compared to placebo, all doses of triazolam resulted in increased amounts of stage 3-4 sleep, and the 0.5 mg dose significantly reduced awakenings (Ps less than 0.05). Although subjects receiving triazolam averaged 21-42 min more total sleep time (TST) than subjects receiving placebo, differences in TST were not statistically significant. Apparent triazolam-mediated benefits to sleep quality resulted in no obvious improvements in performance or alertness levels during subsequent sleep deprivation. It was concluded that the increases in stage 3-4 sleep amounts were most likely due to triazolam-mediated increases arousal thresholds, and the triazolam mediated changes in sleep parameters obtained in the present study were not indicative of substantial changes in the recuperative value of sleep.

The value of serum antimicrosomal antibody testing in screening for symptomatic postpartum thyroid dysfunction.

We investigated the value of a screening program for postpartum thyroiditis in a heterogeneous American population and used serum antithyroid antibodies to identify postpartum women at risk. Blood was drawn from 1034 consecutive women on their second postpartum day and tested for antimicrosomal and antithyroglobulin antibodies by hemagglutination. Seventy-two women (7.0%) were seropositive for antimicrosomal antibodies, but only seven (0.7%) had antithyroglobulin antibodies. There was a significant difference in the racial prevalence of antimicrosomal antibodies, with seropositivity in 52 of 588 white women (8.8%) versus nine of 367 black women (2.5%; p less than 0.001). Thirty-four of 51 (67%) antimicrosomal seropositive women followed at least 6 months post partum developed biochemical thyroid dysfunction and 20 of these patients required treatment for hypothyroidism. The mean (+/- SEM) serum thyroxine and thyrotropin levels in these patients before treatment were 3.0 +/- 0.3 micrograms/dl (normal 6.1 to 12.3 micrograms/dl) and 77 +/- 17 mU/L (normal 0.3 to 4.0 mU/L), respectively. Psychologic interviews revealed a significant increase in impaired concentration, carelessness, depression, and total complaints when patients with postpartum hypothyroidism were compared with postpartum euthyroid women. Medical evidence now suggests that postpartum thyroiditis is a common event and causes significant symptoms in women who develop hypothyroidism. Therefore, we propose that serum antimicrosomal antibody testing of postpartum women provides a feasible cost-effective screening method of identifying women likely to suffer from this disease.

Noradrenergic and cholinergic agents in Korsakoff's syndrome.

Subjects suffering from memory disorders associated with Korsakoff's syndrome were treated with noradrenergic and cholinergic drugs in two phases. In the acute phase, tests of short- and long-term memory were conducted shortly after the administration of methylphenidate, physostigmine, an oral placebo, and an intramuscular placebo. In the chronic phase, the memory tests were given after the subjects had been administered each of the following for 1-week periods: methylphenidate, choline chloride, methylphenidate plus choline chloride, and an oral placebo. Significant improvements were seen in long-term memory scores of patients receiving chronic methylphenidate treatment. Significant improvement was not found in short-term memory measures with any of the drug treatments.

The Galveston Orientation and Amnesia Test. A practical scale to assess cognition after head injury.

The Galveston Orientation and Amnesia Test (GOAT) was developed to evaluate cognition serially during the subacute stage of recovery from closed head injury. This practical scale measures orientation to person, place, and time, and memory for events preceding and following the injury. The distribution of test scores in 50 patients who had recovered from a mild closed head injury was used to define the range of variation in performance and to analyze the effects of demographic factors. In a validity study of 52 closed head-injured patients, the duration of impaired GOAT scores was strongly related to the acute neurosurgical ratings of eye opening, motor responding, and verbal responding on the Glasgow Coma Scale. Duration of post-traumatic amnesia, as defined by the persistence of defective GOAT scores, was longer in patients with computed tomographic evidence of diffuse or bilateral brain injury as compared to cases with focal unilateral lesions. Serial GOAT scores were also predictive of long term level of recovery. Review of the brief cognitive test literature disclosed that several techniques have adequate validity data substantiating their use in the detection of dementia in geriatric, psychiatric, and medical populations. Recommendations for the clinical application of the various brief cognitive tests are discussed.