Sleep Initiation and Maintenance Disorders: Schweitzer PK

Walsh JK, Roth T, Randazzo A, Erman M, Jamieson A, Scharf M, Schweitzer PK, Ware JC. · Sleep Medicine and Research Center, St. Luke's Hospital, St. Louis, Missouri, USA. · Sleep. · Pubmed #11145323 No free full text.

Abstract: CONTEXT: Intermittent use (i.e., a few nights per week) of hypnotic medication is often recommended for the treatment of chronic insomnia despite an absence of efficacy and safety data using this regimen. STUDY OBJECTIVES: To evaluate the clinical efficacy and safety of intermittent pharmacotherapy for chronic insomnia. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, parallel groups, clinical trial at six sleep research sites. PATIENTS: One hundred-sixty-three (115 women, 48 men; mean age 44.1+ SE. 0.9 years), DSM-IV-defined primary insomnia patients were randomized, 134 patients completed the study. INTERVENTIONS: Eight weeks of treatment with either zolpidem 10 mg or placebo. Patients were instructed to take medication when they felt they needed it, but at least three and no more than five times per week. MAIN OUTCOME MEASURES: Investigator and Patient Global Ratings were the primary outcome variables. Secondary measures from daily questionnaires to assess efficacy, rebound insomnia and drug taking behavior. RESULTS: The Investigator's Global Rating indicated that intermittent use of zolpidem produced a significantly better therapeutic effect and significantly reduced insomnia severity throughout the 8-week study relative to placebo. Zolpidem was found to be effective in initiating and maintaining sleep on nights taken, as compared to placebo, based upon the Patient's Global Ratings and all subjective sleep variables. No evidence of rebound insomnia was found on nights that zolpidem was not taken. The number of nights a pill was taken did not differ between groups, nor did frequency of pill taking change in either group across the duration of the study. There were no significant effects of treatment upon quality of life or neurocognitive measures. CONCLUSIONS: Zolpidem 10 mg is effective in treating insomnia when used intermittently, without evidence of discontinuation effects or increased frequency of pill taking.

Walsh JK, Pollak CP, Scharf MB, Schweitzer PK, Vogel GW. · Sleep Medicine and Research Center, St. Luke's Hospital, Chesterfield, MO 63017, USA. · Clin Neuropharmacol. · Pubmed #10682226 No free full text.

Abstract: The present randomized, double-blind, placebo and active-drug controlled, crossover study assessed residual sedation after zaleplon 10 mg, flurazepam 30 mg (as an active control), and placebo, taken during a nocturnal awakening in patients with sleep maintenance insomnia. Twenty-two healthy sleep maintenance insomniacs (11 men; mean age, 42 y) received zaleplon, flurazepam, or placebo after an experimental awakening 3.5 hours after bedtime on two consecutive nights in each of three conditions. Residual sedation was measured with sleep latency testing (5 and 6.5 h postdrug), digit symbol substitution, symbol copying, and subjective sleepiness by visual analog scale, each twice each morning. Zaleplon did not differ from placebo on any measure of residual sedation; flurazepam showed significant sedation on all measures. No residual sedative effects were detected 5 or 6.5 hours after ingestion of zaleplon during the middle of the night by sleep maintenance insomniacs.

Walsh JK, Randazzo AC, Frankowski S, Shannon K, Schweitzer PK, Roth T. · Sleep Medicine & Research Center, St. John's Mercy Medical Center, St. Luke 's Hospital, St. Louis, MO, USA. · Sleep. · Pubmed #16477953 No free full text.

Abstract: STUDY OBJECTIVES: To evaluate the dose- response effects of tiagabine on sleep and safety measures in healthy older adults. DESIGN: Randomized, double-blind, Latin-square design. SETTING: Sleep laboratory. PARTICIPANTS: Twenty-four healthy older adults (11 men, 13 women; mean age 68.0 +/- 6.2 years) INTERVENTIONS: Tiagabine 2, 4, or 8 mg, or placebo, each given on two consecutive nights. MEASUREMENTS AND RESULTS: Polysomnography revealed that compared with placebo, tiagabine 4 mg increased total sleep time, reduced wake after sleep onset, and increased minutes of slow-wave sleep. Tiagabine 8 mg decreased wake after sleep onset, increased slow-wave sleep, and improved a sleep-continuity index. No differences were seen between the 2-mg dose and placebo. Subjective ratings indicated fewer awakenings with the 8-mg dose. Central nervous system adverse events were somewhat higher in the 8-mg condition only. Measures of morning performance were minimally affected. CONCLUSIONS: Research with tiagabine at dosages of 8 mg or less appears warranted in elderly clinical populations.

Walsh JK, Zammit G, Schweitzer PK, Ondrasik J, Roth T. · St. John's Mercy/St. Luke's Hospitals, Sleep Medicine and Research Center, Chesterfield, MO 63017, and Department of Psychology, St. Louis University, St. Louis, MO 63130, USA. · Sleep Med. · Pubmed #16260179 No free full text.

Abstract: BACKGROUND AND PURPOSE: To evaluate the effect of tiagabine on sleep and next-morning alertness and performance in adult patients with primary insomnia. PATIENTS AND METHODS: Patients with primary insomnia, as defined by Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV), received tiagabine 4, 8, 12, 16 mg, and placebo in a randomized, double-blind, five-period, Latin square, crossover study. Efficacy was assessed using polysomnographic and self-report techniques; residual effects were evaluated using the Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT). RESULTS: Fifty-eight patients (40f, 18m; mean age 46.6+/-8.0 years) were randomized. Results showed a significant dose-dependent increase in slow wave sleep percentage with all tiagabine doses, a trend toward a dose-dependent increase in total sleep time, and no effect on latency to persistent sleep. Wake after sleep onset also decreased in a dose-dependent manner, with the 16-mg dose differing significantly from placebo. The tolerability profiles of tiagabine 4 and 8 mg were similar to placebo. The most common adverse events reported following tiagabine 12 and 16 mg were dizziness and nausea. Residual effects were only apparent at 12- and 16-mg doses. CONCLUSIONS: Tiagabine increased slow wave sleep and reduced wake after sleep onset in a dose-dependent manner. Tiagabine dosages up to 8 mg did not compromise next-morning alertness and psychomotor performance in adult patients with primary insomnia. Further investigation of tiagabine doses up to 8 mg is warranted.

Walsh JK, Schweitzer PK. · Unity Sleep Medicine and Research Center, St. Luke's Hospital, Chesterfield, Missouri 63017, USA. · Sleep. · Pubmed #10341388 No free full text.

Abstract: STUDY OBJECTIVE: To assess patterns of pharmacological treatment of insomnia during the period 1987-1996. DESIGN AND MEASUREMENTS: Data were obtained from the National Disease and Therapeutic Index (NDTI; IMS America, Ltd., Plymouth Meeting, PA) which samples office-based physicians in 24 specialties. Drug mentions, a measure of patient contacts in which drug therapy is recommended, with a physician-indicated desired action of "promote sleep" or "sedative night" were compiled for each year. Z-scores were calculated to determine statistical differences over time for total drug mentions, drug mentions by category (hypnotics, non-hypnotic benzodiazepines, antidepressants, or other), and for some individual drugs. RESULTS: Total drug mentions for the treatment of insomnia fell 24.4% from 1987 to 1996. From 1987 to 1996 hypnotic mentions decreased 53.7%, antidepressants increased 146%, "other" drugs decreased by 63.2%, and benzodiazepine non-hypnotics remained relatively unchanged. CONCLUSIONS: Since 1987, overall pharmacological treatment of insomnia has decreased substantially although surveys indicate a stable or increasing prevalence of sleep disturbance. There has also been a dramatic shift to use of antidepressants in lieu of hyponotics for the symptomatic treatment of insomnia despite a paucity of data regarding their efficacy and the potential for serious side effects.