Efficacy and safety of doxepin 6 mg in a four-week outpatient trial of elderly adults with chronic primary insomnia.

INTRODUCTION: The efficacy and safety of doxepin (DXP), a histamine H(1) receptor antagonist, was evaluated in elderly adults with sleep maintenance insomnia. METHODS: This was a randomized, double-blind, placebo-controlled outpatient trial. Elderly adults meeting DSM-IV-TR criteria for primary insomnia were randomized to four weeks of nightly treatment with either DXP 6 mg (N=130) or placebo (PBO; N=124). Efficacy was assessed using patient self-report instruments and clinician ratings. Patient-reported endpoints included subjective total sleep time (sTST), subjective wake after sleep onset (sWASO), latency to sleep onset (LSO), sleep quality, and a Patient Global Impression scale (PGI). The primary endpoint was sTST at week 1. RESULTS: DXP 6 mg produced significantly more sTST and less sWASO at week 1 (both p-values <0.0001) than PBO. These significant improvements versus placebo were maintained at weeks 2-4 (all p-values <0.05). There were no significant differences in LSO for DXP 6 mg versus PBO. DXP 6 mg significantly improved sleep quality (weeks 1, 3, and 4, p<0.05) and several outcome-related parameters, including several items on the PGI, the severity and improvement items of the Clinician Global Impression scale (CGI; weeks 1 and 2) and the Insomnia Severity Index (ISI; weeks 1-4), all versus PBO. There were no reports of anticholinergic effects (e.g., dry mouth) or memory impairment. The safety profile of DXP 6 mg was comparable to that of PBO. CONCLUSIONS: In elderly adults with insomnia, DXP 6 mg produced significant improvements in sleep maintenance, sleep duration, and sleep quality endpoints that were sustained throughout the trial. These data suggest that DXP 6 mg is effective for treating sleep maintenance insomnia and is well-tolerated in elderly adults with chronic primary insomnia.

Efficacy and safety of doxepin 6 mg in a model of transient insomnia.

INTRODUCTION: The efficacy and safety of doxepin (DXP) 6mg tablets were evaluated in healthy adults in a model of transient insomnia. METHODS: This was a randomized, double-blind, parallel-group, placebo-controlled study in healthy adults using a model of transient insomnia. A first-night effect combined with a 3-h phase advance was implemented to induce transient insomnia in healthy adults. Subjects received a single night time dose of placebo (PBO; N=282) or DXP 6mg (N=283) in a sleep laboratory. Efficacy was evaluated objectively (polysomnography; PSG) and subjectively (morning questionnaire). Consistent with the model utilized, the primary endpoint was latency to persistent sleep (LPS); secondary PSG endpoints included wake after sleep onset (WASO; key secondary endpoint), total sleep time (TST), wake time after sleep (WTAS) and sleep efficiency (SE; overall, by quarter of the night and hourly); secondary subjective endpoints included latency to sleep onset (LSO), subjective WASO (sWASO), subjective TST (sTST) and sleep quality. RESULTS: DXP 6mg demonstrated statistically significant improvements in LPS (13min decrease versus PBO; p<0.0001), WASO (39min less than PBO; p<0.0001), TST (51min more than PBO; p<0.0001), WTAS (p<0.0001), overall SE (p<0.0001), SE in each quarter of the night (p<0.0001) and SE in each of the 8h (p⩽0.0003), all versus PBO. Additionally, DXP 6mg significantly improved subjective variables including LSO (p<0.0001), sWASO (p=0.0063), sTST (p<0.0001), and sleep quality (p=0.0004), versus PBO. There was no consistent evidence of next-day residual sedation and also minor sleep stages alterations. The incidence of adverse events was comparable to placebo. CONCLUSIONS: In this model of transient insomnia, DXP 6mg demonstrated significant improvements in sleep onset, sleep maintenance, sleep duration and sleep quality, and also appeared to reduce early morning awakenings. These data suggest that DXP 6mg may be effective and well tolerated in adults experiencing transient insomnia.

Vitamins and sleep: an exploratory study.

STUDY OBJECTIVE: We analyzed archival data from an epidemiology study to test the association between vitamin use and sleep. DESIGN: Random digit dialing was used to recruit 772 people ranging in age from 20 to 98 for a study of people's sleep experience. These individuals completed a set of questionnaires about their sleep, health, and daytime functioning. Five hundred and nineteen of these participants had available vitamin use data. SETTING: Home. PARTICIPANTS: Five hundred and nineteen people participated. Recruitment applied minimal screening criteria and no attempt was made to favor people with or without sleep disturbance. INTERVENTIONS: This survey included no intervention. Participants completed 2 weeks of sleep diaries and a set of questionnaires. Of particular salience to the present study, participants reported their vitamin use in listing all medications and nutritional supplements being used currently. MEASUREMENTS AND RESULTS: For those individuals taking a multivitamin or multiple single vitamins, sleep diaries revealed poorer sleep compared to non-vitamin users in the number and duration of awakenings during the night. After controlling for age, ethnicity, and sex the difference in number of awakenings was still marginally significant. The rate of insomnia, conservatively defined, and consumption of sleep medication were also marginally significantly higher among individuals taking multi-/multiple vitamins compared to those not taking vitamins. CONCLUSIONS: Disturbed sleep maintenance was associated with multi-/multiple vitamin use. Five equally plausible explanations were advanced to explain this association including vitamins cause poor sleep, poor sleepers seek vitamins, and unidentified factors promote both poor sleep and vitamin use. These data are considered preliminary. Methodological characteristics of future studies were described that hold the promise of more clearly illuminating the association between vitamins and sleep.