Criteria For Primary Insomnia Research Articles

Tuina for primary insomnia: a meta-analysis

To systematically evaluate the therapeutic efficacy of tuina therapy for primary insomnia. Nine Chinese and English databases were searched from the inception to May 2017 to identify randomized controlled trials (RCTs) studying tuina therapy for insomnia. The enrolled articles were all RCTs with tuina as the monotherapy or major therapy in the experiment group, with clear diagnostic criteria for primary insomnia well recognized worldwide or in China, and Pittsburgh sleep quality index (PSQI) as one of the outcome measures. Two researchers evaluated the risk of bias and quality of the enrolled studies by following Cochrane Handbook version 5.1.0. The meta-analysis was performed by RevMan version 5.3. Eleven studies were included with a total of 1 076 participants. The Western medication adopted in the control groups were benzodiazepine receptor agonists. The studies were all assessed as high risk of bias for blinding since blinding method was unable to be performed due to the specificity of tuina therapy; no study reported the support of fund or potential interest conflict, so they were all rated unclear for selective reporting. The meta-analysis showed that compared with other traditional Chinese medicine therapies, tuina worked more effectively in reducing the PSQI score (MD=–4.11 0.05); a combination of head and back tuina could more effectively reduce the PSQI score compared with oral administration of Western medication (MD=–2.08<0, 95%CI–3.09 to–1.06, P<0.0001). Tuina can produce more significant efficacy in treating primary insomnia compared with other traditional Chinese medicine therapies and oral administration of Western medication, especially the combination of head and back tuina.

Gender Differences in the Efficacy and Safety of Chronic Nightly Zolpidem.

Studies have shown pharmacokinetic differences for hypnotics in women compared to men, but few studies have assessed either short-or long-term differences in efficacy and safety. To evaluate gender differences in the efficacy and safety of chronic nightly zolpidem (10 mg), we did a post hoc assessment of a large clinical trial. In the trial, participants with primary insomnia (n = 89), ages 23-70, meeting DSM-IV-TR criteria for primary insomnia were randomized, double blind, to nightly zolpidem, 10 mg (n = 47) or placebo (n = 42) 30 minutes before bedtime nightly for 12 months. Polysomnographic sleep on 2 nights in months 1 and 8 and likelihood of next-day sleepiness, rebound insomnia, and dose escalation were evaluated in months 1, 4, and 12. Relative to placebo, zolpidem significantly increased sleep efficiency and reduced sleep latency and wake after sleep onset assessed at months 1 and 8, with no differences in efficacy between women and men and no diminution of efficacy over months. On a next-day multiple sleep latency test (MSLT), no residual sedation was observed for either women or men. No rebound insomnia or dose escalation was seen with no gender differences in either. In adults with primary insomnia, nightly zolpidem administration showed no gender differences in acute or chronic efficacy or in next-day sleepiness. Zolpidem remained efficacious and safe across 12 months. CLINCIAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT01006525; Trial Name: Safety and Efficacy of Chronic Hypnotic Use; http://clinicaltrials.gov/ct2/show/NCT01006525.

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

The efficacy and safety of doxepin (DXP), a histamine H(1) receptor antagonist, was evaluated in elderly adults with sleep maintenance insomnia. 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. 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. 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.

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Journal Digest

Efficacy and Safety of Doxepin 3 and 6 mg in a 35-day Sleep Laboratory Trial in Adults with Chronic Primary Insomnia

To evaluate the efficacy and safety of doxepin (DXP) 3 mg and 6 mg in adults diagnosed with primary insomnia. The study was a randomized, double-blind, parallel-group, placebo-controlled trial. Patients meeting DSM-IV-TR criteria for primary insomnia were randomized to 35 days of nightly treatment with DXP 3 mg (n=75), DXP 6 mg (n=73), or placebo (PBO; n=73), followed by 2 nights of single-blind PBO to evaluate discontinuation (DC) effects. Efficacy was assessed using polysomnography (PSG) and patient reports. Efficacy data were examined for Night (N) 1, N15, and N29. Safety assessments were conducted throughout the study. Compared with PBO, DXP 3 and 6 mg significantly improved wake time after sleep onset (WASO) on N1 (3 mg and 6 mg; P<0.0001), N15 (3 mg P=0.0025; 6 mg P=0.0009), and N29 (3 mg P=0.0248; 6 mg P=0.0009), latency to persistent sleep (LPS) on N1 (3 mg P=0.0047; 6 mg P=0.0007), and total sleep time (TST) on N1 (3 mg and 6 mg P<0.0001), N15 (6 mg P=0.0035), and N29 (3 mg P=0.0261; 6 mg P<0.0001). In terms of early morning awakenings, DXP 3 and 6 mg demonstrated significant improvements in SE in the final quarter of the night on N1, N15, and N29, with the exception of 3 mg on N29 (P=0.0691). Rates of discontinuation were low, and the safety profiles were comparable across the 3 treatment groups. There were no significant next-day residual effects, and there were no spontaneous reports of memory impairment, complex sleep behaviors, anticholinergic effects, weight gain, or increased appetite. Additionally, there was no evidence of rebound insomnia after DXP discontinuation. Five weeks of nightly administration of DXP 3 mg and 6 mg to adults with chronic primary insomnia resulted in significant and sustained improvements in sleep maintenance and early morning awakenings (with the exception of SE in the final quarter of the night on N29 for 3 mg [P=0.0691]). These sleep improvements were not accompanied by next-day residual effects or followed by rebound insomnia or withdrawal effects upon discontinuation. These findings confirm the unique profile of sleep maintenance efficacy and safety of DXP observed in prior studies.

Efficacy and Safety of Doxepin 1 mg and 3 mg in a 12-week Sleep Laboratory and Outpatient Trial of Elderly Subjects with Chronic Primary Insomnia

to evaluate the efficacy and safety of doxepin 1 mg and 3 mg in elderly subjects with chronic primary insomnia. the study was a randomized, double-blind, parallel-group, placebo-controlled trial. Subjects meeting DSM-IV-TR criteria for primary insomnia were randomized to 12 weeks of nightly treatment with doxepin (DXP) 1 mg (n = 77) or 3 mg (n = 82), or placebo (PBO; n = 81). Efficacy was assessed using polysomnography (PSG), patient reports, and clinician ratings. Objective efficacy data are reported for Nights (N) 1, 29, and 85; subjective efficacy data during Weeks 1, 4, and 12; and Clinical Global Impression (CGI) scale and Patient Global Impression (PGI) scale data after Weeks 2, 4, and 12 of treatment. Safety assessments were conducted throughout the study. DXP 3 mg led to significant improvement versus PBO on N1 in wake time after sleep onset (WASO; P < 0.0001; primary endpoint), total sleep time (TST; P < 0.0001), overall sleep efficiency (SE; P < 0.0001), SE in the last quarter of the night (P < 0.0001), and SE in Hour 8 (P < 0.0001). These improvements were sustained at N85 for all variables, with significance maintained for WASO, TST, overall SE, and SE in the last quarter of the night. DXP 3 mg significantly improved patient-reported latency to sleep onset (Weeks 1, 4, and 12), subjective TST (Weeks 1, 4, and 12), and sleep quality (Weeks 1, 4, and 12). Several global outcome-related variables were significantly improved, including the severity and improvement items of the CGI (Weeks 2, 4, and 12), and all 5 items of the PGI (Week 12; 4 items after Weeks 2 and 4). Significant improvements were observed for DXP 1 mg for several measures including WASO, TST, overall SE, and SE in the last quarter of the night at several time points. Rates of discontinuation were low, and the safety profiles were comparable across the 3 treatment groups. There were no significant next-day residual effects; additionally, there were no reports of memory impairment, complex sleep behaviors, anticholinergic effects, weight gain, or increased appetite. DXP 1 mg and 3 mg administered nightly to elderly chronic insomnia patients for 12 weeks resulted in significant and sustained improvements in most endpoints. These improvements were not accompanied by evidence of next-day residual sedation or other significant adverse effects. DXP also demonstrated improvements in both patient- and physician-based ratings of global insomnia outcome. The efficacy of DXP at the doses used in this study is noteworthy with respect to sleep maintenance and early morning awakenings given that these are the primary sleep complaints of the elderly. This study, the longest placebo-controlled, double-blind, polysomnographic trial of nightly pharmacotherapy for insomnia in the elderly, provides the best evidence to date of the sustained efficacy and safety of an insomnia medication in older adults.

Patient-reported benefits from the pre-sleep routine approach to treating insomnia: Findings from a treatment development trial

This uncontrolled trial evaluated the feasibility, acceptability, and initial changes in sleep associated with a novel cognitive-behavioral treatment for insomnia, the pre-sleep routine. Patients were encouraged to develop a “sacred” bedroom space only for sleep or sex, and a ritual for entering it. Nine chronic insomniacs (seven women, mean age, 57.9 ± 12.9 years) who met International Classification of Sleep Disorders Diagnostic and Coding Manual, second edition (ICSD-2) criteria for primary insomnia completed daily sleep diaries throughout four weekly sessions and a 15-min booster session. Post-treatment and 1-month follow-up data indicated that the pre-sleep routine was well liked and associated with numerous self-reported improvements in sleep and daytime functioning. These findings need to be interpreted cautiously in light of the small sample and uncontrolled design.

A polysomnography study of eszopiclone in elderly patients with insomnia

ABSTRACTObjective: To evaluate the safety and efficacy of eszopiclone 2 mg in elderly patients (aged 64-86 years) with chronic insomnia.Methods: This was a randomized, double-blind, placebo-controlled 2‐week study. Patients meeting DSM-IV criteria for primary insomnia and screening polysomnography criteria (wakefulness after sleep onset [WASO] ≥ 20 min and latency to persistent sleep ≥ 20 min) were randomized to 2 weeks of nightly treatment with eszopiclone 2 mg (n = 136) or placebo (n = 128). Efficacy was assessed using polysomnography (Nights 1, 2, 13, and 14) and patient reports (Nights 1–14); safety was assessed using adverse events, clinical labs, physical examination, and vital signs. The mean of all efficacy results during the double-blind period was used for the efficacy analysis.Results: Results indicated that eszopiclone was associated with significantly shorter sleep onset, less WASO, higher sleep efficiency, more total sleep time, and greater patient-reported quality and depth of sleep scores than placebo ( p < 0.05 for all) with a trend in patient-reported morning sleepiness ( p = 0.07). Other measures of daytime functioning (ability to function, daytime alertness, and sense of well-being) were not significantly different between the two treatment groups. Among patients who napped, eszopiclone patients reported fewer naps ( p = 0.03) and less cumulative naptime (median: 98 min placebo, 70 min eszopiclone, p = 0.07). Unpleasant taste, dry mouth, somnolence, and dizziness were higher in the eszopiclone group (12.5%, 8.8%, 6.6%, and 6.6%, respectively) than in the placebo group (0%, 1.6%, 5.5%, and 1.6%, respectively).Conclusion: In this study, eszopiclone was well tolerated and produced significant improvements in both polysomnographic and patient-reported measures of sleep maintenance, sleep induction, and sleep duration in elderly patients with chronic primary insomnia.

Daytime Functioning in Primary Insomnia: Does Attentional Focus Contribute to Real or Perceived Impairment?

A study was conducted to test the proposal that self-focused attention or monitoring exacerbates the perception of poor daytime functioning in the absence of objective deficits among individuals with insomnia. Fifty-one participants meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for primary insomnia were randomly assigned to a self-focus group (viewing themselves on a TV monitor), a monitoring group (instructed to focus on their thoughts, body sensations, mood, and performance), or a no instruction group while completing a battery of neuropsychological tests. The results indicated that all participants performed within published normative ranges on all tests. The groups did not differ on their objective test performance, but the self-focus group perceived their performance on the tests as significantly worse than the no instruction group. These findings suggest that self-focused attention may contribute to perceived impairment in daytime functioning in primary insomnia.

Effect of Tiagabine on Sleep in Elderly Subjects With Primary Insomnia: A Randomized, Double-Blind, Placebo-Controlled Study

This study further evaluated the effects of tiagabine on sleep in elderly subjects with primary insomnia. Elderly subjects (aged 65-85 years) meeting DSM-IV-TR criteria for primary insomnia were randomly assigned to receive tiagabine 2, 4, 6, or 8 mg or placebo on 2 consecutive nights. Efficacy was assessed using standard polysomnography and a postsleep questionnaire. Additional assessments included the Assessment of Daily Functioning, Digit Symbol Substitution Test (for residual effects), and visual analog scale (for sleepiness/alertness). A total of 207 subjects were randomly assigned to study medication (tiagabine: 2 mg, n = 43; 4 mg, n = 38; 6 mg, n = 45; 8 mg, n = 43; placebo, n = 38). Tiagabine did not significantly effect wake after sleep onset, latency to persistent sleep, or total sleep time compared with placebo (P > .05). Significant increases in Stage 3+4 sleep (i.e., slow-wave sleep) were found for tiagabine 4, 6, and 8 mg versus placebo, with a corresponding significant decrease in Stage 1 sleep (P < .05). At 6 and 8 mg, tiagabine also significantly reduced the number of awakenings and increased the ratio of Stage 3+4/(Stage 1 +wake after sleep onset). In general, there were no significant effects on subjects' ratings of sleep or daily functioning with tiagabine 2, 4, and 6 mg versus placebo. These 3 doses had tolerability profiles comparable with that of placebo and were not associated with significant residual effects or reduced alertness. The 8-mg dose, however, significantly decreased subjective total sleep time and refreshing quality of sleep, as well as daily functioning. This dose was associated with troublesome adverse events, significant residual effects, and reduced alertness. In elderly subjects with primary insomnia, tiagabine did not have a significant effect on wake after sleep onset, latency to persistent sleep, total sleep time, or the subjective rating of sleep. Tiagabine 4, 6, and 8 mg significantly increased slow-wave sleep, with a corresponding significant decrease in Stage 1 sleep. Tiagabine was generally well tolerated, with doses of less than 6 mg having tolerability profiles generally similar to that of placebo. The 8-mg dose, however, was associated with troublesome adverse events, residual effects, and reduced alertness.

Doxepin in the treatment of primary insomnia — A placebo-controlled, double-blind, polysomnographic study

BACKGROUND Over recent years, the use of antidepressants for the symptomatic treatment of insomnia has grown substantially, but controlled studies are still lacking. Our study is the first investigation to prove objective efficacy and tolerability of low doses of a sedating antidepressant in a randomized, double-blind, and placebo-controlled manner in patients with primary insomnia. METHOD Forty-seven drug-free patients meeting DSM-IV criteria for primary insomnia (mean +/- SD duration of complaints = 11.2+/-9.7 years) received either 25-50 mg of the tricyclic antidepressant doxepin or placebo for 4 weeks followed by 2 weeks of placebo withdrawal. Sleep was measured by polysomnography at baseline and the first night of application, at 4 weeks of treatment and the first to third night of withdrawal, and after 2 weeks of withdrawal. RESULTS In the doxepin-treated patients who completed the study (N = 20, 47.6+/-11.3), medication significantly increased sleep efficiency after acute (night 1, p < or = .001) and subchronic (night 28, p < or = .05) intake compared with the patients who received placebo (N = 20, 47.4+/-16.8 years of age). Latency to sleep onset was not affected since the patients had normal baseline sleep latencies. Investigators found doxepin to cause significantly (p < or = .05) better global improvement at the first day of treatment. Patients rated sleep quality (p < or = .001) and working ability (p < or = .005) to be significantly improved by doxepin during the whole treatment period. Overall rebound in sleep parameters was not observed, but patients with severe rebound insomnia were significantly more frequent in the doxepin group (night 29, p < .01, night 30, p < or = .01; night 31, p < or = .05). No significant group differences in side effects were found, but 2 doxepin-treated patients dropped out of the study due to specific side effects (increased liver enzymes, leukopenia, and thrombopenia). CONCLUSION The results support the effectiveness of low doses of doxepin to improve sleep and working ability in chronic primary insomniacs, although subjective effects were light to moderate, and in some patients, rebound insomnia and specific side effects have to be considered.

Benzodiazepines and Zolpidem for Chronic Insomnia

To evaluate the efficacy of benzodiazepines and zolpidem tartrate in chronic insomnia based on a quantitative review of literature. Articles from 1966 to 1996 were identified using MEDLINE, by a manual review of relevant journals, and from bibliographies of identified articles. Studies using randomized, double-blind, placebo-controlled, parallel or crossover designs with benzodiazepines or zolpidem in adults younger than 65 years with chronic insomnia (modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for primary insomnia) were selected for review. Self-report and polysomnographic measures of sleep-onset latency, total sleep time, number of awakenings, and sleep quality were selected as outcomes. Twenty-two studies met the selection criteria. A combined test of Pvalues was performed, pooling broadly from the 22 studies to determine whether medication was superior to placebo. A combined test of effect sizes was performed on the subset of studies that reported effect size information to determine the magnitude of medication effect. A homogeneous sample of studies summarized 1894 patients treated for a median duration of 7 days. The combined test of P values demonstrated that medication was superior to placebo in all 4 outcome measures. Treatment response was moderate in magnitude by the combined test of effect sizes. Benzodiazepines and zolpidem produced reliable improvements in commonly measured parameters of sleep in patients with chronic insomnia. Relative to the chronic and recurring course of insomnia, both the limited duration of treatments studied and the lack of follow-up data from controlled trials represent challenges for developing evidence-based guidelines for the use of hypnotics in the management of chronic insomnia.