Sublingual and oral zolpidem for insomnia disorder: a 3-month randomized trial

Objective: To evaluate the safety and efficacy of a 5 mg sublingual dose of zolpidem, compared to a 10 mg oral dose, at bedtime and "as needed" following middle-of-the-night awakenings. Methods: Participants were randomized into an oral group (oral zolpidem 10 mg and sublingual placebo at bedtime and "as-needed") and a sublingual group (oral placebo and sublingual zolpidem 5 mg at bedtime and "as-needed"). Participants underwent medical evaluation, polysomnography, the psychomotor vigilance test, and completed questionnaires. Results: Of 85 patients, 67 met the criteria for insomnia (48±10 years; 79% women) and were randomized. Of these, 46 completed 92±5 days of treatment. Mild-to-moderate adverse events were reported by 25% of the participants, including headache, sleepiness, and dizziness. Both treatments decreased middle-of-the-night awakenings by an average of -3.1±2.3 days/week and increased total sleep time by 1.5 hours. Changes in sleep quality and insomnia severity scores were also favorable and comparable between groups: variation depended on continuation of treatment. Regarding PSG findings, sleep latency decreased more in the sublingual group than the oral group (-14±42 vs. 10±29 min; p = 0.03). The psychomotor vigilance test showed minor residual effects 30 minutes after awakening, which reversed after 2 hours. Conclusions: The safety and efficacy of both zolpidem formulations are comparable. The sublingual 5 mg dose induced sleep more rapidly. Clinical trial registration: NCT01896336

Sublingual and oral zolpidem for insomnia disorder: a 3-month randomized trial.

OBJECTIVE: To evaluate the safety and efficacy of a 5 mg sublingual dose of zolpidem, compared to a 10 mg oral dose, at bedtime and "as needed" following middle-of-the-night awakenings. METHODS: Participants were randomized into an oral group (oral zolpidem 10 mg and sublingual placebo at bedtime and "as-needed") and a sublingual group (oral placebo and sublingual zolpidem 5 mg at bedtime and "as-needed"). Participants underwent medical evaluation, polysomnography, the psychomotor vigilance test, and completed questionnaires. RESULTS: Of 85 patients, 67 met the criteria for insomnia (48±10 years; 79% women) and were randomized. Of these, 46 completed 92±5 days of treatment. Mild-to-moderate adverse events were reported by 25% of the participants, including headache, sleepiness, and dizziness. Both treatments decreased middle-of-the-night awakenings by an average of -3.1±2.3 days/week and increased total sleep time by 1.5 hours. Changes in sleep quality and insomnia severity scores were also favorable and comparable between groups: variation depended on continuation of treatment. Regarding PSG findings, sleep latency decreased more in the sublingual group than the oral group (-14±42 vs. 10±29 min; p = 0.03). The psychomotor vigilance test showed minor residual effects 30 minutes after awakening, which reversed after 2 hours. CONCLUSIONS: The safety and efficacy of both zolpidem formulations are comparable. The sublingual 5 mg dose induced sleep more rapidly. CLINICAL TRIAL REGISTRATION: NCT01896336.

Tobacco smoking and risk for dementia: evidence from the 10/66 population-based longitudinal study.

Objective: This study aimed to estimate the association between tobacco smoking and risk for dementia in seven low- and middle-income countries.Methods: Secondary analysis of the 10/66 population-based cohort study was conducted with 11,143 dementia-free individuals aged 65 years and older who were followed-up for an average of 3.8 years totalling 42,715 person-years. Cox regression with competing-risk analyses was used, controlling for age, gender, number of assets, past hazardous drinking, exercise and self-report of heart disease. Exposure was measured in packyears and smoking status. The number of packyears was calculated by multiplying the average number of packs per day by years of consumption up to 50 years old and up to age at baseline.Results: Meta-analysis of the results from each country yielded non-significant pooled relative risk ratios for all comparisons. There was no difference in risk for any dementia between 'ever smokers' compared to 'never smokers' (HR 0.96; 95% CI 0.82-1.13); 'current smokers' compared to 'never smokers' (HR 0.83; 95% CI 0.66-1.06); 'former smokers' compared to 'never smokers' (HR 1.06; 95% CI 0.88-1.27); 'current smokers' compared to 'former smokers' (HR 0.86; 95% CI 0.66-1.13). Results were similar for Alzheimer's disease (AD) and Vascular Dementia (VaD) as outcomes. Lifetime tobacco consumption (packyears) was not associated with any dementia (HR 1.00; 95% CI 0.99-1.00), nor with AD or VaD.Conclusion: Pooled results from all the countries showed no significant association between smoking and the onset of any dementia. Selective quitting in later-life might have biased the results towards no effect.

Neurocognitive function in patients with residual excessive sleepiness from obstructive sleep apnea: a prospective, controlled study.

OBJECTIVE: This study aimed to evaluate neurocognitive function in adult patients with residual excessive sleepiness (RES) after appropriate treatment of obstructive sleep apnea (OSA) with CPAP and good adherence to treatment. METHODS: This was a prospective controlled study. We included patients of both sexes, aged 35-60 years with OSA and an apnea-hypopnea index >20 ev/h, effectively treated with CPAP, but with a residual Epworth Sleepiness Scale score ≥11. The control group consisted of OSA patients adequately treated with CPAP who did not present with excessive sleepiness after treatment. Both groups underwent the following evaluations: polysomnography, multiple sleep latency testing, depression symptoms, and cognitive assessment. RESULTS: Regarding baseline characteristics, the data were matched for age, years of study, and body mass index. Long-term memory result did not show a significant difference between the two groups (RES group 4.7 ± 2.0; control group 6.5 ± 1.9; p = 0.08). The executive functions were the most affected, with alterations in Wisconsin test, number of categories (RES group: 1.6 ± 1.4; control group: 3.0 ± 1.4; p = 0.01), and semantic verbal fluency test (RES group: 13.6 ± 3.3; control group: 16.9 ± 4.3; p = 0.04). CONCLUSION: In summary, the mean depression scale score in the group with residual excessive sleepiness was significantly higher than that in the control group. Patients with residual excessive sleepiness showed impairment of executive functions but no impairments in other cognitive domains.

Effects of Zolpidem CR on Sleep and Nocturnal Ventilation in Patients with Heart Failure.

STUDY OBJECTIVE: This study aimed to evaluate the effects of zolpidem CR (controlled release) on sleep and nocturnal ventilation in patients with congestive heart failure, a population at risk for insomnia and poor sleep quality. METHODS: Fifteen patients with heart failure (ischemic cardiomyopathy) and ejection fraction ≤ 45% in NYHA functional class I or II were evaluated with full polysomnography in a placebo-controlled, double-blind, randomized trial. Patients underwent three tests: (1) baseline polysomnography and, after randomization, (2) a new test with zolpidem CR 12.5 mg or placebo, and after 1 week, (3) a new polysomnography, crossing the "medication" used. RESULTS: A 16% increase in total sleep time was found with the use of zolpidem CR and an increase in stage 3 NREM sleep (slow wave sleep). The apnea hypopnea index (AHI) did not change with zolpidem CR even after controlling for supine position; however, a slight but significant decrease was observed in lowest oxygen saturation compared with baseline and placebo conditions (83.60 ± 5.51; 84.43 ± 3.80; 80.71 ± 5.18, P = 0.002). CONCLUSION: Zolpidem CR improved sleep structure in patients with heart failure, did not change apnea hypopnea index, but slightly decreased lowest oxygen saturation.

The cholinergic system may play a role in the pathophysiology of residual excessive sleepiness in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a prevalent condition characterized by momentary cessations in breathing during sleep due to intermittent obstruction of the upper airway. OSA has been frequently associated with a number of medical comorbidities. CPAP (continuous positive airway pressure) is the gold standard treatment and is known to improve OSA symptoms, including excessive sleepiness. However, 12-14% of CPAP-treated patients continue to complain of sleepiness despite normalization of ventilation during sleep, and 6% after exclusion of other causes of EDS. This is of great concern because EDS is strongly associated with systemic health disorders, lower work performance, and a high risk of accidents. We hypothesized that decreased central cholinergic activity plays a role in the pathophysiology of residual excessive sleepiness in patients with OSA treated with CPAP. Acetylcholine (Ach) plays a large role in wakefulness physiology, and its levels are reduced in sleepiness. Herein, we discuss the potential role of the cholinergic system in this new clinical condition.