Doxepin is more effective than zolpidem in improving executive function in patients with insomnia disorder.

BACKGROUND : Insomnia disorder is associated with an impairment in cognitive performance. Doxepin and zolpidem have been found to be effective in improving sleep. In this study, we aimed to compare the effects of doxepin and zolpidem on sleep structure and executive function in patients with insomnia disorder. METHODS: Patients with primary insomnia were randomly assigned to receive doxepin 6 mg/day orally or zolpidem 5-10 mg/day orally. Polysomnography (PSG) and the Pittsburgh Sleep Quality Index (PSQI) were used at baseline and after the 8-week treatment to compare clinical efficacy in the two groups. Safety was assessed using the Treatment Emergent Symptom Scale (TESS). Executive function was evaluated using the Wisconsin sorting card test (WSCT). RESULTS: Of 120 patients enrolled in the study, 60 participants were assigned to each group. A total of 109 participants (53 in the doxepin group and 56 in the zolpidem group) completed the study. After treatment, the wake after sleep onset (WASO) and total sleep time (TST) values in the doxepin group were 80.3 ± 21.4 min and 378.9 ± 21.9 min, respectively, which were significantly better than those in the zolpidem group (132.9 ± 26.5 min and 333.2 ± 24.2 min, respectively; (P < 0.05)). The sleep onset latency (SOL) value in the zolpidem group (20.3 ± 4.7 min) was significantly better than that in the doxepin group (28.2 ± 5.6 min; P < 0.05). The sleep efficiency (SE) in the doxepin group was 77.8 ± 4.2%, which was significantly better than that in the zolpidem group (68.6 ± 5.0%; P < 0.05). The PSQI score of the doxepin group was 6.1 ± 1.1, which was significantly lower than that in the zolpidem group (7.9 ± 1.9; P < 0.05). The treatment adverse events in the doxepin group was 23.3%, which was significantly higher than that in the zolpidem group (13.3%; P < 0.05). The WSCT showed a significant improvement in persistent errors (PE), random errors (RE), and categories in the two groups after 8-week treatment, and the improvement in RE and the categories was more obvious in the doxepin group (P < 0.05). CONCLUSIONS: Both doxepin and zolpidem were found to be effective in improving sleep quality, but the effects exhibited different patterns. Doxepin improved executive function more effectively than zolpidem in patients with insomnia disorder.

The effect of temazepam on assessment of severity of obstructive sleep apnea by polysomnography.

PURPOSE: To determine the effect of temazepam on assessment of the severity of obstructive sleep apnea (OSA) by polysomnography (PSG). METHODS: Analysis of diagnostic laboratory-PSG studies was performed in OSA patients who were administered temazepam (10 mg) to facilitate sleep ("temazepam group", n = 73) and in OSA patients (matched for age, gender, body mass index and study date) in whom temazepam was not administered ("control group", n = 73). Sleep- and respiratory-related variables were compared between the groups for the (i) first 3 h of study following temazepam in the temazepam group (when peak blood concentration is expected) or following lights out in the control group, and (ii) entire study duration. RESULTS: Within the first 3 h, no differences in sleep-related variables were observed between the groups. Over the entire study duration, the temazepam group had a reduced total sleep time compared to the control group, likely due to the overnight sleep difficulties that led to its use. Whether measured during the first 3 h of study or over the entire study duration, no significant differences were detected between the groups for any respiratory-related variable, including apnea hypopnea index, arousal index, oxygen desaturation, apnea index, hypopnea index, and event duration. When patients were considered in terms of OSA severity, decreased arousal index was noted in the temazepam group over the entire study duration, but only in those with severe OSA. CONCLUSION: Oral administration of 10 mg of temazepam during the course of PSG does not systematically affect assessment of the severity of OSA by PSG.

Rasagiline improves polysomnographic sleep parameters in patients with Parkinson's disease: a double-blind, baseline-controlled trial.

BACKGROUND AND PURPOSE: The aim was to study the effects of rasagiline on sleep quality in patients with Parkinson's disease (PD) with sleep disturbances. Sleep disorders are common in PD. Rasagiline is widely used in patients with PD, but double-blind polysomnographic trials on its effects on sleep disturbances are missing. METHODS: This was a single-center, double-blind, baseline-controlled investigator-initiated clinical trial of rasagiline (1 mg/day) over 8 weeks in patients with PD with sleep disturbances. Blinding was achieved by running a strategic matched placebo parallel group. Co-primary outcome measures were the changes between baseline and end of the treatment period in sleep maintenance/efficiency as assessed by polysomnography and the Parkinson's Disease Sleep Scale Version 2 (PDSS-2) score. RESULTS: A total of 20 of 30 patients were randomized to rasagiline (mean ± SD age, 69.9 ± 6.9 years; 10 male; Hoehn-Yahr stage, 1.9 ± 0.8). Compared with baseline, sleep maintenance was significantly increased at the end of the treatment period (relative change normalized to baseline, +16.3 ± 27.9%; P = 0.024, paired two-sided t-test) and a positive trend for sleep efficiency was detected (+12.1 ± 28.6%; P = 0.097). Treatment with rasagiline led to significantly decreased wake time after sleep onset, number of arousals, percentage of light sleep and improved daytime sleepiness as measured by the Epworth Sleepiness Scale. We did not observe changes in the co-primary endpoint PDSS-2 score, and no correlations of polysomnographic sleep parameters or PDSS-2 score with motor function (Unified Parkinson's Disease Rating Scale motor score). Rasagiline was well tolerated with no unexpected adverse events. CONCLUSIONS: In patients with PD with sleep disturbances, rasagiline showed beneficial effects on sleep quality as measured by polysomnography. These effects were probably not related to motor improvement or translated into improved overall sleep quality perception by patients.

An observational clinical and video-polysomnographic study of the effects of rotigotine in sleep disorder in Parkinson's disease.

PURPOSE: Sleep disturbance is common in Parkinson's disease (PD) and negatively impacts quality of life. There is little data on how dopamine agonists influence nocturnal sleep in PD, particularly in sleep laboratory data to measure sleep parameters and their changes objectively. The goal of this open-label study was to objectively evaluate the effect of rotigotine on sleep in PD patients by video-polysomnographic methods. METHODS: A total of 25 PD patients with complaints of nocturnal sleep impairment were enrolled. The sleep quality before and after stable rotigotine therapy was evaluated subjectively through questionnaire assessments and objectively measured by video-polysomnographic methods. The Parkinsonism, depression, anxiety, and quality of life of PD patients were also evaluated through questionnaire assessments. RESULTS: At the end of rotigotine treatment, the PD daytime functioning, motor performance, depression, subjective quality of sleep, and the quality of life improved. Video-polysomnographic analysis showed that the sleep efficiency and stage N1% were increased, while the sleep latency, wake after sleep onset, and the periodic leg movements in sleep index were decreased after rotigotine treatment. CONCLUSIONS: Video-polysomnographic analysis confirmed the subjective improvement of sleep after rotigotine treatment. This observation suggests that in PD rotigotine is a treatment option for patients complaining from sleep disturbances.

Distinct Cortical Signatures Associated with Sedation and Respiratory Rate Depression by Morphine in a Pediatric Population.

BACKGROUND: Opioid analgesia is an essential component of perioperative care, but effective analgesia can be limited by excessive sedation and respiratory depression. The cortical signatures associated with sedation by opioids and the relationship between changes in cortical activity and respiratory function are not well understood. The objectives of this study were to identify the electroencephalogram signatures of sedation and respiratory changes induced by morphine in a pediatric population after elective surgery. METHODS: After otologic surgery, patients (14.8 ± 2.8 yr, n = 10) stayed overnight for pain relief with morphine (3 to 10 mg), hydration, and clinical observation. Electroencephalogram activity and polysomnography were performed before and after morphine, and electroencephalogram spectral properties and cardiorespiratory activities were analyzed. RESULTS: Compared to wakefulness and non-rapid eye movement sleep, morphine reduced high-frequency ß1 (13.5 to 20 Hz) and ß2 (20 to 30Hz) electroencephalogram powers (n = 10) and decreased coherence between frontal and occipital ß2 electroencephalogram activities (n = 9), therefore indicating that morphine induced a deep sedative state. Morphine also reduced respiratory rate by 8.3% (n = 10). Interestingly, there was a significant correlation between the reduction in ß1 electroencephalogram activity and the depression in respiratory rate induced by morphine (R = 0.715, n = 10). With significant reduction in ß1 power, respiratory rate was decreased by more than 25%, suggesting that reduction in cortical arousal is associated with the severity of respiratory rate depression. CONCLUSIONS: Analgesic doses of morphine are associated with reduction in respiratory rate when accompanied by reduction in ß1 electroencephalogram power, indicating a powerful effect of cortical arousal state per se in respiratory rate depression by morphine.

Obstructive sleep apnea in Parkinson's disease patients: effect of Sinemet CR taken at bedtime.

PURPOSE: Obstructive sleep apnea (OSA) results from upper airway (UA) obstruction. In Parkinson's disease (PD), levodopa improves UA obstruction during wakefulness. We hypothesized that bedtime controlled-release levodopa (Sinemet CR) is associated with less severe OSA (lower apnea-hypopnea index [AHI]) in PD patients. METHODS: Idiopathic PD subjects underwent nocturnal polysomnography (PSG) and were divided into those taking bedtime Sinemet CR (SinCR+) and those not taking Sinemet CR (SinCR-). Outcomes were compared between groups for PSG recordings analyzed in whole and split at their mid-point with each half analyzed separately, using linear regression. RESULTS: Fifty-seven subjects were studied, eight SinCR+, and 49 SinCR-. They were 65 % male, aged 64.4 ± 10.3 years (mean ± SD), with body mass index 27.26 ± 3.98 kg/m(2). The whole night AHI was 15.6 ± 13.3 and 29.1 ± 20.8 in SinCR+ and SinCR-, respectively (p = 0.07 unadjusted, p = 0.11 adjusted for confounders). A similar trend was observed in the first half of the night. In the second half, the SinCR+ group had significantly lower AHI (beta = -18.8; p = 0.01 adjusted) and respiratory arousal index (beta = -14.2; p = 0.02 adjusted) than the SinCR- group. CONCLUSIONS: Bedtime Sinemet CR appears to reduce OSA in PD patients. There were no significant differences between groups in the first half of the night likely because of residual effects of short-acting levodopa in both groups, while Sinemet CR had residual effect in the second half. These results possibly provide an alternative to help manage OSA and improve sleep quality in PD patients.

Can treatment with statins have a negative influence on the tolerance of mandibular advancement devices?

BACKGROUND: Statins are considered the most effective drugs used in the treatment of dyslipidemias. Some of their adverse effects are related to muscle problems. Myalgias produced by statins appear more often during exercise. Mandibular advancement devices (MAD) force the propulsory and elevatory musculature of the mandible to exercise by making the jaw move forward. The aim of this study is to evaluate the incidence of muscular side effects (referred, spontaneous, or under palpation pain, myofascial pain, mandibular rigidity and fatigue, tension and sensitivity of the masticatory muscles) in a group of patients with a diagnosis of obstructive sleep apnea being treated with MAD. METHODS: This was a prospective study, involving consecutively 104 patients with a diagnosis of OSAS, and who had begun treatment with a custom made oral device. Muscular side effects were collected by anamnesis (verbal request and questionnaires), psychological status and clinical assessment (manual muscle palpation in the masticatory and cervical muscle groups), before and during MAD treatment. RESULTS: Of the total sample, 22.1 % presented muscular side effects with the oral device. However, in patients taking statins, this percentage was 57.1 %, as opposed to 16.7 % of the non-statins patients (p < 0.001). The risk of suffering muscular alterations during oral device treatment is higher in statin patients (odds ratio 6.67, p = 0.002). CONCLUSION: Treatment with statins can give rise to the appearance of undesirable side effects among patients being treated with oral devices.

Acute improvement of pulmonary hemodynamics does not alleviate Cheyne-Stokes respiration in chronic heart failure-a randomized, controlled, double-blind, crossover trial.

OBJECTIVES: This randomized, controlled trial aimed to investigate whether acute improvement of pulmonary congestion would reduce the severity of Cheyne-Stokes respiration (CSR) in patients with chronic heart failure (CHF). METHODS: Twenty-one consecutive patients with CHF and CSR (apnea-hypopnea index [AHI] ≥15/h) underwent right heart catheterization with titration of intravenous (IV) glyceryltrinitrate (GTN) to a maximum tolerable dosage and inhalation of iloprost 10 µg/mL after a washout phase. Maximum tolerable dosages of GTN and iloprost were randomly applied during full cardiorespiratory polysomnography within two split-night procedures and compared with IV or inhaled sodium chloride (NaCl) 0.9 %, respectively. RESULTS: GTN (6.2 ± 1.5 mg/h) and iloprost significantly lowered \mean pulmonary artery pressure (20.1 ± 9.0 to 11.6 ± 4.2 mmHg, p < 0.001 and 16.9 ± 7.9 to 14.2 ± 6.4 mmHg, p < 0.01, respectively). Pulmonary capillary wedge pressure was only reduced by GTN (14.0 ± 5.6 to 7.2 ± 3.9 mmHg, p < 0.001), and there was no significant change in the cardiac index. Sleep studies revealed no significant improvement in markers of CSR severity, including AHI, central apnea index, and CSR cycle length following GTN or iloprost treatment. Significant decreases in blood pressure, mean oxygen saturation, and S3 sleep were documented during GTN infusion. CONCLUSIONS: Acute improvement of pulmonary congestion by GTN had no immediate impact on CSR severity. Future investigations must therefore include longer treatment periods and treatment regimens that have positive, rather than negative, additional effects on peripheral and central chemoreceptors and sleep structure. TRIAL REGISTRATION: German Clinical Trial Registry-ID:DRKS00000467 ( www.germanctr.de ).

Lipid profile after long-term APAP in OSA patients.

PURPOSE: This study aimed to explore the impact of an 8-year therapy with autoadjusting positive airway pressure (APAP) on fasting lipid level in a sample of Portuguese moderate/severe obstructive sleep apnea (OSA) patients. Besides contributing to the comprehension of the complex relationship between dyslipidemia and OSA, it provided new data regarding the effectiveness of a long term APAP treatment. METHODS: Thirty-nine male patients with moderate to severe OSA were included in the study. APAP was prescribed to all patients. Fifteen patients were under lipid-lowering medication throughout the study, and another 15 patients never used lipid-lowering medication at any time during the study. Fasting morning venous blood samples were collected at three time points (baseline 6 months and 8 years) and lipids were estimated. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) 21.0 software. RESULTS: After 8 years of APAP treatment, patients presented a similar body mass index but a significantly less severe daytime sleepiness. Patients on lipid-lowering medication exhibited a higher reduction in total cholesterol than those naïf from that medication, but the reduction was not statistically significant after adjusting for medication and APAP adherence. CONCLUSIONS: Long-term APAP treatment improves OSA but does not seem to contribute to changes in fasting lipids.

Impact of medications on cognitive function in obstructive sleep apnea syndrome.

PURPOSE: Medications can impact cognitive function. Obstructive sleep apnea syndrome (OSAS) is associated with cognitive impairment. There is currently a paucity of data evaluating the impact of medications on sleep architecture and cognition in untreated OSAS. Our objective was to evaluate the impact of obstructive sleep apnea syndrome (OSAS) and medications on cognition by a screening questionnaire called the Mail-In Cognitive Function Screening Instrument (MCFSI). METHODS: We conducted a retrospective chart review on consecutive adults (age > 18 years) with OSAS seen in Medical University of South Carolina Sleep Clinic between January 1, 2012 and May 8, 2013, for whom the Mail-In Cognitive Function Screening Instrument (MCFSI) score was available and who were not on continuous positive airway pressure (CPAP). The correlation between different medications, sleep study variables, and MCFSI scores was studied. RESULTS: Univariate analysis revealed that many medications had significant correlations with MCFSI scores, including antidepressants (p = 0.05), antipsychotics (p = 0.01), anxiolytics (p = 0.005), statins (p = 0.077) and narcotics (p = 0.006). The mean percentage of rapid eye movement (REM) sleep (p = 0.04) and Epworth Sleepiness Scale (p = 0.01) were also significantly correlated with MCFSI scores. Multivariate analysis revealed that Epworth Sleepiness Scale and use of antipsychotics, narcotics, and anxiolytics correlated with higher MCFSI scores (worse cognition) and conversely that statin use was associated with improved cognition. CONCLUSIONS: Medications have a significant impact on cognitive function in OSAS. Thus, medication use should be considered in future studies of cognitive function in patients with OSAS.

Zopiclone effects on breathing at sleep in stable chronic obstructive pulmonary disease.

PURPOSE: More than half of patients with chronic obstructive pulmonary disease (COPD) experiences sleep-related problems and about one fourth uses hypnotics regularly. We explored what the effect zopiclone, a commonly used hypnotic, had on nocturnal gas exchange and the apnea/hypopnea frequency in stable COPD. METHODS: Randomized crossover study of 31 (ten males) inpatients at a pulmonary rehabilitation hospital, median age 64 years, of which 20 had a forced expiratory volume first second <50% of predicted. Subjects investigated in randomized order of either baseline sleep or intervention with 5 mg zopiclone by polysomnography including transcutaneous measurement of carbon dioxide pressure increased (ΔPtcCO2). RESULTS: Zopiclone increased the mean ΔPtcCO2 from baseline both in rapid eye movement (REM) sleep, non-REM sleep, and even in stage N0 (awake after sleep onset) with a mean (SD) of 0.25 (0.40) kPa, 0.22 (0.32) kPa, and 0.14 (0.27) kPa, respectively. Subjects with sleep hypoventilation as defined by the American Academy of Sleep Medicine increased from 6 subjects (19%) to 13 subjects (42%) (P = 0.020). REM sleep minimum oxygen saturation (minSpO2) did not change significantly from baseline median (interquartile range [IQR]) minSpO2 81.8 (12.1) % to zopiclone sleep median (IQR) minSpO2 80.0 (12.0) % (P = 0.766). Interestingly, zopiclone reduced the number of apneas/hypopneas per hour (AHI) in subjects with overlap (AHI ≥ 15) with a median difference (IQR) of -8.5 (7.8) (N = 11, P = 0.016). CONCLUSIONS: In stable COPD, zopiclone moderately increases the mean ΔPtcCO2 without changing minSpO2 at night and reduces AHI in overlap (COPD and obstructive sleep apnea) subjects.

Alcohol at bedtime induces minor changes in sleep stages and blood gases in stable chronic obstructive pulmonary disease.

PURPOSE/BACKGROUND: The purpose of this study is to explore the effect of a moderate dose of alcohol on sleep architecture and respiration in chronic obstructive pulmonary disease (COPD). Alcohol depresses both hypercapnic and hypoxic ventilatory drives in awake, normal individuals and reduces the amount of rapid eye movement (REM) sleep and oxygen saturation (SpO2) in sleeping COPD subjects. METHODS: Prospectively designed, open-label interventional study in a pulmonary rehabilitation hospital. Twenty-six (nine males) stable inpatients, median forced expiratory volume first second (FEV1) 40.5 % of predicted, median age 65 years, investigated by polysomnography including transcutaneous measurement of carbon dioxide pressure increase (ΔPtcCO2) in randomized order of either control sleep or intervention with 0.5 g of ethanol/kilogram bodyweight, taken orally immediately before lights off. RESULTS: Alcohol induced a mean increase (95 % confidence interval, [CI]) in the mean ΔPtcCO2 of 0.10 kPa (0.002-0.206, P = 0.047) and a mean decrease (CI) in the REM-sleep percentage of total sleep time (REM % of TST) of 3.1 % (0.2-6.0), (P = 0.020). Six subjects with apnea/hypopnea index (AHI) ≥15 had fewer apneas/hypopneas during alcohol versus control sleep (mean reduction of AHI 11 (1-20), P = 0.046). Alcohol-sleep changes in SpO2, but not in ΔPtcCO2, correlated with daytime arterial pressures of carbon dioxide (PaCO2) and oxygen (PaO2). CONCLUSION: Occasional use of a moderate, bedtime dose of alcohol has only minor respiratory depressant effects on the majority of COPD subjects, and in a minority even slightly improves respiration during sleep. However, caution is appropriate as this study is small and higher doses of alcohol may result in major respiratory depressive and additional negative health effects.

Home-use servo-ventilation therapy in chronic pain patients with central sleep apnea: initial and 3-month follow-up.

PURPOSE: Opioid treatment of non-malignant chronic pain can result in hypoxemia, hypercarbia, and central sleep apnea. The aim of this study was to determine the initial efficacy of auto servo-ventilation (ASV) and after 3 months of home use. METHODS: This prospective multicenter interventional study recruited chronic pain patients prescribed ≥100 morphine equivalents for at least 4 months. PARTICIPANTS: Following full-night polysomnography (PSG) to confirm the presence of sleep-disordered breathing, patients were randomized to three additional full-night-attended PSGs with continuous positive airway pressure (CPAP), ASV, and servo-ventilation with an initial mandatory pressure support of 6 cm H2O (ASV manual PSmin 6). Following the PSGs, patients were sent home with EncoreAnywhere and ASV with or without mandatory pressure support. RESULTS: Based on the initial PSG studies, CPAP improved but did not normalize the apnea-hypopnea index (AHI), central apnea index (CAI), or hypopnea index (HI), as all remained elevated. Clinically significant reductions were noted after just one night of ASV and ASV manual (PSmin 6). After 3 months of ASV home use, the AHI, CAI, and obstructive apnea index (OAI) were significantly reduced when compared to baseline diagnostic levels and even when compared to respiratory disturbance indices with CPAP treatment. CONCLUSIONS: Initial and home use of ASV for 3 months resulted in significantly lower AHI, CAI, and OAI. This reduction attests to the efficacy of ASV treatment in chronic pain patients on high doses of opioids.

Effect of sertraline on breathing in depressed patients without moderate-to-severe sleep-related breathing disorders.

BACKGROUND: Previous studies have reported that selective serotonin reuptake inhibitors (SSRIs) might improve sleep-related breathing disorders (SRBDs). However, the effects of SSRIs on breathing are not evaluated in subjects without moderate-to-severe SRBDs. Further, many symptoms of depression and SRBDs overlap, and so, it is interesting whether there are interactions between breathing and psychopathologic symptoms during SSRI treatment for depression. METHODS: Data were taken from an open-label 8-week trial of sertraline in depressed patients with insomnia (n = 31). The depressed patients were administered 50 mg sertraline at 8 AM on the first day, and the dosage was subsequently titrated up to a maximum of 200 mg/day during the 8-week trial. All the patients were tested by repeated polysomnography (PSG) (baseline, 1st day, 14th day, 28th day, and 56th day). Sleep-disordered breathing events were categorized as apneas, hypopneas, and respiratory event-related arousals (RERAs). RESULTS: The clinical responses and PSG characteristics improved continuously during the 8-week trial. From the 14th day on, the RERA index during all-night and non-rapid eye movement (NREM) sleep became stable and significantly higher than baseline and the first day (RERA index 7.3 ± 2.2 at baseline, 7.3 ± 2.5 on the 1st day, 4.4 ± 1.9 on the 14th day, 3.9 ± 1.3 on the 28th day, 4.2 ± 2.0 on the 56th day, F = 5.71, P = 0.02; NREM-RERA index 6.2 ± 2.0 at baseline, 6.3 ± 2.3 on the 1st day, 3.2 ± 1.5 on the 14th day, 3.5 ± 0.9 on the 28th day, 3.2 ± 1.7 on the 56th day, F = 4.92, P = 0.03). Additionally, the NREM-apnea index showed a similar pattern to that of the RERA index and reached a significant difference between baseline (1.0 ± 0.5) and the 14th day (0.5 ± 0.4) (KW = 4.28, P = 0.047). Compared to the no-improvement group, the improvement group with a decreasing score rate of the respiratory disturbance index (RDI) greater than or equal to -50 % had a more positive decreasing score rate of slow wave sleep (SWS) (439.0 ± 78.2 vs 373.2 ± 77.9 %, T = 3.46, P = 0.04) and a more negative decreasing score rate on the arousal index (-43.7 ± 16.7 vs -26.6 ± 9.7 %, T = 9.16, P = 0.01), Pittsburgh Sleep Quality Index (PSQI) scores (-65.1 ± 33.7 vs -49.6 ± 21.4 %, T = 4.74, P = 0.05), and Epworth Sleepiness Scale (ESS) scores (-55.7 ± 21.3 vs -36.4 ± 17.5 %, T = 6.44, P = 0.02). DISCUSSION: This research indicates that SRBDs could be improved to some extent by sertraline treatment, which might be more common in patients with relatively more severe sleep-disordered breathing (e.g., RDI ≥ 10 in the current study). Although the sertraline-induced SRBD improvement seems not to have a significant clinical effect, the SRBD improvement group with decreasing score rate of RDI greater than or equal to -50 % has better subjective and objective sleep aspects than the no-improvement group. Thus, the fact that the SRBDs' improvement was related to SSRIs might have a potential clinical benefit in the antidepressant treatment.

The effect of nightly nasal CPAP treatment on nocturnal hypoxemia and sleep disorders in mustard gas-injured patients.

INTRODUCTION: Sleep-related breathing disorders are associated with unusual respiratory pattern or an abnormal reduction in gas exchange during sleep that is common in sulfur mustard (SM) exposure. METHODS: We compared 57 Iranian male patients injured with SM and had any complaints of sleep problems with an age-matched group of 21 Iranian male patients who had complaints of sleep problems and were not chemically injured; this group had Epworth Sleepiness Scale (ESS) above 10 and whom referred for polysomnography. Split-night studies were performed for patients with diagnostic polysomnography for obstructive sleep apnea (OSA) and respiratory events. We then studied respiratory events including episodes of OSA, apnea-hypopnea index (AHI) and respiratory disturbance index (RDI). RESULTS: The mean age in mustard-exposed patients was 48.14±8.04 years and in age-matched group, 48.19±8.39 years. In mustard exposed patients, there were statistical differences for the episodes of OSA (p=0.001), AHI (p=0.001), and RDI (p=0.001) between two segments of split-night studies. In the age-matched group, there were statistically differences for each parameter (episodes of OSA (p=0.001), AHI (p=0.001), and RDI (p=0.001)). There were no significant differences between two groups. CONCLUSION: This study indicated that the incidence of respiratory events and nocturnal hypoxemia during sleep in mustard-exposed patients were high and treatment with CPAP significantly reduced all these events.

Positive airway pressure therapy in patients with opioid-related central sleep apnea.

PURPOSE: This study aims to compare treatment response and adherence rate to positive airway pressure (PAP) in patients with opioid-related central sleep apnea (O-CSA) and idiopathic central sleep apnea (I-CSA). METHODS: We performed a retrospective chart over a 5-year period performed at a VA sleep center. Continuous PAP (CPAP) was prescribed initially for all participants. For those nonresponders (apnea hypopnea index (AHI) of >10/h), bi-level PAP (BiPAP) or adaptive servoventilation (ASV) was instituted upon provider's discretion. Adherence to therapy was checked with the built-in meter. RESULTS: Thirty-four patients with O-CSA and 61 with I-CSA were included in the analysis. The two groups were comparable with respect to age, body mass index (BMI), Epworth Sleepiness Scale, and burden of comorbidities. The mean daily equivalent dose of morphine in the O-CSA was 168 mg (range 30-1,217 mg). In the O-CSA group, 24% of PAP-naïve patients responded to CPAP compared to 38% in the I-CSA group. BiPAP and ASV were comparable in eliminating central events in both O-CSA (66 versus 60 %) and I-CSA (93 versus 90%), respectively. Eight patients (24%) with O-CSA and six patients (10%) with I-CSA were considered nonresponders. The adherence rate was 48 and 24% in the I-CSA group compared to 23 and 18% in the O-CSA group at 3 and 12 months following initiation of effective treatment (p = 0.04 and p = 0.6). CONCLUSIONS: The presence of O-CSA does not preclude an adequate response to CPAP. Adherence rate to PAP was poor in both the O-CSA and I-CSA groups. Further studies are needed to define optimal adherence rate and long-term benefits of PAP in CSA.

The timing between REM sleep behavior disorder and Parkinson's disease.

PURPOSE: In Parkinson's disease (PD) patients, REM sleep behavior disorder (RBD) might precede PD or develop with or after the onset of PD. No previous study has explored differences between these two groups. The aim of this study was therefore to compare clinical features and REM sleep chin electromyographic patterns between patients in whom RBD heralded PD and those in whom RBD occurrence coincided with or followed the clinical manifestations of PD. METHOD: Twenty-seven consecutive PD patients (mean age 67.9 years) were enrolled. Detailed clinical, laboratory, and polysomnographic studies were obtained in all participants. RESULTS: Sixteen of the 27 patients were affected by RBD. These had a significantly higher stage of PD and took significantly higher doses of dopaminergic therapy; their disease duration tended to be longer, and their cognitive status tended to be lower. PD patients in whom RBD preceded PD (n = 6) did not differ from PD patients without RBD in disease parameters, while PD patients in whom RBD developed with or after PD (n = 10) showed a significantly higher disease stage, took significantly higher dopaminergic therapy, and had a longer disease duration. CONCLUSION: Our findings are compatible with the hypothesis that patients in whom RBD precedes, or does not precede, PD might constitute two possibly distinct clinical and physiopathological groups, based on different progressive neuropathological sequences of events.

Treatment of REM sleep behavior disorder with trazodone: report of 3 cases.

Rapid eye movement sleep behavior disorder is a sleep disturbance characterized by the absence of regular paralysis during rapid eye movement sleep, accompanied by dream enactment behavior. The available pharmacotherapy options for treating rapid eye movement sleep behavior disorder are limited, and the utilization of antidepressants has yielded mixed results. We report 3 cases of isolated rapid eye movement sleep behavior disorder improved with trazodone. Doses of 50-100 mg of trazodone at bedtime over 4-6 months resulted in significant clinical improvement. These cases highlight that trazodone could serve as a treatment for isolated rapid eye movement sleep behavior disorder that does not respond to traditional treatments at submaximal dosages. CITATION: Barrow J, Vendrame M. Treatment of REM sleep behavior disorder with trazodone: report of 3 cases. J Clin Sleep Med. 2024;20(5):821-823.

Medication-induced central sleep apnea: a unifying concept.

Medication-induced central sleep apnea (CSA) is one of the eight categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioid medications including sodium oxybate, baclofen, valproic acid, gabapentin, and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid, and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.