Effect of single-administration of D-sorbitol pretreatment on the bitterness and continued willingness to take asenapine: a randomized, single-blind, placebo-controlled, crossover trial.

BACKGROUND: Asenapine has unique orally-related side effects, such as a bitter taste induced by sublingual administration, which often results in discontinuation of the medication. While the FDA has approved black-cherry-flavored asenapine, several countries have prescribed only unflavored versions. Specifically, Asians commonly report experiencing the bitterness of asenapine because they are more sensitive to bitter tastes than other ethnic groups. In this study, with the aim of improving adherence by reducing the bitterness of asenapine, we investigated the effects of D-sorbitol, which reduced the bitterness parameters of taste sensors in our previous basic study on the bitterness and continuity of asenapine among patients with schizophrenia. METHODS: Twenty adult patients with schizophrenia were included in this single-blind, placebo-controlled, crossover trial. Participants rinsed their mouths with single-administration of D-sorbitol or a placebo prior to each administration of asenapine. We then conducted the questionnaires and assessed changes in the bitterness of asenapine (primary end point) and willingness to continue its use (secondary end point). RESULTS: D-sorbitol significantly improved the bitterness of asenapine (p = 0.038). Although it did not significantly increase the willingness to continue asenapine (p = 0.180), it did show improvement over the placebo in enhancing willingness to continue, especially in patients who were not accustomed to its taste. CONCLUSION: Our findings indicate that single-administration of D-sorbitol significantly reduces the bitterness of asenapine. In countries where flavored asenapine is not available, this finding could benefit patients who were not accustomed to its bitter taste. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (jRCTs041210019) on May 14, 2021.

Sensory evaluation of the bitterness of asenapine using D-sorbitol pretreatment: single-blind, placebo-controlled, crossover trial.

BACKGROUND: Antipsychotics are essential in the acute treatment of and maintenance therapy for schizophrenia, but medication adherence and long-term treatment continuity are needed to maximize their effectiveness. Each antipsychotic has various side effects, which may affect adherence. Some patients with schizophrenia are reluctant to take asenapine because of its unique oral-related side effects, such as the bitter taste caused by sublingual administration. Our previous basic research found that D-sorbitol lowered the bitterness parameters of the taste sensors. However, whether D-sorbitol has the same effect in patients remains unclear. Therefore, using a D-sorbitol solution, we aim to evaluate changes in the bitterness of asenapine among patients with schizophrenia. METHODS: In this single-blind, placebo-controlled, crossover trial, we plan to recruit 20 adult patients with schizophrenia spectrum disorder who take sublingual asenapine tablets. The participants will be divided into two groups (n = 10 each). Each group will be given a D-sorbitol or placebo solution on the first day for rinsing before taking the sublingual asenapine tablets. After a 1-day interval, the participants will rinse their mouths again with a different liquid. Questionnaires regarding changes in taste and the willingness to continue asenapine will be conducted before the start of the study and after each rinse. The primary and secondary end points will be a taste evaluation of bitterness, and the willingness to continue asenapine, respectively. Differences in questionnaire scores between the D-sorbitol and placebo solutions will be calculated and analyzed using a McNemar test. DISCUSSION: This study aims to determine the efficacy of D-sorbitol in masking the bitter taste of asenapine. To our knowledge, it is the first intervention study using D-sorbitol for bitter taste of asenapine in patients with schizophrenia. Evidence of the efficacy of D-sorbitol could result in D-sorbitol pretreatment being an easy and inexpensive means of improving adherence to asenapine. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials jRCTs041210019, on May 14, 2021. Ethics approval was obtained from the Nagoya University Clinical Research Review Board.

Comparison of Polysomnography, Single-Channel Electroencephalogram, Fitbit, and Sleep Logs in Patients With Psychiatric Disorders: Cross-Sectional Study.

BACKGROUND: Sleep disturbances are core symptoms of psychiatric disorders. Although various sleep measures have been developed to assess sleep patterns and quality of sleep, the concordance of these measures in patients with psychiatric disorders remains relatively elusive. OBJECTIVE: This study aims to examine the degree of agreement among 3 sleep recording methods and the consistency between subjective and objective sleep measures, with a specific focus on recently developed devices in a population of individuals with psychiatric disorders. METHODS: We analyzed 62 participants for this cross-sectional study, all having data for polysomnography (PSG), Zmachine, Fitbit, and sleep logs. Participants completed questionnaires on their symptoms and estimated sleep duration the morning after the overnight sleep assessment. The interclass correlation coefficients (ICCs) were calculated to evaluate the consistency between sleep parameters obtained from each instrument. Additionally, Bland-Altman plots were used to visually show differences and limits of agreement for sleep parameters measured by PSG, Zmachine, Fitbit, and sleep logs. RESULTS: The findings indicated a moderate agreement between PSG and Zmachine data for total sleep time (ICC=0.46; P<.001), wake after sleep onset (ICC=0.39; P=.002), and sleep efficiency (ICC=0.40; P=.006). In contrast, Fitbit demonstrated notable disagreement with PSG (total sleep time: ICC=0.08; wake after sleep onset: ICC=0.18; sleep efficiency: ICC=0.10) and exhibited particularly large discrepancies from the sleep logs (total sleep time: ICC=-0.01; wake after sleep onset: ICC=0.05; sleep efficiency: ICC=-0.02). Furthermore, subjective and objective concordance among PSG, Zmachine, and sleep logs appeared to be influenced by the severity of the depressive symptoms and obstructive sleep apnea, while these associations were not observed between the Fitbit and other sleep instruments. CONCLUSIONS: Our study results suggest that Fitbit accuracy is reduced in the presence of comorbid clinical symptoms. Although user-friendly, Fitbit has limitations that should be considered when assessing sleep in patients with psychiatric disorders.

Duloxetine attenuates pain in association with downregulation of platelet serotonin transporter in patients with burning mouth syndrome and atypical odontalgia.

OBJECTIVE: The aim of this study was evaluation of the association between severity of pain and expression of total or ubiquitinated serotonin transporter (SERT) protein in patients with burning mouth syndrome and atypical odontalgia (BMS/AO), who were treated by duloxetine. METHODS: Patients with BMS/AO were assessed for severity of pain using the visual analog scale (VAS), and expression of total and ubiquitinated SERT protein in platelets before (baseline) and 12 weeks after duloxetine-treatment. RESULTS: The expression of total and ubiquitinated SERT protein at baseline in all patients (n = 33) were higher and lower, respectively, compared to those in healthy controls. 12 weeks after duloxetine-treatment, there was no difference in the total SERT protein levels between patients (n = 21) and healthy controls. In the 16 patients who could be measured, mean VAS scores and total SERT protein levels were significantly decreased after the treatment, compared to those at baseline. There was tendency for a positive correlation between total SERT protein levels and VAS scores in these patients. CONCLUSIONS: Our findings indicate that duloxetine relieves pain in association with downregulation of platelet SERT expression in patients with BMS/AO.

Prevalence of obstructive sleep apnea as assessed by polysomnography in psychiatric patients with sleep-related problems.

PURPOSE: Patients with psychiatric disorders often complain of sleep disturbances and are frequently suspected of obstructive sleep apnea (OSA). However, data regarding sleep problems evaluated by attended polysomnography (PSG) remain limited in this population. We analyzed the results of attended PSG from psychiatric patients with sleep-related problems to determine the prevalence and features of sleep disorders among this population. METHODS: We retrospectively investigated the attended PSG results of patients with psychiatric disorders: major depressive disorder, bipolar disorder, neurodevelopmental disorder, schizophrenia, neurocognitive disorder, anxiety disorder, somatic symptom disorder. RESULTS: Of 264 patients, 158 men (60%), mean age was 47 ± 19.9 years. More than half of the patients with major depressive disorder (62%), bipolar disorder (70%), schizophrenia (58%), neurocognitive disorders (55%), and somatic symptom disorder (56%) had OSA. Among the psychiatric patients with OSA, 62% of these patients had moderate to severe OSA. The risk factors for OSA were snoring, male, age, and body mass index. The presence of OSA was not associated with the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale score, or benzodiazepine, antipsychotic, or antidepressant use. Other sleep disorders were insomnia (19%), central disorders of hypersomnia (8%), restless legs syndrome/periodic limb movement of sleep (8%), rapid eye movement sleep behavior disorder (7%), and central sleep apnea syndrome (3%). CONCLUSIONS: PSG revealed that moderate to severe OSA was common in psychiatric patients with or without snoring. Subjective symptoms and psychotropics did not predict OSA. Therefore, PSG is needed to reveal sleep conditions in patients with psychiatric disorders.

Driving performance of euthymic outpatients with bipolar disorder undergoing real-world pharmacotherapy.

OBJECTIVE: Medications for the treatment of bipolar disorder (BD) could affect patients' cognitive function. Patients with BD present with neurocognitive impairment even in a remission state. Little research is available on the daily functioning, especially driving performance, of stable outpatients with BD under pharmacological treatment. METHODS: In total, 58 euthymic outpatients with BD undergoing real-world pharmacotherapy and 80 sex- and age-matched healthy controls (HCs) were enrolled. Three driving tasks using a driving simulator-road-tracking, car-following, and harsh-braking-and three cognitive tasks-Continuous Performance Test, Wisconsin Card Sorting Test, and Trail-Making Test-were evaluated. Symptom assessment scales-Young Mania Rating Scale, Structured Interview Guide for the Hamilton Depression Rating Scale, Beck Depression Inventory-II, Social Adaptation Self-evaluation Scale, and Stanford Sleepiness Scale-were also completed. RESULTS: Car-following and road-tracking performance were significantly impaired in patients with BD compared with HCs after adjusting for demographic variables, but these performances generally overlapped. Broad neurocognitive functions were significantly lower in the patients with BD compared to HCs, but car-following performance was significantly negatively correlated with sustained attention only. Although most patients received multiple medications rather than monotherapy, no relationship between prescriptions and driving performance was found. CONCLUSION: Euthymic patients with BD under steady-state pharmacotherapy had impaired driving performance compared with HCs, but the overlapping distributions of driving performance suggested that driving performance is not always deteriorated in patients with BD. Therefore, attentional function may be a useful clinical feature for judging driving aptitude in patients with BD.

Performance of an ambulatory electroencephalogram sleep monitor in patients with psychiatric disorders.

Key clinical symptoms observed among individuals with psychiatric disorders include difficulty falling asleep or maintaining sleep, poor sleep quality and nightmares. Those suffering from sleep disorders often present with symptoms of discontent with regard to sleep quality, timing and quantity, and these symptoms have an adverse impact on function and quality of life. A minimally invasive technique would be preferable in patients with psychiatric disorders, who tend to be sensitive to environmental change. Accordingly, we evaluated the performance of Zmachine Insight Plus, an ambulatory electroencephalography sleep monitor, in patients with psychiatric disorders. One hundred and three patients undergoing polysomnography were enrolled in this study. Zmachine Insight Plus was performed simultaneously with polysomnography. Total sleep time, sleep efficiency, wake after sleep onset, rapid eye movement (REM) sleep, light sleep (stages N1 and N2) and deep sleep (stage N3) were assessed. Total sleep time, sleep efficiency, wake after sleep onset, REM sleep duration and non-REM sleep duration of Zmachine Insight Plus showed a significant correlation with those of polysomnography. Lower sleep efficiency and increased frequency of waking after sleep onset, the arousal index and the apnea-hypopnea index on polysomnography were significantly associated with the difference in sleep parameters between the two methods. Among patients with psychiatric disorders who are sensitive to environmental change, Zmachine Insight Plus would be a useful technique to objectively evaluate sleep quality.

Patient characteristics affecting accurate detection of sleep apnea using a bed sheet-type portable monitor.

PURPOSE: Although performed inside a laboratory, attended polysomnography (PSG) has long been the gold standard for the diagnosis of sleep apnea. However, high costs and long wait times have led to the development of home-based portable monitoring devices. A bed sheet-shaped device called SD102 (Suzuken Co., Nagoya, Japan) has been developed, and its accuracy in evaluating sleep apnea is becoming evident. The purpose of this study was to confirm the accuracy of SD102 in evaluating sleep apnea and to investigate patient characteristics that may contribute to inaccurate test results in patients with suspected obstructive sleep apnea (OSA). METHODS: One hundred and eighty-nine patients simultaneously underwent PSG and portable monitoring by using a home sleep apnea testing (HSAT) device. A blinded, experienced technologist using the American Academy of Sleep Medicine criteria versions 2.1 and 2.3 scored the PSG data and HSAT device data, respectively. RESULTS: The respiratory event index (REI) by HSAT significantly correlated with the apnea-hypopnea index (AHI) by PSG (r = 0.974, p < 0.001). HSAT sensitivity, specificity, and positive and negative predictive values of 0.99, 0.83, 0.95, and 0.97, respectively. Body mass index and arousal index were significantly associated with the difference between REI from SD102 HSAT and AHI from PSG. CONCLUSIONS: This study demonstrates the good agreement between REI and AHI in patients with suspected OSA and suggests that understanding the limitations of different testing methods may help in the accurate detection of OSA.

Effects of sleep-disordered breathing and hypertension on cognitive function in elderly adults.

Purpose: The prevalence of sleep-disordered breathing (SDB) increases with aging. SDB is a risk of hypertension, and both might lead to cognitive decline. However, the role of SDB and hypertension on the pathogenesis of age-related cognitive decline remains unclear. We examined the effects of these two diseases on cognitive function in elderly adults.Methods: Fifty-two elderly individuals (mean age, 69.6 ± 4.0 years) free from impairment in daily living activities participated in this study. Apnea/hypopnea index (AHI) and minimum oxygen saturation (SpO2) were assessed using a portable home monitoring device. We evaluated excessive daytime sleepiness with the Epworth sleepiness scale (ESS). Cognitive performance was assessed using the Wisconsin card sorting test (WCST), continuous performance test-Identical pairs (CPT-IP), and N-back task. Hypertension and diabetes mellitus were evaluated via questionnaire and blood pressure value.Results: The WCST category achievement was significantly lower in participants with minimum SpO2 <90% than those with minimum SpO2 ≥90%. The percentage of correct answer on the 0- and 1-back tasks was significantly lower in the hypertensives than normotensives. Minimum SpO2 was correlated with category achievement on the WCST. Multiple regression analysis including age, sex, body mass index, AHI, minimum SpO2, ESS, hypertension, and diabetes mellitus revealed that hypertension was the most significant factor for percentage correct answers on the 0- and 1-back tasks. There were no significant correlations between body mass index, ESS or diabetes mellitus and the parameters of WCST, CPT-IP, or N-back tasks.Conclusion: In elderly adults, nocturnal hypoxia and hypertension had a negative effect on cognitive function.

Clinical profiles of late-onset psychiatric patients exhibiting incidental REM sleep without atonia.

Rapid eye movement (REM) sleep without atonia (RWA), which is a hallmark of REM sleep behavior disorder (RBD) on polysomnography (PSG), may represent specific characteristics of prodromal Parkinson's disease (PD)/dementia with Lewy bodies (DLB), even when dream-enactment behavior is absent. We investigated the clinical profiles associated with PD/DLB in late-onset psychiatric patients exhibiting incidental RWA. Among patients who underwent PSG in our psychiatric ward, eight with incidental RWA, nine with idiopathic RBD, and seven with PD or DLB who had preceding RBD were included. Clinical variables, including the percentage of RWA in the total REM sleep (%RWA), were compared among the three groups. The frequency of depressive disorders as a primary psychiatric diagnosis and antidepressant usage were significantly higher in the incidental RWA group than in the other groups. There were no differences in the prevalence of supportive features of DLB among the three groups. The median %RWA was significantly lower in the incidental RWA group than in the other groups. Although the cardiac 123I-metaiodobenzylguanidine uptake was significantly higher in the incidental RWA group compared with the other groups, the groups showed overlap in the specific binding ratios on dopamine transporter imaging. All patients in the three groups exhibited cingulate island sign ratios on brain perfusion single-photon emission computed tomography within a threshold of 0.281, which is the optimal cut-off value for a diagnosis of DLB. In this series, late-onset psychiatric patients with incidental RWA partially shared common clinical profiles with idiopathic RBD and PD/DLB.

Improvement of psychiatrists' clinical knowledge of the treatment guidelines for schizophrenia and major depressive disorders using the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' project: A nationwide dissemination, education, and evaluation study.

AIM: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the 'Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)' integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. METHODS: Four hundred thirteen out of 461 psychiatrists attended two 1-day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants' clinical knowledge of the treatment guidelines using self-completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants' demographics and their clinical knowledge scores. RESULTS: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. CONCLUSION: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants' clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders.

Effects of hypnotics on prefrontal cortex activity during a verbal fluency task in healthy male subjects: A near-infrared spectroscopy study.

OBJECTIVE: To assess the effects of hypnotics on prefrontal cortex activity in healthy subjects using near-infrared spectroscopy (NIRS) in a double-blind, placebo-controlled crossover trial. METHODS: Eighteen healthy males received acute doses of ramelteon (8 mg), triazolam (0.125 mg), or placebo in a predetermined randomization schedule, with a washout period of more than 1 week. All subjects performed a verbal fluency task during NIRS assessments at baseline and at 1 and 4 hr post-dose. The number of words correctly generated during the task (behavioral performance) and scores on the Stanford Sleepiness Scale (SSS) were also recorded at each test time. RESULTS: Compared with the placebo, triazolam (0.125 mg) significantly decreased oxyhemoglobin (oxy-Hb) concentration change in NIRS during the posttask period and significantly increased behavioral performance, whereas triazolam (0.125 mg) and ramelteon (8 mg) significantly increased SSS scores. CONCLUSIONS: The differential effects of two types of hypnotics on oxy-Hb change measured by NIRS were observed in acute dosing, suggesting that when assessing brain activity of patients with psychiatric disorders, researchers should consider how certain types of hypnotics can influence brain function. This would also provide useful information to clinicians when prescribing hypnotics suitable for their patients' conditions.

Evaluation method regarding the effect of psychotropic drugs on driving performance: A literature review.

Although automobile driving is necessary for many people, including patients with mental disorders, the influence of psychotropic drugs on driving performance remains unclear and requires scientific verification. Therefore, the objective of this study was to conduct a review of the literature in order to aid the development of a valid evaluation method regarding the influence of medication on driving performance. We conducted a literature search using two sets of terms on PubMed. One set was related to psychotropic drugs, and the other to driving tests. We excluded reviews and case studies and added literature found on other sites. A total of 121 relevant reports were found. The experiments were roughly divided into on-the-road tests (ORT) and driving simulators (DS). Although highway driving tests in ORT are most often used to evaluate driving performance, DS are becoming increasingly common because of their safety and low cost. The validity of evaluation methods for alcohol should be verified; however, we found that there were few validated tests, especially for DS. The scenarios and measurement indices of each DS were different, which makes it difficult to compare the results of DS studies directly. No evaluation indices, except for SD of lateral position, were sufficiently validated. Although highway ORT are the gold standard, DS were shown to have an increasing role in evaluating driving performance. The reliability of DS needs to be established, as does their validation with alcohol in order to accumulate more high-quality evidence.

Early diagnosis of Lewy body disease in patients with late-onset psychiatric disorders using clinical history of rapid eye movement sleep behavior disorder and [123 I]-metaiodobenzylguanidine cardiac scintigraphy.

AIM: Rapid eye movement sleep behavior disorder (RBD) and psychiatric symptoms often antedate the clinical diagnosis of Parkinson's disease or dementia with Lewy bodies. The purpose of this study was to investigate RBD and its relevance to Lewy body disease (LBD) in patients with late-onset psychiatric disorders. METHODS: Study subjects included 19 patients with late-onset psychiatric disorders who exhibited REM sleep without atonia (RWA), which is a hallmark of RBD on polysomnography, at our psychiatric ward. Clinical profiles and radiological findings by cardiac [123 I]-metaiodobenzylguanidine ([123 I]-MIBG) scintigraphy and imaging for the dopamine transporter (DAT) were compared between patients with and without RBD symptoms. The correlations between the percentage of RWA in the total rapid eye movement sleep (%RWA) and radiological findings were also investigated. RESULTS: Nine patients reported RBD symptoms only on specific questioning, but clinical profiles, including the prevalence of antipsychotropic usage, did not differ when compared to the remaining 10 patients without RBD (incidental RWA group). The median %RWA was significantly higher in the definite RBD group than in the incidental RWA group. Although the cardiac [123 I]-MIBG uptake was significantly lower in the definite RBD group than in the incidental RWA group, there was overlap in the specific binding ratio on DAT scan. CONCLUSION: The severity of %RWA was highly correlated with the value of cardiac [123 I]-MIBG uptake, but not with specific binding ratio on DAT scan. Clinical history of RBD and cardiac [123 I]-MIBG scintigraphy are helpful for an early differential diagnosis of LBD from late-onset psychiatric disorders, even before parkinsonism or dementia appears.

Driving performance of stable outpatients with depression undergoing real-world treatment.

AIM: Although the effects of psychotropics on driving ability have received much attention, little research is available on driving performance of stable outpatients with depression undergoing real-world treatment. This observational study investigated driving performance, cognitive functions, and depressive symptomatology of partly remitted outpatients with depression under daily-practice psychopharmacologic treatment. METHODS: Seventy stable outpatients with depression and 67 healthy volunteers were enrolled. Patients' prescriptions were not controlled in order to capture the real-world treatment environment. Participants underwent three driving tasks - road-tracking, car-following, and harsh-braking - using a driving simulator, and three cognitive tasks - Continuous Performance Test, Wisconsin Card Sorting Test, and Trail-Making Test. The Symptom Assessment Scale - Structured Interview Guide for the Hamilton Depression Rating Scale, Beck Depression Inventory-II, Social Adaptation Self-Evaluation Scale, and Stanford Sleepiness Scale were also completed. RESULTS: Although many patients received various pharmacologic treatments, there were no significant differences in the three driving tasks between outpatients with depression and healthy controls. Difficulty of maintaining set in the Wisconsin Card Sorting Test was significantly increased in patients with depression. Results on the Social Adaptation Self-Evaluation Scale were significantly associated with road-tracking and car-following performance, in contrast to results on the Hamilton Depression Rating Scale and the Beck Depression Inventory-II. CONCLUSION: We conclude that partly remitted depressive patients under steady-state pharmacologic treatment do not differ from healthy controls with respect to driving performance, which seems to be more affected by psychosocial functioning than by pharmacologic agents. This, however, should be investigated systematically in an off/on study.

REM sleep without atonia in middle-aged and older psychiatric patients and Lewy body disease: a case series.

OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is commonly associated with Lewy body disease, narcolepsy, or depression. In contrast, the relationship between REM sleep without atonia (RWA), which is a hallmark of RBD on polysomnography, and clinical characteristics remains unclear. The purpose of this study is to investigate the clinical features of psychiatric patients exhibiting RWA and its relevance to Lewy body disease. METHODS: Of 55 consecutive patients who underwent polysomnography at the psychiatric ward, 25 patients with sleep apnea syndrome were excluded, and 12 patients exhibiting RWA were identified. The clinical profiles were compared between the groups with and without RWA. RESULTS: The mean age and the frequency of neurocognitive disorders were significantly higher in 12 patients with RWA than in 18 without. Only five of the 12 patients exhibiting RWA had episodes of dream-enactment behavior, and fulfilled the clinical criteria for RBD. Two young patients were diagnosed with narcolepsy, while the other middle-aged and older patients fulfilled the clinical criteria for Parkinson's disease (n = 1), dementia with Lewy bodies (n = 4), idiopathic RBD (n = 2), and major depressive disorder (MDD) (n = 3). The patients with MDD exhibited constipation and/or olfactory dysfunction. Moreover, neuroimaging examinations in the patients with MDD revealed isolated occipital hypoperfusion in three patients and mild dopamine transporter deficit in one patient. CONCLUSIONS: Rapid eye movement sleep without atonia itself may be associated with specific clinical profiles, even when dream-enactment behavior is absent. Continued follow-up of the patients with MDD exhibiting RWA is warranted to determine if they represent the prodromal Parkinson's disease/dementia with Lewy bodies. Copyright © 2016 John Wiley & Sons, Ltd.