Polysomnographic features associated with clonazepam and melatonin treatment in isolated REM sleep behavior disorder: Time for new therapeutic approaches?

AIMS: Although clonazepam (CLO) and melatonin (MLT) are the most frequently used treatments for REM sleep behavior disorder, the polysomnographic features associated with their use are little known. The aim of this study was to evaluate polysomnographic and clinical parameters of patients with idiopathic/isolated REM sleep behavior disorder (iRBD) treated chronically with CLO, sustained-release MLT, alone or in combination, and in a group of drug-free iRBD patients. METHODS: A total of 96 patients were enrolled: 43 drug-free, 21 with CLO (0.5-2 mg), 20 with sustained-release MLT (1-4 mg), and 12 taking a combination of them (same doses). Clinical variables and polysomnography were collected. RESULTS: Although clinical improvement was reported in all groups, MLT impacted sleep architecture more than the other treatments, with significant and large increase in N3 stage, moderate reduction in N2 and REM sleep, and moderate increase in REM latency. CLO moderately increased the percentage of both REM sleep and especially N2, while reducing N1 and wakefulness. Patients treated with both CLO and MLT did not show major changes in sleep architecture. CONCLUSION: These results suggest that the administration of MLT or CLO impacts (positively) on sleep parameters of iRBD patients. However, there is a need to better stratify patients, in order to treat them in a targeted manner, depending on the patient's individual sleep architecture and expected differential effects of these agents.

Rapid Eye Movement Sleep Behavior Disorder: Management and Prognostic Counseling.

Management of rapid eye movement sleep behavior disorder (RBD) includes reducing injurious dream-enactment behaviors, risk of injury to self and bedpartner, and vivid or disruptive dreams and improving sleep quality and bedpartner sleep disruption. Safety precautions should be reviewed at each visit. Medications to reduce RBD symptoms such as melatonin, clonazepam, pramipexole, and rivastigmine should be considered for most patients. Isolated RBD confers a high lifetime risk of neurodegenerative diseases with a latency often spanning many years. A patient-centered shared decision-making approach to risk disclosure is recommended. Knowledge of the risk allows for life planning and participation in research.

A case of prazosin in treatment of rapid eye movement sleep behavior disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream-enactment behaviors that emerge during a loss of REM sleep atonia. Untreated RBD carries risks for physical injury from falls or other traumatic events during dream enactment as well as risk of injury to the bed partner. Currently, melatonin and clonazepam are the mainstay pharmacological therapies for RBD. However, therapeutic response to these medications is variable. While older adults are most vulnerable to RBD, they are also particularly vulnerable to the adverse effects of benzodiazepines, including increased risk of falls, cognitive impairment, and increased risk of Alzheimer disease. Prazosin is a centrally active alpha-1 adrenergic receptor antagonist often prescribed for trauma nightmares characterized by REM sleep without atonia in patients with posttraumatic stress disorder. We report a case of successful RBD management with prazosin in a patient in whom high-dose melatonin was ineffective. Although there was no observable reduction in dream-enactment behaviors with high-dose melatonin, the possibility of a synergistic effect of prazosin combined with melatonin cannot be ruled out. This case report supports further evaluation of prazosin as a potential therapeutic for RBD. CITATION: Cho Y, Iliff JJ, Lim MM, Raskind M, Peskind E. A case of prazosin in treatment of rapid eye movement sleep behavior disorder. J Clin Sleep Med. 2024;20(2):319-321.

A rare case of tongue biting during sleep in childhood.

Bleeding tongue-biting episodes during sleep are a rare and alarming situation that can negatively impact the child's and parents' sleep, affecting their quality of life. Although highly suggestive of epilepsy, a differential diagnosis should be made with sleep-related movement disorders such as bruxism, hypnic myoclonus, facio-mandibular myoclonus, and geniospasm when this hypothesis is excluded. The clinical history, electroencephalogram, and video-polysomnography are essential for diagnostic assessment. Treatment with clonazepam can be necessary in the presence of frequent tongue biting that causes severe injuries and sleep disturbance. This study reports the challenging case of managing and diagnosing a 2-year-old boy with recurrent tongue biting during sleep since he was 12 months old, causing bleeding lacerations, frequent awakenings, and significant sleep impairment with daytime consequences for him and his family. CITATION: Cascais I, Ashworth J, Ribeiro L, Freitas J, Rios M. A rare case of tongue biting during sleep in childhood. J Clin Sleep Med. 2024;20(4):653-656.

Pharmacological treatments in panic disorder in adults: a network meta-analysis.

BACKGROUND: A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines. OBJECTIVES: To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses. MAIN RESULTS: Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low. AUTHORS' CONCLUSIONS: In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.

Treatment of severe tardive dyskinesia with concurrent administration of olanzapine, clonazepam, baclofen, and gabapentin: a case report.

BACKGROUND: Long-term use of antipsychotics or other dopamine antagonists can result in the extrapyramidal side effect of tardive dyskinesia (TD).Case presentation: An 18-year-old female patient experienced abnormal speech and behavior and because of an equivocal diagnosis, she was given daily doses of 300 mg of quetiapine and 60 mg of ziprasidone. She had used these medications for 2 years before the appearance of involuntary abnormal movements. These movements, which were classified as TD, steadily worsened and markedly interfered with her daily life. Following a trial-and-error course of therapy with vitamin E, vitamin B6, amantadine, valproic acid sodium, lorazepam, and diazepam, the drugs were gradually reduced and stopped, yet the aberrant movements persisted. Finally, the patient was given olanzapine, clonazepam, baclofen, and gabapentin. The Abnormal Involuntary Movement Scale was used to assess changes in the patient's condition. Her TD was efficiently managed through co-administration of olanzapine, clonazepam, baclofen, and gabapentin. CONCLUSIONS: The possibility of TD inducing by antipsychotic use is a clinical concern, even though atypical antipsychotics decrease the incidence of extrapyramidal side effects, and it cannot be entirely excluded. This report provides useful insights into the management of TD and will help clinicians manage similar cases.

REM behavior disorder: When Parkinson's disease meets Morpheus.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by the absence of normal muscle atonia during REM sleep, resulting in excessive motor activity while dreaming. RBD can be classified as isolated which is the strongest clinical marker of prodromal synucleinopathy, or secondary, associated with other neurological diseases, mainly Parkinson's disease (PD) and dementia with Lewy bodies. The diagnosis of RBD must be systematically documented by a video polysomnography in the case of isolated RBD. PD associated with RBD may represent a distinct phenotype compared to PD without RBD, indicating a more severe and widespread synucleinopathy. Clinically, it is associated with poorer motor and cognitive performance, more severe non-motor symptoms, and faster disease progression. Imaging studies have revealed broader brain damage and significant alterations in cerebral metabolism and neurotransmission in PD patients with RBD. The management of RBD involves safety precautions and pharmacotherapy. Safety measures aim to minimize the risk of injury during RBD episodes and include creating a safe sleeping environment and separating the patient from their bed partner if necessary. Pharmacotherapy options include clonazepam and melatonin. Clonazepam must be cautiously prescribed in older patients due to potential side effects.

Utilization of Antiseizure Medications in Women of Childbearing Age With Epilepsy and Nonepilepsy Indications: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Antiseizure medications (ASMs) are among the most commonly prescribed teratogenic drugs in women of childbearing age. Limited data exist on utilization patterns across different indications for therapy and for the newer-generation ASMs in this population. Thus, we assessed the pattern of ASM use in women of childbearing age with epilepsy and nonepilepsy indications (pain and psychiatric disorders). METHODS: We conducted a retrospective analysis of deidentified administrative data submitted to the Optum Clinformatics database. Eligible participants included women aged 12-50 years who filled ASMs between year 2011 and 2017. Participants were followed from date of index prescription filled to study end or insurance disenrollment, whichever came first. For the overall cohort and potential therapy indications, we assessed the type and frequency of ASMs filled; proportion of participants on monotherapy, polytherapy, or treatment switching; and duration of continuous use. Trends were characterized using annual percent change from study start to study end. RESULTS: Our analysis included 465,131 participants who filled 603,916 distinct ASM prescriptions. At baseline, most of the participants had chronic pain (51.0%) and psychiatric disorders (32.7%), with epilepsy the least common (0.9%). The most frequently dispensed were diazepam (24.3%), lorazepam (20.1%), gabapentin (17.4%), clonazepam (12.7%), topiramate (11.3%), and lamotrigine (4.6%). Significant linear increase in trends were observed with gabapentin (annual percent change [95% CI]: 8.4 [7.3-9.4]; p < 0.001) and levetiracetam (3.4 [0.7-6.2]; p = 0.022) and decreasing trends for diazepam (-3.5 [-2.4 to 4.5]; p < 0.001) and clonazepam (-3.4 [-2.3 to 4.5]; p = 0.001). No significant change in trend was observed with valproate (-0.4 [-2.7 to 1.9]; p = 0.651), while nonlinear changes in trends were observed with lorazepam, topiramate, lamotrigine, and pregabalin. DISCUSSION: Decreasing trends were observed with older ASMs in the overall cohort and across the potential indications for therapy. Conversely, increasing trends were seen with the newer ASMs. Considering the risk of teratogenicity associated with the newer medications largely unknown, counseling and education in addition to a careful consideration of the benefits vs potential risks should remain pivotal when prescribing ASMs for women of childbearing age.

Post-hypoxic myoclonus; what we know and gaps in knowledge.

Post-hypoxic myoclonus (PHM) is a rare neurological complication having two different variants depending on acute or chronic onset after cardiopulmonary resuscitation following cardiac arrest: myoclonic status epilepticus (MSE) and Lance-Adams syndrome (LAS) respectively. Clinical and simultaneous electro-encephalographic (EEG) and electromyographic (EMG) tracing can distinguish between the two. Anecdotal treatment with benzodiazepines and anaesthetics (in the case of MSE) have been tried. Although limited evidence is available, valproic acid, clonazepam and levetiracetam, either in combination with other drugs or alone, have shown to control epilepsy associated with LAS effectively. Deep brain stimulation is a novel and promising advance in LAS treatment.

Clonazepam Loading Dose in Status Epilepticus: Is More Always Better?

BACKGROUND AND OBJECTIVES: Benzodiazepines are the first treatment line in status epilepticus (SE). Despite their well-established benefit, benzodiazepines are frequently underdosed with potential detrimental consequences. In some European countries, clonazepam (CLZ) is commonly used as the first line treatment. The aim of this study was to explore the correlation between CLZ loading doses and SE outcome. METHODS: This study included a retrospective analysis of a prospective registry in Lausanne, Switzerland (CHUV Lausanne University Hospital), including all SE episodes treated between February 2016 and February 2021. Only adults (> 16 years old) were included with CLZ used as the first treatment line. Post-anoxic SE were excluded because of significant differences in physiopathology and prognosis. Patient characteristics, SE features, the validated SE severity score (STESS), and treatment characteristics were prospectively recorded. We considered loading doses of 0.015 mg/kg or higher (following commonly recommended loading doses) as high doses. We analyzed outcome in terms of number of treatment lines after the CLZ, proportion of refractory episodes, intubation for airways protection, intubation for SE treatment, and mortality. We performed univariable analyses to investigate the association between loading doses and clinical response. A multivariable stepwise backward binary logistic regression was applied for adjusting for potential confounders. Multivariable linear regression was similarly used to analyze CLZ dose as a continuous variable. RESULTS: We collected 251 SE episodes in 225 adult patients. Median CLZ loading dose was 0.010 mg/kg. CLZ high doses were used in 21.9% of SE episodes (in 43.8% for > 80% of the high dose). Thirteen percent of patients with SE were intubated for airways control, while intubation was needed in 12.7% for SE treatment. High CLZ loading doses were independently associated with younger age (median 62 versus 68 years old, p = 0.002), lesser weight (65 kg versus 75 kg, p = 0.001) and more frequent intubation for airways protection (23% vs 11%, p = 0.013), but differing CLZ dose was not associated with any outcome parameter. CONCLUSION: CLZ high doses were more frequently used for SE treatment in younger patients with healthy weight and were more often associated with intubation for airways protection, probably as an adverse event. Varying CLZ dose did not alter outcome in SE, raising the possibility that commonly recommended doses are above what is needed, at least in some patients. Our results suggest that CLZ doses in SE may be individualized depending on the clinical setting.

Quantitative measurement of motor activity during sleep in isolated REM sleep behavior disorder patients using actigraphy before and after treatment with clonazepam.

STUDY OBJECTIVES: We conducted a prospective study to quantify motor activity during sleep measured by actigraphy before and after 3 months of treatment with clonazepam in patients with video-polysomnography (vPSG) confirmed isolated rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: The motor activity amount (MAA) and the motor activity block (MAB) during sleep were obtained from actigraphy. Then, we compared quantitative actigraphic measures with the results of the REM sleep behavior disorder questionnaire for the previous 3-month period (RBDQ-3M) and of the Clinical Global Impression-Improvement scale (CGI-I), and analyzed correlations between baseline vPSG measures and actigraphic measures. RESULTS: Twenty-three iRBD patients were included in the study. After medication treatment, large activity MAA dropped in 39% of patients, and the number of MABs decreased in 30% of patients when applying 50% reduction criteria. 52% of patients showed more than 50% improvement in either one. On the other hand, 43% of patients answered "much or very much improved" on the CGI-I, and RBDQ-3M was reduced by more than half in 35% of patients. However, there was no significant association between the subjective and objective measures. Phasic submental muscle activity during REM sleep was highly correlated with small activity MAA (Spearman's rho = 0.78, p < .001) while proximal and axial movements during REM sleep correlated with large activity MAA (rho = 0.47, p = .030 for proximal movements, rho = 0.47, p = .032 for axial movements). CONCLUSIONS: Our findings imply that quantifying motor activity during sleep using actigraphy can objectively assess therapeutic response in drug trials in patients with iRBD.

Therapeutic effects of clonazepam in patients with burning mouth syndrome and various symptoms or psychological conditions.

Burning mouth syndrome (BMS) is frequently accompanied by dysgeusia and xerostomia. Clonazepam has been widely prescribed and is effective, but it is unclear whether clonazepam also affects the symptoms that accompany BMS, or whether such symptoms affect treatment outcomes. Here, we investigated the therapeutic outcomes in BMS patients with various symptoms or comorbidities. We retrospectively reviewed 41 patients diagnosed with BMS between June 2010 and June 2021 at a single institution. Patients were instructed to take clonazepam for 6 weeks. Before the first dose, burning pain intensity was measured using a visual analog scale (VAS); the unstimulated salivary flow rate (USFR), psychologic characteristics, site(s) of pain, and any taste disturbance were evaluated. Burning pain intensity was measured again after 6 weeks. Thirty-one of the 41 patents (75.7%) exhibited a depressed mood, whereas more than 67.8% of the patients exhibited anxiety. Subjective xerostomia was reported by ten patients (24.3%). The mean salivary flow rate was 0.69 mL/min and hyposalivation (an unstimulated salivary flow rate ≤ 0.5 mL/min) was apparent in ten patients (24.3%). Dysgeusia was present in 20 patients (48.7%); a bitter taste (n = 15, 75%) was reported by the largest proportion of patients. Patients who reported a bitter taste responded best in terms of burning pain reduction after 6 weeks (n = 4, 26.6%). Overall, 32 patients (78%) reported decreased oral burning pain after clonazepam (mean VAS score changed from 6.56 to 5.34) use. Patients who reported taste disturbances exhibited a significantly greater decrease in burning pain, compared with other patients (mean VAS score changed from 6.41 to 4.58) (p = 0.02). Clonazepam significantly improved burning pain in BMS patients who had taste disturbances.

Clonazepam for the management of sleep disorders.

BACKGROUND: The objectives of this review and meta-analysis of polysomnographic data are those to focus on the clinical use of clonazepam for the management of sleep disorders by re-analyzing clinical trials and randomized clinical trials which have been published in peer-reviewed journals. METHODS: A review of the literature including clinical trials and randomized controlled trials was performed in PubMed®, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. A random effects model meta-analysis was then carried out for the four more frequently reported polysomnographic measures: total sleep time, sleep latency, sleep efficiency, and periodic leg movement during sleep (PLMS) index. RESULTS: A total of 33 articles were retrieved and screened in full text, of which 18 met the criteria for review; among the latter, nine met the criteria for meta-analysis. The studies included in the review involved patients with insomnia, REM sleep behavior disorder, sleep bruxism, and restless leg syndrome or PLMS which reported, most often, an increase in total sleep time with clonazepam. A clear sleep-promoting effect of clonazepam was found also by meta-analysis. DISCUSSION AND CONCLUSIONS: Our results indicate that the pharmacological treatment of sleep disorders with clonazepam must always be personalized according to the type of patient, the risk of addiction and the concomitant presence of respiratory disorders are key factors to take into account. However, in light of the clinical evidence of the few studies in the literature on the different types of disorders, more studies on the use of clonazepam (also in association with first choice treatments) are definitely needed.

Home nocturnal infrared video to record non-rapid eye movement sleep parasomnias.

To assess the feasibility, the acceptability and the usefulness of home nocturnal infrared video in recording the frequency and the complexity of non-rapid eye movement sleep parasomnias in adults, and in monitoring the treatment response. Twenty adult patients (10 males, median age 27.5 years) with a diagnosis of non-rapid eye movement parasomnia were consecutively enrolled. They had a face-to-face interview, completed self-reported questionnaires to assess clinical characteristics and performed a video-polysomnography in the Sleep Unit. Patients were then monitored at home during at least five consecutive nights using infrared-triggered cameras. They completed a sleep diary and questionnaires to evaluate the number of parasomniac episodes at home and the acceptability of the home nocturnal infrared video recording. Behavioural analyses were performed on home nocturnal infrared video and video-polysomnography recordings. Eight patients treated by clonazepam underwent a second home nocturnal infrared video recording during five consecutive days. All patients had at least one parasomniac episode during the home nocturnal infrared video monitoring, compared with 75% during the video-polysomnography. A minimum of three consecutive nights with home nocturnal infrared video was required to record at least one parasomniac episode. Most patients underestimated the frequency of episodes on the sleep diary compared with home nocturnal infrared video. Episodes recorded at home were often more complex than those recorded during the video-polysomnography. The user-perceived acceptability of the home nocturnal infrared video assessment was excellent. The frequency and the complexity of the parasomniac episodes decreased with clonazepam. Home nocturnal infrared video has good feasibility and acceptability, and may improve the evaluation of the phenotype and severity of the non-rapid eye movement parasomnias and of the treatment response in an ecological setting.

Comparative efficacy of prolonged-release melatonin versus clonazepam for isolated rapid eye movement sleep behavior disorder.

PURPOSE: Clonazepam and melatonin are recommended as first-line treatments for isolated rapid eye movement (REM) sleep behavior disorder (iRBD). This study aimed to compare their efficacy and safety in REM sleep without atonia (RWA) and RBD-related symptoms. METHODS: This prospective, open-label, randomized trial included patients with video-polysomnography-confirmed iRBD. The patients were randomly assigned to receive either clonazepam 0.5 mg or prolonged-release (PR) melatonin 2 mg 30 min before bedtime for 4 weeks. The primary outcome was changes in RWA on follow-up polysomnography (PSG). Secondary endpoints were changes in other PSG parameters, clinical global improvement-impression scale (CGI-I) scores, and sleep questionnaire scores. The safety endpoint was adverse events. RESULTS: Of 40 patients with probable RBD considered, 34 were enrolled in the study and randomized. Visual scoring parameters of RWA indices were reduced, and automatic scoring parameters tended to be improved after clonazepam treatment but not after PR melatonin treatment. The proportion of N2 sleep was increased, and N3 and REM sleep were decreased only in the clonazepam group. The clonazepam group tended to answer "much or very much improvement" on the CGI-I more frequently than the PR melatonin group (p = 0.068). Daytime sleepiness and insomnia symptoms were reduced after PR melatonin but not after clonazepam. Depressive symptoms increased after clonazepam. Four of the patients (13.3%) reported mild to moderate adverse events, which were similar between the two groups. CONCLUSION: Four weeks of clonazepam, but not PR melatonin, improved RWA. RBD symptom improvement tended to be better after clonazepam than PR melatonin in exchange for increased depressive symptoms and daytime sleepiness. CLINICALTRIALS: gov identifier: NCT03255642 (first submitted August 21, 2017).

Low-dose naltrexone for treatment of burning mouth syndrome.

OBJECTIVE: The International Classification of Disease defines burning mouth syndrome (BMS) as a chronic intraoral burning sensation, with no identifiable local or systemic cause. Since current management is often unsatisfactory, the aim of this report is to describe a new treatment modality (i.e., low-dose naltrexone [LDN]). STUDY DESIGN: A 62-year-old woman presented with the complaint of burning on the tongue of 3 years' duration. Existing comorbidities were fibromyalgia, irritable bowel syndrome, headache, and interstitial cystitis. Her reported pain intensity ranged from 2/10 (morning) to 8/10 (evening) on a numeric rating scale. With the diagnosis of BMS and hyposalivation, and in light of her current clonazepam use and fibromyalgia, a dry mouth protocol and LDN (3 mg) were prescribed. RESULTS: After 1 month, her pain intensity decreased by 50%, with no pain upon awakening. After 2 months, the widespread pain associated with her chronic morbidities also reduced by 50%, and her headache disappeared. After adjusting LDN dose to 4.5 mg, the patient was stable at 6 months, with 50% reduction of widespread pain and 2/10 BMS pain, and no reported side effects. CONCLUSIONS: These preliminary results suggest that LDN may be a feasible and effective treatment for BMS, especially in patients' refractory to traditional treatment.

Therapies for sleep bruxism in dentistry: A critical evaluation of systematic reviews.

The aim of the study was to evaluate the methodological quality and the risk of bias of systematic reviews with regard to the literature on therapies for sleep bruxism (SB) in dentistry, applying the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews) qualitative guide, as well as the effectiveness of various kinds of treatment of SB. Initially, a total of 1,499 articles were obtained from 4 databases and 2 websites. Relevant articles were obtained from the PubMed, Scopus, Cochrane, and Embase databases as well as from Google Scholar and OpenGrey. Six systematic reviews that met the eligibility criteria were included. The methodological quality of all systematic reviews, assessed with the AMSTAR 2 tool, was critically low. Regarding treatment effectiveness, 5 systematic reviews reported on pharmacological management (botulinum toxin type A (BTX-A), clonazepam and clonidine), 2 reported on oral appliances (OAs) (stabilizing splints and mandibular advancement devices (MADs)) and 1 study addressed the effects of biofeedback (BF). The results of the therapies were diverse and confusing. The available research is not conclusive, and does not show clear evidence or a consensus on the part of researchers on the most effective treatment for the management of SB. More research of better methodological quality is needed in this area.

Management of REM sleep behavior disorder: an American Academy of Sleep Medicine clinical practice guideline.

INTRODUCTION: This guideline establishes clinical practice recommendations for the management of rapid eye movement sleep behavior disorder (RBD) in adults. METHODS: The American Academy of Sleep Medicine (AASM) commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. The task force provided a summary of the relevant literature and the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations. GOOD PRACTICE STATEMENT: The following good practice statement is based on expert consensus, and its implementation is necessary for the appropriate and effective management of patients with RBD: It is critically important to help patients maintain a safe sleeping environment to prevent potentially injurious nocturnal behaviors. In particular, the removal of bedside weapons, or objects that could inflict injury if thrown or wielded against a bed partner, is of paramount importance. Sharp furniture like nightstands should be moved away or their edges and headboard should be padded. To reduce the risk of injurious falls, a soft carpet, rug, or mat should be placed next to the bed. Patients with severe, uncontrolled RBD should be recommended to sleep separately from their partners, or at the minimum, to place a pillow between themselves and their partners. RECOMMENDATIONS: The following recommendations, with medications listed in alphabetical order, are a guide for clinicians in choosing a specific treatment for RBD in adults. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation (ie, "We suggest…") is one that requires that the clinician use clinical knowledge and experience and strongly consider the patient's values and preferences to determine the best course of action.Adult patients with isolated RBD.1. The AASM suggests that clinicians use clonazepam (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL).2. * The AASM suggests that clinicians use immediate-release melatonin (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL).3. * The AASM suggests that clinicians use pramipexole (vs no treatment) for the treatment of isolated RBD in adults. (CONDITIONAL).4. The AASM suggests that clinicians use transdermal rivastigmine (vs no treatment) for the treatment of isolated RBD in adults with mild cognitive impairment. (CONDITIONAL).Adult patients with secondary RBD due to medical condition.5. * The AASM suggests that clinicians use clonazepam (vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL).6. * The AASM suggests that clinicians use immediate-release melatonin (vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL).7. The AASM suggests that clinicians use transdermal rivastigmine (vs no treatment) for the treatment of secondary RBD due to medical condition (Parkinson disease) in adults. (CONDITIONAL).8. * The AASM suggests that clinicians not use deep brain stimulation (DBS; vs no treatment) for the treatment of secondary RBD due to medical condition in adults. (CONDITIONAL).Adult patients with drug-induced RBD.9. * The AASM suggests that clinicians use drug discontinuation (vs drug continuation) for the treatment of drug-induced RBD in adults. (CONDITIONAL).* The Recommendations section of this paper includes remarks that provide additional context to guide clinicians with implementation of this recommendation. CITATION: Howell M, Avidan AY, Foldvary-Schaefer N, et al. Management of REM sleep behavior disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2023;19(4):759-768.

Breastfeeding while on treatment with antiseizure medications: a systematic review from the ILAE Women Task Force

We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short- and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.

Botulinum toxin A for management of refractory concurrent buccal and inferior alveolar nerve post-traumatic neuropathies: a case report.

Painful post-traumatic trigeminal neuropathy (PPTTN) can result from iatrogenic injury to one or more branches of the trigeminal nerve during oral surgical procedures such as tooth extractions. Like other chronic neuropathic pain conditions, PPTTN can significantly alter the patient's quality of life, especially when pharmacological treatment is ineffective or not tolerated. As such, new treatment options have been investigated, including local injections of botulinum toxin type A (BTX-A). A 29-year-old woman presented to our tertiary orofacial pain clinic for evaluation of chronic electric shock-like pain attacks and severe allodynia in the territory of the right inferior alveolar nerve and buccal nerve following right mandibular third molar extraction 3 years prior. Following several failed attempts at classic pharmacological management (including carbamazepine, venlafaxine, duloxetine, pregabalin, clonazepam, and amitriptyline), BTX-A injections were administered in the vicinity of the right mental nerve. This treatment provided significant improvement in the patient's condition and overall quality of life with no significant adverse effects. Because both neuropathies were significantly improved by remote BTX-A injections, this case report provides preliminary clinical evidence supporting spinopetal transport of BTX-A, as shown in animal models, as an underlying pathophysiological mechanism of BTX-A-mediated analgesia.