Kolla, Bhanu Prakash

Over 37% of pregnant women report excessive daytime sleepiness or hypersomnia during the first trimester, and commonly throughout the remaining trimesters of pregnancy and the postpartum period. The clinical presentation and symptoms of central disorders of hypersomnolence (CDH) such as narcolepsy, idiopathic hypersomnia, or excessive daytime sleepiness secondary to shift work or obstructive sleep apnea may be confounded by physiological changes in sleep architecture and hormonal fluctuations occurring during pregnancy. These overlapping features may cause delays in diagnosis and treatment, impacting quality of life, maternal functioning, and overall health. Management of CDH during pregnancy and lactation requires careful consideration of maternal benefits, potential side effects of medications and fetal and neonatal safety. Here, we present a case of idiopathic hypersomnia and detail management and outcomes during pregnancy and lactation. We briefly review the existing literature on prevalence, pathophysiological mechanisms, diagnostic challenges, objective findings, and risks posed by CDH in pregnancy and lactation. In this narrative review for primary care clinicians, we also summarize currently available evidence regarding the efficacy, teratogenic and other risks of pharmacologic agents used in the treatment of CDH in pregnancy and lactation. Lastly, we provide a clinical algorithm for management of CDH during pregnancy and lactation.

Abstract Introduction Clinical hypnosis is among the limited treatment options currently available to mitigate the symptom burden associated with parasomnias; however, there is scant literature regarding its effectiveness. We conducted a retrospective cohort study to examine the efficacy of clinical hypnosis in treating parasomnias. Methods We included all adult patients with research authorization on file who were referred for clinical hypnosis for the management of parasomnias at the Mayo Clinic Center for Sleep Medicine. Data on demographics, type and frequency of parasomnia(s), number of hypnosis sessions, concurrent medication(s), and polysomnographic variables were extracted. Information about the efficacy of treatment, including patient reports of change in intensity and frequency was extracted where available. A Clinical Global Impression-Improvement (CGI-I) score was assigned based on review of the follow up note. Results A total of 134 patients received clinical hypnosis. A majority of the sample was female (65.67%) with a median age of 41.5 years. The most common indications were non-rapid eye movement (REM) parasomnia (33), REM sleep behavior disorder (27), nightmare disorder (24), parasomnia overlap disorder (11), and sleep-related eating disorder (8). Follow up data were available on 76 patients (56.71%). Of these, a total of 47/76 (61.84%) reported subjective improvement in parasomnias following hypnosis. The median CGI-I score was 3.07±1.22; a total of 23/76 (30.26%) reported substantial improvement and 19/76 (25.0%) reported some impovement based on the CGI scores. Conclusion A majority of patients reported improvement in symptoms. Clinical hypnosis was effective for both non-REM and REM parasomnias. Given its relative safety and minimal potential adverse effects, clinical hypnosis remains an effective first-line treatment option for parasomnias. Support (if any)

Abstract Introduction Zolpidem is a commonly prescribed FDA- approved hypnotic. In 2013, the FDA recommended reducing maximum dosing of zolpidem in female patients due to concern for slower elimination time as compared to their male counterparts. Despite this, none of the FDA warnings or communications cited published studies that support the claim that women are at increased risk of adverse events. Subsequent prescribing data has shifted to reflect FDA recommendations. In this study we examined risks of using above FDA recommended doses in female patients. Methods This is a retrospective chart review including all adult female patients (> 18 years old) evaluated and managed at the Mayo Clinic Center for Sleep Medicine between 1/1/2024 to 12/31/2024. Detailed review of Mayo Clinic’s EMR was accomplished with subjects on zolpidem split into supratherapeutic and non-supratherapeutic dosing groups. Subjects were relegated to the above maximum dose group if they were ever prescribed FDA-defined supratherapeutic dosing (>5 mg IR formulation or >6.25 mg ER formulation) for a >1 week period. Adverse events were defined as: falls, parasomnias, and cognitive impairment determined via ICD-10-CM codes that occurred at any period following zolpidem initiation. We analyzed rates of adverse effects using chi-square test of independence and Fischer’s exact test in patients with or without supratherapeutic dosing. Results 435 female patients met inclusion criteria. Among the demographic characteristics, only weight was associated with receiving a higher dose of zolpidem (P< 0.001). There were similar rates of adverse effects in both dosing groups with 11.4% of female patients on supratherapeutic dosing as compared to 10.9% of female patients on non-supratherapeutic dosing reporting adverse effects (chi-square test of independence (X2=6.5, N=435, p=0.99) or Fischer’s exact test (OR=1.05, p=0.87). Conclusion Overall, there was not a significant difference in rates of adverse events in female patients receiving supratherapeutic vs non-supratherapeutic doses of zolpidem during the time frame described. Further studies are warranted to better elucidate longitudinal risk of adverse effects related to gender-related differences with zolpidem dosing. Support (if any)

Abstract Introduction Observational studies have reported associations between hypnotic use and increased risk of cognitive decline. These findings may reflect confounding from insomnia severity, healthcare utilization, and comorbidity burden. We evaluated whether hypnotic exposure is independently associated with incident mild cognitive impairment (MCI) or dementia after rigorous adjustment, including a comprehensive propensity score (PS) and Apolipoprotein E (APOE) ε4 status. Methods We conducted a retrospective cohort study using a biobank sample with linked electronic health records and genetic data. Hypnotic exposure was derived from orders data and categorized as unexposed (n=27,055), single prescription (n=4243), shorter-term use (n=3999), long-term use (≥6 orders for ≥1 year; n=3214), and by drug class: benzodiazepines (n=376), Z-drugs (n=6222), trazodone (n=2395), and mixed exposure (≥2 classes; n=2435). Incident MCI/dementia diagnoses (ICD-9/10) occurring ≥12 months after initial prescription constituted outcomes. The PS modeled likelihood of receiving hypnotics based on demographics; sleep-related conditions; healthcare utilization (record length, visit frequency, diagnostic burden); psychiatric comorbidities; alcohol use and chronic pain. Hypnotic users were 1:2 matched to unexposed individuals on age, sex, healthcare utilization, and PS. Cox proportional hazards models with a 60-month lag tested associations of exposure category, duration, and class with outcomes. Models adjusted for all PS covariates, cardiovascular risk score, and APOE ε4 status. Results Matched but unadjusted analyses suggested slightly higher hazards of MCI/dementia among hypnotic users versus unexposed (HR=1.08; CI=0.99–1.18). However, after PS adjustment and APOE ε4 inclusion, hypnotic users showed significantly lower hazards (HR=0.81; CI=0.74–0.89). Class-specific analyses indicated reduced hazards for Z-drugs (HR=0.83; CI=0.74–0.93), trazodone (HR=0.71; CI=0.60–0.86), and mixed users (HR=0.79; CI=0.68–0.91), with all classes showing lower hazards than benzodiazepine-only users. Long-term hypnotic use was associated with lower hazards than no prescription (HR=0.69; CI=0.61–0.80), single prescription (HR=0.81; CI=0.68–0.97), or short-term use (HR=0.76; CI=0.65–0.90). Conclusion The elevated cognitive risk among hypnotic users appears largely attributable to underlying clinical/utilization factors rather than hypnotic exposure itself. After comprehensive confounding control, all hypnotic classes except benzodiazepines demonstrated lower risk of MCI/dementia. These findings underscore the need for rigorous adjustment in studies of insomnia pharmacotherapy and suggest potential protective effects of certain hypnotics that warrant further investigation. Support (if any) None

Abstract There is a bidirectional relationship between substance use disorders and sleep disturbances. Substance misuse, including chronic use of alcohol, cannabis, opioids, and cocaine, impacts both the subjective quality and objective measures of sleep. In turn, sleep disturbances, including insomnia, have been linked to the initiation, maintenance, and relapse of substance use disorder. This chapter summarizes recent research findings on the characteristics of sleep disturbances among individuals with substance use disorders. It then discusses available tools to aid sleep clinicians in diagnosing substance use disorders in their patients. Finally, it outlines key options and considerations for non-pharmacological and pharmacological treatments of sleep disorders in the substance use disorder population.