Substance Use, Hospitalizations, and Co-Occurring Disorders among Patients Transferred from a Needle Exchange Program to Opioid Maintenance Treatment

Opioid use disorders (OUD) is a relapsing condition with high mortality. Opioid maintenance treatment (OMT) reduces heroin use, and overall morbidity and mortality. The prevalence of psychiatric and substance use disorders, potential baseline predictors for psychiatric hospitalization, and psychiatric diagnoses at follow-up were investigated and may give hints about possible preventative strategies. The medical records for 71 patients were reviewed 36 months following referral to OMT from a needle exchange program (NEP). Their psychiatric diagnoses and hospitalizations were identified. Their baseline characteristics were assessed for potential differences between hospitalized versus non-hospitalized patients and between patients with and without psychiatric diagnoses in a longitudinal observational study without controls. A regression analysis was performed to identify predictors for hospitalization when controlling for OMT status. Sixty-five percent of the patients were hospitalized at least once with a psychiatric diagnosis. Substance-related reasons were prevalent, and detoxification occurred among 59% of patients, with sedative- hypnotics (benzodiazepines, zopiclone, zolpidem, and pregabalin) being the substance used by 52% of patients. Baseline use of these drugs and/or buprenorphine predicted for hospitalization when controlling for OMT status. During the follow-up period, 72% of patients met the criteria for a psychiatric diagnosis other than OUD. The prevalence of non-substance use disorders overlapping with SUD was 41%, and that overlapping with anxiety disorder was 27% of all participants. Increased attention to psychiatric co-occurring disorders in the treatment of OUD is required and the importance of addressing sedative-hypnotics use when initiating OMT is highlighted.

Evaluation of Antioxidant and Protease-inhibitory Potential of Ethanolic Extract of Myristica fragrans (Nutmeg)

Introduction: Myristica fragrans is an important commercial plant used for spices. The plant has been traditionally used as an anticancer, anti inflammatory, antioxidant, sedative hypnotics and antimicrobial agent. Plants have played an important role in maintaining human health & improving the quality of human life for thousands of years and have served humans well as valuable components of medicines. Methods: Ethanolic extract of myristica fragrans was obtained by hot percolation method. Preliminary Phytochemical screening of the extract was done .Antioxidant and anti inflammatory potential of ethanolic extract of myristica fragrans was analysed. The data were analysed statistically using two – way analysis of variance (ANOVA) and Tukey’s multiple range test to assess the significance of individual variations between the groups. In Tukey’s test, significance was considered at the level of p<0.05. Results: Ethanolic extract of Myristica fragrans (Nutmeg) was rich in the phytoconstituents such as alkaloids, flavonoids, terpenoids and saponins. IC50 of antioxidant activity of ethanolic extract of Myristica fragrans was found to be 300 µg/ml. IC50 of anti-inflammatory potential of the ethanolic extract of Myristica fragrans was found to be 360 µg/ml. Conclusion: From the study, it was evident that the ethanolic extract of myristica fragrans has significant antioxidant and anti-inflammatory potential. In future, the extract can be validated as a drug formulation.

P097 Incidence of abnormal dreams and nightmares with lemborexant in adults with insomnia: results from two Phase 3 studies

Introduction Abnormal dreams and nightmares have been reported by insomnia patients before and after treatment with sedative-hypnotics. Since dual-orexin-receptor-antagonists such as lemborexant (LEM; approved in multiple countries for adult insomnia) increase REM sleep, during which dream content is more likely to be recalled, we assessed the frequency of nightmares/abnormal dreams in Phase 3 studies. Methods Study 303 (SUNRISE-2) was a 12mo, randomized, double-blind, placebo (PBO)-controlled (first 6mo [Period 1]), phase 3 study that enrolled subjects ≥18y with insomnia disorder and ISI scores ≥15. During Period 1, the safety analysis set (SAS) included: PBO, n=319; LEM 5mg, (LEM5), n=314; LEM 10mg (LEM10), n=314. Study 304 (SUNRISE-1) was a 1mo, randomized, double-blind, PBO- and active-controlled (zolpidem tartrate extended-release 6.25mg [ZOL-ER]) study of LEM5 and LEM10. The SAS included: PBO, n=209; ZOL-ER, n=263; LEM5, n=266; LEM10, n=268. Results In Study 303, Period 1, 28/947 subjects (3.0%) reported nightmares (n=12; PBO-1; LEM5-4; LEM10-7) or abnormal dreams (n=17; PBO-6; LEM5-7; LEM10-4) as treatment-emergent adverse events (TEAEs). In Study 304, 12/1006 subjects (1.2%) reported nightmares (n=4; PBO-1; ZOL-ER-0; LEM5-2; LEM10-1) or abnormal dreams (n=8; PBO-1; ZOL-ER-3; LEM5-0; LEM10-4). 32/40 subjects (80.0%) reporting these events were female (% females in the studies: 303=67.9%; 304=86.4%). In the LEM groups, 11/28 subjects (39.3%) reported the TEAE within 3 days of treatment initiation. There were 2 TEAEs of nightmare/abnormal dreams during the PBO run-in prior to randomization. Conclusion Abnormal dreams/nightmares were not common events in either study. Incidence was slightly higher with LEM10 and proportional to enrollment based on sex.

Relationship between levels of mindfulness and substance use pattern

ABSTRACT Objective Evaluate the association between levels of mindfulness and sociodemographic characteristics and pattern of drug use of individuals seeking treatment in a University Service Specialized in Substance Use Disorders. Methods This is a cross-sectional study with 164 individuals over 18 years of age seeking treatment for the use of psychoactive substances in the June 2018-December 2019 period, using a questionnaire for sociodemographic data, the Mindful Attention Awareness Scale (MAAS) self-reporting instrument, and the Alcohol, Smoking, and Substance Involvement Screening Test. Results An association was found between low levels of mindfulness mainly with the individual risk of being a medium/high-risk user of sedative-hypnotic drugs (p = 0.020). A borderline association was also found between MAAS and the risk of the individual being a medium/high risk of alcohol (p = 0.053) and with a more severe pattern of substance use (p = 0.065). Conclusion Individuals seeking treatment for substance use presented impairments in the attentional aspect of mindfulness and levels of mindfulness seem to protect against behaviors related to substance use, especially against the use of high/moderate risk of sedative-hypnotics.

BDZs, designer BDZs, and Z-drugs: pharmacology and misuse insights

: Benzodiazepines (BZDs) are a widely prescribed class of sedative-hypnotics compounds for the treatment of a broad range of conditions as anxiety and obsessive-compulsive disorders, phobias, sleep related problems associated with insomnia and for the management of alcohol and GHB withdrawal. Zolpidem, zopiclone and zaleplon, commonly known as Z-drugs are non-benzodiazepine hypnotic drug with pharmacology similar to BDZs. Despite their usefulness, BDZs and Z-drugs present a potential for abuse and dependence. Moreover, the non-medical use of BDZs is a well-known phenomenon and represents an increasingly widespread public health problem since is associated with an elevated risk of serious health consequences or fatal overdose, especially among specific group of users. The spectrum of BDZs and Z-drugs misuse is extended by new synthetic BDZs, which may pose high risks to users, since the majority have never undergone clinical trials or tests and consequently their pharmacology and toxicology is largely unknown.

834 Help Me Stop Eating Please…

Introduction Sleep related eating disorder (SRED) is an uncommon NREM parasomnia, predominantly seen in females in their 20s and 30s and is commonly associated with sleep walking, daytime eating disorders (anorexia and bulimia) and use of certain sedative-hypnotics. Here, we describe a case of unique therapeutic dilemma in a middle-aged female, in whom SRED affected the use of continuous positive airway pressure device (CPAP) for her obstructive sleep apnea (OSA) which lead to worsening sleep quality and daytime functionality. Report of case(s) 42-year-old female with history of migraines and OSA, came to the clinic with 6-month history of SRED which started after the demise of her husband and was associated with significant weight gain and injuries. During typical episode, she would take CPAP mask off, walk down the stairs and eat in the kitchen area and then fall asleep in the living area. She denied predilection for particular food, food allergies, consumption of inedible materials or use of offending drugs. Upon further inquiry, she reported recent unsuccessful attempts at smoking cessation, frequent nighttime smoking, significant body image issues and discontinuation of topiramate use for her migraines recently. Telemedicine visit limited the physical examination but included increase in BMI from 32 to 35 kg/m2. Compliance report, sleep diary and surveillance videos were consistent with the history with compliance report showing 17% of nights with optimal usage and 59% of nights with any usage. Beside locking the food, safety measures and napping, we recommended her to use clonazepam 1.5 mg. Unfortunately, she continued to have episodes. She was then started on Topiramate 50 mg which was gradually increased to 100 mg with reduction in her episodes and increase in her compliance to 60%. Conclusion In sleep medicine, treatment of OSA usually precede the treatment of comorbid conditions. However, SRED with comorbid OSA, requires a reverse strategy where improvement in compliance and coexisting daytime symptoms requires the treatment of SRED first. Moreover, detailed history to investigate the potential precipitating factors, co-existing medical and sleep conditions can help with choice of therapy e.g. patients with depression and SRED can benefit from Selective Serotonin Reuptake Inhibitors rather than other choices. Support (if any):

353 A Direct-to-Patient Mailing about Sedative-Hypnotics and Online CBT-I: Participant Reported Use of Study Materials

Introduction Cognitive behavioral therapy for insomnia (CBT-I) is recommended as first-line treatment for chronic insomnia disorder for all adults. Older adults are often prescribed sedative-hypnotics (e.g., benzodiazepine receptor agonists, BRAs) for insomnia, despite observational studies showing these medications increase risk of falls, fractures, and cognitive decline. In an ongoing randomized controlled trial, we are testing “Sleep EducatioN Information Sent Directly to Patients (SEND),” a novel program combining direct-to-patient mailing with information about access to an online CBT-I resource, compared to a similarly structured control condition. In the current study, we surveyed participants in both groups to examine their self-reported use of intervention or control materials. Methods In the larger trial, 1,672 Veteran participants (aged &gt;=65 years, receiving care from a Colorado VA facility, and prescribed a BRA) were randomized to receive the SEND intervention brochure with information on how to access a free, anonymous online CBT-I resource (n=836) or control condition brochure with information about general sleep education (n=836). Six months after the initial brochure mailing, all participants were mailed a blinded survey querying participants’ recollection and use of the mailed materials. We used chi-squared tests to compare survey responses for SEND versus control groups. Results 354 surveys were returned by study participants (overall response rate: 21%; SEND: 172 [20%], control: 182 [22%]). Respondents were 94% male with mean age 71.7 years (no difference between groups). In the SEND group, 97 (56%) reported receiving the brochure, 18 (10%) visited the website, and 14 (8%) discussed the brochure with their provider. No significant differences between groups were observed in the number of participants who reported receiving the brochure (chi2=2.96, p=.085); visiting the website (chi2=0.0253, p=.874); or discussing the brochure with their provider (chi2=1.91, p=.167). Conclusion At 6-months follow-up, over half of participants recalled receiving a mailing about sedative-hypnotics. A modest number reported visiting the online CBT-I program and a similar number discussed the materials with their healthcare provider. Similar results between groups suggest successful blinding of the intervention and control participants. If successful, the SEND intervention may provide a low-touch, low-cost approach to address BRA over-use in some older adults. Support (if any):

Patient-Specific Sedation Management via Deep Reinforcement Learning

Introduction: Developing reliable medication dosing guidelines is challenging because individual dose–response relationships are mitigated by both static (e. g., demographic) and dynamic factors (e.g., kidney function). In recent years, several data-driven medication dosing models have been proposed for sedatives, but these approaches have been limited in their ability to assess interindividual differences and compute individualized doses.Objective: The primary objective of this study is to develop an individualized framework for sedative–hypnotics dosing.Method: Using publicly available data (1,757 patients) from the MIMIC IV intensive care unit database, we developed a sedation management agent using deep reinforcement learning. More specifically, we modeled the sedative dosing problem as a Markov Decision Process and developed an RL agent based on a deep deterministic policy gradient approach with a prioritized experience replay buffer to find the optimal policy. We assessed our method's ability to jointly learn an optimal personalized policy for propofol and fentanyl, which are among commonly prescribed sedative–hypnotics for intensive care unit sedation. We compared our model's medication performance against the recorded behavior of clinicians on unseen data.Results: Experimental results demonstrate that our proposed model would assist clinicians in making the right decision based on patients' evolving clinical phenotype. The RL agent was 8% better at managing sedation and 26% better at managing mean arterial compared to the clinicians' policy; a two-sample t-test validated that these performance improvements were statistically significant (p &lt; 0.05).Conclusion: The results validate that our model had better performance in maintaining control variables within their target range, thereby jointly maintaining patients' health conditions and managing their sedation.