Deutetrabenazine (Austedo) is approved by the FDA for treatment of tardive dyskinesia (TD) in adults. In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine. The objective of this study was to evaluate the long-term safety and tolerability of deutetrabenazine in patients with TD at 3 years.

Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used for calculating AE frequencies. This analysis reports results up to Week 158.

A total of 343 patients were enrolled (111 received placebo and 232 received deutetrabenazine in the parent studies). At the time of this analysis, 183 patients were still receiving treatment; 259 completed 1 year, 172 completed 2 years, and 41 completed 3 years. There were 623 patient-years of exposure. More than 40% of patients reached the maximum dose. EAIRs of AEs were comparable to or lower than those observed in the ARM-TD and AIM-TD short-term randomized trials of deutetrabenazine vs. placebo. The frequency of SAEs (EAIR 0.10) was similar to that observed with short-term placebo (0.33) and short-term deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.06), dose reduction (0.10), and dose suspension (0.05) were uncommon.

These results support the safety outcomes observed in the ARM-TD and AIM-TD parent studies and the safety of deutetrabenazine for long-term use in patients with TD.

Funding Acknowledgements: This study was funded by Teva Pharmaceuticals, Petach Tikva, Israel

Opioid use disorder (OUD) is a serious public health threat. Pharmacotherapy, commonly known as medications for opioid use disorder (MOUD), is established as the cornerstone of OUD treatment. MOUDs reduce likelihood of relapse, promote recovery, and save lives. However, many clinicians are still reluctant to use these medications, in part due to inadequate training and experience. In light of the ongoing opioid overdose epidemic, it has become ever more important for clinicians to confidently and thoughtfully deploy these medications to help patients struggling with OUD. To aid busy clinicians, we have put together a review of the extant literature on three FDA-approved pharmacotherapy options—methadone, buprenorphine, and extended-release naltrexone—with a heavy focus on practical clinical application. We discuss how to effectively engage patients with OUD and initiate them on MOUDs—especially when their primary misused drug is fentanyl. We also review novel strategies, such as buprenorphine microinduction, as well as suggested best practice to effectively transition between MOUDs. Finally, we synthesize our review and recommendations in an algorithmic flowchart to provide visually compelling information.

No Funding

The association of sleep disorders and post-traumatic stress disorder (PTSD) is almost universal. Nightmares are not only one of the most commonly associated but also featured as a diagnostic criterion for PTSD. PTSD-related nightmares are particularly distressing, may impair functioning and increase risk of suicide. No specific pharmacologic agent has been demonstrated to impair dreaming. Inhibition of PTSD-related nightmares with pramipexole has not heretofore been described. Such a case is presented.

Case study - This 60 year-old male with PTSD and trauma-related nightmares upon introduction of pramipexole 0.5mg PO qHS for Restless Leg Syndrome (RLS) had total elimination of dreams, which recurred upon discontinuation of this agent as a result of insomnia and increased anxiety. A lower dose of 0.375mg qHS provided optimal RLS-symptom control and overall improved tolerance despite nightmare recurrence.

Abnormalities on Neurological examination: Recent recall: 2 of 4 objects without improvement with reinforcement. Able to spell the word “world” forwards but not backwards. Abstract thought impaired. Chemosensory testing: Anosmia and normogeusia. Motor: Drift: mild right pronator drift with right cerebellar spooning and right abductor digiti minimi sign. Reflexes: 3+ brachioradialis and biceps bilaterally, absent ankle jerks. Other: CT scan with and without contrast: normal.

Nightmares related to PTSD may occur during Rapid Eye Movement (REM) sleep and non-REM sleep. Underlying sympathetic activation may lead to disruptive motor behavior similar to that seen in REM sleep behavior disorder. The exact mechanism of action by which inhibition of dreams occurred with use of pramipexole is unclear. Such a response is consistent with prior documented evidence of REM sleep suppression with low-dose pramipexole such as it‘s efficacy in reducing the intensity and frequency of nightmares and dream enactment related to REM sleep behavior disorder. Further research on therapeutic interventions that target nightmares directly may be beneficial for the management of patients with PTSD.

While physical activity has been shown to promote positive mental health and aid in treatment, the association between involvement in other activities and depressive symptoms among adolescents remains unclear. We sought to fill a gap in the literature by examining relationships between involvement in sports, art, and leadership activities during high school and depressive symptoms among adolescents. Hypothesis: We hypothesized that all types of involvement would be associated with lower levels of depressive symptoms.

We performed a secondary data analysis using the 2016 Minnesota Student Survey, a population-based survey of students in grades 9 and 11 (N=81,885). Descriptive sample statistics (e.g., frequencies) and chi-square tests, stratified by sex, were used to examine relationships between depressive symptoms and involvement in different extracurricular activities among males and females. Analyses were performed using SPSS.

For males and females, involvement in sports was associated with lower levels of depression, compared to non-involvement. Compared to males who did not participate in arts (16.6%), those who did were significantly more likely to report depressive symptoms (21.2%). In addition, females involved in leadership activities were significantly less likely to report depressive symptoms (21.9%) than those who were not involved in these activities (28.7%). Consistent with previous research, females were more likely to report depressive symptoms than males. Females also were more likely to participate in arts and leadership activities.

For males and females, sports participation, and for females, involvement in leadership activities, may represent protective factors against depressive symptoms during adolescence. However, clinicians might consider inquiring about depressive symptoms among adolescent males involved in art-related activities.

To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.

In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.

Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).

343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.

These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.

Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA

Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel

To understand that tinnitus may be an aura for sleep paralysis.

Sleep paralysis is a transient-paralysis which occurs during awakening or falling asleep (Wilson, 1928). Those affected experience symptoms including visual, auditory, and haptic hallucinations, voluntary motor paralysis with intact ocular and respiratory motor movements, and diffuse or localized paresthesias. Sleep paralysis associated with tinnitus as an aura, has not heretofore been described.

A 34 year-old, right-handed female presented with a 13 year history of sleep paralysis. One month prior, she began to notice tinnitus prior to the onset of sleep paralysis. The tinnitus was bilateral, high-pitched, with a volume intensity of 5/10, lasting seven seconds prior to sleep initiation. She denied hearing loss, vertigo, dizziness, cataplexy, deja vu and jamais vu. After termination of tinnitus, she experienced paresthesia, “like at a dentist’s office” radiating from her posterior neck, to her tongue and down to her toes. She described seeing a white-shadowy male figure moving around her room, lasting seven seconds. Accompanied by a masculine “ahh” sound, lasting for three seconds. The sleep paralysis occurred after these events, lasting up to eight hours, or until her husband wakes her.

Abnormalities in Physical Examination: General Examination: right arm hemangioma 4 by 5cm. Reflexes: absent bilateral brachioradialis, 1+ bilateral quadriceps femoris and bilateral Achilles tendon. Neuropsychiatric Examination: Calibrated Finger Rub Auditory Screening Test: faint 70 AU (normal).

Tinnitus has been described as an aura for migraines (Schankin, 2014), temporal lobe epilepsy (TLE) (Florindo, 2006), and narcolepsy-cataplexy (Marco, 1978). These epochs may represent amigranous migraines, which initially present with tinnitus that occurs both during the day and night, forcing the patient to be partially awoken at night with induction of the sleep paralysis sequence. It would be worthwhile to query those with narcolepsy or sleep paralysis if tinnitus precedes the event.

Social anxiety disorder is a mental illness that often occurs in adolescents or early adulthood. When engaging in social interactions, students may feel shy, embarrassed, and uneasy, and thus unwilling to socialize in public. All leads to a gradual decline in their social functions. Many factors including growth environment, genetic factors, levels of neurotransmitters and hormones, as well as certain psychological shocks contribute to social anxiety disorders. In order to explore more treatment and intervention methods for social anxiety disorder, the impact mechanism and effectiveness of digital reading promotion activities in university libraries on college students’ social anxiety disorder were analyzed.

120 college students with social anxiety disorder in a certain university were randomly divided into an experimental group and a control group. The experimental group participated in digital reading promotion activities in the university library. Before and after treatment, the patients were evaluated using Symptom Checklist 90 (SCL-90), Liebowitz Social Anxiety Scale (LSAS), and Hamilton Anxiety Scale (HAMA).

After participating in reading promotion activities, the scores of the Hamilton Anxiety Scale, Social Anxiety Scale, and Symptom Checklist in the experimental group were lower than those before participation (P<0.05), and the difference was statistically significant.

Digital reading promotion activities have a positive impact on social anxiety disorders among college students. Small-scale reading activities can encourage students to go out and socialize, help students establish confidence, help them change their irrational cognition, and overcome psychological fears.

2016 Tianjin education planning project (No. vesp3003).