0357 Pimavanserin 34mg at Bedtime for Insomnia in Veterans with Post-traumatic Stress Disorder: Open-label Case Series

Abstract

Abstract Introduction There is a critical need for effective and feasible interventions to address insomnia associated with post-traumatic stress disorder (PTSD). Several lines of evidence suggest that pimavanserin, a 5-HT2A inverse agonist approved by the FDA for the treatment of Parkinson's disease psychosis, may benefit PTSD-related sleep disturbances. We conducted a pilot, open-label study of pimavanserin 34mg at bedtime for the treatment of PTSD-associated insomnia to preliminarily assess the feasibility of this intervention and tolerability of our protocol (NCT04188392). Methods Adult, male and female Veterans with chronic insomnia disorder and PTSD received fixed dose, open label pimavansern 34mg at bedtime for 6 weeks. Subjects completed 7 days of actigraphy monitoring and two consecutive in-lab polysomnograms (PSGs) pre-treatment. Safety and adherence were assessed in-person at weeks 3 and 6 and otherwise weekly via telephone. Actigraphy monitoring and a closeout PSG were repeated at week 6. Primary outcomes were recruitment and retention rates, defined as the total number of subjects recruited into treatment (goal n=6) and treatment completion rates (goal 75%), respectively. Results A total of 6 subjects (mean age 35.3 [S.D. 6.3] years, 2 [33.3%] female, 2 (33.3%] black or African American, 2 [33.3%] Hispanic, 4 [66.7%] comorbid depression) were recruited over 5.8 months. One subject was found to have mild OSA (AHI 5.6). Insomnia Severity Index (ISI) scores were in the severe range for 4 of 6 [66.7%] subjects. All subjects (100%) completed treatment. There were no serious adverse events or medication discontinuations due to adverse events. Preliminary analyses revealed a greater tend toward improvement on subjective measures of insomnia compared to objective sleep measures. Conclusion This open-label case series provides preliminary evidence for the tolerability of pimavanserin in Veterans with PTSD-associated insomnia and feasibility of our protocol. A larger, randomized controlled trial is needed to detect a meaningful clinical difference in insomnia severity following treatment with pimavanserin. Support (if any) Michael E. DeBakey VA Medical Center Seed & Bridge Award; Center for Alzheimer's and Neurodegenerative Diseases, Baylor College of Medicine