Candidate: Dr. Melissa Beth Jones completed medical school at Drexel University College of Medicine, psychiatry residency at University of Illinois at Chicago, clinical fellowship in Behavioral Neurology & Neuropsychiatry at Baylor College of Medicine (BCM), and a research fellowship in the South Central Mental Illness, Research, Education and Clinical Center (MIRECC) at the Michael E. DeBakey VA Medical Center (MEDVAMC). She is currently a faculty psychiatrist in the Mental Health Care Line at MEDVAMC and Assistant Professor of Psychiatry at BCM. She has published 6 first-authored and 2 co-authored peer-reviewed manuscripts and 1 first-authored book chapter. Dr. Jones aspires to become an independent clinician-scientist designing and executing clinical trials of novel interventions for sleep, post- traumatic stress disorder (PTSD), and other neuropsychiatric conditions impacting US Veterans. She eventually aims to use these interventions to modify the risk or emergence of neurodegenerative disorders. Career Development and Goals: During this award period, Dr. Jones will obtain the necessary training in clinical trial design and execution, biostatistics, and research assessments of insomnia and PTSD required for her to achieve research independence as an interventionalist treating these and other prevalent neuropsychiatric disturbances. This training is accomplished through meetings with her mentorship team, formal coursework in statistics and pharmacology, and supplemental instruction in sleep medicine. Environment: The MEDVAMC and Center for Innovation Quality, Effectiveness and Safety (IQuEST) provide the ideal research and training environments to complete the proposed project. MEDVAMC provides mental health care to the largest number of unique Veterans in the country. IQuEST is the premiere center for health services research in the southwest region. Research: There is a critical need for effective interventions to address the prevalent and refractory insomnia associated with PTSD. Several lines of evidence suggest that pimavanserin, a 5-HT2A inverse agonist, may benefit PTSD-related sleep disturbances. Accordingly, Aim 1 is to conduct a preliminary randomized clinical trial (RCT) of the efficacy of pimavanserin 34mg administered at bedtime for 8 weeks for the treatment of insomnia in Veterans with PTSD. 48 adult male and female Veterans with chronic insomnia disorder and PTSD are randomized to receive either pimavanserin 34mg or placebo at bedtime for 8 weeks; mean change in insomnia severity is compared between groups pre- and post-treatment. While Aim 1 examines subjective measures of sleep, Aim 2 characterizes objective measures of sleep with polysomnography and actigraphy pre- and post-treatment. Aim 3 (exploratory) examines whether pimavanserin 34mg at bedtime for 8 weeks reduces the severity of stress-related psychopathology in US Veterans with PTSD and insomnia compared to placebo. This pilot RCT informs on the feasibility and tolera...