1/2 Cognitive Behavioral Therapy and Trazodone Effects on Sleep and Blood Pressure in Insomnia Phenotypes Based on Objective Sleep Duration: A Sequential Cohort/Randomized Controlled Trial

PROJECT SUMMARY Insomnia is a prevalent health problem associated with adverse cardiovascular, metabolic, and mental health outcomes. Previously proposed subtypes, based on traditional clinical measures, have poor reliability and validity and have not proven useful for guiding insomnia treatment decisions. Based on a large base of preliminary data from various domains and several investigative groups, we have identified a particular phenotype, insomnia with short sleep duration (ISS), that is associated with increased risk for adverse health outcomes, greater physiological hyperarousal as indicated by hypothalamic-pituitary-adrenal (HPA) axis activation, and worse response to Cognitive-Behavioral Treatment for Insomnia (CBT-I). The proposed study represents the next logical extension of our previous observations: To determine the efficacy of CBT-I in individuals with ISS vs. Insomnia with normal sleep duration (INS) among adults with elevated blood pressure (BP), and to examine the efficacy of trazodone among non-remitters to CBT-I. CBT-I is recommended as first-line treatment for insomnia, and trazodone is a widely-prescribed but grossly understudied medication for insomnia. In addition, our pilot data demonstrate differential efficacy of CBT-I and trazodone in ISS and INS: trazodone, but not CBT-I, increases objective total sleep time (TST), and lowers BP and evening cortisol in ISS. We will conduct a 4-site cohort study followed by a placebo-controlled RCT in 600 adults (≥18y) with insomnia. The cohort study will examine the efficacy of CBT-l among individuals with ISS vs. INS phenotypes (n=300 each), defined by polysomnographic (PSG) TST. The subsequent RCT will compare the efficacy of trazodone vs. placebo among CBT-I non-remitters. Investigators at the 4 study sites (Hershey, Denver, Pittsburg, and Quebec) have a long history of collaboration and successful completion of NIH-funded mechanistic and clinical trial studies. Our primary outcome will be the insomnia remission at 8 weeks, defined as Insomnia Severity Index (ISI)