Effects of trazodone versus cognitive behavioral therapy in the insomnia with short sleep duration phenotype: A preliminary study

Study Objectives: The insomnia with objective short sleep duration phenotype is associated with increased risk for adverse health outcomes, physiological hyperarousal, and a blunted response to cognitive behavioral therapy for insomnia (CBT-I).Whether insomnia with objective short sleep duration responds better to pharmacological treatment compared to CBT-I has not been examined. Methods: Participants included 15 patients with chronic insomnia (86.7% female), aged 45.3 ± 8.1 years. Eight patients were randomized to CBT-I and 7 to trazodone. Patients were examined with 2 weeks of actigraphy, salivary cortisol, and the insomnia severity index at 3 time points (pretreatment, 3-month posttreatment, and 6-month follow-up). Mixed between-within-subjects analysis of variance and univariate analysis of covariance were conducted to assess the impact of trazodone and CBT-I on patients' total sleep time, salivary cortisol, and insomnia severity index scores across the 3 time points. Results: Trazodone, but not CBT-I, significantly lengthened total sleep time (when measured with actigraphy) both at posttreatment (51.01 minutes vs -11.73 minutes; P =.051; Cohen's d = 1.383) and at follow-up (50.35 minutes vs -7.56 minutes; P =.012; Cohen's d = 1.725), respectively. In addition, trazodone, but not CBT-I, showed a clinically meaningful decrease in salivary cortisol from pretreatment to posttreatment (-36.07% vs -11.70%; Cohen's d = 0.793) and from pretreatment to follow-up (-21.37%vs -5.79%; Cohen's d = 0.284), respectively. Finally, therewere no differences on insomnia severity index scores between the trazodone and the CBT-I groups. Conclusions: The current preliminary, open-label, randomized trial suggests that trazodone, but not CBT-I, significantly improves objective sleep duration and reduces hypothalamic-pituitary-adrenal axis activation, suggesting a differential treatment response in the insomnia with objective short sleep duration phenotype.