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

Abstract

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, there were 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.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: Study of Trazodone & Cognitive Behavioral Therapy to Treat Insomnia; URL: https://ichgcp.net/clinical-trials-registry/NCT01348542; Identifier: NCT01348542.

Keywords: cognitive-behavioral therapy for insomnia; cortisol; insomnia; insomnia short sleep duration phenotype; total sleep time; trazodone.

© 2020 American Academy of Sleep Medicine.

Figures

Figure 1. Study timeline.

BMI = body mass index, CBT-I = cognitive behavioral therapy for insomnia, ISI = Insomnia Severity Index, ISS = insomnia with objective short sleep duration, PSG = polysomnography.

Figure 2. Total sleep time during 2-week actigraphy with ad libitum TIB across 3 time points.

Data are mean and standard deviation values for TST, where the solid lines represent the CBT-I group and the dotted lines represent the trazodone group. CBT-I = cognitive behavioral therapy for insomnia, TIB = time in bed, TST = total sleep time.

Figure 3. Percentage change in postmeridian salivary cortisol levels from pretreatment to posttreatment and to follow-up.

Data are mean and standard error values for percentage change in cortisol levels, where the solid lines represent the CBT-I group and the dotted lines represent the trazodone group. CBT-I = cognitive behavioral therapy for insomnia.