An exploratory analysis of the association of circadian rhythm dysregulation and insomnia with suicidal ideation over the course of treatment in individuals with depression, insomnia, and suicidal ideation

Abstract

Study objectives: Sleep disturbance is significantly associated with suicidal ideation. However, the majority of past research has examined the relationship between insomnia and suicidality. The current exploratory study examined the relationship of circadian rhythm dysregulation (eveningness, seasonality, and rhythmicity) with suicidality.

Methods: We examined the association of insomnia, eveningness, seasonality, and rhythmicity with suicidal ideation in 103 participants with depression, insomnia, and suicidality within a larger 8-week double-blinded randomized control trial primarily examining whether cautious use of zolpidem extended-release or placebo reduced suicidal ideation. All participants additionally received an open-label selective serotonin reuptake inhibitor. Methodological strengths of the current analyses included consideration of multiple sleep-wake constructs, adjustment for relevant covariates, investigation of relationships over the course of treatment, and use of both self-report measures and objective measurement with actigraphy.

Results: Over the course of treatment, self-reported eveningness and greater insomnia severity were independently correlated with greater suicidal ideation, whereas actigraphic delayed sleep timing was related to suicidal ideation at a trend level. At the end of treatment, those with greater suicidal ideation demonstrated lower actigraphic activity levels. There were no significant relationships between self-reported seasonality and actigraphic measures of sleep disturbance and suicidality.

Conclusions: Self-reported delays in sleep timing, objectively lower activity levels, and self-reported insomnia severity correlated independently with greater suicidal ideation in those with depression, insomnia, and suicidality. These exploratory findings highlight the need to consider sleep-wake constructs more broadly in those with suicidality in future research studies in order to improve more definitively both assessment and intervention efforts.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: Reducing Suicidal Ideation through Insomnia Treatment; URL: https://ichgcp.net/clinical-trials-registry/NCT01689909; Identifier: NCT01689909 Rumble ME, McCall MV, Dickson DA, Krystal AD, Rosenquist PB, Benca RM. An exploratory analysis of the association of circadian rhythm dysregulation and insomnia with suicidal ideation over the course of treatment in individuals with depression, insomnia, and suicidal ideation. J Clin Sleep Med. 2020;16(8):XXX-XXX.

Keywords: circadian rhythm; depression; eveningness; insomnia; rhythmicity; suicidal ideation.

Conflict of interest statement

All authors have seen and approved the manuscript. Work for this manuscript was performed at the authors’ affiliated institutions. This work was supported by the National Institutes of Health (grant nos. MH095776, MH095780, and MH095778). Conflicts of interest: Dr. Rumble receives grant support from Merck. Dr. McCall receives grant support from Merck, MECTA, and VistaGen, is a consultant to Sage and Jazz, is on a speakers’ bureau with CME Outfitters, and receives royalties from Wolters Kluwer. Dr. Krystal receives grant support from NIH, Janssen, Jazz, Axsome, and Reveal Biosensors, and is a consultant to Adare, Eisai, Ferring, Galderma, Harmony Biosciences, Idorsia, Janssen, Jazz, Merck, Neurocrine, and Takeda. Dr. Benca is a consultant for Eisai, Genomind, Jazz, and Merck. The other authors report no conflicts of interests.

© 2020 American Academy of Sleep Medicine.

Figures

Figure 1. Actigraphic data by hour during the first week of treatment (week 1) for participants with higher and lower Scale for Suicide Ideation (SSI) scores, adjusted by depression severity, insomnia severity, and treatment assignment.

Figure 2. Actigraphic data by hour during the last week of treatment (week 8) for participants with higher and lower Scale for Suicide Ideation (SSI) scores, adjusted by depression severity, insomnia severity, and treatment assignment