Insomnia severity is an indicator of suicidal ideation during a depression clinical trial

Abstract

Objective: Insomnia has been linked to suicidal ideas and suicide death in cross-sectional and longitudinal population-based studies. A link between insomnia and suicide has not been previously examined in the setting of a clinical trial. Herein we describe the relationship between insomnia and suicidal thinking during the course of a clinical trial for depression with insomnia.

Methods: Sixty patients aged 41.5±12.5 years (2/3 women) with major depressive episode and symptoms of insomnia received open-label fluoxetine for 9 weeks and also received blinded, randomized eszopiclone 3mg or placebo at bedtime after the first week of fluoxetine. Insomnia symptoms were assessed with the Insomnia Severity Index (ISI), and suicidal ideation was assessed with The Scale for Suicide Ideation (SSI). Depression symptoms were assessed with the depressed mood item and the anhedonia item from the Hamilton Rating Scale for Depression-24 (HRSD24), as well as a sum score for all non-sleep and non-suicide items from the HRSD (HRSD20). Measurements were taken at baseline and weeks 1, 2, 4, 6, and 8. SSI was examined by generalized linear mixed models for repeated measures as the outcome of interest for all 60 participants with ISI and various mood symptoms as independent variables, with adjustment for age, gender, treatment assignment, and baseline SSI.

Results: Higher levels of insomnia corresponded to significantly greater intensity of suicidal thinking (p<0.01). The depressed mood item of the HRSD, and the sum of the HRSD20, both corresponded to greater suicidal thinking (p<0.001). The anhedonia item did not correspond with suicidal thinking. When both ISI and the depressed mood item, or ISI and the anhedonia item, were included together in the same model, the ISI remained an independent predictor of suicidal thinking.

Conclusions: The results support the concept that insomnia may be a useful indicator for suicidal ideation and now extend this idea into clinical trials. Insomnia remains an independent indicator of suicidal ideation, even taking into account the core symptoms of depression such as depressed mood and anhedonia. The complaint of insomnia during a depression clinical trial might indicate that more direct questioning about suicide is warranted.

Trial registration: ClinicalTrials.gov NCT00247624.

Figure 1

V1: Visit 1 - the first face to face baseline visit V2: Visit 2 - the end of one week of medication-free prospective baseline assessment V3: Visit 3 – the end of one week of open-label fluoxetine 20 mg V4: Visit 4 – the end of the first week of eszopiclone (ESZ) or placebo added to fluoxetine V5: Visit 5 – the end of the second week of ESZ/placebo added to fluoxetine V6: Visit 6 – the end of the fourth week of ESZ/placebo added to fluoxetine V7: Visit 7 – the end of the sixth week of ESZ/placebo added to fluoxetine V8: Visit 8 – the end of the eighth week of ESZ/placebo added to fluoxetine