Clinical trial NCT01689909: Reducing Suicidal Ideation Through Insomnia Treatment
Official title: Reducing Suicidal Ideation Through Insomnia Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Insomnia
Depression
Suicidal Ideation
Keywords: Insomnia
Depression
Suicidal ideation
Zolpidem CR
Placebo
Lead sponsor: Augusta University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Wake Forest University Health Sciences
name: University of Wisconsin, Madison
name: Duke University
First posted: 2012-09-21
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Epidemiologic reports have linked insomnia to suicidal ideation and suicide death. However, no studies have determined whether treating insomnia decreases the risk of suicidality. We have new data indicating that (1) the link between insomnia and suicidal ideation holds true in clinical trials of depressed insomniacs, (2) dysfunctional cognitions about sleep are related to suicidal ideas, and (3) treatment of insomnia with hypnotics leads to a reduction of suicidal ideation. We now propose to test whether cautious use of hypnotics in suicidal, depressed insomniacs may reduce suicide risk in a multi-site clinical trial.

Detailed description: Primary Aim: We will assess the effect of treating insomnia with hypnotic medication on the intensity of suicidal ideation in depressed outpatients with insomnia and suicidal ideation.

-Hypothesis 1. Treatment of depressed, insomniac and suicidal outpatients with open-label fluoxetine (FLX) and blinded zolpidem controlled release (ZOL) will reduce suicidal ideation more than treatment with FLX and blinded placebo.

Secondary Aim: We will examine whether reduced suicidal ideation in depressed insomniacs is mediated through reduced dysfunctional beliefs about sleep, reduced hopelessness, or fewer nightmares.

* Hypothesis 2a. Reduction in suicidal ideation will be mediated through reductions in dysfunctional beliefs about sleep.
* Hypothesis 2b. Reduction in suicidal ideation will be mediated through reductions in hopelessness.
* Hypothesis 2c. Reduction in suicidal ideation is mediated through fewer nightmares.

Tertiary Aim: We will confirm findings from our prior pilot studies that treatment of insomnia in depressed insomniacs leads to improvements in health-related quality of life, especially in women.

Exploratory Aim: We will archive actigraphy data to permit future examination to confirm our preliminary data that actigraphic activity decreases as suicidal ideation resolves.

Overview of the Need for and Management of a Collaborative Application: The sample sizes required to satisfy the Aims are relatively large, necessitating the pooled recruiting resources of 3 sites. Georgia Regents University (GRU) will serve both as the coordinating/data management site, as well as a recruiting site, with Duke and Wisconsin as recruiting sites. Project management will be coordinated through an Executive Committee of site principal investigators, under the supervision of a Data and Safety Monitoring Board.

Impact on the Field: This application has the potential to change providers' practice in the approach to treating insomnia in depressed patients with mild-moderate suicidal ideation. It may also reveal the mechanisms whereby insomnia increases the risk for suicidal ideation and behavior, and begin to examine whether there is an actigraphic "signature" for reductions in suicidal ideation. When these lessons are applied to the clinical world, they can be applied with low cost.

Eligibility criteria: Inclusion Criteria:

* Persons 18-65 years of age
* Persons with confirmed DSM-IV diagnosis of MDE by SCID
* Persons with Research Diagnostic Criteria diagnosis of insomnia
* Persons free of all psychotropic medications for one week before baseline assessment, except that prior FLX treatment will require 4 weeks of abstinence, and MAOIs will require 2 weeks of abstinence.
* Persons with Scale for Suicide Ideation (SSI) scores \>2
* Persons with Hamilton Rating Scale for Depression (HRSD24) score \>20
* Persons with Mini Mental State Exam (MMSE) score \>24
* Persons with Insomnia Severity Index (ISI) score \> 7
* Persons with habitual sleep latency \> or = 30 minutes or wake time in the middle of the night of \> or = 30 minutes, and sleep efficiency \< 85%

Exclusion Criteria:

* Non-English speaking, reading, writing persons
* Persons who pose imminent danger to self or others
* Persons with severe suicidal ideation (C-SSRS Suicidal Ideation Score \>3)
* Persons with clinical diagnosis of dementia
* Persons with active or past diagnosis of alcohol or substance abuse, bipolar disorder, schizophrenia per the SCID
* Persons who screen positive for moderate-severe sleep apnea (AHI \>10) or a prior sleep laboratory-confirmed diagnosis of a primary sleep disorder, such as sleep apnea or periodic limb movement disorder.
* Persons with BMI \> 50
* Persons with a self-reported history of napping \> 2 times per week (as these are associated with sleep apnea and periodic limb movement disorder in depressed insomniacs)
* Persons who might be harmed by exposure to hypnotics, including pregnant women and patients with respiratory conditions

Primary outcomes:
measure: Scale for Suicide Ideation Index (SSI)
timeFrame: Over 8 weeks of treatment
measure: Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale
timeFrame: 8 weeks of treatment
Secondary outcomes:
measure: Dysfunctional Beliefs and Attitudes About Sleep
timeFrame: 8 weeks of treatment
measure: Disturbing Dreams and Nightmares Severity Index (DDNSI)
timeFrame: 8 weeks of treatment
measure: Beck Hopelessness Scale (BHS)
timeFrame: 8 weeks of treatment
measure: Hamilton Rating Scale for Depression (HAM-D)
timeFrame: 8 weeks of treatment
measure: Insomnia Severity Index (ISI)
timeFrame: 8 weeks of treatment
Other outcomes:
measure: Basis-32 - the Daily Living and Role Functioning (DLRF) Subscale
timeFrame: 8 weeks of treatment
measure: Actigraphy
timeFrame: 8 weeks of treatment
Locations:
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Wake Forest
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Madison
country: United States
facility: University of Wisconsin- Madison
state: Wisconsin
Study officials:
affiliation: Augusta University
name: William V McCall, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Witt KG, Hetrick SE, Rajaram G, Hazell P, Taylor Salisbury TL, Townsend E, Hawton K. Psychosocial interventions for self-harm in adults. Cochrane Database Syst Rev. 2021 Apr 22;4(4):CD013668. doi: 10.1002/14651858.CD013668.pub2.
citation: McCall WV, Benca RM, Rumble ME, Krystal AD. Blinding and bias in a hypnotic clinical trial. Hum Psychopharmacol. 2021 Jan;36(1):1-5. doi: 10.1002/hup.2757. Epub 2020 Sep 11.
citation: Rumble ME, McCall WV, 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 Aug 15;16(8):1311-1319. doi: 10.5664/jcsm.8508.
citation: McCall WV, Benca RM, Rosenquist PB, Youssef NA, McCloud L, Newman JC, Case D, Rumble ME, Szabo ST, Phillips M, Krystal AD. Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT): A Randomized Clinical Trial. Am J Psychiatry. 2019 Nov 1;176(11):957-965. doi: 10.1176/appi.ajp.2019.19030267. Epub 2019 Sep 20.
citation: McCall WV, Benca RM, Rumble ME, Case D, Rosenquist PB, Krystal AD. Prevalence of obstructive sleep apnea in suicidal patients with major depressive disorder. J Psychiatr Res. 2019 Sep;116:147-150. doi: 10.1016/j.jpsychires.2019.06.015. Epub 2019 Jun 19.