Reducing Suicidal Ideation Through Insomnia Treatment

NCT ID: NCT01689909

Last Updated: 2022-02-16

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

103 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-12-06

Study Completion Date

2018-01-01

Brief Summary

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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

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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.

Conditions

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Insomnia Depression Suicidal Ideation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Zolpidem-CR

Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks

Group Type ACTIVE_COMPARATOR

Zolpidem-CR

Intervention Type DRUG

Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks

Placebo

Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks

Interventions

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Zolpidem-CR

Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks

Intervention Type DRUG

Placebo

Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks

Intervention Type DRUG

Other Intervention Names

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Ambien CR

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role collaborator

Augusta University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William V McCall, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Augusta University

Locations

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Georgia Regents University

Augusta, Georgia, United States

Site Status

Duke University School of Medicine

Durham, North Carolina, United States

Site Status

Wake Forest University School of Medicine

Wake Forest, North Carolina, United States

Site Status

University of Wisconsin- Madison

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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McCall WV, Mercado K, Dzurny TN, McCloud LL, Krystal AD, Benca RM, Rosenquist PB, Looney SW. Insomnia and the effect of zolpidem-extended-release on the sleep items of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia, and suicidal ideation: Relationship to patient age. J Psychopharmacol. 2024 Sep;38(9):827-831. doi: 10.1177/02698811241268900. Epub 2024 Aug 9.

Reference Type DERIVED
PMID: 39119911 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33884617 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32918323 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32329435 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31537089 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31238203 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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1R01MH095776

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01MH095776-01A1

Identifier Type: NIH

Identifier Source: org_study_id

View Link

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