Reducing Suicidal Ideation Through Insomnia Treatment

Study Overview
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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.

Official Title
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Reducing Suicidal Ideation Through Insomnia Treatment

Conditions
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Insomnia, Depression, Suicidal Ideation

Intervention / Treatment
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* Drug: Zolpidem-CR
* Drug: Placebo


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zolpidem-CR<br>Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks | Drug: Zolpidem-CR<br>* Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks<br>* Other names: Ambien CR;|
| Placebo Comparator: Placebo<br>Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks | Drug: Placebo<br>* Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scale for Suicide Ideation Index (SSI) | This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation | Over 8 weeks of treatment | 
| Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale | The suicide ideation scale of the C-SSRS is rated 0-5, with 0 meaning no suicidal ideation, 1 meaning a wish t be dead, 2 meaning non-specific active suicidal thoughts, 3 meaning active suicidal ideation with any methods but no plan or intent, 4 meaning active suicidal ideation with some intent but no specific plan, and 5 meaning active suicidal ideation with intent and a specific plan | 8 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dysfunctional Beliefs and Attitudes About Sleep | The Dysfunctional Beliefs and Attitudes About Sleep scale has 16 items and is self administered. Each item is scored 0-10. The total score is an average of the scores of the 16 items. Hence the range of the total score is also 0-10, with higher scores indicating greater dysfunctional beliefs about sleep | 8 weeks of treatment | 
| Disturbing Dreams and Nightmares Severity Index (DDNSI) | This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares | 8 weeks of treatment | 
| Beck Hopelessness Scale (BHS) | The Beck Hopelessness Scale is self administered and has 20 'true/false' choices. Some items are reversed scored. The range of scores for the total is 0-20, with higher scores indicating greater hopelessness | 8 weeks of treatment | 
| Hamilton Rating Scale for Depression (HAM-D) | This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression | 8 weeks of treatment | 
| Insomnia Severity Index (ISI) | The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia | 8 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insomnia, Depression, Suicidal ideation, Zolpidem CR, Placebo