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Lithium for Suicidal Behavior in Mood Disorders (Li+)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01928446
Recruitment Status : Active, not recruiting
First Posted : August 26, 2013
Last Update Posted : April 22, 2019
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:

Observational evidence and findings from clinical trials conducted for other reasons suggest that lithium, a drug used for the treatment of bipolar disorder, and, to a lesser extent, depression, may reduce rates of suicides and suicide attempts. However, this hypothesis has not yet been adequately examined in a randomized clinical trial conducted specifically to test lithium's efficacy in preventing suicides. This clinical trial fills this gap.

This study is feasible within the Department of Veterans Affairs (VA) because it is a large, integrated health system with existing programs for identifying patients at risk for suicide and delivering enhanced services. In VA, approximately 12,000 patients with depression or bipolar disorder survive a suicide attempt or related behavior each year, and 15% of them repeat within one year. Experimental treatment in this study will supplement usual care for major depression or bipolar disorder, as well as VA's standard, enhanced management for patients at high risk.

The investigators will recruit 1862 study participants, from approximately 30 VA Hospitals. Participants will be patients with bipolar disorder or depression who have survived a recent episode of suicidal self-directed violence or were hospitalized specifically to prevent suicide. Randomly, half will receive lithium, and half will receive placebo. Neither the patients nor their doctors will know whether a particular person has received lithium or placebo. The treatment will be administered and the patients will be followed for one year, after which patients will go back to usual care. Recruitment will occur over 3 years.

The investigators are primarily interested in whether lithium leads to increases in the time to the first repeated episode of suicidal behavior, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide. In addition, this study will allow us to explore whether lithium decreases the total number of suicidal behaviors, and whether it has comparable effects on impulsive and non-impulsive behaviors. If there is an effect of lithium, the investigators will be interested in whether or not it could be attributed to improved control of the underlying mental health condition, or, alternatively, whether it represents a direct effect of suicide-related behavior.

Condition or disease Intervention/treatment Phase
Depressive Disorder Bipolar Disorder Suicide Suicide, Attempted Drug: Lithium Drug: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1862 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: CSP #590 - Lithium for Suicidal Behavior in Mood Disorders
Actual Study Start Date : July 8, 2015
Estimated Primary Completion Date : May 31, 2019
Estimated Study Completion Date : August 30, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Lithium
Lithium in the form of extended release lithium carbonate. Subjects will be started on 600 mg/day (300mg bid) until steady state at target plasma levels between 0.6 and 0.8 meq/liter is achieved. The lowest dose will be 300 mg/day. Lithium will be prescribed for the duration of follow-up (1 year).
Drug: Lithium
Lithium in the form of extended release lithium carbonate. Subjects will be started on 600 mg/day (300mg bid) until steady state at target plasma levels between 0.6 and 0.8 meq/liter is achieved. The lowest dose will be 300 mg/day. Lithium will be prescribed for the duration of follow-up (1 year).

Placebo Comparator: Placebo
Placebo tablets will be given to the subjects for the duration of follow-up (1 year). Dose adjustments will mimic the intervention arm of the study
Drug: Placebo
Oral placebo tablets will be administered for the duration of follow-up (1 year).

Primary Outcome Measures :
  1. Time to the first repeated episode of suicidal self-directed violence, including suicide attempts, interrupted attempts and hospitalizations for prevention of attempts. [ Time Frame: Primary outcome is assessed from randomization up to 12 months. ]

    The primary hypothesis tested is that lithium augmentation of enhanced usual care is superior to enhanced usual care plus placebo for the prevention of repeated episodes of suicidal self-directed violence over time. The investigators posit a one-year repeat rate of 15% in the placebo group and a 37% reduction of events in the intervention group.

    Suicidal self-directed violence includes non-fatal suicide attempts, interrupted attempts (attempts interrupted by patient or by others), hospitalization to prevent suicide and deaths from suicide.

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Must be a Veteran of the United States Armed Forces
  • Survived an episode of suicidal self-directed violence (including suicide attempts and interrupted attempts) that occurred within six months of admission to the study, or they were admitted within the past six months to a mental health inpatient unit specifically to prevent suicide
  • Have a diagnosis of an affective disorder meeting DSM-IV-TR (2000) criteria for Bipolar I Disorder, Bipolar II Disorder, or current or recurrent Major Depressive Disorder
  • Are able and willing to identify one or more family members, friends, or other contacts and give permission for both clinical providers and the Research Team to contact them if the patient cannot be reached
  • Are able to provide informed consent
  • There is concurrence from the patient's mental health provider about inclusion/exclusion criteria and confirmation of the providers' willingness to work with the research team in managing the patient during the course of the study. The provider responsible for the patient's general medical care has been made aware of the participation
  • Must be registered at a VA Medical Center

Exclusion Criteria:

  • Schizophrenia or schizoaffective disorder
  • Cognitive impairment defined as a Brief Orientation Memory and Concentration Test score > 10
  • Lack of decision-making capacity to evaluate the risks versus the benefits of participation as determined by Jeste's brief instrument for assessing decisional capacity, or adjudication of incompetence and the appointment of a guardian or conservator
  • Six or more previous lifetime suicide attempts as ascertained through SPAN, reports from family, or patient self-report
  • Current or recent (within six months) use of lithium
  • History of significant adverse effects of lithium as ascertained through the medical record or self-report
  • Unstable medical conditions or specific medical comorbidity:

    • Congestive heart failure by Framingham criteria
    • QTc greater than or equal to 450 ms for men and greater than or equal to 460 ms for women
    • Chronic renal failure defined by national Kidney Foundation Disease Outcome Quality Initiative (KDOQI) criteria
  • Any possibility of being pregnant or not on appropriate birth control
  • Lactation and breastfeeding
  • Concurrent medications:

    • All diuretics except amiloride
    • Haloperidol
    • Clozapine
  • Active substance abuse:

    • Active alcohol or opiate dependence requiring medically supervised withdrawal and stabilization
    • Active cocaine, methamphetamine, other stimulant, hallucinogen, or cannabis abuse requiring stabilization
  • Enrollment in another randomized interventional clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01928446

  Show 28 Study Locations
Sponsors and Collaborators
VA Office of Research and Development
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Study Chair: Ira R Katz, MD PhD Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

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Responsible Party: VA Office of Research and Development Identifier: NCT01928446     History of Changes
Other Study ID Numbers: 590
First Posted: August 26, 2013    Key Record Dates
Last Update Posted: April 22, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual Participant Data will be made available after study closure only to research credentialed Veterans Affairs researchers who submit a valid study question to their IRB of record. A Data Use Agreement will be in effect between the researcher and the coordinating center

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by VA Office of Research and Development:
Double-blind methods
Clinical Trials, Randomized

Additional relevant MeSH terms:
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Depressive Disorder
Bipolar Disorder
Mood Disorders
Suicide, Attempted
Pathologic Processes
Mental Disorders
Behavioral Symptoms
Bipolar and Related Disorders
Self-Injurious Behavior
Lithium Carbonate
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs