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Lithium for Suicidal Behavior in Mood Disorders (Li+)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2014 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01928446
First received: August 15, 2013
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Depressive Disorder
Bipolar Disorder
Suicide
Suicide, Attempted
Drug: Lithium
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: CSP #590 - Lithium for Suicidal Behavior in Mood Disorders

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]

    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. We 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.



Estimated Enrollment: 1862
Study Start Date: January 2015
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 patients 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).

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  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Survived an episode of suicidal self-directed violence (including suicide attempts and interrupted attempts) that occurred within three months of admission to the study, or they were admitted within the past three 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 and primary care providers 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

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:

    • Diuretics
    • Angiotensin Converting Enzyme Inhibitors
    • Angiotensin II Receptor Antagonists
    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01928446

Contacts
Contact: Matthew Liang, MD (857) 364-6116 Matthew.Liang@va.gov
Contact: Natalie C Morgenstern, MPH (857) 364-5495 Natalie.Morgenstern@va.gov

  Show 29 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Ira R. Katz, MD PhD Philadelphia VA Medical Center, Philadelphia, PA
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01928446     History of Changes
Other Study ID Numbers: 590
Study First Received: August 15, 2013
Last Updated: September 16, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Lithium
Placebos
Double-blind methods
Clinical Trials, Randomized
Veterans

Additional relevant MeSH terms:
Mood Disorders
Affective Disorders, Psychotic
Bipolar Disorder
Depression
Depressive Disorder
Disease
Suicide
Suicide, Attempted
Behavioral Symptoms
Mental Disorders
Pathologic Processes
Self-Injurious Behavior
Lithium
Lithium Carbonate
Antidepressive Agents
Antimanic Agents
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 27, 2014