Lithium for Suicidal Behavior in Mood Disorders

NCT01928446 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 590
• Study Type: interventional
• Target: 519
• Locations: 1 country
• Sites: 28

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.

Conditions

Depressive Disorder; Bipolar Disorder; Suicide; Suicide, Attempted

Keywords

Lithium; Placebo; Double-blind methods; Clinical Trials, Randomized; Veterans

Outcome Measures

Primary Outcomes (2)

• Time to Event Hazard Rate. Event is a First Repeated Episode of Suicide Related Event, Including Suicide Attempts, Interrupted Attempts and Hospitalizations for Prevention of Attempts.

  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.

  1 year

• Number of Compliant Participants With Episode of Self-directed Violence (Per Protocol Analyses)

  Compliance is defined as taking 80% or more of study medication over the entire clinical trial. Episode of self-directed violence is defined as: First Repeated Episode of Suicide Related Event, Including Suicide Attempts, Interrupted Attempts, Hospitalization to Prevent Suicide and death.

  1 year

Secondary Outcomes (1)

• Number of Participants With Subtypes of Suicidal Self-directed Violence for All Recurring Events

  1 year

Study Arms (2)

Lithium

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Lithium DRUG

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).

Lithium

Placebo DRUG

Oral placebo tablets will be administered for the duration of follow-up (1 year).

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Must be registered at a VA Medical Center
• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (28)

Phoenix VA Health Care System, Phoenix, AZ

Phoenix, Arizona, 85012, United States

Location

Southern Arizona VA Health Care System, Tucson, AZ

Tucson, Arizona, 85723, United States

Location

Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR

North Little Rock, Arkansas, 72114-1706, United States

Location

VA Loma Linda Healthcare System, Loma Linda, CA

Loma Linda, California, 92357, United States

Location

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1290, United States

Location

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161, United States

Location

VA Eastern Colorado Health Care System, Denver, CO

Denver, Colorado, 80220, United States

Location

Miami VA Healthcare System, Miami, FL

Miami, Florida, 33125, United States

Location

Orlando VA Medical Center, Orlando, FL

Orlando, Florida, 32803, United States

Location

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033, United States

Location

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, 60141-5000, United States

Location

Richard L. Roudebush VA Medical Center, Indianapolis, IN

Indianapolis, Indiana, 46202-2884, United States

Location

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130, United States

Location

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, 55417, United States

Location

VA Southern Nevada Healthcare System, North Las Vegas, NV

Las Vegas, Nevada, 89106, United States

Location

VA Sierra Nevada Health Care System, Reno, NV

Reno, Nevada, 89502, United States

Location

Asheville VA Medical Center, Asheville, NC

Asheville, North Carolina, 28805, United States

Location

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106, United States

Location

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97239, United States

Location

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Philadelphia, Pennsylvania, 19104-4551, United States

Location

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

Pittsburgh, Pennsylvania, 15240, United States

Location

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, 75216, United States

Location

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

Location

Central Texas Veterans Health Care System, Temple, TX

Temple, Texas, 76504, United States

Location

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, 84148, United States

Location

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108, United States

Location

William S. Middleton Memorial Veterans Hospital, Madison, WI

Madison, Wisconsin, 53705, United States

Location

Clement J. Zablocki VA Medical Center, Milwaukee, WI

Milwaukee, Wisconsin, 53295-1000, United States

Location

Related Publications (1)

• Katz IR, Rogers MP, Lew R, Thwin SS, Doros G, Ahearn E, Ostacher MJ, DeLisi LE, Smith EG, Ringer RJ, Ferguson R, Hoffman B, Kaufman JS, Paik JM, Conrad CH, Holmberg EF, Boney TY, Huang GD, Liang MH; Li+ plus Investigators. Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Jan 1;79(1):24-32. doi: 10.1001/jamapsychiatry.2021.3170.

  PMID: 34787653 RESULT

MeSH Terms

Conditions

Depressive Disorder; Bipolar Disorder; Suicide; Suicide, Attempted

Interventions

Lithium

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Bipolar and Related Disorders; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Results Point of Contact

• Title: Ryan E. Ferguson, ScD, MPH, Director
• Organization: Boston CSP Coordinating Center

Ryan.Ferguson@va.gov

1-857-364-4201

Study Officials

• Ira R Katz, MD PhD

  Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2013
• First Posted: August 26, 2013
• Study Start: July 8, 2015
• Primary Completion: August 13, 2019
• Study Completion: August 13, 2019
• Last Updated: April 29, 2024
• Results First Posted: June 24, 2021

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

US (28)